Spontaneous regression of hepatocellular carcinoma.

A 72-year-old Caucasian woman suffered from histologically-proven advanced hepatic cancer, for which she received no treatment. She had been a regular drinker for a long time. Serologic markers for hepatitis B and C were negative. In spite of her poor prognosis, she remained in good clinical condition and at 14 months of follow up the hepatocellular carcinoma could not be visualised any more radiologically. At that time the serum alpha foetoprotein concentration was normal. At present, 28 months after diagnosis, the patient is doing well and her tumour still appears to be in complete spontaneous remission.

Effectiveness of quadruple therapy using lansoprazole, instead of omeprazole, in curing Helicobacter pylori infection.

BACKGROUND: Omeprazole enhances the efficacy of bismuth-based triple therapy. It is unknown whether the same is true for other proton pump inhibitors. Lansoprazole has superior anti-Helicobacter activity in vitro and possibly also in vivo; therefore we investigated quadruple therapy with lansoprazole. MATERIALS AND METHODS: In two studies performed in separate hospitals, a total of 67 Helicobacter pylori-positive patients were treated with 7-day quadruple therapy (lansoprazole, colloidal bismuth subcitrate, tetracycline, and metronidazole) after 3 days of lansoprazole pretreatment. Testing for cure was done by endoscopy in study 1 and by breath test in study 2. RESULTS: Cure rates per protocol were 31 of 31 (100%) in study 1 and 30 of 32 (94%) in study 2. Intention-to-treat cure rates were 31 of 35 (89%) in study 1 and 30 of 32 (94%) in study 2. Cured overall were 32 of 34 with a metronidazole sensitive strain and 3 of 3 with a metronidazole-resistant strain. Data on side effects were collected from 51 patients. Twelve (21%) had no side effects, 27 (53%) had mild side effects, 10 (20%) had moderate side effects, but only 2 (4%) had severe side effects. Side effects, never were the reason that a patient stopped taking the medication. CONCLUSIONS: The results with lansoprazole-quadruple therapy are comparable to the historic control group treated with omeprazole-quadruple therapy. The cure rare is very high, and although mild to moderate side effects occurred in many patients, everybody finished the treatment regime.

Long-term follow-up after cure of Helicobacter pylori infection with 4 days of quadruple therapy.

BACKGROUND: We have shown that 4 days of quadruple therapy after omeprazole pre-treatment is an effective therapy for curing H. pylori infection. In this study we investigated whether this regimen would maintain the high cure rate during long-term follow-up. Some recent studies have reported high recurrence rates after apparent cure. Apparently not all methods to test for cure have sufficient sensitivity to pick up small numbers of residual bacteria. This study also served to investigate whether our methods to test for cure 5-6 weeks post-treatment were reliable. METHODS: All patients from a previous study were invited to return for a 14C-urea breath test and serology. A representative group of 37 patients (76%) returned for a urea breath test and serology. The mean follow-up was 14.7 months (range 11.4-23.6 months). RESULTS: None of the 37 patients had a positive urea breath test results. IgG antibody titres fell steadily in all patients, showing a mean decrease of 83% at the end of the follow-up. None of the patients showed an increase in titre. Reinfection was therefore 0% (0 of 37). CONCLUSION: Four days of quadruple therapy seems to be an effective therapy for the eradication of H. pylori as evidenced after long-term follow-up. Our biopsy methodology is reliable in identifying treatment failures 5-6 weeks post-treatment.

Regional enteritis complicating malignant lymphoma.

We describe a patient presenting with palpable lymph nodes due to non-Hodgkin's lymphoma. Chemotherapy induced complete remission. One year later he complained of cramping abdominal pain, diarrhoea and bloody stools all due to Crohn's disease of the colon. There are only a few more patients described with a combination of inflammatory bowel disease and malignant lymphoma. So far there is no explanation for the co-incidence of the two diseases.

Only four days of quadruple therapy can effectively cure Helicobacter pylori infection.

