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.

Identification of a new coeliac disease subgroup: antiendomysial and anti-transglutaminase antibodies of IgG class in the absence of selective IgA deficiency.

OBJECTIVE: The aim of the present study was to increase the sensitivity of the antiendomysial antibody (EMA) test by evaluating also EMAs of IgG1 isotype. DESIGN AND SUBJECTS: Over the last 2 years, serum EMAs IgA and IgG1 were determined in 1399 patients, referred to our gastrointestinal unit due to clinical suspicion of malabsorption. Serum anti-tissue transglutaminase (tTG) antibodies IgA and IgG, as well as total IgA levels, were also investigated. Furthermore, EMAs IgA and IgG1 were evaluated in biopsy culture supernatants. Biopsy specimens were also admitted to histological and immunohistochemical evaluation. Twenty-six patients with gastroenterological disease other than coeliac disease (CD) were used as a disease control group. Ninety-nine blood donors were used as a healthy control group. RESULTS: Diagnosis of CD was based on histological findings in the 110/1399 patients showing EMA IgA positivity, and in a further 56/1399 patients presenting both EMA IgA and IgG1 positivity in sera as well as in culture supernatants. Of the remaining 1233 EMA IgA-negative patients, 60 showed only EMA IgG1 positivity both in sera and in culture supernatants. It is noteworthy that anti-tissue transglutaminase antibodies IgG (anti-tTG) were positive in all 60 EMA IgG1-positive patients as well. By contrast, a selective IgA deficiency was found in only 11 out of the 60 EMA IgG1-positive patients. Villous height/crypt depth ratio was < 3:1 in 38 of the 60 EMA IgG1-positive patients (63.3%), whilst overexpression of ICAM-1 and CD25 was observed in all these patients. CONCLUSIONS: In this study, we observed a group of CD patients who were EMA IgG1-positive even in the absence of EMA IgA positivity and IgA deficiency. The diagnosis was based on the finding of the gluten-dependent clinical and histological features typical of CD. Data emerging from the present investigation thus suggest that the prevalence of CD should be reassessed and that the determination of EMA IgG1 could offer a new tool in the diagnostic armamentarium of CD.

Combined oral sodium butyrate and mesalazine treatment compared to oral mesalazine alone in ulcerative colitis: randomized, double-blind, placebo-controlled pilot study.

Butyrate represents the main source of energy for colonic epithelial cells; however, its availability/utilization is impaired in ulcerative colitis (UC). In the present randomized, double-blind, placebo-controlled pilot study, the safety and efficacy of colonic targeted oral sodium butyrate tablets, coated with a pH-dependent soluble polymer, have been evaluated in ulcerative colitis. Thirty patients with mild to moderate colitis underwent a six-week course of oral sodium butyrate (4 g/day) plus oral mesalazine (2.4 g/day), (Group A) or of oral mesalazine plus placebo (Group B). Clinical, endoscopic, and histologic data were collected at the beginning and the end of the study. Twenty-five patients completed the study (12 in group A, 13 in group B). No untoward side effects were reported. In group A, seven patients underwent remission and four improved; in Group B the numbers were 5 and 5, respectively. After treatment, all clinical parameters had significantly improved in both treatment arms compared to pretreatment findings. The UC disease activity index (UCDAI) score decreased from 7.27 +/- 2.02 to 2.58 +/- 2.19 (P < 0.05) in the combined treatment group and from 6.07 +/-1.60 to 3.46 +/- 1.98 (P < 0.05) in group B. The endoscopic and histologic scores also significantly improved after treatment in both groups (P < 0.05). The difference between the two treatment arms was not significant, but a significantly better improvement vs baseline values (P < 0.05) was observed in the combined treatment group vs the mesalazine group, when considering both the clinical index (delta9.58 +/- 4.19 vs 5.92 +/- 3.48) and the UCDAI score (delta4.67 +/- 2.19 vs 2.54 +/- 2.18). A more favorable trend, although not significant, was observed for all individual parameters in group A. In conclusion, results of the present pilot study indicate that oral butyrate is safe and well tolerated. These data also suggest that oral butyrate may improve the efficacy of oral mesalazine in active ulcerative colitis and prompt the need of a large scale investigation to confirm the present findings.

From Roma88 to Roma99: back to the future.

Some objectives of the Rome International Congress of Gastroenterology and Digestive Endoscopy (1988) and their development during the past eleven years are described in the perspective of Roma99, the Seventh United European Gastroenterology Week.

Noninvasive estimate of bile flux through the gallbladder in humans.

