Relapse of low-grade gastric MALT lymphoma after Helicobacter pylori eradication: true relapse or persistence? Long-term post-treatment follow-up of a multicenter trial in the north-east of Italy and evaluation of the diagnostic protocol's adequacy.

The effect of eradication of Helicobacter pylori on early stage gastric low-grade MALT lymphoma in 76 patients with follow-up of at least 1 year (12-63 months, mean 28) is reported. No regression was found in five cases after 12-48 months. In one case surgical resection detected the involvement of perigastric lymph nodes overlooked by endoscopic ultrasonography (EUS). Neither progression of the disease nor a high-grade component was documented by repeated gastric mappings, EUS and complete stagings in the other four cases. After histological remission five relapses of low-grade and one relapse of high-grade MALT lymphoma were found 12-48 months after eradication. Subsequent histological remission, without any additional therapy, was found in three relapsed cases. A rapid and persistent histological remission was obtained in 56 patients (73%). A late remission was observed in six cases. Monoclonal remission was found in half of the patients and was frequently delayed. Persistent monoclonality was associated with histological remission in the vast majority of patients. Our data confirm H. pylori eradication as the first choice therapy for early stage gastric low-grade MALT lymphoma and recommend extensive bioptic mapping and endoscopic sonography both in the local staging and in the regression evaluation. The rare cases of late remission encourage us to wait for at least 1 year after eradication of H. pylori. Longer follow-up studies will clarify the meaning of histological relapse/persistence and late remission. The study of non-responder cases could show us a step in lymphomagenesis.

Cough threshold in reflux oesophagitis: influence of acid and of laryngeal and oesophageal damage.

BACKGROUND: Gastro-oesophageal reflux is often associated with cough. Patients with reflux show an enhanced tussive response to bronchial irritants, even in the absence of respiratory symptoms. AIM: To investigate the effect of mucosal damage (either oesophageal or laryngeal) and of oesophageal acid flooding on cough threshold in reflux patients. PATIENTS: We studied 21 patients with reflux oesophagitis and digestive symptoms. Respiratory diseases, smoking, and use of drugs influencing cough were considered exclusion criteria. METHODS: Patients underwent pH monitoring, manometry, digestive endoscopy, laryngoscopy, and methacholine challenge. We evaluated the cough response to inhaled capsaicin (expressed as PD5, the dose producing five coughs) before therapy, after five days of omeprazole therapy, and when oesophageal and laryngeal damage had healed. RESULTS: In all patients spirometry and methacholine challenge were normal. Thirteen patients had posterior laryngitis and eight complained of coughing. Twenty patients showed an enhanced cough response (basal PD5 0.92 (0.47) nM; mean (SEM)) which improved after five and 60 days (2.87 (0.82) and 5.88 (0.85) nM; p<0.0001). The severity of oesophagitis did not influence PD5 variation. On the contrary, the response to treatment was significantly different in patients with and without laryngitis (p = 0.038). In patients with no laryngitis, the cough threshold improved after five days with no further change thereafter. In patients with laryngitis, the cough threshold improved after five days and improved further after 60 days. Proximal and distal oesophageal acid exposure did not influence PD5. Heartburn disappeared during the first five days but the decrease in cough and throat clearing were slower. CONCLUSIONS: Patients with reflux oesophagitis have a decreased cough threshold. This is related to both laryngeal inflammation and acid flooding of the oesophagus but not to the severity of oesophagitis. Omeprazole improves not only respiratory and gastro-oesophageal symptoms but also the cough threshold.

Efficacy and safety of three 7-day Helicobacter pylori eradication regimens containing ranitidine bismuth citrate.

