E Corazziari

Small volume isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in treatment of chronic nonorganic constipation

The present multicenter double-blind placebo-controlled trial evaluates the therapeutic effectiveness of small-volume daily doses of an isosmotic polyethylene glycol (PEG) electrolyte solution in the treatment of chronic nonorganic constipation. After a complete diagnostic investigation, patients still constipated at the end of a four-week placebo-treatment run-in period were enrolled and randomized to receive either placebo or PEG solution 250 ml twice a day for the following eight weeks. Patients were assessed at four and eight weeks of treatment, and they reported frequency and modality of evacuation, use of laxatives, and relevant symptoms daily on a diary card. Oroanal and segmental large-bowel transit times were assessed with radiopaque markers during the fourth week of the run-in period and the last week of the treatment period. During the study period, dietary fiber and liquids were standardized and laxatives were allowed only after five consecutive days without a bowel movement. Of the 55 patients enrolled, five dropped out, three because of adverse events and two for reasons unrelated to therapy; another two were excluded from the efficacy analysis because of protocol violation. Of the remaining 48 patients (37 women, age 42±15 years, mean±sd), 23 were assigned to placebo and 25 to PEG treatment. In comparison to placebo, PEG solution induced a statistically significant increase in weekly bowel frequency at four weeks and at the end of the study (PEG: 4.8±2.3 vs placebo: 2.8±1.6;P<0.002) and a significant decrease in straining at defecation (P<0.01), stool consistency (P<0.02), and use of laxatives (P<0.03). Oroanal, left colon, and rectal transit times were significantly shortened by PEG treatment. There was no difference between controls and PEG-treated patients as far as abdominal symptoms and side effects were concerned. In conclusion, PEG solution at 250 ml twice a day is effective in increasing bowel frequency, accelerating colorectal transit times, and improving difficult evacuation in patients with chronic nonorganic constipation and is devoid of significant side effects.

Crohn's disease: A comparative prospective study of transabdominal ultrasonography, small intestine contrast ultrasonography, and small bowel enema

Background: Small intestine contrast ultrasonography (SICUS), when performed after distention of the small bowel lumen with an iso‐osmolar polyethylene glycol electrolyte‐balanced solution, shows high sensitivity (100%) and specificity (97%) in detecting small bowel abnormalities in patients who have not received a diagnosis but in whom there is a suspicion of intestinal diseases. The diagnostic yield of SICUS remains to be established in detecting small bowel lesions in patients with proven Crohns disease (CD) in comparison with transabdominal ultrasonography (TUS), and in relationship to the experience of the operator, using small bowel enema (SBE) as the “gold standard.” Aim: The aim of this study was to evaluate the diagnostic value of SICUS, when performed by a sonologist with 1 year of experience, and TUS, when performed by a sonologist with 10 years of experience, compared to SBE in the assessment of the site, extension, and stenosis of small intestinal lesions in CD patients. Patients and Methods: A total of 28 consecutive patients (men, 16; women, 12; age range, 21 to 60 yr) with a diagnosis of CD underwent TUS and SICUS, which were performed by 2 sonologists who were unaware of the radiologic findings, on the same day. SICUS was performed after the ingestion of 375 mL of a polyethylene glycol contrast solution. A standard SBE was performed on a different day by an expert radiologist who was unaware of the sonographic findings. Results: Sensitivities in the detection of small bowel lesions were 96% for TUS and 100% for SICUS. Compared with SBE, SICUS detected the presence of 4 lesions in the jejunum that had been missed by TUS. The mean (±SD) extent of the ileal disease was 22 ± 12.5 cm when measured during SBE, 14.5 ± 8.6 cm when measured during TUS, and 19.5 ± 12.5 cm when measured during SICUS [P = 0.05 (SICUS versus SBE)]. The correlation of the extension of the lesions between SICUS and SBE (r = 0.88) was better than that between TUS and SBE (r = 0.64). The sensitivities of TUS and SICUS in the detection of at least 1 stricture were 76% and 94%, respectively. Sensitivity and specificity in assessing prestenotic dilatation were 50% and 100%, respectively, at TUS, and 100% and 90%, respectively, at SICUS. Conclusion: In inexperienced hands, SICUS is a more accurate technique for assessing CD lesions, and the accuracy is better than that of TUS performed by an expert sonologist. The use of SICUS, instead of SBE, could be indicated for the follow‐up of patients with CD.