AIM: To determine whether 4 days of quadruple therapy using bismuth, tetracycline and metronidazole combined with omeprazole is effective treatment for Helicobacter pylori infection. METHODS: Non-ulcer dyspepsia, as well as chronic peptic ulcer patients with biopsy-proven H. pylori infection received 4 days of quadruple therapy. They were pretreated with 3 days of omeprazole. At least 5-6 weeks later, endoscopy was repeated with 10 biopsies for urease test, histology and culture to establish cure of infection. RESULTS: None of the 54 patients included was lost to follow-up but two had a 14C-urea breath test instead of endoscopy. Side-effects did not interfere with compliance. Forty-nine out of 54 patients (91%; 95% CI: 80-97%) were cured. Metronidazole susceptibility data were available from 43 pre-treatment isolates. Of these 38/40 (95%) with a metronidazole-sensitive strain, and one of three with a metronidazole-resistant strain were cured. CONCLUSIONS: Four days of quadruple therapy after omeprazole pre-treatment is a feasible, well tolerated, and effective treatment for H. pylori infection, especially in those carrying a metronidazole-sensitive strain. It seems that in quadruple therapy, cure rate and treatment duration have a non-linear relation. Our results need confirmation, but for patients suffering from side-effects with the 7-day regimen stopping treatment after 4 days is justified.

Quadruple therapy compared with dual therapy for eradication of Helicobacter pylori in ulcer patients: results of a randomized prospective single-centre study.

OBJECTIVE: To assess the efficacy and side-effect profile of two currently advocated treatment regimens for eradicating Helicobacter pylori. DESIGN: A randomized, controlled, open, single-centre study. SETTING: A community hospital in The Netherlands. PARTICIPANTS: Seventy-six consecutive patients with (chronic) ulcer disease and biopsy-proven H. pylori infection, but without active ulceration at the time of inclusion. INTERVENTIONS: Patients were randomly allocated to 1 week of quadruple therapy with omeprazole, bismuth, tetracycline and metronidazole (group 1) or 2 weeks of dual therapy with omeprazole and amoxicillin (group 2). Group 1 patients were pretreated with omeprazole for 3 days. MAIN OUTCOME MEASURES: Cure was confirmed by obtaining 10 endoscopic biopsies for urease testing, histology and culture 6 weeks after treatment. Side-effects were scored on a standard questionnaire. RESULTS: Three patients were lost to follow-up. In the 'intention to treat' analysis 37 (92.5%) of 40 patients in group 1 were cured compared with 20 (55.6%) of 36 patients in group 2 (P < 0.001). The difference in efficacy was 36.9% (95% confidence interval 18.7-55.1%). Side-effects were fewer and milder in group 2, but all patients in both groups were able to complete the course of treatment. CONCLUSION: Dual therapy is significantly less effective in curing H. pylori infection in peptic ulcer patients than quadruple therapy. No patients were intolerant to either treatment. On the basis of the low efficacy of dual therapy, we believe that this therapy should not be used as a first-line treatment strategy. We confirmed our previous finding that 1 week of quadruple therapy is tolerated well and that it is highly effective against metronidazole-sensitive as well as metronidazole-resistant strains of H. pylori.

[Methotrexate as possible treatment in refractory chronic inflammatory intestinal disease]. / Methotrexaat als mogelijke behandeling bij refractaire chronische inflammatoire darmziekte.

OBJECTIVE: To determine the value of low dose methotrexate therapy in chronic inflammatory bowel disease. SETTING: Catharina Hospital and Diaconessenhuis, Eindhoven, and St. Joseph Hospital, Veldhoven. DESIGN: Descriptive. METHOD: From 1988 until 1993 we treated 15 patients 16 times (one patient was treated twice) with methotrexate 25 mg i.m. once a week during 12 weeks, followed by a tapering oral dose. Our population consisted of 4 men and 11 women with a mean age of 31 year. The diagnosis was Crohn ileitis (1 patient), Crohn colitis (8), ileocolitis (4) and ulcerative colitis (2). The indication for methotrexate was resistance to therapy (9) and steroid dependency (7). Retrospectively the disease activity was determined after 1, 2 and 3 months of therapy. RESULTS: The mean defaecation frequency went down from 7 to 2 times daily after 12 weeks, the ESR from 47 to 17 mm/1st hour, the thrombocytes from 436 x 10(9)/l to 325 x 10(9)/l and the prednisone dose could be lowered from 22 mg to 15 mg after 3 months. In 13/16 treatment cases there was a subjective positive response to methotrexate. Initial response was seen within 4 weeks. No serious side effects were seen. After 10 of the 13 response episodes the disease recurred. CONCLUSION: Methotrexate 25 mg once a week i.m. was associated with a subjective and objective improvement in 12/15 patients, but the risk of recurrence after tapering appears to be large.

