Survival rate and prognostic factors in patients with intestinal failure.

BACKGROUND: Intestinal failure impairs nutritional status and survival expectance. Though intestinal adaptation and enteral independence may be achieved, artificial nutrition is needed in about half of the patients. AIMS: This study is aimed at assessing the causes of death, survival rate, enteral independence in time, and factors affecting the clinical outcome in a group of patients with intestinal insufficiency. PATIENTS: Sixty-eight patients with intestinal insufficiency, due to major intestinal resection in 60 cases (short bowel syndrome) (remnant intestine length 101-150 cm in 31 cases, 50-100 cm in 23 cases, <50 cm in 6 cases), and due to chronic idiopathic pseudo-obstruction in 8 cases, were enrolled and followed-up for (median) 36 months (25th and 75th percentile in 12 and 60 months, respectively). In 60 short bowel syndrome patients, the main conditions that led to intestinal failure were ischemic bowel (28), major surgery complications or severe adhesions (17), radiation enteritis (10), Chron's disease, intestinal tuberculosis, small bowel lymphoma and trauma (others). METHODS: Seventeen variables age, underlying disorders, length of remnant bowel, type of surgery, hospital stay, type of nutrition (hospital and home) and its variations in time, causes of death, survival rate and time were considered. Statistical analysis was carried out by Mann-Whitney U-test, Pearson chi2, Spearman correlation test, Kaplan-Meyer method and Cox's proportion hazards regression model. RESULTS: At the time of admission to the hospital, none of the patients had nutritional independence, 54 (79.4%) were on parenteral nutrition and 14 (20.6%) were on enteral nutrition. At the time of discharge, 23 (33.8%) patients showed enteral independence, 39 were on home parenteral nutrition, 3 on enteral nutrition + i.v. feeding, 1 on enteral nutrition, and 2 needed oral supplementation with hydroelectrolyte solutions only. After a median value of 36 months, 30 and 2 patients were on home parenteral nutrition and enteral nutrition + i.v. feeding, respectively, 2 on enteral nutrition, 2 on oral supplementation with hydroelectrolyte solutions, and 26 cases reached enteral independence. A significant relationship was detected between the length of remnant bowel and types of nutrition at both admission (r = 0.38; P = 0.001) and discharge (r = 0.48; P = 0.001), parenteral nutrition being more frequent in patients with very short bowel. Twenty-two patients (32.4%) died (4 from newly occurring malignancies), 40 (58.8%) survived, and 6 (8.8%) were lost to the follow-up. Eleven of 22 patients died from conditions related to intestinal failure (8 cases) and/or home parenteral nutrition complications (3 cases). At 12, 24, 36, 48, 60 and 72 months, survival rates were 95.4, 93.3, 88.1, 78.6, 78.6 and 65.5%, respectively, but it was significantly lower for patients with <50 cm of remnant bowel than those with longer residual intestine (P < 0.05), and in patients who started home parenteral nutrition above the age of 45 years (P < 0.02). Survival rate was higher in patients with enteral independence than those with enteral dependence (P < 0.05). Better survival rates were registered in patients with chronic obstructive intestinal pseudo-obstruction and major surgery complications, whereas ischemic bowel and even more radiation enteritis were associated with a lower survival expectance. CONCLUSIONS: Actuarial survival rate of patients with intestinal failure quotes 88 and 78% at 3 and 5 years, respectively. It is influenced by the length of remnant intestine, age at the start of home parenteral nutrition, enteral independence and, to some extent at least, by the primary disorder. Enteral independence can be achieved in time by about 40% of the patients with intestinal insufficiency, but for home parenteral nutrition-dependent cases, intravenous feeding can be stopped in less than one out of five patients during a median 3-year period.

Gastric emptying of realistic meals with and without gluten in patients with coeliac disease. Effect of jejunal mucosal recovery.

