Esophageal dysfunction in syndrome X.

Syndrome X is defined as anginal chest pain accompanied by objective signs of ischemia on exercise testing or myocardial scintigraphy, but with angiographically "normal" coronary arteries. The etiology of this enticing syndrome is still not known. Besides myocardial ischemia, esophageal dysfunction and visceral hypersensitivity may play a role in the development of pain. The purpose of this study was to study esophageal function and visceral sensitivity in patients with syndrome X. Twenty consecutive patients with the diagnosis of syndrome X were investigated with esophageal manometry and a 24-hour pH recording. Visceral esophageal sensitivity was explored by balloon distention of the distal esophagus, as well as by instillation of acid. Twelve patients (67% of the 18 evaluated) had some abnormality on 24-hour pH monitoring; 2 had abnormal global acid exposure time (pH <4) and 7 had symptoms coincidental with episodes of pH <4. Seven patients (35%) had esophageal dysmotility including 5 with the "nutcracker" esophagus. Esophageal hypersensitivity to acid (n = 9) or distention (n = 13) was seen in 14 of the 20 patients. Eleven patients received acid suppressive therapy that resulted in amelioration of chest pain in 8 (73%). Thus, results suggest that esophageal hypersensitivity rather than gross functional abnormality is an important factor for the development of chest pain in patients with syndrome X, and that acid in the context of a hypersensitive esophagus is the main culprit. Acid suppression may ameliorate pain in a substantial proportion of patients.

Nutcracker oesophagus: a double-blind, placebo-controlled, cross-over study of the effects of lansoprazole.

BACKGROUND: Nutcracker oesophagus is characterized by high-amplitude oesophageal contractions. Recent data have shown a high prevalence of gastro-oesophageal acid reflux in patients with nutcracker oesophagus and, in open-label trials, patients seemed to benefit from acid suppression. Therefore, it has been suggested that non-cardiac chest pain in patients with nutcracker oesophagus may be related to reflux rather than to the motor abnormality itself. AIMS: To investigate the effect of intensive acid-suppressive treatment on chest pain in patients with nutcracker oesophagus. METHODS: Nineteen patients with nutcracker oesophagus received lansoprazole or placebo in a double-blind, randomized, cross-over study. RESULTS: Significant reductions in pain intensity (P < 0.006) and pain duration (P < 0.05) were registered during the study. The magnitude of symptom relief achieved with lansoprazole did not differ significantly from that achieved with placebo. The motility pattern did not change during the study. CONCLUSIONS: This study does not prove that acid-suppressive therapy is effective for pain relief in nutcracker oesophagus. As the amelioration of pain was not accompanied by any change in the nutcracker oesophagus pattern, it is unlikely that the high-amplitude oesophageal contractions are the cause of pain. Thus, the possible role of acid in the pathophysiology of pain in nutcracker oesophagus needs further study.

Endoscopic bile duct stent placement as a predictor of outcome following endoscopic sphincterotomy in patients with suspected sphincter of Oddi dysfunction.

OBJECTIVES: To determine whether symptomatic improvement following placement of endoscopic stent across the biliary sphincter could predict the longer-term clinical outcome after endoscopic sphincterotomy (ES). METHODS: Twenty-three post-cholecystectomy patients with suspected sphincter of Oddi dysfunction underwent, sequentially, sphincter of Oddi manometry, endoscopic stent placement, ES, and follow-up for a further 6-12 months. RESULTS: Eight (35%) patients either did not respond (n = 5), did not tolerate the stent (n = 1) or relapsed during stenting (n = 2). Only the patient who did not tolerate the stent from the outset (12%) improved after ES. Of five patients who responded to stenting and had ES within 8 weeks, only two (40%) remained asymptomatic. In contrast, of 10 patients who were pain-free during 12-14 weeks of stenting, nine (90%) continued to be asymptomatic after ES. All seven patients with an elevated sphincter of Oddi pressure responded to stenting and six benefited from sphincter ablation. Five (31%) of 16 patients who had normal sphincter pressure and had improvement after 12-14 weeks of stenting remained free from pain following ES. ES resulted in long-term freedom from pain in 12 of the 23 patients: six of the seven patients with elevated sphincter of Oddi pressure and six of the 16 subjects with normal manometry (P < 0.05). CONCLUSION: Freedom from symptoms during at least 12 weeks of stenting predicted a favourable outcome after ES, irrespective of sphincter of Oddi pressure. Patients who failed to improve or showed improvement only with short-term stenting were less likely to benefit.

C-peptide concentration in pancreatic juice obtained during endoscopic pancreatography in patients with and without insulinoma.

