Laparoscopic or conventional Nissen fundoplication for gastro-oesophageal reflux disease: randomised clinical trial. The Netherlands Antireflux Surgery Study Group.

BACKGROUND: For the surgical treatment of gastrooesophageal reflux disease (GORD), laparoscopic Nissen fundoplication has largely replaced the open procedure. Retrospective and prospective non-randomised studies have shown similar results after laparoscopic Nissen fundoplication compared with the open procedure. METHODS: In a multicentre randomised trial candidates for surgical treatment of GORD were randomly assigned to either laparoscopic or open 360 degrees Nissen fundoplication. Primary endpoints were dysphagia, recurrent GORD, and intrathoracic hernia. Secondary endpoints were effectiveness and quality of life. This planned interim analysis focuses on endpoints and complications and in-hospital costs. FINDINGS: At the time of interim analysis, 11 patients in the laparoscopic group and one in the conventional group had reached a primary endpoint (p=0.01; relative risk=8.8, 95% CI 1.2-66.3). This difference was caused mainly by whether or not patients had dysphagia (seven patients in the laparoscopic group and none in the conventional group, p=0.016). INTERPRETATION: Although laparoscopic Nissen fundoplication was as effective as the open procedure in controlling reflux, the significantly higher risk of reaching a primary endpoint in the laparoscopic group led us to stop the study.

The prevalence of gastroesophageal reflux disease in institutionalized intellectually disabled individuals.

OBJECTIVE: The prevalence of gastroesophageal reflux disease (GERD) was randomly investigated among Dutch and Belgian intellectually disabled individuals. METHODS: In six institutes including 1607 residents, 435 persons with IQ <50 underwent 24-h esophageal pH-metry and were scored for possible predisposing factors and characteristic reflux symptoms. In 49 (11.2%) cases the test failed because of technical reasons. A pathological pH test was defined as a pH <4 for >4.5% of the measured time. Subjects with a pathological pH test (patients) were compared with those with a normal pH test (controls). RESULTS: Of the remaining individuals, 51.8% (200/386) showed a normal pH test, whereas 186 showed a pathological pH test (median duration pH <4: 14.2%, range: 4.5-78.4%). As possible predisposing factors scoliosis, cerebral palsy, use of anticonvulsant drugs or other benzodiazepines, and IQ <35 were found, whereas symptoms such as vomiting, hematemesis, rumination, and depressive symptoms were indicative for reflux. At endoscopy reflux esophagitis was diagnosed in 129 of the 186 patients (69.4%). In 61 (47.3%) of 129 patients, grade I, 43 (33.3%) grade II, 25 (19.4%) grade III/IV (Savary-Miller) were found. Barrett's esophagus was found in 18 (14.0%) and peptic strictures in five (3.9%) cases. CONCLUSIONS: An abnormal 24-h pH-metry and symptoms suggestive for GERD were documented frequently in a large cohort of institutionalized intellectually disabled individuals. Further endoscopical evaluation confirmed the diagnosis of reflux esophagitis in the majority of these individuals.

Gastro-oesophageal reflux disease in institutionalised intellectually disabled individuals.

BACKGROUND: The prevalence of reflux oesophagitis (RO) in the normally intellectual population is about 2%, while this condition in the intellectually disabled has an estimated prevalence of 10%. METHODS: We investigated the presence of RO among 1687 intellectually disabled, with an IQ < 50, from 5 different institutes in the Netherlands. All were scored for possible associated factors and reflux symptoms, and compared with the overall population (n = 1580) from the same institutes (controls). Also, the effect of treatment on symptoms was evaluated after at least one year of therapy. RESULTS: Gastro-oesophageal reflux disease (GORD) was suspected clinically in 169 patients based on the following symptoms: vomiting, haematemesis, anaemia, rumination or behaviour problems. At endoscopy RO was diagnosed in 107 of 1687 patients (6.4%): 17 (15.9%) grade I, 34 (31.8%) gr. II, 42 (39.3%) gr. III and 14 (13.1%) gr. IV RO (Savary-Miller classification). Cerebral palsy, constipation, anticonvulsant drugs, an IQ < 35, underweight and gastrostomy feeding appeared to be possible associated factors, while as reflux symptoms persistent vomiting, haematemesis, iron deficiency anaemia, rumination, and behaviour problems were found. Concerning therapy, surgery was found to be effective in 38%, H2 receptor antagonists in 60% and the proton-pump inhibitor omeprazole in 96%. CONCLUSIONS: In this group of Dutch intellectually disabled patients with IQ < 50 RO was diagnosed in about 6% (107 of 1687), mostly severe grades of oesophagitis. Several possible associated factors were significantly present. From non-specific reflux symptoms persistent vomiting was the most indicative factor. In this population the most effective treatment of RO was long-term omeprazole therapy.

