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INTRODUCTION: Transoral incisionless fundoplication (TIF) with the EsophyX(™) device is reported to be effective for creating a continent gastroesophageal valve and for good functional results, as measured by pH impedance in patients with gastroesophageal reflux disease (GERD). The aim of this study is to assess the long-term effect of TIF in patients with symptomatic GERD. PATIENTS AND METHODS: TIF 2.0 fundoplication was done in 42 consecutive patients. All were studied with GERD-HRQL and GERD-QUAL questionnaires, upper gastrointestinal (GI) endoscopy, esophageal manometry, and 24 h pH impedance before and at 6, 12, and 24 months after TIF. RESULTS: In all, 35 patients completed 6-month follow-up; 21 (60.0%) completely stopped proton pump inhibitor (PPI) therapy, 6 (17.1%) more than halved it, and 8 (22.9%) continued with the same dose as before the procedure. There were 26 patients with complete 24-month follow-up; 11 (42.3%) completely stopped PPI therapy, 7 (26.9%) more than halved it, and 8 (30.8%) were taking the same dose as before the procedure. Hiatal hernia and ineffective esophageal motility seemed to raise the risk of recurrence of symptoms (p = 0.02 and p < 0.001, respectively). The number of fasteners deployed during TIF was the only factor predictive of successful outcome (p = 0.018). CONCLUSIONS: TIF using the EsophyX device allowed withdrawal or reduction of PPI in about 77% of patients at 6-month follow-up and about 69% at 24 months. Larger number of fasteners deployed during TIF was predictive of positive outcome; pre-TIF ineffective esophageal motility and hiatal hernia raised the risk of recurrence of GERD symptoms, but were not significant from a prospective point of view.

In a previous uncontrolled study, a reduction of rectal distensibility and volume thresholds for sensations have been related to the occurrence of fecal urgency and/or increased stool frequency after stapled hemorrhoidopexy. The aim of this study was to compare rectal symptoms and sensory-motor function after stapled hemorrhoidopexy and Milligan–Morgan hemorrhoidectomy. The clinical records of 12 (four women) and ten patients (four women) with third- and fourth-degree hemorrhoids, respectively, who underwent stapled hemorrhoidopexy or Milligan–Morgan’s hemorrhoidectomy, were evaluated. One week before and 6 months after surgery, rectal motor and sensory response to distension was assessed by an electronic barostat, and bowel and rectal symptoms were recorded by means of a 7-day diary and Bristol Index scale and psychological symptoms with SCL-90 questionnaire. Rectal distensibility and volume thresholds for sensations were significantly lower after surgery (P

Stapled hemorrhoidopexy is designed to replace the hemorrhoids into the anal canal by excising the redundant rectal mucosa above the anorectal ring, thus resulting in an intrarectal suture. Few studies have evaluated rectal function after this procedure. This prospective study was designed to use the electronic barostat to assess whether rectal motor and sensory functions change after stapled hemorrhoidopexy.Ten patients (4 women, mean age, 46 +/- 9 years) with third-degree and fourth-degree hemorrhoids who underwent stapled hemorrhoidopexy were studied. One week before and six months after surgery, they underwent three different rectal distensions (pressure-controlled stepwise, volume-controlled stepwise, and ramp) controlled by an electronic barostat.Rectal distensibility was significantly lower after surgery during pressure stepwise (P = 0.01), during volume stepwise (P = 0.006), and during ramp distension (P = 0.001). Volume thresholds for desire to defecate, urgency, and discomfort were significantly lower after surgery during all three distensions (P0.05). Volume threshold for first perception also was significantly lower after surgery during volume ramp distension (P = 0.01).Rectal distensibility and volume thresholds for sensations decrease after stapled hemorrhoidopexy. These impairments persist for at least six months after surgery.

Based on improvements of abdominal pain during treatment, more recently introduced drug treatments for constipation, tegaserod, lubiprotsone and linaclotide, sought and obtained approval for irritable bowel syndrome with constipation (IBS-C) as well. The aim of the current study was to determine whether the observed decreases in pain level were unique effects or a consequence of their laxative properties, which can also be seen in other agents. METHODS: The pubmed databank was searched for clinical trials in constipation and IBSC to identify publications that provided detailed data on changes in bowel movement frequency and pain intensity for time points before and after a therapeutic intervention. The results were abstracted and subjected to a meta-regression analysis. RESULTS: A total of 23 fully reported trials (9 IBS-C) met entry criteria. When normalized to a 5 point scale, pain ratings were higher in IBS-C 2.50 [2.32-2.68] compared to data obtained in studies on constipation (2.15 [1.96-2.33]; P=0.008), while weekly bowel movement frequency were lower in constipation with 1.95 [1.68-2.28] versus 2.75 [2.40-3.11] in IBS-C (P=0.006). Using changes in pain intensity as dependent variable, the meta-regression demonstrated a significant correlation between treatment-induced increases in bowel frequency and decreased pain ratings. CONCLUSION: This analysis of composite data suggests that the effective treatment of constipation decreases discomfort independent of specific drug mechanisms, thus arguing against an additional benefit of newer and often more costly medications.