ERCP was performed in three patients with insulinoma. One had a large malignant tumor, while the remaining two had small tumours. In two of these patients pancreatic juice was collected for C-peptide determination. Pancreatography was performed and pancreatic juice was obtained in seven other subjects comprising: five control subjects and two patients in whom insulinoma was suspected because of symptoms suggestive of hypoglycaemia. Pancreatography was normal in all subjects except the patient with a large insulinoma in whom an obstruction of the main pancreatic duct was found. The maximal C-peptide concentrations in pancreatic juice of patients with insulinoma were found to be several-fold higher than in the control subjects and in one of the patients in whom insulinoma was suspected but unproven. The remaining patient with suspected insulinoma had a maximal C-peptide concentration comparable with those found in patients with proven insulinoma. Thus remarkable differences in maximal C-peptide concentrations obtained in patients with and without insulinoma were found. However, the clinical significance of the findings needs further evaluation. The value of ERP in patients with suspected insulinoma may be twofold: an obstruction of the main pancreatic duct may indicate a large, hardly resectable tumour; in patients in whom the duct is unaffected the relation between the tumour as visualized by angiography, and the duct, is of value for the surgeon when planning the operation.

Obstructive jaundice due to isolated tuberculosis of the pancreas: endoscopic treatment instead of surgery?

The optimal treatment for relieving biliary obstruction due to isolated pancreatic tuberculosis has not so far been defined, and most previously reported patients were treated surgically. We describe a 17-year-old, immunocompetent girl who was admitted with obstructive jaundice caused by a tuberculous mass in the head of the pancreas. Antituberculous therapy alone failed to alleviate the jaundice, and she was therefore treated by stent insertion and, subsequently, balloon dilation of the common bile duct stricture. At follow-up 5 years later, magnetic resonance cholangiopancreatography showed no evidence of stricture in the common bile duct.

The secretin-CCK test and a modified Lundh test. A comparative study.

A comparison has been made between a modified Lundh test and the secretin-CCK test. Thirty-four patients with pancreatic disease (chronic pancreatitis, n = 25; recurrent pancreatitis, n = 5; and pancreatic carcinoma, n = 4) and 20 patients with other gastrointestinal disorders were studied. The results showed that estimation of trypsin secretion, irrespective of the mode of stimulation, had a low sensitivity in detecting pancreatic disease. Estimation of bicarbonate secretion after secretin stimulation provided a more sensitive test, especially for disclosing chronic pancreatitis.

Longer term outcome of steroid refractory ulcerative colitis treated with intravenous cyclosporine without subsequent oral cyclosporine maintenance therapy.

BACKGROUND AND AIMS: Intravenous cyclosporine (Cy) is increasingly used in patients with severe ulcerative colitis who fail to respond to corticosteroids. However, in spite of subsequent oral Cy maintenance therapy almost one-half of the initial responders need colectomy within a year. In light of the drug's limited efficacy and potential toxicity use of oral long-term Cy can be questioned. PATIENTS AND METHODS: Nineteen patients with steroid refractory severe ulcerative colitis were treated intravenously with Cy. RESULTS: Of the 19 patients 14 (76%) achieved remission. Six of the patients (46%) remained in remission for 12-61 months. Eight patients experienced one to four flares during the year after treatment. However, except for one patient who needed another course of intravenous Cy, all responded to corticosteroids. The duration of remission since the last flare in these patients (five received azathioprin) was 10-36 months. None of the patients needed colectomy because of symptoms. CONCLUSION: These preliminary data suggest that a course of intravenous Cy can turn corticosteroid-refractory ulcerative colitis to corticosteroids responsive. The outcome of patients not receiving oral Cy maintenance therapy appears to be satisfactory. Azathioprin maintenance therapy can probably be reserved for select patients.

Effect of midazolam on sphincter of Oddi motility.

Midazolam is a more recent benzodiazepine used for sedation during endoscopic procedures, including sphincter of Oddi (SO) manometry. However, the effect of this drug on the human SO has so far not been studied. In this paper we explored the effect of midazolam on human SO motility by means of endoscopic manometry. Twelve patients with suspected SO dysfunction were investigated. We found that in patients with normal manometry findings, midazolam had no effect on the sphincter motility. In contrast, in all patients with elevated SO pressure (SOP), as well as in one of the three patients with borderline SO tone, midazolam (2.5 mg i.v.) produced a relaxatory effect. Due to this effect the final readings were affected in three out of five patients, i.e. the abnormally elevated SOP decreased to a borderline level in two and in the remaining patient the borderline level in two and in the remaining patient the borderline SOP decreased to normal. In one other patient with a markedly elevated SOP the additional injection of 2.5 mg of midazolam caused a further decrease in SOP to a borderline level. We conclude that midazolam, due to its relaxatory effect on SO, appears to be a less suitable sedative for SO manometry.

Exocrine pancreatic function, fecal fat, and blood glucose in patients with pancreatitis.

