Simultaneous evaluation of a pancreas-specific antigen and a pancreatic cancer-associated antigen in pancreatic carcinoma.

A pancreas cancer-associated antigen (PCAA) and a pancreas-specific antigen (PaA) were simultaneously quantitated by enzyme-linked immunosorbent assays in serum specimens from 51 normal controls, 76 pancreatic cancers, 194 nonpancreatic cancers, and 22 benign pancreatic diseases. Primary immunological reagents used in the enzyme-linked immunosorbent assays were our polyclonal antibodies produced in rabbits against purified PCAA and PaA. Results revealed discordance of these two markers in pancreatic cancer, suggesting that the presence of these two biochemically and immunologically distinct pancreas proteins in patients' serum may reflect different biological aspects of cancer. The combination test resulted in a better sensitivity and specificity for pancreatic cancer, 90 and 85%, respectively, than either PCAA or PaA assay alone. This study demonstrated that the combination of serum PCAA and PaA tests yields an additive clinical value and may be a useful adjunctive aid for the immunodiagnosis of the pancreatic cancer.

Purification and characterization of a human pancreas-specific antigen.

A pancreas-specific antigen was identified by immunologic techniques and purified from saline extract of human pancreas. The purified pancreas-specific antigen was shown to be homogeneous by polyacrylamide gel electrophoresis under both denaturing and non-denaturing conditions. It had a molecular weight of 44000 as estimated by gel filtration or sodium dodecyl sulfate-gel electrophoresis, and a sedimentation coefficient of 3.4 S as analyzed by sucrose gradient centrifugation. Pancreas-specific antigen possessed an isoelectric point of 4.9 and migrated to alpha-beta region upon immunoelectrophoresis. By colorimetric assay procedures, pancreas-specific antigen exhibited no enzyme activity, such as amylase, protease, esterase, lipase, acid phosphatase, alkaline phosphatase peroxidase, deoxyribonuclease or ribonuclease. Immunoreactivity of pancreas-specific antigen was sensitive to proteolytic enzymes, perchloric acid and high temperature (70 degrees C, 10 min); but insensitive to neuraminidase or beta-glucosidase. Immunohistochemical staining revealed that pancreas-specific antigen was located in acinar cells of human pancreas. In addition, a higher concentration of pancreas-specific antigen was detected in pancreatic juice than in the saline extract of pancreas. This newly identified pancreas-specific antigen, therefore, may be a useful marker protein in physiological studies of pancreas and pancreatic secretion.

Acid-inhibitory effects of omeprazole and lansoprazole in Helicobacter pylori-negative healthy subjects.

BACKGROUND: Omeprazole 20 mg once daily (o.d.) and lansoprazole 30 mg o.d. have similar acid-inhibitory effects in healthy Helicobacter pylori-positive subjects. However, little is known about the acid-inhibitory effects of the o.d. and twice daily (b.d.) doses in H. pylori-negative subjects. AIM: To compare the decrease in gastric acidity of omeprazole 20 mg (o.d. and b.d.) with lansoprazole 30 mg (o.d. and b.d.) in healthy H. pylori-negative subjects on day 6-7 of dosing. METHODS: A randomized, investigator-blind, crossover study design was used. Intragastric pH was measured continuously with glass electrodes positioned in the gastric corpus. Sixteen H. pylori-negative subjects, whose intragastric acidity fell below pH 4 for 70% of a 24-h baseline period. were entered in the study. RESULTS: Both dosing regimens of omeprazole and lansoprazole significantly increased median gastric pH and percentages of time above pH 4 during the entire 24-h period, night- and daytime, compared to baseline. There were no significant differences in median gastric pH values or time above pH thresholds 3, 4 and 5 between the o.d. dosing regimens. During the night the percentage of time spent above pH 3 and 4 was significantly higher with omeprazole 20 mg b.d. than with lansoprazole 30 mg b.d. CONCLUSIONS: This comparative study demonstrates that daily doses of omeprazole 20 mg and lansoprazole 30 mg are equally effective in raising intragastric pH in H. pylori-negative subjects on day 6 of dosing. During the night, omeprazole 20 mg b.d. provides superior gastric acid suppression compared to lansoprazole 30 mg b.d.

Ranitidine bismuth citrate with clarithromycin versus omeprazole with amoxycillin in the cure of Helicobacter pylori infection.

