Parenteral control of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome

Parenteral control of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome is increasingly required; however, existing methods of determining the required dose are cumbersome and not applicable in all centers. A previous study suggested that the required parenteral dose of histamine H₂-receptor antagonists correlated with the previous oral dose. In the present study, in 31 patients with Zollinger-Ellison syndrome we evaluated the hypothesis that an effective parenteral histamine H₂-receptor antagonist dose could be predicted from the previous oral dose. Twenty-three patients were taking oral ranitidine (mean 1.3 g/day), six patients famotidine (152 mg/day), and two patients cimetidine (1.8 g/day). Each patient was treated with a continuous intravenous infusion of the equivalent dose of ranitidine (mean dose 1 mg/kg/hr with 35% requiring 0.5 mg/kg/hr, 49% 1 mg/kg/hr, 3% 1.5 mg/kg/hr, 10% 2 mg/kg/hr, and 3% 2.5 mg/kg/hr. This dose of ranitidine acutely controlled acid secretion (<10 meq/hr) in all patients. To evaluate long-term efficacy and safety, 20 patients were maintained on this dose through the peri-and postoperative periods. Mean duration was 7.1 days with 25% treated 3–5 days, 40% 6–8 days, 30% 8–10 days, and 5%>10 days. The predicted dose continued to control acid secretion in 95% of patients with one patient requiring one dose adjustment. No biochemical, clinical, or hematological toxicity was seen, although ranitidine was stopped in one patient because of skin rash. These results demonstrate that the parenteral dose of ranitidine required to control acid secretion in patients with Zollinger-Ellison syndrome can be predicted from the oral dose. This predicted dose will be acutely effective in all patients in reducing acid secretion to <10 meq/hr, the established level of control, will remain effective in 95% of patients for up to 11 days, and is safe. By utilizing the oral dose to predict the intravenous dose, repeated dose titrations will be avoided and thus this method should be generally useful in all settings.     

Zollinger-Ellison phenotype in the absence of hypergastrinemia and islet-cell tumor

Patients with the Zollinger-Ellison syndrome are characterized by islet-cell tumors, striking gastric acid hypersecretion, and peptic ulcer disease. They often experience severe abdominal pain, diarrhea, and gastrointestinal bleeding with potentially life-threatening consequences. It is a rare syndrome caused by nonbeta cell islet-cell tumors (gastrinomas) located in or in proximity to the pancreas. These tumors freely secrete gastrin, a peptide hormone that serves as a powerful stimulant of gastric acid secretion. Exuberant secretion of gastrin from the gastrinomas produces severe gastric acid hypersecretion that often leads to impressive peptic ulcer disease and the constellation of symptoms listed above. We describe a patient presenting with clinical manifestations characteristic of the ZES with strikingly elevated gastric acid secretion, multiple ulcers in the first and second portions of the duodenum and diarrhea, but in absence of islet-cell tumor and/or hypergastrinemia.     

Peptic ulcer is prevalent among shift workers

To elucidate sleep disturbances in the etiology of peptic ulcers, the prevalence of peptic ulcer disease was compared among shift workers and daytime workers. The subjects (N=11,657) were employees of various institutions, such as factories, banks, or schools, and had undergone a mass x-ray examination of the upper gastrointestinal tract. With present shift workers (N=2269), the prevalence of gastric ulcers was 2.38% (N=54) and that of duodenal ulcers, 1.37% (N=31). With the past shift workers (N=2111), the prevalence of gastric ulcers was 1.52% (N=32) and that of duodenal ulcers, 0.62% (N=13). On the contrary, with the daytime workers (N=6525) the prevalence of gastric ulcer was 1.03% (N=67) and that of duodenal ulcer, 0.69% (N=45). The working schedule for 752 examinees was unknown. The prevalence of gastric and duodenal ulcers was higher with shift workers than daytime workers. Thus, shift work involving sleep disturbances may play an important role in the development of peptic ulcers.     