BACKGROUND: Few data are available on disturbed gastric emptying in patients with coeliac disease. The aims of the study were to investigate (a) the presence of delayed gastric emptying: (b) the acute effect on gastric emptying of gliadin; and (c) the effect of jejunal recovery on gastric emptying of meals with or without gluten in such patients. METHODS: We measured gastric emptying of two meals in 16 patients with coeliac disease; one meal contained gliadin. Results were compared with those obtained in 24 controls. In 12 patients, both measurements were repeated after mucosal recovery. Statistical analysis was performed using the analysis of variance for repeated measurements and Student's t test. Mean +/- 1 s(mean) (standard error of the mean) are shown. RESULTS: No difference was found in fasting and in maximal antral sections after the two meals. On entry, gastric emptying was significantly (P < 0.001) delayed compared to controls both after the meal containing gluten (326.9 +/- 12.4 min versus controls 213.5 +/- 11.5) and after the gluten-free meal (315.3 +/- 16.7 min). After jejunal recovery, emptying of the meal containing gluten remained unchanged (337 +/- 18.9 min), whereas emptying of the gluten-free meal was significantly shortened (280.6 +/- 10.5 min; P < 0.001). CONCLUSIONS: In coeliac disease there is an impairment of gastric emptying which is at least partially reversible. This suggests either an immunological disorder or that unabsorbed meal constituents are responsible for an ileal-brake effect.

Gastric emptying of solid meals in achalasic patients after successful pneumatic dilatation of the cardia.

Gastric emptying of a solid meal was measured by ultrasound scanning in 16 achalasic patients following successful pneumatic dilatation of the lower esophageal sphincter. The data were compared with those of a control group of 15 healthy subjects. Fasting and maximal postcibal antral sections were very similar in the two groups. On the contrary, the time interval before maximal antral dilatation, and the time necessary for the emptying of half or of the whole meal were significantly longer in the achalasic patients than in the controls. Half of the achalasic patients had longer emptying times than the upper normal limit. The percentage of the meal retained in the antrum at each hourly interval was significantly higher in the achalasic group. The finding of a high prevalence of gastric emptying disturbances suggests that the functional derangement in achalasia is not limited to the esophagus.

Fecal fat measurement in the presence of long- and medium-chain triglycerides and fatty acids. Comparison of three methods.

BACKGROUND: It has been suggested that some of the limitations of the Van de Kamer method for fecal fat measurement could be overcome with the Jeejeebhoy method or the near-infrared reflectance assay. METHODS: To test this hypothesis, a fecal fat test was carried out with the three methods, adding butter or MCT oil to the diet of four steatorrhoic patients. An in vitro recovery study of long- and medium-chain triglycerides was also performed. RESULTS: The Jeejeebhoy method measured long- and medium-chain fats more accurately than the Van de Kamer method. It found consistently higher steatorrhea values. Mean results of the near-infrared reflectance analysis resembled those of the Van de Kamer method, but with wide discordance of individual data. CONCLUSION: The Jeejeebhoy method is more accurate than the Van de Kamer method for fecal fat measurement. The difference may be clinically relevant when most fecal fatty acids derive from medium-chain triglycerides. Near-infrared reflectance may be a viable proposition only when a greater degree of approximation is acceptable.

Medium-chain triglyceride absorption in patients with pancreatic insufficiency.

BACKGROUND: The role of medium-chain triglycerides (MCTs) in the management of patients with pancreatic insufficiency is controversial. The aim of the study was to evaluate the absorption of MCTs in the presence of pancreatic insufficiency and the effect of pancreatic extracts on MCT absorption so as to clarify whether the replacement of usual dietary fats with MCTs is cost-effective. METHODS: Six patients with severe pancreatic steatorrhea were for 5 days fed a low-fat diet to which butter (long-chain triglycerides (LCTs)) or MCT oil was added, with and without pancreatic extracts, in a crossover design. RESULTS: Fecal weight and nitrogen losses were the same during MCT and LCT intake. Steatorrhea was substantial during both periods but was significantly lower during MCT than LCT intake. Fecal weight and nitrogen and fat losses were reduced by pancreatic extracts in both diets. Steatorrhea was the same when MCTs and LCTs were consumed together with pancreatic extracts. CONCLUSIONS: MCTs are absorbed better than LCTs in the presence of pancreatic insufficiency but require pancreatic extracts for optimal absorption. No advantage is to be expected from replacing usual dietary fats with MCTs if pancreatic supplements are used.

Gastric emptying and dyspeptic symptoms in patients with gastroesophageal reflux.

