Willem Dekker

Double-Blind Comparison of Slow-Release 5-Aminosalicylateand Sulfasalazine in Remission Maintenance in Ulcerative Colitis

The results of a clinical trial comparing slow-release 5-aminosalicylic acid tablets (Pentasa) and enteric-coated sulfasalazine tablets (Salazopyrin) with regard to the efficacy of maintaining ulcerative colitis patients in remission for 12 mo and with regard to safety of treatment are reported. Seventy-five patients with ulcerative colitis in remission for between 1 mo and 5 yr were included for analysis. Forty-nine men and 26 women, aged between 18 and 79 yr, received either Pentasa t.i.d. (1500 mg) plus Salazopyrin placebo or Salazopyrin t.i.d. (3 g) plus Pentasa placebo daily. Patients were assessed clinically, endoscopically, and histologically before and 3, 6, 9, and 12 mo after the start of treatment. Life-table analysis showed ongoing remission after 6 and 12 mo for Pentasa to be 63% (26 of 41) and 54% (22 of 41) and for Salazopyrin 72% (22 of 31) and 46% (14 of 31). These differences were not statistically significant. Three patients treated with Salazopyrin were withdrawn because of severe erythrodermia, anxiety and backache, and pregnancy, respectively. One patient on Salazopyrin experienced transient rises in serum urea, creatinine, and lactic dehydrogenase and another patient in this group reported slight reversible loss of hair. In the Pentasa group no side effects were recorded. We conclude that Pentasa is a well-tolerated drug, equally effective as Salazopyrin in maintenance of remission of ulcerative colitis.

Lansoprazole 30mg versus omeprazole 40mg in the treatment of reflux oesophagitis grade II, III and IVa (a Dutch multicentre trial)

Objectives: To compare the efficacy and safety of lansoprazole 30 mg daily (LAN30) and omeprazole 40mg daily (OME40) in the treatment of moderate (Savary–Miller grade II) as well as severe reflux oesophagitis (grade III/IVa). Design: A double-blind, randomized, multicentre study, involving 211 patients at 29 Dutch hospitals. Methods: Healing was assessed by endoscopy, performed on admission, after 4 weeks and after 8 weeks if the patient was not healed after 4 weeks. Symptom relief was determined by symptom assessments at the same time points. Safety was evaluated by determining the incidence of adverse events. Results: There was no significant difference in intention-to-treat (ITT) healing rates after 4 weeks (LAN30 87.5%, OME40 80.6%; 95% Cl (–4.0; +17.8)) and in the ITT overall healing (LAN30 96.1%, OME40 93.1 %; 95% Cl (–4.2; +10.2)) rates between the LAN30 and the OME40 group. Relief of reflux-related symptoms at 4 weeks as well as 8 weeks did not differ significantly between the treatment groups. No difference in the incidence of adverse events was observed between the groups. Conclusion: Treatment of patients with reflux oesophagitis grade II, III or IVa with LAN30 was as effective as with OME40 with respect to healing as well as symptom relief. European Journal of Gastroenterology & Hepatology 1996, 8:1101–1106

Comparison of beclomethasone dipropionate and prednisolone 21-phosphate enemas in the treatment of ulcerative proctitis.

In a double-blind randomized clinical trial 18 patients with exacerbations of distal ulcerative colitis were treated for 4 weeks with enemas containing either prednisolone 21-phosphate 30 mg (PP) or beclomethasone dipropionate 1 mg (BDP) a surface-active corticosteroid. All 8 patients treated with PP showed clinical and endoscopic improvement in contrast with only 4 of 10 patients treated with BDP. Endocrinologic evaluation showed a significant decrease in morning plasma cortisol, in cortisol increase after synacthen, and in urinary free cortisol excretion after PP therapy, but no changes in these variables after BDP therapy. We conclude that PP enemas are more active in the treatment of ulcerative proctitis, but they cause a suppression of the adrenal cortex, in contrast to BDP.