Small intestine contrast ultrasonography: an alternative to radiology in the assessment of small bowel disease.

Background: Radiology and transabdominal ultrasonography (TUS) are used in the evaluation of the small bowel; however, the former technique is limited by radiation exposure, and the latter by its inability to visualize the entire small bowel. Aim: To evaluate the diagnostic accuracy of small intestine contrast ultrasonography (SICUS) to assess the presence, number, site, and extension of small bowel lesions. Subjects and Methods: TUS, SICUS, and small bowel follow‐through (SBFT) were performed in 148 consecutive patients (78 women; age range, 12 to 89 yr), 91 with undiagnosed conditions, and 57 with previously diagnosed Crohns disease (CD). Results: In the undiagnosed patients, the sensitivity and specificity of TUS and SICUS were 57% and 100%, and 94.3% and 98%, respectively. In the CD patients, the sensitivity of TUS and SICUS was 87.3% and 98%, respectively. In comparison with SBFT, the extension of lesions was correctly assessed with SICUS and greatly underestimated with TUS. The concordance index between SBFT and SICUS for the number and site of lesions was 1 and 1 (P < 0.001), respectively, in undiagnosed patients, and 0.81 and 0.83 (P < 0.001), respectively, in CD patients. Between SBFT and TUS, the concordance index was 0.28 and 0.27 (not significant), respectively, in undiagnosed patients, and 0.28 and 0.31 (not significant), respectively, in CD patients. Conclusions: The diagnostic accuracy of SICUS is comparable to that of a radiologic examination, and is superior to that of TUS in detecting the presence, number, extension, and sites of small bowel lesions. These findings support the use of noninvasive SICUS for an initial investigation when small bowel disease is suspected and in the follow‐up of CD patients.

Effect of wheat bran in treatment of chronic nonorganic constipation : a double-blind controlled trial

After a two-week basal period, 24 patients were randomly allocated to receive, with a crossover double-blind design, for two consecutive four-week periods, bran (20 g/24 hr) or placebo. The daily intake of water and dietary fibers was standardized. Symptomatology, oroanal transit time, bowel frequency, and stool weight were assessed in basal conditions and at week 4 and 8 of the treatment. Oroanal transit time decreased and bowel frequency and stool weight increased significantly during both bran and placebo administration in comparison with basal period. Bran treatment was more effective than placebo in improving bowel frequency and oroanal transit. During bran treatment oroanal transit time became normal only in patients with slow colonic transit and not in those with slow rectal transit. Neither the occurrence nor the severity of the most frequent accompanying symptoms of chronic constipation differed significantly between placebo and bran treatments.

Gastrointestinal transit time, frequency of defecation, and anorectal manometry in healthy and constipated children.

Total gastrointestinal transit time (TGITT), frequency of defecation, and anorectal manometry were evaluated in 63 pediatric patients referred for chronic nonorganic constipation; in 39, segmental transit times of the right and left colon and rectum were also measured. TGITT was significantly longer in chronically constipated children than in matched normal controls. Although bowel frequency was highly significantly correlated with TGITT in patients with prolonged transit time, not all children with prolonged TGITT had reduced bowel frequency. Moreover, not all children with constipation had prolonged TGITT. In children with idiopathic chronic constipation, slowing of intestinal transit occurred most frequently at the level of the distal colon and rectum. Anorectal motility variables were not significantly different in children with functional chronic constipation and in normal children. Maximal resting and pressure and mean intrarectal distending volume causing threshold inhibition in constipated patients did not significantly differ from the control values. Therefore, anorectal manometry did not detect relevant motor abnormalities in constipated children.