Ileal pouch arthritis: a case report.

A patient is described with arthritis of both wrists and tendinitis of one achilles tendon in the presence of severe pouchitis. The rapid disappearance of arthritis and tendinitis after removal of the pouch strongly suggests their relationship. The pathogenesis of arthritis in pouchitis has not been elucidated but may be the same as in ulcerative colitis. Rheumatologists should be aware of the occurrence of arthritis in patients with ulcerative colitis after the construction of an ileo-anal anastomosis with a so-called pouch.

Effects of Nissen fundoplication on gastro-oesophageal reflux and oesophageal motor function.

BACKGROUND: Nissen fundoplication reduces gastro-oesophageal reflux effectively, but the mechanisms through which this effect is brought about have remained rather obscure. METHODS: In this study the effect of fundoplication on oesophageal acid exposure, oesophageal body motility, and lower oesophageal sphincter pressure (LOSP) was assessed prospectively. Eleven patients were studied before and 3 months after a floppy Nissen fundoplication. A Dent sleeve was used to measure LOSP, and ambulatory pH and pressure monitoring were used to evaluate oesophageal motor function. RESULTS: Gastro-oesophageal reflux was significantly decreased after fundoplication without an increase in LOSP. The motor function of the oesophageal body was not affected by the antireflux procedure. CONCLUSIONS: Nissen fundoplication is an effective antireflux operation, even though the procedure does not increase LOSP, and the motility pattern of the oesophageal body is not affected by the construction of a floppy fundic wrap.

Oesophageal motility and gastro-oesophageal reflux before and after healing of reflux oesophagitis. A study using 24 hour ambulatory pH and pressure monitoring.

In this study 24 hour oesophageal pH and pressure monitoring was used to assess oesophageal motility and acid clearance in 27 patients with reflux oesophagitis (Savary-Miller grades I-IV), before and after healing of oesophagitis. After the first 24 hour study patients were treated with omeprazole 40 mg for 8-24 weeks. After endoscopically verified healing and withdrawing omeprazole for four days 24 hour monitoring was repeated. A total of 106,630 pressure events was analysed. No significant differences were found for any of the motility variables, especially the number and the type of contractions, the peristaltic amplitude, duration, and propagation velocity did not show any changes. Separate analysis of motility variables before and after healing in the low and high grade oesophagitis groups yielded similar results. Oesophageal motor response to reflux was investigated by analysis of all contractions occurring in the two minute period after the onset of each reflux episode. Both motor response and oesophageal acid exposure (% time pH < 4, number of reflux episodes) did not change after healing of oesophagitis, thus implying that acid clearance remained unchanged. These results indicate that impaired motility in reflux oesophagitis is either an irreversible consequence of oesophageal inflammation, or a (pre-existent) factor in its pathogenesis.

Ambulatory esophageal pressure and pH monitoring in patients with high-grade reflux esophagitis.

Using conventional manometry and 24-hr ambulatory pressure and pH monitoring, we investigated esophageal motility and the esophageal motor response to reflux in 11 patients with reflux esophagitis Savary-Miller grade III and IV, and an age- and sex-matched group of 11 healthy controls. The patients had a significantly increased esophageal acid exposure. Conventional manometry showed a significantly decreased LES pressure and distal peristaltic amplitude in patients. The 24-hr monitoring yielded a significant decrease in peristaltic contraction duration and peristaltic propagation velocity in the patient group. Distal peristaltic amplitude was not decreased. Analysis of the contractions occurring in the 2-min period after each reflux episode showed a reduced number of contractions during the upright period, caused by a significantly decreased number of peristaltic contractions. During the supine period, there was a trend towards an increased number of contractions. It is concluded that esophageal motor activity and the response to reflux are impaired in patients with high-grade reflux esophagitis. However, the abnormalities found are only minor and are unlikely to play an important role in the pathogenesis of reflux esophagitis.

Esophageal motility in low-grade reflux esophagitis, evaluated by stationary and 24-hour ambulatory manometry.