Peptic ulcer disease in the elderly in Singapore

Of 460 patients with peptic ulcer disease seen over a 30-month period, there were 174 elderly patients (defined as ? 60 years old), constituting 38%. In this group of elderly, gastric ulcers (GU) were observed more frequently than duodenal ulcers (DU) with a ratio of 1.6: 1 and the male to female ratio was 1.7: 1. In patients < 60 years old, there were more DU than GU with a ratio of 2.7: 1, and a higher male to female ratio of 3.7: 1. Seventy-two per cent of the elderly had at least one other medical condition with 20% having three or more medical problems. Hypertension and ischaemic heart disease were the most frequently encountered illnesses. Half the elderly presented with upper abdominal pain and one-third had an atypical presentation. Analgesic ingestion in the preceding 4 weeks was present in 29% of the elderly. In the elderly, bleeding was the most frequent complication occurring in 50%; perforation occurred in 2%. In those with bleeding ulcers, 44% had history of analgesic usage. The mortality of bleeding peptic ulcer in the elderly, was 11% and this was largely due to concurrent medical conditions. Only two deaths occurred due to bleeding ulcer.     

Roux-limb motility after total gastrectomy and Roux-en-Y anastomosis in patients with zollinger-ellison syndrome

The Roux-en-Y syndrome was defined as chronic nausea, intermittent vomiting, and chronic abdominal pain worsened by eating in patients who have undergone a gastrojejunostomy Roux-en-Y reconstruction for peptic ulcer. When these patients fasted, the Roux limb showed striking abnormalities in motor function; when postprandial, they failed to convert to normal fed-state motor activity. In contrast, patients with Zollinger-Ellison syndrome do well after similar surgery; they can eat most foods and maintain their body weight. We studied the motility of the Roux limb and jejunum in six patients with Zollinger-Ellison after an esophagojejunostomy Roux-en-Y anastomosis. Roux-limb motor activity in these patients, as characterized by the migrating motor complex, was more frequent, well organized, and in synchrony with the remaining jejunum; most subjects also converted to the fed state after a liquid meal. We suggest that the enteric nervous system is intact and functions normally in patients who have had a Roux-en-Y reconstruction for ulcer disease secondary to Zollinger-Ellison, but not in patients with idiopathic peptic ulcer disease.This work was supported in part by the National Institutes of Health Clinical Research Center grant RR-00073.This material was published in abstract from (Gastroenterology 98:A366, 1990) and presented as posters at the meetings of the American Gastroenterological Association., San Antonio, Texas, 1990, and the North American Conference of Gastroenterology Fellows, San Diego, California, 1991.     

Peptic ulcer bleeding patients with Rockall scores ≥6 are at risk of long‐term ulcer rebleeding: A 3.5‐year prospective longitudinal study

Background and Aim

Patients with high Rockall scores have increased risk of rebleeding and mortality within 30 days after peptic ulcer bleeding, but long‐term outcomes deserve follow‐up after cessation of proton pump inhibitors. The paper aimed to validate whether patients with high Rockall scores have more recurrent ulcer bleeding in a 3.5‐year longitudinal cohort.

Methods

Between August 2011 and July 2014, 368 patients with peptic ulcer bleeding were prospectively enrolled after endoscopic hemostasis to receive proton pump inhibitors for at least 8 to 16 weeks. These subjects were categorized into either a Rockall scores ≥6 group (n = 257) or a Rockall scores <6 group (n = 111) and followed up until July of 2015 to assess recurrent ulcer bleeding.

Results

The proportion of patients with rebleeding during the 3.5‐year follow‐up was higher in patients with Rockall scores ≥6 than in those with scores <6 (10.51 vs. 3.63 per 100 person‐year, P = 0.004, log–rank test). Among patients with Rockall scores ≥6, activated partial thromboplastin time prolonged ≥1.5‐fold (P = 0.045), American Society of Anesthesiologists physical status class ≥III (P = 0.02), and gastric ulcer (P = 0.04) were three additional independent factors found to increase rebleeding risk. The cumulative rebleeding rate was higher in patients with Rockall scores ≥6 with more than or equal to any two additional factors than in those with fewer than two additional factors (15.69 vs. 7.63 per 100 person‐year, P = 0.012, log–rank test).