OBJECTIVES: To clarify 1) whether gastric emptying of a mixed meal is delayed in patients with gastroesophageal reflux and 2) the relationship between dyspeptic symptoms and delayed gastric emptying in refluxers. METHODS: Gastric emptying of a solid meal was studied by ultrasound in 25 patients with pathological esophageal acid exposure. Gastric emptying was then assessed in relation to upper digestive endoscopy, esophageal manometry, 24-h pH monitoring and quantification of symptoms of reflux- and dysmotility-like dyspepsia. RESULTS: Fifteen of 25 refluxers had esophagitis, and 15 were "dyspeptic". Refluxers exhibited a significant delay in gastric emptying compared with controls [307.6 (21.0) vs. 209 (10.4) min, p < 0.001). Patients with delayed emptying had low LES pressure [11.9 (2.1) vs. 18.6 (2.1) mm Hg, p < 0.05]. There was no correlation between delayed emptying and either pH monitoring or presence of esophagitis. There were no differences in any of the pH monitoring parameters between refluxers with and without coexisting dysmotility-like symptoms. CONCLUSIONS: Gastric emptying of a solid meal is markedly delayed in patients with gastroesophageal reflux. However, no direct causal link was found between delayed emptying and reflux. Our data suggest the presence of a motility disorder in gastroesophageal reflux which is not confined to the esophagogastric junction.

Fecal fat concentration in the screening of steatorrhea.

We studied if the fecal fat concentration as measured by the near infrared reflectance analysis in a spot sample is an acceptable screening test for malabsorption. This measurement was compared with the more complex fat balance in 120 patients with a suspected malabsorption [53 with chronic pancreatic disorders (CP), 67 with other digestive disorders (nCP)]. The fecal fat concentration proved to be well correlated with steatorrhea in CP (r = 0.86) but not in nCP (r = 0.35). A fat concentration of 9 g% had a sensitivity and a specificity for steatorrhea of 88.8% and of 97.1% in CP, but only of 53.8% and of 94.4% respectively in nCP. The fecal fat concentration was significantly higher in CP than in nCP, even considering patients with steatorrhea only; however, the overlap between the two groups was too high to suggest a clinical usefulness of this test in the differential diagnosis of steatorrheas. It is concluded that the fat concentration in a small sample, easily obtained also in outpatients, is useful in the selection of patients with chronic pancreatitis to submit to a proper fat balance study.

Pathological esophageal acidification and pneumatic dilitation in achalasic patients. Too much or not enough?

Endoscopy, esophageal manometry and pH monitoring, gastric emptying test, and heartburn quantification on a visual analog scale were performed in 22 achalasic patients in order to clarify which events are associated with pathological esophageal acidification after successful LES dilatation. Five patients presented pathological acidification. Dilatation reduced LES tone from 38.3 +/- 4.2 to 14.6 +/- 1.1 mm Hg (mean +/- SEM); there was, however, no difference between nonrefluxers and refluxers (14.8 +/- 1.2 vs 13.8 +/- 2.5 mm Hg). The emptying time in achalasic patients was delayed compared to controls (315.9 +/- 20.9 min vs 209 +/- 10.4) due to prolonged lag-phase and reduced slope of the antral section-time curve, but, again, there was no difference between refluxers and nonrefluxers. The acid clearance was delayed in refluxers compared to nonrefluxers (15.9 +/- 4.5 vs 2.5 +/- 1.8 min, P<0.05). Two refluxers presented grade 1 esophagitis; one of them developed an esophageal ulcer. The heartburn score was the same in refluxers and nonrefluxers. Pathological acidification after pneumatic dilatation is associated with persistent problems in esophageal emptying rather than with excessive sphincter divulsion.

Omeprazole causes delay in gastric emptying of digestible meals.

We have studied gastric emptying of a solid, realistic meal (800 cal, 15% protein, 45% fat, 40% carbohydrate) in 21 healthy subjects twice, with and without a four-day pretreatment with 40 mg omeprazole. The last dose of the drug was taken 24 hr before the test, to avoid hypothetical nonsecretory side effects of the drug . Gastric emptying was measured by ultrasound of antral diameters. The results show that basal and maximal postprandial antral cross-sectional areas were the same during the two tests. A greater residual distention of the antrum was present throughout the study after the omeprazole treatment, the difference being significant at time 120 and 240. Omeprazole induced a highly significant delay in gastric emptying [control 199.6 (12.6) vs omeprazole 230.9 (12.7) min, mean (1 SEM); P<0.003]. The delay was not due to a prolonged lag phase, but rather to an effect on the slope of the emptying curve. This study shows that in normal subjects omeprazole delays gastric emptying of a digestible solid meal.