Randomized study comparing 1 with 2 weeks of quadruple therapy for eradicating Helicobacter pylori.

OBJECTIVES: We investigated whether the recommended 2-wk triple therapy for eradicating Helicobacter pylori could be reduced to 1 wk, and thus we tried to determine the optimal treatment duration for triple therapy. METHODS: A group of 111 consecutive patients with H. pylori-proven chronic peptic ulcer disease was entered in a randomized study comparing the side effects, compliance, and eradication rates with either 1 wk or 2 wk of traditional triple therapy in combination with an H2 receptor antagonist (quadruple therapy). RESULTS: Follow-up data were available for 109 patients. Eradication for 1 wk of treatment was 53/56 (95%) [95% confidence interval (CI), 89-100%] and for the 2-wk treatment schedule was 50/53 (94%) (95% CI, 88-100%). Therefore 1-wk quadruple therapy appears sufficient, and prolonging treatment does not increase efficacy. Compliance with quadruple therapy is better when the duration of treatment decreases from 2 to 1 wk. One-week quadruple therapy seems feasible for most patients. CONCLUSIONS: Because of the high eradication rate and good tolerability of this short course of quadruple therapy, we recommend it as first-line anti-Helicobacter treatment in a compliant population.

[Endoscopic studies of the digestive tract as a service for family practitioners; experience in the Eindhoven area]. / Endoscopisch onderzoek van de tractus digestivus als service voor de huisarts; ervaringen in de regio Eindhoven.

In May 1989 an open access endoscopy service for general practitioners (GPs) was started in the region of Eindhoven. In the four hospitals covering a population of 500,000 inhabitants, served by 200 GPs, uniform working agreements were made. We evaluated the endoscopies performed in 1990 and compared the total number of endoscopies with that of gastrointestinal X-rays. A total of 996 open access gastroscopies were performed. The most important diagnoses were: peptic ulcer (19%), oesophagitis (16%), bulbitis (9%) and carcinoma (1.5%). The diagnostic yield was 57%. A total of 509 GP-referred sigmoidoscopies were performed. The most important diagnoses were: haemorrhoids and anal fissure (28%), colitis (15%), diverticulosis (12%), neoplastic polyps (11%) and carcinoma (4%). The diagnostic yield was 77%. Compared with 1989 the total number of gastroscopies, requested by GPs and by specialists, increased by 15% of which two-thirds were requested by the GPs. In this period the reduction of barium meals was 11% which was almost exclusively due to the specialist group. Sigmoidoscopies increased by 7%, entirely due to the GP group. The number of barium enemas remained constant. Open access endoscopy resulted in an increase endoscopies with only a partial substitution of radiological examinations. The increase in endoscopic examinations in the GP group did not result in a decline in the specialist group. The total diagnostic yield was 64%.

Two sisters with coeliac disease and jejunal cancer: just a coincidence?

Two sisters with asymptomatic coeliac disease are described; they both developed a primary jejunal cancer at the same age. While screening the family, a third sister was found to have coeliac disease, but without detectable cancer in the small intestine or stomach. These findings suggest an increased susceptibility in this family for carcinoma developing secondary to asymptomatic coeliac disease. We conclude that the finding in a patient of the combination of coeliac disease and malignancy in the digestive tract is sufficient reason to investigate the first-degree relatives with regard to the presence of coeliac disease and a secondary carcinoma.

