Chris J. J. Mulder

Proton pump inhibitors (PPIs) have proved to be effective in treating reflux oesophagitis. Until now, no study had compared the PPIs omeprazole Multiple Unit Pellet System (MUPS), lansoprazole and pantoprazole in patients with reflux oesophagitis. To compare omeprazole MUPS 20 mg, lansoprazole 30 mg and pantoprazole 40 mg for treatment effect in symptomatic reflux oesophagitis. Patients with grade I–IV symptomatic reflux oesophagitis were randomized to double-blind omeprazole 20 mg once morning, lansoprazole 30 mg o.m. or pantoprazole 40 mg o.m. Patient satisfaction and symptoms were evaluated after 4 and 8 weeks. Patients not satisfied after 8 weeks were treated for another 4 weeks with omeprazole 40 mg MUPS (open). Successful treatment was followed by 3 months’ maintenance treatment with omeprazole MUPS 20 mg (patients satisfied after 4 or 8 weeks) or omeprazole MUPS 40 mg (patients satisfied after 12 weeks). On intention-to-treat (ITT) analysis (n = 461) at 4 and 8 weeks, respectively, 84% and 87% (omeprazole MUPS), 78% and 81% (lansoprazole), and 84% and 89% (pantoprazole) were free of heartburn. Equivalence was found between omeprazole MUPS and pantoprazole (heartburn relief), but not with lansoprazole. Patient satisfaction after 4 and 8 weeks, respectively, was 79% and 89% (omeprazole MUPS), 76% and 86% (lansoprazole), and 79% and 91% (pantoprazole). Patient satisfaction was similar in all treatment groups. During maintenance, 87% in the omeprazole MUPS 20 mg group and 81% in the omeprazole MUPS 40 mg group were satisfied after 3 months. Omeprazole MUPS 20 mg and pantoprazole 40 mg have equivalent efficacy in the treatment of reflux oesophagitis. Based on patient satisfaction, omeprazole MUPS 20 mg, lansoprazole 30 mg and pantoprazole 40 mg are equally effective.

The pharyngoesophageal diverticulum has been called Zenker's diverticulum (ZD); we define the latter as a posterior diverticulum with its neck proximal to the cricopharyngeal muscle. Most authors consider such pouches to be a type of esophageal diverticulum. Diverticula are outpouchings of one or more layers of the esophageal wall, and occur in three main areas: 1) immediately above the upper esophageal sphincter (ZD); 2) near the midpoint of the esophagus (traction diverticulum); and 3) immediately above the lower esophageal sphincter (epiphrenic diverticulum).

Refractory coeliac disease (RCD) is a rare diagnosis made after the exclusion of any disorder mimicking CD and after initial or subsequent failure of a strict gluten-free diet (GFD) to restore normal intestinal architecture. In the past, treatments such as steroids, cyclosporin and azathioprine have been tried, but literature on this subject consists mainly of case reports. Interleukin-10 (IL-10) may be beneficial in RCD because of its inhibitory effect on T-lymphocyte- and monocyte-driven immune responses. We performed a pilot, non-randomized, open label study to evaluate recombinant human IL-10 in RCD. IL-10 (8 mcg/kg) was administered subcutaneously, three times a week for 3 months in 10 RCD patients. Small bowel biopsies were taken at T = 0, T = 3 months and T = 9 months. The mucosal histopathology at 3 months was the primary end point for evaluation of efficacy. Evaluations of clinical features, malabsorption parameters and safety were made prior to, during and after treatment. Before treatment, all RCD patients had partial to total villous atrophy (Marsh III ABC). Two patients dropped out of the study: one because of headaches, the other because of thrombocytopenia. In the remaining eight patients, after 3 months of IL-10 treatment histology was unchanged in five patients, improved in two patients and deteriorated in one patient. Disappearance of villous atrophy was seen in only one patient. Three patients reported a clinical response, i.e. relief of fatigue, abdominal complaints and diarrhoea. After stopping IL-10 treatment the symptoms recurred. The laboratory parameters remained the same during treatment and in follow-up. In conclusion, in our study group of 10 RCD patients, IL-10 in the given dosage was not overall effective in our study group of RCD patients. Two dropped out because of side effects and in only one patient did we see a normalization of villous architecture.