Acute noncardiac chest pain in a coronary care unit: Acute noncardiac chest pain in a coronary care unit. Evaluation by 24-hour pressure and pH recording of the esophagus

Twenty-four-hour recording of esophageal pressure and pH was performed successfully in 41 patients admitted to the coronary care unit of a general hospital who had an episode of acute, prolonged retrosternal chest pain and who were initially suspected of suffering from coronary artery disease (severe angina pectoris, myocardial infarction), but in whom the pain was subsequently shown not to be of cardiac origin. The recordings were analyzed with fully automated techniques. A pain episode was considered to be related to abnormal esophageal motility when contraction amplitudes or durations in the pain episode exceeded the patients upper limit of normal (97.5th percentile) or when the proportion of abnormal propagated contractions (simultaneous, nontransmitted) in the pain episode was significantly increased (chi 2 test). Thirty patients (73%) had one or more pain episodes (in total 63 pain episodes) during the 24-hour recording. Forty-three percent of the pain episodes was related to abnormal motility and 30% to reflux, and 27% was not related to esophageal function disturbance. Using the criterium that the symptom index had to be greater than or equal to 75%, it was found that the pain was related to reflux in 13 patients (43%) and to motor abnormalities in 10 patients (33%). It is concluded that in the majority of patients acutely admitted with noncardiac chest pain, esophageal motor abnormalities and reflux can be shown to be the likely cause of the symptoms.

Therapeutic investigations in primary sclerosing cholangitis

There is no consensus about the necessity and the possibility of therapy in primary sclerosing cholangitis. In some patients rapid deterioration of liver function may occur due to recurrent cholangitis and cholestasis. In one such patient, we obtained radiological evidence that the cholestasis was caused, not entirely by end-stage fibrotic scarring as interpreted upon surgical exploration, but, at least in part, by biliary stasis secondary to marked irregular narrowing of the extrahepatic bile ducts, together with precipitate formation. Moreover, the biliary ductular narrowing appeared to be partly reversible, indicating that edema and inflammation were responsible for part of the narrowing. These observations prompted us to evaluate topical lavage by nasobiliary drainage, first with saline, and then followed by corticosteroid solution in eight consecutive patients with recurrent cholangitis. Based upon clinical and biochemical evaluation, our preliminary results may be summarized as favorable. However, a large-scale multicenter controlled study will be required to prove the usefulness of this approach.

Early gastric cancer : a clinicopathologic study

We report our experience, between 1973 and 1989 of 302 patients with gastric cancer in a Dutch general hospital. In 144 (47.7%) of them gastric resection was performed. Twenty-eight patients had early gastric cancer (EGC) (9.3% of the entire series and 19.4% of the resected specimens). Multicentricity of EGC was noted in 3 patients (10.7%). The incidence of EGC decreased slightly during consecutive 8-year intervals. There were 16 men and 12 women (mean age 64 and 66 years, respectively). Standard biphasic contrast radiographic studies of the upper gastrointestinal tract diagnosed or suggested malignancy in all but one patient. Endoscopy with directed biopsy diagnosed malignancy in all patients. Twenty-one lesions (67.7%) were localized to the antral region. Type IIc was most frequent (38.7%). There were 21 intestinal-type and 10 diffuse-type EGC by the Lauren classification. The incidence of intestinal-type EGC decreased during two consecutive 8-year periods. All type I and IIa lesions were of the intestinal type, whereas all diffuse-type EGCs were either type IIc or III. Lymph node metastasis was observed in 9.7% of the lesions. The incidence of lymph node metastasis increased from 0% in mucosal cancer to 20% in submucosal cancer. The overall 5-year survival rate was 91.3%: (diffuse type 100% and intestinal type 85.7%). The 5-year survival rate was 100% in mucosal cancer and 81.8% in submucosal cancer.

Prevalence of subtypes of intestinal metaplasia in gastric antral mucosa

A prospective gastroscopic-bioptic study of 533 patients was performed to assess the prevalence and distribution of intestinal metaplasia (IM) and its subtypes in the antral mucosa of patients with various upper intestinal disorders and to assess whether the presence of certain IM subtypes might be of help in selecting patients for careful endoscopic-bioptic surveillance in the screening for gastric carcinoma. IM was found in 135 patients (25.3%). Its prevalence increased with age (P<0.001) and was strongly associated with intestinal-type carcinoma as compared to diffuse-type carcinoma (P<0.001), gastritis (P<0.001), and gastric ulcer (P<0.05). Type I IM was predominant (98.5%), whereas types II and III IM, respectively, were found in 77.8% and 15.6% of the patients with IM. No difference in the prevalence of type I and II IM was found among the various gastric disease states. Type III IM was strongly associated with intestinal-type carcinoma as compared to either benign lesions (P<0.01) or diffuse-type carcinoma. These results suggest that type III IM may play a special role in the histogenesis of intestinal-type carcinoma and suggest that the finding of this IM subtype in gastric biopsies may possibly be of help in identifying patients at greater risk of developing carcinoma.