Gallbladder sensitivity to cholecystokinin in coeliac disease. Correlation of gallbladder contraction with plasma cholecystokinin-like immunoreactivity during infusion of cerulein.

The present study was undertaken to determine whether alterations in the gallbladder sensitivity to cholecystokinin (CCK), apart from a reduced endogenous CCK secretion, contribute to the abnormally decreased postprandial gallbladder contraction in patients with coeliac disease. Gallbladder emptying, measured by cholescintigraphy, and plasma CCK levels, measured by radioimmunoassay, were studied during infusion of graded doses of the CCK analog cerulein in six coeliac patients with subtotal villous atrophy, six coeliac patients on a gluten-free diet with normal villous architecture, and nine control subjects. Both in the patients and in the controls infusion of stepwise increasing doses of cerulein, in the range of 1-16 ng.kg-1.h-1, induced dose-related changes in plasma CCK-like immunoreactivity (CCK-LI) (r = 0.99; p less than 0.001) and gallbladder emptying (r greater than 0.97; p less than 0.01-p less than 0.001). Plasma CCK-LI and gallbladder responses were not significantly different among untreated coeliac patients, treated coeliac patients, and controls. Gallbladder sensitivity to cerulein in untreated and treated coeliac patients was not significantly different from that in controls. It is concluded that the abnormally decreased gallbladder contraction in coeliac patients is the result of a reduced endogenous CCK secretion and not of a lack of end-organ responsiveness to CCK.

[Medium-long-term good results of vertical gastroplasty in the treatment of morbid obesity]. / Goede resultaten op middellange termijn van verticale maagverdeling ter behandeling van overmatige vetzucht.

To determine the long-term results of the surgical treatment of patients with morbid obesity, a retrospective analysis of the patients in whom a vertical banded gastroplasty according to Mason was performed in the period 1982-1990 was carried out in the department of General Surgery, St. Joseph Hospital, Veldhoven, the Netherlands. In a series of 20 patients (4 men and 16 women) with a mean age of 32 (17-53) years who were eligible for treatment according to international criteria surgery was performed. The preoperative weight averaged 124 (94-207) kg and the mean preoperative excess weight was 60 (37-132) kg. Immediate postoperative complications occurred in 5 and late complications in 7 patients. Revision for technical complications was necessary in 2 patients. Twelve patients were followed up for more than 4 years. The mean weight loss after 4 years was 37 (18-89) kg, which was 28 (18-43) per cent of the mean preoperative weight and 62 (31-89) per cent of the mean preoperative excess weight. The 4-year results were unsatisfactory (less than 50 percent excess weight loss) in 3 of the 12 patients. It is concluded that vertical banded gastroplasty in our hands seems a relatively safe and effective surgical method of achieving sustained weight loss in most patients.

Effect of truncal vagotomy on cholecystokinin release, gallbladder contraction, and gallbladder sensitivity to cholecystokinin in humans.

The present study was undertaken to investigate the gastric and intestinal phase of stimulation of postprandial gallbladder contraction and endogenous cholecystokinin secretion in patients with truncal vagotomy and pyloroplasty. Gallbladder emptying, measured by cholescintigraphy, and endogenous cholecystokinin secretion, measured by radioimmunoassay, were studied after both intragastric and intraduodenal administration of corn oil. In addition, the gallbladder responsiveness to cholecystokinin was investigated by infusion of stepwise increasing doses of exogenous cholecystokinin. In the 6 patients with truncal vagotomy, plasma CCK and gallbladder responses to intraduodenal fat were significantly delayed compared to normal subjects. In contrast, the onset of the plasma cholecystokinin increase and gallbladder emptying after intragastric fat was significantly earlier in the vagotomized patients compared with the normal subjects. In the normal subjects, plasma cholecystokinin and gallbladder responses to intragastric fat were significantly lower during the first 25 min after stimulation compared with the results after intraduodenal fat, whereas in the patients with truncal vagotomy and pyloroplasty, no differences in plasma cholecystokinin and gallbladder responses were found according to the site of fat stimulation. The gallbladder-emptying response to exogenous cholecystokinin increased significantly in patients who had undergone truncal vagotomy. It is concluded (a) that truncal vagotomy with pyloroplasty influences the timing but not the magnitude of fat-stimulated gallbladder contraction and endogenous cholecystokinin secretion; and (b) that the sensitivity of the gallbladder to endogenous and exogenous cholecystokinin is significantly increased in patients with truncal vagotomy.