BACKGROUND: This multicentre, randomized study was designed to assess the clinical efficacy, safety and tolerability of three novel 7-day triple therapies containing ranitidine bismuth citrate (RBC) and two antibiotics. METHODS: We studied patients with non-ulcer dyspepsia and gastritis who were randomly assigned to one of three treatment regimens given for 7 days in a b.d. dosing schedule: RBC 400 mg plus clarithromycin 250 mg and tinidazole 500 mg (RBCCT): RBC 400 mg plus clarithromycin 500 mg and amoxycillin 1 g (RBCCA); RBC 400 mg plus tinidazole 500 mg and amoxycillin 1 g (RBCTA). H. pylori status was determined by CLO-test, histology and 13C-urea breath test. A repeat breath test was performed at least 28 days after completion of therapy to assess eradication. RESULTS: One hundred and fifty-seven patients were eligible for intention-to-treat analysis (ITT) and 140 patients completed the study and returned for assessment of eradication. Intention-to-treat cure rates were 78% with RBCCT, 71% with RBCCA and 61% with RBCTA. An all-patients-treated analysis (APT), performed on evaluable patients, demonstrated eradication rates of 85% with RBCCT, 81% with RBCCA and 70% with RBCTA. No statistically significant difference was found between treatment groups. Twenty-four patients experienced side-effects, but in only seven cases was treatment discontinued due to adverse events. CONCLUSIONS: A 7-day course of RBC, clarithromycin and either tinidazole or amoxycillin provides a good rate of H. pylori eradication. Three novel RBC-based triple therapies proved to be safe and well tolerated, with discontinuations due to side-effects occurring in less than 5% of cases.

Major early complications from diagnostic and therapeutic ERCP: a prospective multicenter study.

BACKGROUND: There is a lack of multicenter prospective studies on complications of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). METHODS: We studied 2769 consecutive patients undergoing ERCP at nine centers in the Triveneto region of Italy over a 2-year period. Six centers performed ERCP on less than 200 patients per year (small centers). General and ERCP-specific major complications were predefined. Data were collected at the time of ERCP, before discharge, and in cases of readmission within 30 days. ERCP was defined as therapeutic when endoscopic sphincterotomy (n = 1583), precut (n = 419), or drainage (n = 701) had been carried out, singularly or in combination. RESULTS: One hundred eleven major complications (4.0%) were recorded: moderate-severe pancreatitis 36 (1.3%), cholangitis 24 (0.87%), hemorrhage 21 (0.76%), duodenal perforation 16 (0.58%), others 14 (0.51%). Among 942 diagnostic ERCPs there were 13 major complications (1.38%) and 2 deaths (0.21%), whereas among 1827 therapeutic ERCPs there were 98 major complications (5.4%) and 9 deaths (0.49%). The difference in the incidence of complications between diagnostic and therapeutic ERCPs was statistically significant (p < 0.0001). Small center and precut were recognized as independent risk factors for overall major complications of therapeutic ERCP, whereas the following risk factors were identified in relation to specific complications: (1) pancreatitis: age less than 70 years, pancreatic duct opacification, and nondilated common bile duct; (2) cholangitis: small center, jaundice; (3) hemorrhage: small center; and (4) retroperitoneal duodenal perforation: precut, intramural injection of contrast medium, and Billroth II gastrectomy. CONCLUSIONS: Major complications are mostly associated with therapeutic procedures and low case volume. Present data support a policy of centralization of ERCP in referral centers. A more selected and safer use of precut may be expected to further limit the adverse events of ERCP.

Achalasia. A possible late cause of postpolio dysphagia.

The aim of this paper is to describe a patient with severe postpolio problems who developed achalasia. A 66-year-old patient came to our observation for severe dysphagia. He had suffered from paralytic poliomyelitis at the age of 7 months and had severe residual deficits. At the age of 62 he presented with sudden pain localized in the distribution of the C4 and C5 dermatomes and an inability to abduct the left arm. At the time, he experienced only occasional and mild dysphagia; his esophagus was not dilated and emptied normally. Over the following months his muscular function improved, but dysphagia worsened. We found a megaesophagus with a sigmoid appearance and the manometric features of achalasia. Pneumatic dilatation produced good resolution of dysphagia. A year later manometry showed the reappearance of peristalsis after all wet swallows. In patients with postpolio dysphagia, the possible presence of achalasia must be considered.

Nd:YAG laser versus polidocanol injection for palliation of esophageal malignancy: a prospective, randomized study.