OBJECTIVE: The aim of this study was to assess whether a single noninvasive technique, ultrasonography, is able in vivo: 1) to evaluate the time-related patterns of gallbladder bile storage and emptying, and 2) to quantitate the amount of bile flux through the gallbladder (GB). METHODS: Healthy volunteers were submitted to the simultaneous assessment of gallbladder volume variations by frequent serial ultrasonographic (US) measurements and of hepatic bile flow through the GB by quantitative cholescintigraphy (QC) during continuous i.v. infusion of 99 mTc-HIDA. An ad hoc mathematical analysis of US GB volume measurements was used to estimate the amount of bile flux through the GB. The QC-derived measurements of the flux of hepatic bile through the GB was used to substantiate the US-derived estimates. RESULTS: The curves expressing the time-related GB handling of hepatic bile obtained independently from US and QC measurements were statistically equivalent, and both techniques showed that the patterns and the amount of hepatic bile handled by the gallbladder after meal ingestion is remarkably different during three successive phases. After meals, hepatic bile was mainly 1) stored in the GB in the first phase; 2) emptied from the GB in a second phase; and 3) stored in the GB in the third phase. The ultrasonographic analysis estimated that 1) 23.8+/-12.5 ml (0.44+/-0.11 ml/min), 5.1+/-3.9 ml (0.15+/-0.10 ml/min), and 33.2+/-10.5 ml (0.53+/-0.16 ml/min) of hepatic bile entered into the GB during the three successive postprandial phases, and 2) the entire amount of bile flowing bidirectionally through the cystic duct, during the observation period (132.6+/-23.3 ml) was about five-fold greater than that estimated by the usually employed variables. CONCLUSION: The proposed mathematical analysis of frequent ultrasonographic measurements of the GB volumes enables one to estimate noninvasively the flux of bile through the gallbladder in humans.

[Teaching humanities to the students of the medical faculties, reasons and why]. / Le ragioni per un insegnamento delle humanitites agli studenti delle facolta di medicina.

There are many reasons to include a programme of human sciences, literature and art in the undergraduate medical curriculum. In the present text, the implications of three reasons are described, namely the increasing demand of health by a rapidly changing society, the need for practising whole person medicine and for improving the doctor the rational and moral awareness of his/her clinical objectives. The possible ways of introducing humanities in the medical curriculum, some international experiences and the role of Medical faculites in interacting with other University disciplines are discussed.

Angiotensin-converting enzyme activity in stools of healthy subjects and patients with celiac disease.

Angiotensin-converting enzyme (ACE) is a dipeptidylcarboxypeptidase that occurs in three types of cells: endothelial, epithelial, and neuroepithelial. ACE activity is present in plasma, urine, and vascular endothelium. High levels of ACE are found in the brush border of human small bowel. The aim of this study was to evaluate ACE activity in human stools and to find a correlation with the intestinal loss of epithelial cells. Fifteen healthy subjects (HS) (8 males, 7 females; age range 6-56 years), 20 patients with celiac disease (CD) (11 males, 9 females; age range 15-53 years), and 18 patients with CD in remission after a gluten-free diet (CD-GFD) (8 males, 10 females; age range 14-54 years) were enrolled in the study. The fecal ACE activity was measured in all groups. Fecal samples were kept at -20 degrees C for a subsequent test. In HS, fecal ACE activity was 21.03 +/- 16.17 nmol/min/100 g (mean +/- SD). In patients with CD with subtotal mucosa atrophy, ACE activity was significantly higher (113 +/- 88.94) than in HS and CD on GFD (36.65 +/- 23.9). We have demonstrated ACE activity in human stools. ACE activity in stools seems to derive from the microvilli of the intestinal mucosa, thus suggesting the potential usefulness of ACE determination as an index of enterocyte damage.

Gluten-sensitive disease with mild enteropathy.

BACKGROUND & AIMS: Celiac disease is a permanent gluten intolerance strongly associated with HLA class II antigens and possibly showing milder changes of mucosal architecture. Ten patients with symptoms suggesting celiac disease and serum antiendomysium antibodies with normal mucosal architecture were studied. METHODS: Immunohistochemical detection of mucosal immune activation and HLA typings were performed. RESULTS: Mucosal immune activation, with normal mucosal architecture and normal gamma/delta+ intraepithelial lymphocytes counts, was found on a gluten-containing diet. In 3 of 6 patients, multiple biopsy specimens showed one sample with severe villous atrophy. Clinical and immunomorphologic features were strictly gluten dependent. The mucosal immune activation was elicited in vitro by gliadin. Only 4 patients had the typical HLA typing of celiac disease. CONCLUSIONS: Gluten-sensitive celiac-like symptoms may occur in patients with serum antiendomysium antibodies, apparently normal intestinal mucosa, and HLA typing not commonly associated with celiac disease. These patients should undergo multiple biopsies, and signs of immunologic activation should be sought accurately; in the presence of mucosal immune activation, a trial with a gluten-free diet should be encouraged to detect gluten dependency. In vitro immunologic response of small intestinal mucosa to gliadin may support the diagnosis of gluten-sensitive enteropathy.