Whereas previous studies have unequivocally shown that esophageal motility is abnormal in patients with severe reflux esophagitis, the results of motility testing in patients with low-grade esophagitis are inconsistent. We studied 27 patients with Savary grade I and II esophagitis and 24 healthy controls matched for age and sex. Both underwent conventional manometry and 24-h ambulatory pH and pressure monitoring. Esophageal acid exposure was greater in patients than controls. The mean lower esophageal sphincter pressure was significantly lower in esophagitis patients [1.46 +/- 0.09 vs. 1.79 +/- 0.11 kPa (10.98 +/- 0.68 vs. 13.46 +/- 0.83 mm Hg)]. The total number of contractions recorded in the 24-h period was not different in the patient group (2168 +/- 108.4 vs. 2033 +/- 130.5), but esophagitis patients had an increased number of nontransmitted contractions (968 +/- 39.4 vs. 773 +/- 50.2, p < 0.01). A tendency toward a decreased prevalence of peristaltic contractions just failed to reach statistical significance (p = 0.07). Both conventional manometry and 24-h monitoring showed no significant difference in peristaltic amplitude between the two groups. Differences in contraction duration (2.02 +/- 0.08 vs. 2.39 +/- 0.12 s, p < 0.01) and velocity of the peristaltic wave (3.65 +/- 0.10 vs. 4.63 +/- 0.13 cm/s, p < 0.01) were only detected by 24-h monitoring. The findings made in this study do not support the concept that impaired esophageal peristalsis is a major factor in the pathogenesis of low-grade esophagitis.

Oesophageal motor response to reflux is not impaired in reflux oesophagitis.

Whether the oesophageal motor response to reflux, as recorded over 24 hours, is impaired in patients with reflux oesophagitis was investigated. Twenty three patients with oesophagitis (Savary-Miller grades I-IV) and 23 control subjects matched for age and sex underwent 24 hour ambulatory pH and pressure monitoring. All contractions occurring in the 2 minute period after the onset of each reflux episode were analysed automatically using dedicated computer algorithms. A total of 2085 reflux episodes occurred--1513 in patients and 572 in controls. Oesophageal acid exposure was greater (p < 0.01) in patients than in controls (mean (SEM) % time pH < 4 13.3 (1.7) and 5.3 (0.9)%, respectively). The mean duration of the supine reflux episodes was longer (p < 0.01) in patients (11.2 (2.8) minutes) than in controls (5.1 (1.8) minutes). In the upright period, no significant differences in the motor response to reflux were found. In the supine period, the patients showed a higher number of reflux induced contractions (4.40 (0.61) v 1.62 (0.31), p < 0.01), a higher contraction amplitude (4.55 (0.42) v 2.99 (0.71) kPa, p < 0.02) and longer contractions (1.86 (0.19) v 1.32 (0.29) seconds, p < 0.05). The percentages of peristaltic and simultaneous contractions that occurred in response to supine reflux did not differ between the two groups. In patients with reflux oesophagitis the motor response of the oesophagus to reflux is not impaired. During the supine period the response is even stronger than in healthy controls.

Analysis of 24-hour esophageal pressure and pH data in unselected patients with noncardiac chest pain.

Fourty-four unselected patients with noncardiac chest pain were studied using conventional manometry with additional edrophonium provocation and 24-hour ambulatory esophageal pH and pressure recording with a system developed by our group. New, fully automated techniques of statistical analysis of the complete set of esophageal pressure and pH signals were used to examine the temporal relation between pain, esophageal motility disturbances, and gastroesophageal reflux. The analysis used the 97.5th percentile of amplitude and duration of all esophageal contractions in each patient as well as a chi 2 test of the distribution of contraction types to determine whether a pain episode was related to abnormal motility or not. The edrophonium test results were positive in 2 patients. Only 25 patients (56.8%) had at least one pain episode (total, 111 episodes) during 24-hour recording. Thirty-three percent of the pain episodes were related to reflux and 23.4% to abnormal motility, and 43.2% were not related to an esophageal function disturbance. In the patient-oriented analysis in this study, it was required for a positive correlation that the symptom index (percentage of related pain episodes) was higher than 75%. It was found that the pain was related to reflux in 2 patients (4.6%), to reflux and motor abnormalities in 4 (9.2%), and to motor abnormalities in 2 patients (4.6%). In 36 patients (81.8%), no relation with an esophageal abnormality could be established, either because the patients had no pain during the 24-hour study, or because the pain seemed unrelated to reflux or abnormal motility.

Fatal acute liver failure associated with pirprofen. Report of a case and a review of the literature.