Palliation is often the only treatment that can be offered to patients affected by esophageal malignancy. This prospective study was carried out in order to compare two endoscopic palliative treatments: Nd:YAG laser and local injection of 3% polidocanol. We randomized 34 patients with inoperable malignancies to one of the two treatments. After the first course, 88.8% of the patients in the laser group and 81.5% in the polidocanol group were able to swallow a normal oral caloric intake. Only one major complication (esophageal perforation) was observed (polidocanol group) and was successfully treated with endoscopic placement of a prosthesis. We believe that both techniques are safe and effective for the palliation of esophageal malignant strictures but that polidocanol injection is cheap, simple, and more widely available.

Does the combination of a human fibrin sealant with ranitidine accelerate the healing of duodenal ulcer?

Human fibrin sealant (Tissucol) has been used in surgery for its haemostatic and sealing actions and stimulating effect on tissue regeneration. Recently it has been used in endoscopy, but controlled trials are not yet available. The aim of this study was to evaluate the efficacy of Tissucol on the healing rate of duodenal ulcers (DU). Thirty nine previously untreated DU patients received ranitidine 150 bid plus endoscopically applied either placebo (19 patients) or Tissucol (20 patients). Sixty-five percent of the patients in the Tissucol group and 21% in the control group healed after two weeks (p less than 0.02), 75 and 52.6% respectively after 4 weeks (NS). The endoscopic application of Tissucol seems to influence the healing of duodenal ulcer and its use could be suggested in selected patients with DU.

Calcium and parathyroid hormone behaviour after exogenous secretin infusion in man.

The response of serum calcium, PTH, CT and gastrin to an infusion of secretin (3 CU/kg/h) over a period of 90 min was studied in ten healthy males and two female patients with hypoparathyroidism. In the healthy males serum calcium, after a transient fall, significantly increased at 45 min after the onset of the infusion (P less than 0.001). Serum iPTH rose significantly within 5 min whereas serum CT and gastrin concentrations did not change. The two hypoparathyroid patients did not show any variations in either serum iPTH or calcium. These findings suggest that infusion of pharmacological doses of secretin into normal subjects modifies serum calcium, and that this change is due to PTH release.

Presence of duodenopancreatic feedback in minipigs and possible interference from the bile.

In two minipigs chronic pancreatic and duodenal fistulas, which allowed the diversion and the intestinal replacement of pancreatic secretion, were prepared. In a third minipig a chronic biliary fistula was also prepared so the bile secretion could be fed back into the intestine through a duodenal catheter. In these animals a chronic gastric fistula was made so gastric secretion could also be collected. Diversion-replacement of pure pancreatic juice and of bile were carried out in the fasting state. This study confirms the presence of a feedback regulatory mechanism in exocrine pancreatic secretion in the pig. Moreover, it suggests that bile can interfere with this phenomenon.

Effect of exogenous gastrointestinal peptides containing the C-terminal tetrapeptide of gastrin on calcium, calcitonin and parathormone serum levels in man.

Gastrointestinal hormones containing the C-terminal tetrapeptide of gastrin are involved in calcium homeostasis. The aim of this study was to investigate: 1) the effect of a standard meal (schedule a) and of a duodenal infusion of 5% aminoacid solution (schedule b) on calcium, CT and PTH serum levels in man; 2) the behaviour of these parameters during I.V. infusions of pentagastrin (mcg 1.5/Kg-hour), sincalide (mcg 0.04/Kg-hour) and caerulein (ng 75/Kg-hour) (schedule c). In order to avoid any possible interference by endogenous secretin release, schedule c was performed in 5 patients previously submitted to total gastrectomy. Schedule a and b were studied in 5 healthy volunteers. After a standard meal a slight increase of CT and PTH was measured. Duodenal infusion of aminoacid was followed by hypocalcaemia and slight but constant rise of CT levels, without significant variations of circulating PTH. Pentagastrin, sincalide and caerulein induced a slight but significant hypocalcaemia and a rise of serum CT levels, together with a significant increase of serum PTH. These findings suggest that peptides containing the C-terminal tetrapeptide of gastrin directly affect calcium homeostasis in the absence of secretin release.

Fasting serum gastrin in primary hyperparathyroidism and in chronic hypercalcemia.