AIM: To compare the efficacy of ranitidine bismuth citrate plus clarithromycin (RBC-C) vs. omeprazole plus amoxycillin (OME-AMO) in the cure of Helicobacter pylori infection. METHODS: In this double-blind, multicentre, parallel-group study 122 H. pylori-positive patients with active duodenal ulcer or gastritis, with confirmed history of duodenal ulcer, were randomized to treatment with ranitidine bismuth citrate 400 mg b.d. plus clarithromycin 500 mg b.d. or omeprazole 20 mg b.d. plus amoxycillin 1000 mg b.d. for 14 days, followed by 14 days of ranitidine bismuth citrate 400 mg b.d. or omeprazole 20 mg once daily, respectively, to facilitate ulcer healing. Endoscopy was carried out at the start of the study and 28 days after the end of treatment. At each endoscopy four biopsies were obtained from the antrum and four biopsies from the corpus, for rapid urease test, histology and culture. H. pylori infection was defined as a positive urease test, confirmed by histology or culture. Cure of H. pylori infection was defined as negative urease test, histology or culture from both sites. RESULTS: Per-protocol, all-patients-treated and intention-to-treat cure rates (95% confidence interval) were, respectively, 90% (81-89%), 90% (82-89%) and 84% (74-93%) for ranitidine bismuth citrate plus clarithromycin, and 39% (27-54%), 44% (31-57%) and 41% (29-53%) for omeprazole plus amoxycillin, P < 0.00001. Both regimens were well tolerated. Eight patients were lost to follow-up, for lack of efficacy (one patient), adverse events (three patients) or refusal of second endoscopy (four patients). CONCLUSION: Ranitidine bismuth citrate 400 mg b.d. with clarithromycin 500 mg b.d. is superior to omeprazole 20 mg b.d. with amoxycillin 1000 mg b.d. Ranitidine bismuth citrate with clarithromycin is the first dual therapy with high cure rates and good tolerance, and is easy to take. It may therefore prove a suitable first-line treatment in H. pylori infection.

Omeprazole (20 mg o.m.) versus ranitidine (150 mg b.d.) in duodenal ulcer healing and pain relief.

The object of this double-blind, multicentre study was to compare duodenal ulcer healing rates after 2 to 4 weeks of treatment with either 20 mg omeprazole o.m. or 150 mg ranitidine b.d. One hundred and eighty-one patients were randomized: 91 received omeprazole and 90 received ranitidine. In a per protocol analysis at 2 weeks, 63% of the patients were healed on omeprazole and 65% of the patients were healed on ranitidine (N.S.); at 4 weeks 91% were healed in the omeprazole group and 96% were healed in the ranitidine group. There were no differences in ulcer symptom relief between the two groups. There were no significant changes in laboratory values in either of the groups. Adverse events were few and mainly mild and transient. We conclude that both omeprazole (20 mg o.m.) and ranitidine (150 mg b.d.) result in rapid, ulcer healing rates.

Evaluation of a human pancreas-specific antigen by enzyme-linked immunosorbent assay.

A sensitive sandwich-type enzyme immunosorbent assay has been developed for quantitation of a new human pancreas-specific antigen (PaA). With this method, PaA at a concentration as low as 0.8 ng/ml can be detected. The assay was reproducible as shown by the coefficients of variation for within (4.8%) and between (6.1%) assays. Serum PaA levels from 51 healthy persons ranged from less than 4 to 34 ng/ml. Using 21.5 ng/ml (the upper 97.5 percentile of normal controls) as an upper limit, 42 of 60 pancreatic cancer (70%), 3 of 14 pancreatitis (21%) and 2 of 6 cholelithiasis (33%) had an elevated PaA. Very few patients with other cancers were shown to have an elevated PaA: 3/40 (8%) of lung cancer, 2/43 (5%) of colorectal cancer, 3/40 (8%) of prostate cancer and 1/39 (3%) of breast cancer. The sensitivity and specificity of the serum PaA test for the detection of pancreatic cancer were calculated to be 70% and 95%, respectively. These results indicate that PaA may be useful as an adjunctive tool in immunodiagnosis of pancreatic cancer.

Erroneous diagnosis of distal intestinal obstruction syndrome in cystic fibrosis: clinical impact of abdominal ultrasonography.

OBJECTIVE: To describe the use of abdominal ultrasonography in the differential diagnosis of distal intestinal obstruction syndrome (DIOS). DESIGN: Four case reports. SETTING: Adult cystic fibrosis centre (140 patients). PATIENTS: Four cystic fibrosis patients presenting over 18 months with clinical symptoms suggestive of a DIOS which could not be substantiated. OUTCOME: In all cases abdominal ultrasound was valuable in making a diagnosis. CONCLUSION: Abdominal ultrasound is a useful diagnostic tool for differentiating a DIOS from other abdominal conditions.

[Use of an endoprosthesis in the treatment of bile leakage from the cystic duct following laparoscopic cholecystectomy]. / Behandeling met een endoprothese van gallekkage uit de ductus cysticus na laparoscopische cholecystectomie.