Achalasia. A possible late cause of postpolio dysphagia.

The aim of this paper is to describe a patient with severe postpolio problems who developed achalasia. A 66-year-old patient came to our observation for severe dysphagia. He had suffered from paralytic poliomyelitis at the age of 7 months and had severe residual deficits. At the age of 62 he presented with sudden pain localized in the distribution of the C4 and C5 dermatomes and an inability to abduct the left arm. At the time, he experienced only occasional and mild dysphagia; his esophagus was not dilated and emptied normally. Over the following months his muscular function improved, but dysphagia worsened. We found a megaesophagus with a sigmoid appearance and the manometric features of achalasia. Pneumatic dilatation produced good resolution of dysphagia. A year later manometry showed the reappearance of peristalsis after all wet swallows. In patients with postpolio dysphagia, the possible presence of achalasia must be considered.

Fractional urinary clearance of immunoreactive lipase in chronic pancreatic disease.

Using an immunoenzymatic method, we studied lipase in the serum and urine of 23 controls, 22 chronic pancreatitis patients in symptomatic remission, and in 9 patients with proven pancreatic cancer. Serum and urine lipase and its fractional urinary clearance were compared with those of amylase and immunoreactive trypsin. Lipase immunoreactivity was detectable in the urine of 81.5% of the studied subjects (controls: 82%, chronic pancreatitis: 86%, pancreatic cancer: 66%); its output was higher than the upper limit of controls in 31.8% of chronic pancreatitis and in only 1 of pancreatic cancer, and it was significantly correlated with the urinary output of trypsin (r = 0.487, P less than 0.001), but not with that of amylase. A significant correlation was found between urinary output and serum levels for lipase, but not for trypsin or amylase. Fractional clearance of lipase was of the same magnitude as that of trypsin but only 0.1% that of amylase. 19% of chronic pancreatitis and pancreatic cancer showed a fractional clearance of lipase above the upper limit of controls, compared with 45% for trypsin and 3.2% for amylase. No difference in urinary clearance of the three enzymes was found between chronic pancreatitis and pancreatic cancer. In conclusion, although of no diagnostic relevance in pain-free patients with chronic pancreatic disease, this measurement can provide information on the mechanisms of renal excretion of pancreatic enzymes.

Gastric emptying of solids is markedly delayed when meals are fried.

We studied the effect of heat-treated fats on gastric emptying. Eight healthy asymptomatic volunteers (five males; age 28-41 years) ate on different days and in random order two meals identical in contents (pasta, tomato, beef, olive oil, carrots, orange, water; 870 kcal males, 700 kcal females; 47% of calories from carbohydrate, 36% from fat, 17% from protein), but cooked differently (fats fried or not). Ultrasound measurement of antral diameters was used to calculate basal antral section, its maximal dilation after the meal, the time necessary for total emptying, and the percent retention at hourly intervals. No difference was found in basal and maximal antral diameters after the two meals. On the contrary, total gastric emptying was significantly delayed after the fried meal [317.1 (24.12) vs 226.7 (18.4) min, mean (1 SEM); P < 0.002]. A significantly greater percentage of maximal antral distension was still present between 120 and 240 min after the fried meal. The glycemic response and hunger feeling were the same after the two meals, whereas there was a longer persistence of satiety and epigastric fullness after the fried meal. In conclusion, gastric emptying can be influenced not only by the meal content, but also by the way it is cooked.

Near infrared reflectance measurement of nitrogen faecal losses.

Chemical methods of measuring nitrogen in stools are complex, unpleasant, and therefore rarely performed. Recently, near infrared reflectance (NIRA) has been suggested for stool analysis. The aim of this study was to evaluate the possible application of this method in routine faecal nitrogen measurement. Nitrogen concentration and daily output were measured in the stools of 83 patients using NIRA and, for comparison, the Kjeldahl method. Nitrogen concentration and output ranged between 0.4-2.72 g% and 0.45-8.96 g/day respectively. Correlation coefficients (r), of 0.89 and 0.97 were found between the two methods for concentration and output respectively, and similar values were found in patients on enteral nutrition. Repeated measurements from the same stool collection, requiring only a few minutes, allowed homogenisation to be avoided. NIRA seems to be an easy, fast, and reliable alternative to chemical assays of nitrogen measurement in the management of patients with digestive disorders.