Exocrine pancreatic function, as revealed by bicarbonate output after secretion stimulation and trypsin output after CCK stimulation, fecal fat excretion, and glucose tolerance were studied in 40 patients with pancreatitis. A high fecal fat excretion and an abnormal glucose tolerance were found in about three quarters of the patients with markedly reduced bicarbonate output (less than 0.15 mmol . h-1 . kg-1). Normal fecal fat excretion was observed in five of six and normal glucose tolerance in all patients who had a normal bicarbonate output (greater than 0.30 mmol . h-1 . kg-1). All of the patients with abnormal glucose tolerance had impaired bicarbonate output. The trypsin output after CCK stimulation was not more closely related either to the fecal fat excretion or to the glucose tolerance.

HBsAg-negative chronic active hepatitis and mixed connective tissue disease syndrome. An unusual association observed in two patients.

Two patients are described who suffered from both HBsAg-negative chronic active hepatitis and mixed connective tissue disease syndrome. The diagnosis of liver disease was made prior to the diagnosis of collagenosis in one of the patients, whereas the opposite was the case in the other. In spite of the fact that symptoms and laboratory data suggesting both diagnoses were present from the moment of presentation, there was a considerable delay in establishing the second diagnosis in both patients. To our knowledge, this is the first report on an association between chronic active hepatitis and mixed connective tissue disease syndrome. It illustrates the difficulties when diagnosing overlap conditions.

Endoscopic management of pancreatic disease.

Since its introduction in 1968, ERCP has developed from being a purely diagnostic method, mostly used in the investigation of unexplained upper abdominal pain, to an invaluable tool for the management of patients with pancreatic disorders. In cases with severe gallstone pancreatitis, the biliary obstruction is disclosed and relieved by ERCP and ES. In patients with severe acute pancreatitis of other aetiologies, as well as in post-traumatic pancreatitis, ERCP is indispensable for revealing complications (e.g. pancreatic duct rupture) and/or for planning the treatment strategy. Furthermore, in cases of pancreatitis not related to alcohol or gallstones, it often demonstrates causes which may be treatable, and it is also useful for evaluation of the gland after massive pancreatic necrosis. Moreover, ERCP is helpful in establishing the diagnosis of chronic pancreatitis and its complications as well as in demonstrating morphological grounds for therapeutic intervention. Although the indications, limitations, and practicability of the different techniques of therapeutic ERCP in various pancreatic diseases still remain to be defined, the method appears to offer an alternative to surgery, particularly in cases in which operative treatment is technically difficult and the results are less favourable. Frequency and severity of complications associated with both diagnostic and therapeutic ERCP seem to be, at least in the hands of experts, reasonably low.

Endoscopic treatment of anastomotic strictures in Crohn's disease.

The results of endoscopic balloon dilatation in 27 patients with anastomotic strictures caused by Crohn's disease are reported. All patients had obstructive symptoms not responding to corticosteroids and of such a degree that resection or strictureplasty was considered necessary. The patients were followed up for 7 to 38 months after their first dilatation. Eighteen patients were more or less free from obstructive symptoms while the results were less favourable in the remaining nine patients. The median time after the latest surgical intervention was seven years in the group with a successful outcome and 1.6 years in the group with a poor outcome, which may indicate that some patients have a more aggressive form of Crohn's disease where balloon dilatation is only of moderate value. However, all patients experienced at least a temporary effect, so that balloon dilatation can be considered for use in situations where it is desirable to postpone surgery.

Occurrence of Clostridium difficile toxin in inflammatory bowel disease.

The occurrence of Clostridium difficile toxin in faeces has been studied in 53 inpatients with inflammatory bowel disease (IBD) at 57 admissions. Before faecal sampling of the patients had had sulphasalazine therapy--17 for more than 1 year--and 16 patients had taken antibiotics on 20 occasions within the last year. The toxin was found in 3 out of 57 samples (5%). In all cases it could be detected only in undiluted stool filtrate. None of the patients was treated for the C. difficile infection; remission was achieved in two of the patients, whereas the third patient with severe ulcerative colitis was referred to colectomy. Our results suggest that neither IBD as such nor long-term sulphasalazine therapy predisposes to occurrence of C. difficile toxin. Antibiotic therapy in these patients does not imply a higher risk of toxin occurrence than in other patients. In our region there is no need for routine screening for this in symptomatic patients with IBD.

Intensive intravenous treatment of ulcerative colitis.

Two hundred four courses of intensive intravenous treatment were given to 158 patients with ulcerative colitis. The remission rates in the severe, moderate, or mild attacks were 55.7%, 86.9%, and 91.8%. Total colitis had a great impact on the results, especially in severe attacks. Of these patients, 52.8% were operated on within 3 wk. The relapse rate was exponential, and during the first year 48.1% of the patients in remission relapsed. The extent of the colitis, severity of the attack, or duration of intensive intravenous treatment had no influence on the time of relapse. Twelve patients with chronic continuous disease were given intensive intravenous treatment. No long-term benefit was seen in patients with total ulcerative colitis, but half of those with less extensive colitis showed a good to excellent response to treatment.