The case is reported of a female aged 32 years in whom, after laparoscopic cholecystectomy performed because of symptomatic gallbladder calculi, leakage from the cystic duct occurred. After percutaneous drainage of the perihepatic bile collection, endoscopic retrograde cholangiopancreatography (ERCP) with papillotomy was performed; since this proved insufficient, an endoprosthesis was inserted into the common bile duct by ERCP, following which the bile leakage ceased.

[Gastrostomy tubes inserted with radiologic techniques]. / Voedingskatheters ingebracht met radiologische technieken.

Radiologic techniques can be used for patients in need of long-term enteral nutritional support. In particular, these techniques can provide solutions when endoscopic techniques cannot be performed. Percutaneous radiologic gastrostomy is an alternative to percutaneous endoscopic gastrostomy. Percutaneous radiologic transgastric jejunostomy should be reserved for patients with proven gastroesophageal reflux. When both are not possible, percutaneous radiologic jejunostomy is indicated. Percutaneous radiologic gastrostomy and percutaneous radiologic transgastric jejunostomy have a high technical success rate (> or = 91-95%). The success rate of percutaneous radiologic jejunostomy is lower (85-88%). With radiologic techniques, major complications occur in 0.5-13% of cases. The percentage of complications for percutaneous radiologic gastrostomy and percutaneous radiologic transgastric jejunostomy are lower than those for percutaneous radiologic jejunostomy. The less serious, mostly late-onset complications (2.9-13%) are usually easy to treat. Radiologic techniques have a higher initial success rate but more late-onset complications than endoscopic techniques.

Age at diagnosis of inflammatory bowel disease influences early development of colorectal cancer in inflammatory bowel disease patients: a nationwide, long-term survey.

BACKGROUND: Data on clinical characteristics of patients with inflammatory bowel disease (IBD)-related colorectal cancer (CRC) are scarce and mainly originate from tertiary referral centres. We studied patient and disease characteristics of IBD-related CRC in a nationwide IBD cohort in general hospitals. Main outcome parameters were time to develop CRC, and factors associated with early CRC development. METHODS: All IBD patients diagnosed with CRC between 1 January 1990 and 1 July 2006 were identified using a nationwide automated pathology database (PALGA). Patient charts were assessed to confirm diagnosis and collect clinical data. Early CRC was defined as CRC diagnosed less than 8 years after IBD diagnosis. Statistical analysis was performed using descriptive statistics, independent t tests, binary logistic regression and Cox-regression analysis. RESULTS: Diagnosis of IBD-related CRC was confirmed in 251 patients (171 ulcerative colitis, 77 Crohn's disease, 3 unclassified colitis), 161 males (64 %). Median time from IBD diagnosis to CRC diagnosis was 12 years (IQR 4-20); 89 patients (35 %) developed early CRC. Type of IBD, gender, concomitant PSC, pseudopolyps, extent of inflammation, and medication use were not related to early CRC (p > 0.05). IBD diagnosis at older age (HR for 10 years older age 2.25; 95 % CI 1.92-2.63) was related to early CRC. Twenty-three patients (12 %) had been included in a surveillance programme prior to CRC diagnosis. Patients in the surveillance group had a significantly better tumor stage (p = 0.004). CONCLUSIONS: We emphasize the problem of a high proportion of IBD-associated CRCs developing before the recommended start of surveillance. Therefore, we suggest that older age at IBD onset could be an additional factor to start surveillance in IBD patients.

Efficacy of different doses of cimetidine in the treatment of reflux esophagitis. A review of three large, double-blind, controlled trials.

Four different cimetidine dosage regimens--800 mg u.i.d. HS or nocte, 800 mg u.i.d. dinnertime, 400 mg q.i.d., and 800 mg b.i.d.--were investigated for the treatment of reflux esophagitis in three independent large-scale, double-blind, controlled multicenter trials in which more than 1100 patients participated. Analysis of the data shows that the percentage of endoscopic healing after 6 and 12 weeks of treatment was fairly constant in patients with the same endoscopic grade of severity of reflux esophagitis at the start of treatment, whether they were treated with 800 mg u.i.d. (HS or dinnertime), 800 mg b.i.d., or 400 mg q.i.d. Healing percentages after 12 weeks of therapy ranged from 79%-92% for grade I, from 65%-70% for grade II, and from 41%-54% for grade III. Differences within the three grades for the various treatment regimens did not reach statistical significance. Symptomatic improvement was evaluated with the Standardized Total Heartburn Index, which is based on frequency and severity of heartburn as well as on the number of patients in the study population experiencing heartburn at a given time in relation to the total heartburn load at the start of the study. All three treatment schedules resulted in a substantial reduction of the Standardized Total Heartburn Index. Treatment with cimetidine, 800 mg u.i.d., for 6-12 weeks was efficacious in the majority of patients with reflux esophagitis grade I-III. Symptom relief was superior with dosing after dinner time compared with dosing HS. A single dose of 800 mg administered after the evening meal approached the efficacy achieved with 400 mg q.i.d. Based on these objectives and symptomatic results, a u.i.d. cimetidine regimen appears to be the treatment of choice for the initial approach of a patient with reflux esophagitis. A u.i.d. regimen may enhance patient compliance, comfort, and safety as well as ease of prescription while also being less expensive.