Role of the gastric phase in fat-induced gallbladder contraction and cholecystokinin secretion in humans.

The present study was undertaken to investigate the role of the gastric phase of fat-induced gallbladder contraction and endogenous cholecystokinin (CCK) secretion in humans. Gallbladder emptying, measured by cholescintigraphy, and endogenous CCK secretion, measured by radioimmunoassay, were studied in healthy subjects after both intragastric and intra-intestinal administration of corn oil. In addition, patients with partial gastrectomy were investigated to study the effect of accelerated gastric emptying. In the healthy subjects, intragastric administration of fat resulted in a significantly (P less than 0.05) later increase in plasma CCK levels (20 +/- 2 min) compared to intraintestinal fat (5 +/- 1 min). Similarly, the onset of gallbladder emptying was significantly (P less than 0.05) delayed after intragastric fat (20 +/- 2 min) compared to intestinal fat (10 +/- 1 min). In the healthy subjects the integrated plasma CCK response to intragastric fat was significantly (P less than 0.005-P less than 0.01) reduced from 10 to 30 min. In the patients with partial gastrectomy the rise in plasma CCK (10 +/- 1 min) and the onset of gallbladder emptying (15 +/- 2 min) were in the same range after intra-intestinal and intragastric fat. No significant differences in plasma CCK levels, integrated CCK response or gallbladder emptying were found in the patients according to the site of fat application. It is concluded that endogenous CCK secretion and gallbladder emptying in response to intragastric fat are significantly delayed in healthy subjects but not in patients with partial gastrectomy, in whom gastric emptying is accelerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Delayed plasma cholecystokinin and gallbladder responses to intestinal fat in patients with Billroth I and II gastrectomy.

This study was undertaken to examine the intestinal phase of cholecystokinin (CCK) secretion and gallbladder contraction in patients who had undergone partial gastrectomy. Plasma CCK concentrations, measured by radioimmunoassay, and gallbladder contraction, measured by cholescintigraphy, were studied after intestinal administration of fat. Fasting plasma CCK concentrations were in the same range in nine patients who had undergone Billroth I gastrectomy (1.0 +/- 0.2 pmol/L), in nine patients who had undergone Billroth II gastrectomy (1.4 +/- 0.2 pmol/L), and in nine normal subjects (1.5 +/- 0.4 pmol/L). The peak increments in plasma CCK after intestinal fat were significantly (p less than 0.05) lower in patients with partial gastrectomy (5.4 +/- 0.6 pmol/L) compared with normal subjects (7.9 +/- 0.8 pmol/L). The integrated plasma CCK secretion was significantly (p less than 0.01 to p less than 0.05) reduced during the first 30 minutes in patients after Billroth I (74 +/- 11 pmol/1.30 min) and Billroth II gastrectomy (51 +/- 11 pmol/1.30 min) compared with normal subjects (122 +/- 18 pmol/1.30 min). Similarly, the start of gallbladder emptying was significantly (p less than 0.05) delayed in patients after partial gastrectomy. After 1 hour, however, the integrated plasma CCK response and gallbladder emptying were in the same range in Billroth I patients (186 +/- 34 pmol/1.60 min, 60% +/- 7%), Billroth II patients (175 +/- 17 pmol/1.60 min, 63% +/- 7%) and normal subjects (190 +/- 18 pmol/1.60 min, 55% +/- 6%). It is concluded that in patients who have undergone partial gastrectomy plasma CCK and gallbladder responses to intestinal fat are significantly delayed but reach normal levels beyond 30 minutes.