In order to investigate the frequency of fasting hypergastrinaemia in primary hyperparathyroidism (A) and in chronic hypercalcaemia (B), in 40 and 16 patients respectively gastrin, parathyroid hormone (PTH) and serum calcium levels were measured and compared with those of a control group (40 subjects) with similar distribution of sex and age. Moreover, possible linear relationships between these parameters were investigated. Notwithstanding significant differences in calcium and PTH levels between the three groups (A: high PTH, high Ca++; B: low PTH, high Ca++; C: normal PTH and Ca++ levels), no significant difference in gastrin levels were found. However, in the first group, a marked increase of gastrin was observed in one patient, very probably affected by a gastrin-secreting tumor (positive secretin test). While no linear relationship between PTH and gastrin values was present in all the three groups, a significant correlation between serum calcium and fasting gastrin was detectable in the group A, ruling-out the above mentioned patient. Present data suggest that PTH does not modify gastrin levels and that chronic moderate hypercalcaemia does not raise serum fasting gastrin, at least in clinical conditions. Moreover, the frequency of hypergastrinaemia in hyperparathyroidism is very low and it seems to be present only in patients with gastrin-secreting tumors.

Hereditary pancreatitis: morphological pictures (ERCP) in the youngest member of a family.

Endoscopic retrograde cholangiopancreatography (ERCP) pictures of the pancreatic duct and of the biliary tract are described in the youngest member of a family with hereditary pancreatitis. The endoscopic changes are very similar to those usually observed in patients affected by chronic relapsing pancreatitis. Morphological changes were particularly marked in the body and tail of the pancreas. However, no abnormal changes were observed in the biliary tract.

Serum fasting gastrin levels after short-term treatment with cimetidine in patients with duodenal ulcer.

The behaviour of serum gastrin fasting levels was studied in 39 randomized patients with proven duodenal ulcer, 21 receiving cimetidine (1 g/day) and 18 placebo for 28 days. No significant variations of gastrin fasting values were found, but in four patients given cimetidine a relevant increase was observed at the end of the treatment. One out of 6 patients, previously treated with placebo, showed a marked increase of fasting gastrin levels after a second trial of cimetidine. No increase of G-17 was observed in the patients showing fasting hypergastrinemia after cimetidine. The present study seems to confirm some previous observations and it seems to suggest the possibility that in some patients cimetidine could induce hypergastrinemia.

Fasting serum cholecystokinin immunoreactivity in chronic relapsing pancreatitis.

An increase in fasting cholecystokinin (CCK) levels has been reported in patients with pancreatic insufficiency, but the relationship of these findings to the clinical conditions has not been established. We, therefore, measured fasting serum CCK-like immunoreactivity in 70 patients with chronic relapsing pancreatitis (CRP) (38 non-surgically treated and 32 previously surgically treated) and in 44 healthy subjects. The radioimmunoassay detected three circulating forms of CCK. The mean value of the CCK levels in CRP (260.3 +/- 300.8 pg/ml) was significantly higher than that of the controls (56.6 +/- 61.7 pg/ml) (p less than 0.001), but in 39 (56.7%) of the 70 CRP cases the CCK was in the normal range. A smaller overlap with the controls was observed in the non-surgically than in the surgically treated patients (45 vs. 71.8%). In the 38 non-surgically treated CRP cases no relationship was observed between the CCK levels and each of the following parameters: age, length of history, presence or absence of pancreatic calcification, nutritional and alcoholic habits, and the results of exocrine function tests. The absence of the last-mentioned correlation is somewhat unexpected if the high CCK levels are due to the interruption of a feedback loop for CCK secretion. However, previous pancreatic surgical drainage and/or treatment with pancreatic enzymes, present in almost all these patients, could have an effect on CCK behaviour.

The role of caerulein in tests of exocrine pancreatic function.

Secretin (1 CU/Kg) plus Caerulein (100 ng/Kg) or Cholecystokinin (1 or 2 IvyU/Kg) were given by rapid intravenous injection (Schedule 1) or by continuous infusion (Schedule 2) to 63 control subjects (C) and 69 patients affected by chronic pancreatitis (CP). Duodenal juice was collected for two and four 30-minute periods in schedule 1 and schedule 2, respectively. Volume, bicarbonate, and enzyme content were measured. Secretin-Daerulein, by rapid intravenous injection, showed a strong overlapping between C and CP values and led to some side-effects. Secretin-Caerulein by continuous intravenous infusion gave almost identical results as the Secretin-Cholecystokinin.