Elastase-1 vs trypsin, lipase and amylase serum levels in pancreatic diseases.

Serum levels of elastase-1 were measured in 174 patients with pancreatic diseases and in 131 controls and were compared with the circulating levels of trypsin, lipase and amylase and with clinical data. In 48 patients with chronic pancreatitis serum enzyme levels were also compared with the pancreatic exocrine capacity. About 50% of the patients with chronic pancreatic disease showed increased levels of serum elastase, sometimes even in the face of long lasting pain-free periods, and/or of severe pancreatic impairment. On the contrary, serum trypsin and lipase were almost always either normal or below the normal range in the absence of painful relapses and/or in the presence of an impairment of the exocrine pancreatic function. A strict correlation was found between elastase-1 and trypsin (r = 0.778) and lipase (r = 0.834). However, controls and patients with chronic pancreatic diseases behaved differently, an increase in trypsin and in lipase levels being associated in the patients with chronic pancreatitis with an increase in elastase-1 values significantly larger than that observed in controls. These findings raise the hypothesis, at present unproven, that trypsin and lipase serum assays are more reliable indices of pancreatic exocrine function, whereas serum elastase-1 levels may indicate the presence of acute pancreatic episodes, even if subclinical, the importance of which, in the natural history of the disease, remains unknown.

Cough threshold in reflux oesophagitis: influence of acid and of laryngeal and oesophageal damage.

BACKGROUND: Gastro-oesophageal reflux is often associated with cough. Patients with reflux show an enhanced tussive response to bronchial irritants, even in the absence of respiratory symptoms. AIM: To investigate the effect of mucosal damage (either oesophageal or laryngeal) and of oesophageal acid flooding on cough threshold in reflux patients. PATIENTS: We studied 21 patients with reflux oesophagitis and digestive symptoms. Respiratory diseases, smoking, and use of drugs influencing cough were considered exclusion criteria. METHODS: Patients underwent pH monitoring, manometry, digestive endoscopy, laryngoscopy, and methacholine challenge. We evaluated the cough response to inhaled capsaicin (expressed as PD5, the dose producing five coughs) before therapy, after five days of omeprazole therapy, and when oesophageal and laryngeal damage had healed. RESULTS: In all patients spirometry and methacholine challenge were normal. Thirteen patients had posterior laryngitis and eight complained of coughing. Twenty patients showed an enhanced cough response (basal PD5 0.92 (0.47) nM; mean (SEM)) which improved after five and 60 days (2.87 (0.82) and 5.88 (0.85) nM; p<0.0001). The severity of oesophagitis did not influence PD5 variation. On the contrary, the response to treatment was significantly different in patients with and without laryngitis (p = 0.038). In patients with no laryngitis, the cough threshold improved after five days with no further change thereafter. In patients with laryngitis, the cough threshold improved after five days and improved further after 60 days. Proximal and distal oesophageal acid exposure did not influence PD5. Heartburn disappeared during the first five days but the decrease in cough and throat clearing were slower. CONCLUSIONS: Patients with reflux oesophagitis have a decreased cough threshold. This is related to both laryngeal inflammation and acid flooding of the oesophagus but not to the severity of oesophagitis. Omeprazole improves not only respiratory and gastro-oesophageal symptoms but also the cough threshold.

Tussive effect of capsaicin in patients with gastroesophageal reflux without cough.