Esophageal dysfunction as a cause of angina pectoris (linked angina) : does it exist ?

PURPOSE The differentiation between cardiac and esophageal causes of retrosternal chest pain is notoriously difficult. Theoretically, cardiac and esophageal causes may coexist. It has also been reported that gastroesophageal reflux and esophageal motor abnormalities may elicit myocardial ischemia and chest pain, a phenomenon called linked angina pectoris. The aim of this study was to assess the incidence of esophageal abnormalities as a cause of retrosternal chest pain in patients with previously documented coronary artery disease. PATIENTS AND METHODS Thirty consecutive patients were studied, all of whom had undergone coronary arteriography. The patients were studied after they were admitted to the coronary care unit with an attack of typical chest pain. On electrocardiograms (ECGs) taken during pain, 15 patients (group I) had new signs of ischemia; the other 15 patients (group II) did not. In none of the patients were cardiac enzymes elevated. As soon as possible, but within 2 hours after admission, combined 24-hour recording of esophageal pressure and pH was performed. During chest pain, 12-lead ECG recording was carried out. RESULTS In group I, all 15 patients experienced one or more pain episodes during admission, 25 of which were associated with ischemic electrocardiographic changes. The other two episodes were reflux-related. Only one of the 25 ischemia-associated pain episodes was also reflux-related, ie, it was preceded by a reflux episode. In group II, 19 chest pain episodes occurred in 11 patients. None of these was associated with electrocardiographic changes, but 8 were associated with reflux (42%) and 8 with abnormal esophageal motility (42%). CONCLUSION Linked angina is a rare phenomenon.

Pentasa in Lieu of Sulfasalazine

Excerpt To the editor: 5-Aminosalicylic acid (5-ASA) is the effective moiety of sulfasalazine. The sulfapyridine moiety is usually considered to be the cause of intolerance in most of the patients ...

p21waf1/Cip1 expression and the p53/MDM2 feedback loop in gastric carcinogenesis

Data are non-existent regarding coincidental alterations in the expression of p53 and its downstream target genes MDM2 and p21(Waf1/Cip1) in gastric carcinogenesis. An immunohistochemical study was therefore performed to examine the interrelationships of p53, MDM2, and p21(Waf1/Cip1) expression in a series of Caucasian early gastric carcinomas and precursor lesions. In normal gastric mucosa, chronic gastritis, and intestinal metaplasia, the surface cells expressed p21(Waf1/Cip1) in the absence of detectable nuclear p53 and MDM2 protein. Nuclear p53 protein accumulation was found in 60 per cent of the carcinomas, with significant differences in staining characteristics between the Lauren types in the absence of detectable MDM2 protein ( p< 0.005). Nearly 80 per cent of the carcinomas expressed p21(Waf1/Cip1), irrespective of Lauren type. Stratification of the carcinomas according to histological grade and growth pattern did not result in significant differences in p53 and p21(Waf1/Cip1) expression. Finally, no significant correlation was found between overall p53 and p21(Waf1/Cip1) expression in early gastric carcinomas. It is concluded that p21(Waf1/Cip1) expression in the non-neoplastic mucosa most likely relates to cell senescence and/or terminal differentiation, perhaps even in a p53-independent manner. In view of p53/MDM2 homeostasis, the differences in p53 staining characteristics between intestinal and diffuse-type carcinomas probably result, at least in part, from a difference in the prevalence of p53 gene mutations. Moreover, p53-independent induction of p21(Waf1/Cip1) expression apparently occurs in a considerable proportion of early carcinomas. Finally, in contrast to other carcinomas, p21(Waf1/Cip1) expression is not significantly correlated with histological grade in gastric carcinomas, suggesting possible defects downstream of p21(Waf1/Cip1) as an underlying cause for this apparent discrepancy.