G A A b st ra ct s overlapping (PD and ED) had the lowest scores in the 5 components of PAGI-QOL (P

Treatment of opioid-induced constipation (OIC) is becoming a relevant clinical challenge as most of the treatments demonstrated to be more effective than placebo in treating OIC have safety issues limiting a broad clinical application. Naloxegol is the first orally administered, peripherally acting, µ opioid receptor antagonist approved by the FDA and EMA specifically for the treatment of noncancer patients with OIC. This review summarizes the results of the studies regarding the effects of naloxegol in OIC. Pharmacodynamic studies have demonstrated that naloxegol was able to inhibit gastrointestinal opioid effects while preserving central analgesic actions. Phase II and phase III studies in patients with noncancer OIC have confirmed the efficacy of naloxegol to inhibit OIC, and the most consistent efficacy was seen with the 25-mg dose once daily. Side effects were mainly gastrointestinal in origin (and usually transient and mild) and there were no signs of opioid withdrawal in the studies. Safety and tolerability were shown in a long-term safety study. Considering its efficacy, safety, route of administration and the limitations of most of the other available treatments, naloxegol has the potential to become the first-line treatment for noncancer patients with OIC.

Summary Background It is unclear whether decreased serotonin transporter function contributes to sensorimotor abnormalities in irritable bowel syndrome. Aim To study the influence of acute serotonin transporter inhibition on colonic sensorimotor function in man. Methods Ten healthy subjects (five men, aged 20–29 years) underwent a combined manometry/barostat study of the descending colon on two occasions. Stepwise distentions by 2 mmHg increments were performed until discomfort. Subsequently, placebo or citalopram 20 mg were administered i.v. over 20 min and distentions were repeated. Afterwards, isobaric tone measurements were performed 30 min before and 90 min after ingestion of a meal. High-amplitude propagated contractions, colonic motility index, colonic compliance, sensitivity and colonic response to a meal after placebo or citalopram were compared by t-test and two-way anova. Results Citalopram induced a significant increase in colonic motility index (5.6 ± 0.9 to 0.8 ± 1.9 mL*min, P

Perception of colonic distension, which is enhanced in a subset of patients with irritable bowel syndrome, requires activation of mechanoreceptors. In animal studies, distension activates both in series ("tension") and in parallel ("elongation") mechanoreceptors. During active contractions against a fixed volume balloon, tension receptors are activated without elongation of receptor activation.To evaluate the role of tension receptors in the perception of mechanical stimuli from the colon in healthy subjects.A 700 ml balloon connected to a barostat-manometer assembly was placed in the descending colon of 10 healthy subjects. After volume controlled distension (50 ml/2 minutes) to assess the first perception threshold, fixed volume subthreshold distension (122 (16) ml) was maintained for a 30 minute period before and after administration of neostigmine 0.5 mg intravenously. Mean intraballoon pressure, number, amplitude, and duration of contractions, and frequency of sensations were analysed. The period after neostigmine was divided into 10 second intervals and evaluated for the occurrence of contractions and onset of sensations. Fisher's exact test was applied to calculate the sensation-contraction association probability (SAP) as (1.0-p)x100%.Neostigmine increased intraballoon pressure (p0.01), number of contractions (p0.01), and number of sensations (p0.01) per minute in all subjects. In seven of 10 subjects a significant association (SAP95%) was found between sensations and contractions. In the remaining subjects, contractions were not associated with sensations and had lower amplitude (p0.05) and duration (p0.01) compared with contractions in the other seven subjects.In humans, tension receptors are involved in mediating colonic mechanosensitivity.