A simple method for the quantification of biliary reflux.

99mTc-diethyl-IDA is completely excreted into the bile. When cholecystokinin is given after priming of the biliary tract with this tracer, gallbladder contraction leads to expulsion of bile into the duodenum. At the same time cholecystokinin causes contraction of the pylorus, which should normally prevent substantial reflux of tracer into the stomach. We have applied these physiological characteristics in a method to quantify biliary gastric reflux. Fourteen controls had a median reflux of 4.3% of the intravenous dose (93% of controls had values less than 9%). In 18 patients with Billroth II gastrectomies the median reflux was 46% (p less than 0.001). Patients with chronic gastritis (no. = 18) had also increased reflux (median 18.1%, p less than 0.001). The same was found in gastric ulcer (no. = 18, median 11.8%, p less than 0.003). In duodenal ulcer (no. = 7) increased reflux existed in only two patients with pyloric deformation. Patients with hiatal hernia did not show increased reflux (no. = 10, median 2.2%). Bilirubin measurements tended to underestimate reflux in pathological cases, whereas bile acid measurements and reflux percentages of tracer showed a close relationship (r = 0.87, p less than 0.001).

Double-blind crossover trial of prostaglandin E2 in postgastrectomy reflux gastritis.

Excessive Enterogastric reflux following partial gastrectomy is believed to be responsible for bilious regurgitation, vomiting, nausea, and epigastric pain. At endoscopy, striking erythema and inflammatory changes of the gastric mucosa may be seen. The nonsurgical treatment for this syndrome is unsatisfactory. Because of the potential pathogenetic role of regurgitating bile acids, lysolecithin, and pancreatic secretions, it seemed relevant to find out whether prostaglandin E2 (PGE2) in a dose of 0.5 mg qid could protect the gastric mucosa from further damage and thereby lead to symptomatic improvement. The results of this controlled doubled-blind crossover trial, comparing PGE2 and placebo, in the treatment of postgastrectomy reflux gastritis reveal no significant differences between PGE2 and placebo with regard to symptoms, endoscopic features, and histologic evidence of inflammatory changes. Thus, prostaglandin E2 in the dose used appears incapable of improving postgastrectomy reflux gastritis in patients with mild to moderate degrees of this entity.

Comparison of the combination of cholestyramine/alginates with placebo in the treatment of postgastrectomy biliary reflux gastritis.

Postgastrectomy biliary reflux gastritis is quite common. Several drugs have been used in its treatment, including the bile acid-binding resin cholestyramine, which seemed ineffective, possibly because of its rapid disappearance from the gastric remnant. It was suggested that by using alginates, which form a raft floating on the gastric contents, cholestyramine would be retained in the stomach for a longer period. 32 patients received either placebo or cholestyramine/alginates/bicarbonate (CAB). Gastroscopy with biopsies, laboratory studies and physical examination were performed before and after the trial. A two week intervals patients were interviewed about the effect on symptoms. A detailed Y-ray study was made of 5 patients, in which a series of pictures was taken after ingestion either of placebo or CAB together with a novel contrast medium. There was no statistical difference between treatment groups with respect to symptoms, gastroscopy or histological findings, nor did the X-ray study show any difference in retention time between placebo and CAB.

Lactoferrin in pure pancreatic juice.

Lactoferrin as assayed by a radial immunodiffusion technique was studied in pure pancreatic juice collected at endoscopic retrograde cholangiopancreatography from 23 patients with chronic pancreatitis, 12 with acute pancreatitis, 21 with pancreatic cancer, and 29 cases of nonpancreatic gastrointestinal disease. No clear difference between lactoferrin concentrations in the chronic pancreatitis patients and other groups was found. Moreover, most lactoferrin levels were below the limit of detection in our assay. In addition, lactoferrin total protein ratios did not appear to be of value in the differential diagnosis of chronic pancreatitis. These results seem to be in contrast to the findings of other authors, who measured lactoferrin in duodenal fluid--which is unreliable, in our opinion--or who mainly studied chronic pancreatitis patients and few other pancreatic diseases. Lactoferrin might well be a nonspecific marker for serious pancreatic inflammation.