Anorectal function in multiple system atrophy and Parkinson's disease

This study was designed to investigate anorectal function in Parkinsons disease and multiple system atrophy (MSA). After a standardized interview, 17 patients with Parkinsons disease (PD) and 16 patients with multiple system atrophy (MSA) underwent anorectal manometry with a continuously perfused multi‐lumen catheter, located to record pressures from the anal canal, and a balloon for rectal distension. Data were analyzed by observers blind to the neurologic diagnosis. Disease duration was shorter in the MSA than in the PD group (6 + 4 versus 10 + 5 yrs, p <0.05). Most patients reported a bowel frequency of less than three evacuations per week and some patients had fecal incontinence. Most manometric recordings disclosed an abnormal pattern during straining (a paradoxic contraction or lack of inhibition) in 13 patients with MSA and 11 patients with PD. Mean anal pressures and rectal sensitivity threshold were not significantly higher in the MSA group, whereas the inhibitory anal reflex and rectal compliance thresholds were within the normal range in both groups. Manometric patterns did not differentiate patients with MSA from patients with PD. Most patients in both groups showed an abnormal straining pattern, decreased anal tone, or both dysfunctions. In conclusion, our findings suggest that although bowel and anorectal dysfunctions do not differentiate MSA from PD, both abnormalities occur earlier and develop faster in MSA than in PD.

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.

Outcome of endoscopic sphincterotomy in post cholecystectomy patients with sphincter of Oddi dysfunction as predicted by manometry and quantitative choledochoscintigraphy

Background: Sphincter of Oddi dysfunction is diagnosed at manometry and, after cholecystectomy, non-invasively at quantitative choledochoscintigraphy. Patients may benefit from endoscopic sphincterotomy. Aims: The aim of this study was to assess the usefulness of choledochoscintigraphy compared with manometry in predicting outcome of sphincterotomy in post cholecystectomy patients with sphincter of Oddi dysfunction. Patients and methods: Thirty patients with biliary-type pain complying with the Rome diagnostic criteria of sphincter of Oddi dysfunction and belonging to biliary group I and II were subjected to clinical evaluation, choledochoscintigraphic assessment of the hepatic hilum-duodenum transit time, endoscopic retrograde cholangiopancreatography, and perendoscopic manometry. Twenty two biliary group I and II patients with prolonged hepatic hilum-duodenum transit times were invited to undergo sphincterotomy. Fourteen patients underwent sphincterotomy; eight refused. Clinical and scintigraphic assessments were performed at follow up. Results: Hepatic hilum-duodenum transit time was delayed in all patients with manometric evidence of sphincter of Oddi dysfunction, in all biliary group I patients and in 64% of biliary group II patients. At follow up, all patients who underwent sphincterotomy were symptom free and hepatic hilum-duodenum transit time had either normalised or significantly improved. A favourable post sphincterotomy outcome was predicted in 93% of cases at choledochoscintigraphy and in 57% at manometry. Conclusions: Quantitative choledochoscintigraphy is a useful and non-invasive test to diagnose sphincter of Oddi dysfunction as well as a reliable predictor of sphincterotomy outcome in post cholecystectomy biliary group I and II patients, irrespective of clinical classification and manometric findings.

Rectal sensitivity in chronic constipation

Rectal sensitivity is often reduced in patients affected by chronic constipation, but it is not known whether this alteration differs according to the severity and the site(s)of the slowing of gastrointestinal transit. Moreover, it is not known whether alteration precedes or follows bowel complaints. In this study, perception of intrarectal distension was evaluated in 28 healthy controls, in 20 patients complaining of constipation and with a normal gastrointestinal transit time (<96hr),and in 44 patients complaining of constipation and with a prolonged gastrointestinal transit time (>96hr).Within the latter group,perception to intrarectal distension was analyzed in patients with slowing of transit in the rectum only, in the colon only, and in both the rectum and the colon. In a subgroup of 22 patients, rectal sensitivity was evaluated before and after treatment. Rectal sensitivity was found to be reduced significantly in constipated patients;it was more severely reduced in patients with objective evidence of prolonged gastrointestinal transit time and with slow transit in the rectum. Rectal sensitivity improved in patients who responded to treatment and did not vary significantly in nonresponders.

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.