Background & Aims: Studies in health have shown that tension-sensitive mechanoreceptors mediate sensitivity to gastric distention. A role for these mechanoreceptors in perception or symptoms in hypersensitive functional dyspepsia (FD) has not been established. Tension-sensitive mechanoreceptors are activated during phasic contractions and inactivated during gastric relaxation. The aim of the present study was to investigate whether hypersensitive FD patients perceive spontaneous changes in fundic wall tension and whether fundus-relaxing drugs decrease sensitivity to gastric distention and meal-related symptoms. Methods: Fifty patients were selected after a barostat study established gastric hypersensitivity. In 12 patients, an intragastric balloon was inflated with a fixed volume just below perception thresholds and patients were asked to indicate changes in perception on a keypad, and the relationship between perception and contractions was analyzed. In 20 patients, we studied the influence of the fundus-relaxing drug sumatriptan on sensitivity to gastric distention. In, respectively, 10 and 8 patients, we studied the influence of the fundus-relaxing drugs sumatriptan and clonidine on meal-related symptoms. Results: The majority of patients had a statistically significant association between perception and phasic isovolumetric contractions. Pretreatment with sumatriptan increased both pressures and volumes needed to induce first perception and discomfort. Pretreatment with sumatriptan and clonidine both significantly decreased meal-induced symptoms. Conclusions: Patients with hypersensitivity to gastric distention perceive isovolumetric phasic contractions of the proximal stomach. Fundus-relaxing drugs decrease sensitivity to gastric distention and decrease meal-induced symptoms in these patients. The findings are compatible with involvement of tension mechanoreceptors in symptom generation in hypersensitive FD.

Epidemiological studies suggest considerable overlap between functional dyspepsia (FD) and irritable bowel syndrome (IBS).The aim of the present study was to investigate whether coexisting IBS is also associated with symptom pattern or pathophysiology in FD.In 309 consecutive FD patients (207 women, age 42 +/- 0.8 yr), questionnaires were used to assess the dyspepsia symptom pattern and the Rome II criteria for IBS. The overall symptom severity was calculated adding the severity score (0-3, 0 = absent, 3 = severe) of eight dyspepsia symptoms. All patients underwent Helicobacter pylori testing, gastric barostat to determine sensitivity to distention and accommodation to a meal, and gastric emptying breath test.Fifty-four percent of the patients had FD alone, whereas 46% had FD + IBS. FD + IBS patients were more likely to be female (75%vs 60%, p0.01) and to have a greater weight loss (5.4 +/- 0.6 vs 3.5 +/- 0.4 kg, p0.05). Coexisting IBS did not increase the risk of having any of the dyspeptic symptoms but the overall symptom severity was significantly higher in FD + IBS (12.4 +/- 0.4 vs 9.8 +/- 0.3, p0.01). FD + IBS patients had a lower threshold for first perception (2.9 +/- 0.3 vs 3.8 +/- 0.3 mmHg, p0.05) and for discomfort (7.9 +/- 0.4 vs 9.5 +/- 0.5 mmHg, p0.05) and a greater prevalence of hypersensitivity to gastric distention (44%vs 28%, p0.05). Gastric emptying, accommodation to a meal, and prevalence of H. pylori infection did not differ in the two groups.About half of the FD patients fulfill the Rome II criteria for IBS. FD + IBS is more prevalent in female patients and is associated with a higher weight loss, with greater overall symptom severity, and with hypersensitivity to distention.

Tegaserod is a selective partial agonist acting on serotonergic type 4 receptors (5-HT(4)). Pharmacodynamic studies indicate that tegaserod is able to stimulate gut propulsion and secretion with a net prokinetic effect. In contrast to other 5-HT(4) agonists endowed with a complex pharmacological profile, tegaserod has a reliable prokinetic activity in the colon. Clinical trials show that tegaserod is effective and safe in the treatment of patients with irritable bowel syndrome. In particular, tegaserod relieves symptoms of abdominal pain, discomfort, abdominal bloating and constipation.

Few data exist on the prevalence of genetic hemochromatosis among diabetic patients.To compare the prevalence of genetic hemochromatosis in diabetic patients and a matched control group and to evaluate the accuracy of iron-related indexes in detecting hemochromatosis.Cross-sectional study.Diabetes clinics of four hospitals in northern Italy.894 diabetic patients (117 with type 1 diabetes and 777 with type 2 diabetes) and 467 matched controls.Transferrin saturation and serum ferritin levels were measured in all study participants. After secondary iron overload was excluded as the cause of persistently elevated transferrin saturation and serum ferritin levels, liver biopsy was performed and siderosis was estimated semiquantitatively and quantitatively. A hepatic iron index greater than 1.9 was considered diagnostic for hemochromatosis.Hemochromatosis was diagnosed in 12 patients with type 2 diabetes (prevalence, 1.34% [95% CI, 0.7% to 2.3%]) and 1 control (prevalence, 0.2% [CI, 0.1% to 1.4%]; P = 0.032). The odds ratio of hemochromatosis in association with diabetes was 6.3 (CI, 1.1 to 37.7). Measurement of transferrin saturation was the most sensitive test for hemochromatosis.Genetic hemochromatosis is frequently not diagnosed in patients with diabetes, although it is a hallmark of the disease. Screening for hemochromatosis could be beneficial for patients with diabetes.