The treatment of coeliac disease (CD) is straightforward and simple: life-long adherence to a gluten-free diet. However, in a small subgroup of patients, the clinical and histological abnormalities persist or recur. This non-responsiveness leaves a poorly understood syndrome known as refractory coeliac disease (RCD). A specific definition of RCD is lacking in the literature. We speculate that RCD may appear in a subgroup of coeliacs with persisting histologic abnormalities. In all patients screened for RCD we look for DQ2 and DQ8. In non-DQ2/DQ8 patients we reconsider the diagnosis of CD and of auto-immune enteropathy. Most of the patients referred to us because of suspicion of RCD are affected by other diseases. Probably the commonest cause of non-responsiveness is continued gluten intake. Exocrine pancreas insufficiency, hyperthyroid disease, collagenous colitis are other common explanations. RCD and enteropathy-associated T cell lymphomas (EATL) can be distinguished by intra-epithelial lymphocyte phenotyping and TCR-gamma gene rearrangements. In RCD, an unexplained sustained stimulation of T cell cytotoxic activity is present. Immunosuppressive treatment might moderate this. Cyclosporine has been reported as a resounding success in case reports; however, our results were disappointing. We suggest azathioprine and steroids in RCD without aberrant T-lymphocytes in their mucosa. However, in RCD with aberrant T-lymphocytes we suggest chemotherapy. As the prognosis of EATLs is extremely poor the early detection of RCD with aberrant T cells is crucial.

A Zenker's diverticulum (ZD) is a posterior diverticulum with its neck proximal to the cricopharyngeal muscle. Patients typically present after the age of 60 with symptoms ranging from weeks to years. The classical treatment in the past was surgical, which is still the case in the US. They treat them in general with open myotomy and diverticulectomy. Since the 1950s ENT physicians treat them with rigid endoscopes and cut the bridge between the ZD and the esophagus. This method is widely used throughout western Europe. However, many symptomatic elderly patients are poor surgical/ENT candidates. In 1995, two groups from Brazil and The Netherlands reported their first results with a gastroscopic treatment, in which the ZD bridge is cut with a precut needle/monopolar forceps. Recently, argon plasma coagulation has also been introduced in this field. All these treatments seem effective. Comparative trials between these approaches are now long overdue, since all these modalities will work in the hands of experienced "Zenker specialists".

Zenker’s diverticulum (ZD) is a common cause of dysphagia in the elderly. Many symptomatic elderly are poor candidates for surgery and/or ear, nose and throat treatment. The author’s first experiences with gastroscopic treatment by cutting the Zenker bridge to allow an overflow have recently been published. Only patients with contraindications for general anesthesia were accepted to the pilot group. However, the author now treats all ZD patients in this manner. One hundred and twenty‐five patients (male to female ratio 1.6) were referred for treatment from 1993 to 1997. After introduction of the gastroscope into the esophagus, a nasogastric tube was positioned to treat a ZD bridge with a height of less than 1 cm. The ZD bridge was divided by argon plasma coagulation, if necessary, in combination with monopolar forceps, Savary dilator and/or precut needle. All patients received antibiotics, topical anesthesia to the throat, if necessary, and intravenous midazolam, if possible. Radiography was performed after treatment. Normalization of the diet was allowed when the x‐ray showed no signs of leakage. All patients referred for treatment were treated successfully. The median age was 77 years (range 41 to 100 years). Symptomatic improvement was seen in all patients after treatment. Complications included subcutaneous emphysema (n=17), mediastinal emphysema (n=5) and bleeding (n=2). One patient (95 years of age) died in her nursing home 27 days after treatment due to massive pulmonary embolism. The thirty‐day mortality rate was otherwise zero. Three patients had been previously treated by surgeons and 12 by ear, nose and throat physicians, without sufficient improvement; all were adequately treated by the author. The mean number of treatment sessions was 1.8. This approach seems safe and effective. Treatment of every patient was possible and was carried out, even in patients in very poor condition, without general anesthesia.