The aim of this study was to clarify the influence of gastroesophageal reflux (GER) on cough threshold in patients with digestive symptoms but free from respiratory involvement. Of 57 consecutive subjects referred for 24-h esophageal pH monitoring because of digestive reflux symptoms, 29 patients free from respiratory disorders were studied. They underwent esophageal pH monitoring and manometry, upper gastrointestinal endoscopy, pulmonary function tests, and methacholine and capsaicin challenges. The methacholine test was performed by inhalation of increasing doses of methacholine up to 4,000 micrograms; the results were expressed as the dose causing a 20% decrease in FEV1 from baseline (PD20). The capsaicin threshold was evaluated by inhalation of increasing doses of capsaicin from 0.3 up to 9.84 nmol, expressing the results as the dose of capsaicin eliciting five coughs (PD5). Fifteen patients were considered refluxers on the basis of a total esophageal acid exposure time above 4.7%. Esophagitis grade 0 was found in 15 patients, grade 1 in seven patients, grade 2 in seven patients. PD5 was significantly lower in refluxers (median 0.51 micrograms, range 0.22 to 19.8) than in nonrefluxers (19.8 micrograms, range 0.31 to 19.8) (p < 0.001); there was no difference in baseline ventilatory parameters and in airway responsiveness to methacholine between the two groups. All patients with a pathologic acid exposure time but one had a low cough threshold, irrespective of the presence or absence of esophagitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric emptying of a solid meal is accelerated by the removal of dietary fibre naturally present in food.

Exogenous fibre added to liquid meals delays gastric emptying. Its effect on solid meals is uncertain, and nothing is known of the effect on gastric emptying of fibre naturally present in food. This study therefore looked at gastric emptying of two different solid meals in eight healthy subjects and their blood glucose responses. The meals were exactly equivalent except for the total dietary fibre content (high fibre 20 g, low fibre 4 g of dietary fibre per 1000 kcal) and supplied 870 kcal (700 kcal women), 47% of which was from carbohydrates, 36% from fats, and 17% from proteins. Ultrasonography was used to measure antral diameters before the meal (basal), immediately after it (time 0), and at 30, 60, 120, 180, 240, and 300 minutes. In addition, subjects filled in a questionnaire on their feelings of hunger, epigastric fullness, and satiety before the meal and at hourly intervals after it. Basal and maximal postprandial antral sections were similar for the two meals (basal section: 283.9 (29.5) v 340.9 (44.7) mm2 for the low and the high fibre meal, NS; maximal postprandial section: 1726 (101.9) v 1593 (120.4) mm2, NS). Total gastric emptying time was significantly reduced by fibre removal (186.0 (15.6) v 231.7 (17.3) minutes after the low and the high fibre meal, p < 0.05). Blood glucose was higher after the low fibre meal, and the area under the glycaemic curve significantly greater (226 (23.1) v 160 (20.0) mmol/min/dl-1, p < 0.05). No difference was found in satiety or fullness feelings, but hunger returned more rapidly after the low fibre meal. In conclusion, fibre naturally present in food delays gastric emptying of a solid meal, reduces the glycaemic response, and delays the return of hunger.

Simultaneous measurement of gastric emptying of a solid meal by ultrasound and by scintigraphy.

OBJECTIVE: Although ultrasonic imaging may represent a valid alternative to scintigraphy for measurement of gastric emptying, most studies comparing the two methods have been carried out with liquid meals. The aim of this study was to compare scintigraphic and ultrasonographic measurements of gastric emptying of a solid meal in healthy subjects and in patients with possible delay in emptying. METHODS: Nineteen subjects were studied: five controls, six patients with gastroesophageal reflux, and eight patients with dysmotility-like dyspepsia. Gastric emptying was measured by both scintigraphy and ultrasonography after ingestion of an 800-calorie solid, realistic meal containing 99mTc-labeled chicken liver. Scintigraphic measurements were made every 15 min for 6 h, and ultrasonic imaging of antral sections was undertaken every 15 min for the first 1 h and every 30 min thereafter. Total emptying times were calculated independently using the two methods, and the emptying patterns recorded by the two methods were compared. RESULTS: Maximal antral dilation occurred 30 min (range 0-90 min) after the end of the meal and persisted until 96 +/- 42 min, by which time gastric radioactivity had decreased from its maximum by 43% +/- 23%. From this time on, the antral cross-sectional area returned toward the basal value, declining faster than the gastric counts recorded by scintigraphy. Total emptying times measured by ultrasound and by scintigraphy were in good agreement in all subjects, with a mean difference of only 4.5 min (limits of agreement, -17.1 to 21.6 min). CONCLUSIONS: Ultrasonographic measurement of antral cross-sectional area provides a valid alternative to scintigraphy for the measurement of total gastric emptying of a solid meal. It is less reliable if other parameters of gastric emptying such as T(1/2) are required.