Short-chain fatty acid topical treatment in distal ulcerative colitis.

BACKGROUND: Some evidence indicates that short-chain fatty acid (SCFA) enemas are effective in the treatment of distal ulcerative colitis. METHODS: In a randomized, double-blind, placebo-controlled study, we tested the efficacy of a 6-week course of topical SCFA (100 mL, twice daily enemas of sodium acetate 80 mmol/L, sodium propionate 30 mmol/L and sodium butyrate 40 mmol/L) in 40 patients with mild to moderate distal colitis. Clinical, endoscopic and histological data were collected at the beginning and end of the study. RESULTS: Fourteen patients on SCFA improved (overall score 11.3 +/- 2.0 vs. 7.4 +/- 3.5) as compared to five in the placebo group (overall score 10.0 +/- 1.9 vs. 8.9 +/- 2.5). In the SCFA-treated group all parameters significantly improved except the number of bowel motions, whereas no significant changes were recorded in the control group. A statistically significant difference between the two treatment regimens, however, was observed only for intestinal bleeding (P < 0.05), urgency (P < 0.02) and the patient self-evaluation score (P < 0.05). This was probably due to the random inclusion of more patients with moderate disease into the SCFA-treated group, thus causing pretrial differences between the two groups. CONCLUSION: The present study confirms that irrigation with SCFA enemas is effective in distal colitis, and may represent an alternative therapeutic tool in the treatment of the disease.

Topical treatment of refractory distal ulcerative colitis with 5-ASA and sodium butyrate.

Nine patients with distal ulcerative colitis refractory to standard therapy were treated with intrarectal instillation of a sodium butyrate solution and 5-ASA. A marked clinical, endoscopical and, to a smaller extent, histological improvement was observed in seven of nine patients. The clinical improvement usually occurred within the second week of therapy, and thus earlier than in previous cases treated with butyrate alone. This preliminary experience suggests that the combined butyrate-5-ASA treatment may prove a useful therapeutic tool in refractory distal ulcerative colitis and possibly increase the effectiveness of the individual therapeutic regimens.

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.

Effect of endogenous cholecystokinin on postprandial gallbladder refilling. Ultrasonographic study in healthy subjects and in gallstone patients.

The postprandial release of cholecystokinin (CCK) regulates gallbladder (GB) contraction but little is known about the role, if any, of the still-elevated CCK blood levels on subsequent GB refilling. To assess the role of CCK in GB refilling, a CCK-receptor antagonist, loxiglumide, or saline were infused intravenously in a random double-blind fashion after the ingestion of a liquid test meal in 16 healthy subjects. An identical study protocol was performed in 10 GB "contractor" patient with radiolucent stones to ascertain whether the reported reduced CCK effect on GB emptying also affects GB refilling. GB volumes were assessed ultrasonographically in the fasting state and for 150 min at 15-min intervals after meal ingestion. GB volumes during postprandial refilling were significantly greater during loxiglumide than placebo infusion (P < 0.01), but they did not differ between gallstone and control subjects. In conclusion, postprandial endogenous CCK has a relevant role in delaying GB refilling, and this effect is not altered in patients with radiolucent gallstones.

Duplex-Doppler evaluation of intestinal peristalsis in patients with bowel obstruction.

Duplex-Doppler was used to visualize intestinal peristalsis in 30 patients with intestinal distension. The series included 12 patients with acute mechanical obstruction, 13 with long-standing mechanical obstruction, and five with paralytic ileus. The Duplex-Doppler recordings showed several patterns characterized by different degrees of intensity and frequency of the signals according to the type of obstruction, its duration, and the site of Doppler sampling relative to the obstructed segment. Duplex-Doppler evaluation provided both qualitative and quantitative data about intestinal peristalsis, allowing differentiation between mechanical and paralytic ileus. The visualization of intestinal segments having different degrees of peristaltic activity proved useful in localizing the site of mechanical obstruction.

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.

Gallbladder volume variations after meal ingestion.