Background: Handicapped patients with advanced neurological impairment and dysphagia require gastrostomy feeding and are associated with gastroesophageal reflux disease (GERD). Concurrent fundoplication is often recommended at the time of gastrostomy placement (GP) in those patients because of avoiding long-term anti-reflux medication or preventing future reflux symptoms. Fundoplication has recently been thrown doubts about its indication in those patients because of unignorable complications and the high incidence of recurrence of GERD. It was aimed in this study to conduct a retrospective review of the outcome of handicapped patients with GP alone. Methods: The subjects consisted of 60 profoundly handicapped patients requiring tube feeding, aged 1 yr to 33 yrs (median 9 yrs), who underwent GP alone. The operative criteria included no or medically controllable reflux symptoms. Operative procedure was laparoscopic in 53 and open in 7. They were divided into two groups based on % esophageal total time pH

Background and aimsThe functional gastrointestinal disorders (FGIDs) are extremely common conditions associated with a considerable personal, social and health economic burden. Managing FGIDs in clinical practice is challenging because of the uncertainty of symptom-based diagnosis, the high frequency of overlap between these conditions and the limited efficacy of available therapies. It has often been argued that successful drug development and management of FGIDs requires knowledge of the underlying pathophysiology. Numerous and highly variable candidate pathophysiological mechanisms have been implicated in the generation of FGID symptoms, but there is no current consensus on how to best define the relevance of these disturbances.MethodsA group of international experts on FGIDs developed plausibility criteria that should be fulfilled by relevant pathophysiological mechanisms in FGIDs.ResultsFive criteria are proposed: (1) the presence of the abnormality in a subset of patients, (2) temporal association between proposed mechanism and symptom(s), (3) correlation between the level of impairment of the mechanism and symptom(s), (4) induction of the symptom(s) by provoking the pathophysiological abnormality in healthy subjects and (5) treatment response by a therapy specifically correcting the underlying disorder or congruent natural history of symptoms and dysfunction in the absence of specific therapy. Based on strength of evidence for these five criteria according to the Grading of Recommendations Assessment, Development and Evaluation system, a plausibility score can be calculated for each mechanism.ConclusionEvaluation of the strength of evidence for candidate pathophysiological abnormalities fulfilling these five plausibility criteria will help to identify the most relevant mechanisms to target for novel diagnostic approaches and for the development of new therapies.

Increased serum transferrin saturation and ferritin levels have been reported in chronic alcoholics.To evaluate modifications in serum iron-related indexes in chronic alcohol abusers with and without cirrhosis, at enrolment and after complete alcohol withdrawal.Fifty-one consecutive chronic alcohol abusers, 33 without and 18 with cirrhosis.Liver function tests were performed and transferrin saturation percent and serum ferritin levels measured at time 0 and after 7 and 14 days of complete alcohol withdrawal.Duration of alcohol abuse was significantly longer in patients with cirrhosis than in those without (24 +/- 13 SD vs 18 +/- 13 SD years, p0.01). A concomitant increase in transferrin saturation percent and serum ferritin was found in 60% of the cirrhotics and 45% of the non cirrhotic group. During the observation period, transferrin saturation percent and serum ferritin fell significantly in both groups (from 59 +/- 33 SD to 36 +/- 22% SD, p0.05, and from 900 +/- 933 SD to 469 +/- 457 SD ng/ml, p0.01, in cirrhotics, and from 46 +/- 30 SD to 27 +/- 12% SD, p0.01, and from 702 +/- 602 SD to 340 +/- 29 SD ng/ml, p0.01, in non cirrhotics).Iron-related indexes increase with chronic alcohol abuse and return to normal rapidly after complete alcohol withdrawal. In chronic alcoholics the timing of determinations of iron-related indexes is crucial, and screening for possible concomitant genetic haemochromatosis must be postponed.

A 69-year-old male chronic alcohol abuser suffering from diarrhoea and with a number of discrete pruriginous and erythematous lesions of the trunk was referred to our Unit with a diagnosis of idiopathic eosinophilic colitis in order that we might determine corticosteroid treatment. Diagnosis was based on the presence of marked peripheral eosinophilia and massive eosinophilic infiltration at colonic biopsy, and the exclusion of parasitic infection by means of two different microscopic stool examinations of five samples. However, repeated stool examinations of ten samples collected on separate days and evidence of impaired cell-mediated immunity allowed a definite diagnosis of Strongyloides stercoralis autoinfection or hyperinfection. Due to the poor sensitivity of stool examination in the diagnosis of Strongyloides stercoralis infection, a careful search for this parasite should be made in all patients with comparable clinical findings before formulating a diagnosis of idiopathic eosinophilic colitis, because consequent steroid treatment may have a fatal outcome by inducing widespread dissemination of the parasite.