This report is about a 71-yr-old woman who suffered from acute liver failure, induced by the nonsteroidal antiinflammatory drug, pirprofen. She presented with jaundice 6 weeks after starting treatment with 800 mg pirprofen daily. She is the fifth patient described in the literature to die from pirprofen-induced hepatotoxicity.

[The value of ambulatory 24-hour esophageal manometry in the diagnosis of retrosternal pain of non-cardiac origin]. / De waarde van ambulante 24-uursslokdarmmanometrie bij de diagnostiek van retrosternale pijn van niet-cardiale origine.

The clinical relevance of a system of ambulatory 24-hour oesophageal pressure and pH recording with automated data analysis was investigated in 33 unselected patients with non-cardiac chest pain. After conventional manometry with edrophonium (Tensilon) provocation, 24-hour oesophageal pH and pressure monitoring was performed. In 17 patients conventional manometry, edrophonium provocation and 24-hour pH recording revealed an oesophageal origin of the symptoms: 6 patients had oesophageal motility disorders, 3 were positive responders to edrophonium and 8 had chest pain associated with gastro-oesophageal reflux. In none of the patients who had a pain attack during prolonged oesophageal pressure recording, was a new motility disorder detected.

Olsalazine as an alternative therapy in a patient with sulfasalazine-induced eosinophilic pneumonia.

A man with Crohn's colitis developed eosinophilic pneumonia after treatment with sulfasalazine. Challenge with sulfapyridine revealed that this component of sulfasalazine was the likely causative agent. Treatment with olsalazine, a 5-aminosalicylic acid compound (disodium-azodisalicylate), was well tolerated without recurrence of pulmonary symptoms.

Immunoglobulin-containing cells in liver biopsies of patients with chronic hepatitis and primary biliary cirrhosis.

The numbers of IgA, IgM and IgG-containing cells were studied by means of an indirect immunoperoxidase technique and morphometry in liver biopsies of patients with primary biliary cirrhosis and chronic hepatitis, in whom serum immunoglobulin concentrations were also determined. In patients with primary biliary cirrhosis the absolute and relative number of IgM-containing cells in the liver was significantly higher, whereas the absolute and relative number of IgG-containing cells in the liver was significantly lower compared to patients with chronic hepatitis. IgM-containing cells in liver biopsies of patients with primary biliary cirrhosis correlated strongly with their serum IgM levels. It is concluded that determination of the pattern of immunoglobulin containing cells in liver biopsies may help in the differentiation of primary biliary cirrhosis from chronic hepatitis and that local production of IgM in the liver may contribute significantly to the high serum IgM levels in patients with primary biliary cirrhosis.

Intramural hematoma of the duodenum in a patient with chronic pancreatitis.

Intramural hematoma of the duodenum is usually caused by blunt abdominal injury. Sometimes this lesion occurs in patients with coagulation disturbances or pancreatic disease such as chronic pancreatitis. There also appears to be a link with alcohol abuse. We describe the case-history of a 45-year-old male with chronic pancreatitis who presented with abdominal pain. The diagnosis of a space-occupying process of the duodenum was made and subsequently a pancreatico-duodenectomy was performed. The duodenum revealed an intramural hematoma, the pancreas showed signs of mild chronic pancreatitis.

Human antibodies to immunoglobulin A (IgA). A radioimmunological method for differentiation between anti-IgA antibodies and IgA in the serum of IgA deficient individuals.

In the sera of 12 out of 27 individuals with IgA deficiency (serum level below 0.02 mg IgA/ml) class-specific anti-IgA antibodies were demonstrated by haemagglutination. These sera showed false-positive results in a solid-phase inhibition radioimmunoassay (RIST) (apparent IgA concentration between 0.6 and 13.7 microgram IgA/ml) indicating that the RIST is not an appropriate test for the analysis of serum of IgA deficient individuals. A modification of the RIST is proposed (titration RIA) that permits differentiation between low levels of IgA and class-specific anti-IgA antibodies. With this test IgA deficient individuals could be classified as those with low but detectable levels of IgA and those with class-specific anti-IgA antibodies. A computer procedure was developed to calculate both the amount and the avidity (K) of the anti-IgA antibodies and to simulate the assay system. The K value calculated from experimental points proved to be an overestimation of the K value which fitted most adequately in the simulation. The comparison of the results with clinical findings indicated a possible correlation between the amount and the avidity of the anti-IgA antibodies and the appearance of anaphylactic reactions after transfusion of IgA.