OBJECTIVE: To assess gallbladder (GB) volume variations in response to a standard meal. METHODS: We assessed these variations with ultrasonography at brief intervals over the postprandial period, which included the emptying and refilling phases of the GB. RESULTS: During both emptying and refilling of the GB, the volume fluctuated continuously, with brief alternating volume decrements and increments. The phases of emptying and refilling appear to be the net result of the algebraic sum of these volume fluctuations. In the emptying phase, the volume decrements showed a greater volume (35.7 +/- 10.7 ml vs. 14.8 +/- 8.4 ml) and lasted longer (158 +/- 37 min vs. 85 +/- 44 min) than the volume increments, whereas the opposite took place in the refilling phase (4.3 +/- 3.4 ml vs. 16.4 +/- 12.2 ml; 39 +/- 20 min vs. 84 +/- 37 min). CONCLUSION: It is probable that the continuous GB volume fluctuations are the expression of hepatic bile recycling in the GB during the entire postprandial period, and the amount of bile recycled by the GB is greater during the emptying than the refilling phase.

Perendoscopic manometry of the distal ileum and ileocecal junction: technique, normal patterns, and comparison with transileostomy manometry.

The technique of perendoscopic manometry was used to study the motor patterns of the ileocecal junction and distal ileum. An expert endoscopist cannulated the distal ileum of 20 unsedated subjects in 260 +/- 252 (mean +/- SD) seconds, causing no discomfort beyond that of an ordinary colonoscopic examination. No sphincter-like motor activity was detected at the ileocecal junction, and four distinct motility patterns were identified in the distal ileum: (1) tone variations, (2) slow phasic contractions, (3) regular rapid phasic contractions, and (4) prolonged rapid phasic contractions. Previous appendectomy and insertion of the colonoscope into the distal ileum to position the manometric catheter did not affect the manometric recordings. Perendoscopic manometry of the distal ileum was compared with transileostomy manometry in 9 subjects. Perendoscopic and transileostomy manometric recordings showed the same motor patterns except for a longer occurrence of tone variations with perendoscopic manometry. In conclusion, this study shows that perendoscopic manometry of the distal ileum and ileocecal junction is feasible; recorded motor patterns are not affected.

Hepatoduodenal bile transit in cholecystectomized subjects. Relationship with sphincter of Oddi function and diagnostic value.

The hepatic hilum-duodenum transit time (HHDT) was evaluated in cholecystectomized subjects to assess its relationship with the motor function of the sphincter of Oddi (SO) and its diagnostic accuracy in the detection of SO dysfunction. The study was performed in asymptomatic controls and symptomatic patients with SO dysfunction before and after sphincterotomy. HHDT showed a direct correlation with manometric SO maximal basal pressure (r = 0.77; P < 0.001) but not with SO phasic activity. In sphincterotomized subjects HHDT did not differ from that of the asymptomatic subjects, and HHDT, which was prolonged before sphincterotomy, normalized after sphincterotomy. HHDT had a 100% specificity and an 83% sensitivity in diagnosing SO dysfunction when compared to SO manometry. In conclusion, the cholescintigraphic HHDT is mainly related to the SO maximal basal pressure, presenting an elevated specificity and a satisfactory sensitivity in the diagnosis of SO dysfunction in cholecystectomized subjects.

Effects of intraluminal acidification on oesophageal motor activity.

This study assessed the effect of prolonged intraluminal acidification on the motor activity of the entire oesophageal body (under controlled conditions). Intraoesophageal pressures were recorded in 13 endoscopy negative subjects with gastro-oesophageal reflux disease in whom saline, HC1 0.1 N, and saline solutions were infused (1.5 ml/min) blindly in the oesophageal body, 6 cm distal to the upper oesophageal sphincter for three consecutive periods of 45 minutes each. These findings were compared with those of a control group. Intraoesophageal acidification caused an increase in the deglutition frequency (p < 0.02), the occurrence of multipeaked waves (p < 0.04) as well as a decrease of the propagating velocity (p < 0.04) of the primary peristaltic contractions. Furthermore, intraoesophageal acidification determined an increase, at all levels of the oesophagus, of the duration (p < 0.04) and, more noticeable in the proximal oesophageal body, of the amplitude (p < 0.02) of primary peristaltic contraction waves. In conclusion prolonged intraoesophageal acidification can considerably affect frequency of deglutition, morphology, and propagating patterns of primary peristaltic contractions. This study shows that these effects are independent from volume distension of the oesophagus and supports the presence of acid sensitive receptors in the oesophageal mucosa.