Conclusions

Patients with Rockall scores ≥6 are at risk of long‐term recurrent peptic ulcer bleeding. The risk can be independently increased by the presence of activated partial thromboplastin time prolonged ≥1.5‐fold, American Society of Anesthesiologists class ≥III, and gastric ulcer in patients with Rockall scores ≥6.     

Peptic ulcer of the gastric tube after esophagectomy for cancer: clinical implications

The use of the stomach as an esophageal substitute has become a well-established treatment procedure after esophagectomy for cancer. During the procedure, a bilateral truncal vagotomy is performed, which should prevent the occurrence of acid-related diseases in the gastric tube and in the remaining esophagus. We report the case of a man who presented a plugged perforated peptic ulcer that subsequently decompensated following endoscopic examination 1 year after a transthoracic esophagectomy with neoadjuvant chemo-radiation for a middle third squamous cell carcinoma. Resection of the ulcer and suture with a pleural patch was performed. There was no evidence of recurrent malignancy at time of surgery. The pathophysiology of gastric tube ulcer is multifactorial. Long-term treatment with an anti-secretory proton pump inhibitor may decrease esophageal complications of duodeno-gastric-esophageal reflux and could prevent the recurrence of gastric tube ulcers.     

Association between ulcer site and outcome in complicated peptic ulcer disease: a Danish nationwide cohort study

Objective: Mortality rates in complicated peptic ulcer disease are high. This study aimed to examine the prognostic importance of ulcer site in patients with peptic ulcer bleeding (PUB) and perforated peptic ulcer (PPU).

Materials and methods: Design: a nationwide cohort study with prospective and consecutive data collection. Population: all patients treated for PUB and PPU at Danish hospitals between 2003 and 2014. Data: demographic and clinical data reported to the Danish Clinical Registry of Emergency Surgery. Outcome measures: 90- and 30-d mortality and re-intervention. Statistics: the crude and adjusted association between ulcer site (gastric and duodenal) and the outcome measures of interest were assessed by binary logistic regression analysis.

Results: Some 20,059 patients with PUB and 4273 patients with PPU were included; 90-d mortality was 15.3% for PUB and 29.8% for PPU; 30-d mortality was 10.2% and 24.7%, respectively. Duodenal bleeding ulcer, as compared to gastric ulcer (GU), was associated with a significantly increased risk of all-cause mortality within 90 and 30 d, and with re-intervention: adjusted odds ratio (OR) 1.47 (95% confidence interval 1.30–1.67); p?p?p?p?=?0.698, OR 0.93 (0.78 to 1.10); p?=?0.409, and OR 0.97 (0.80–1.19); p?=?0.799, respectively.

Conclusions: DU site is a significant predictor of death and re-intervention in patients with PUB, as compared to GU site. This does not seem to be the case for patients with PPU.     

Complications associated with ulcer recurrence following gastric surgery for ulcer disease

The present study is an attempt to assess the risks of the complications associated with recurrent ulcers in patients who have undergone gastric surgery and to determine whether these risks differ from those observed in patients receiving long term maintenance treatment with H2-receptor antagonists for ulcer disease. One hundred and thirty studies reported in the literature during the past three decades have been analysed to determine both the approximate rate of ulcer recurrence and the proportion of patients with recurrent ulcers who have presented with either haemorrhage or perforation following the various types of gastric surgery for ulcer disease. From these data, estimates of the risks of haemorrhage and of perforation during the years following gastric surgery have been calculated. Vagotomy and antrectomy is associated with a low risk of ulcer recurrence (< 1%) and the risk of complications in later years is accordingly very small (< 0.5°/o). Partial gastrectomy, although associated with low recurrence rates, has a higher risk of complications (1.3% for haemorrhage, 0.3% for perforation) because the proportion of recurrent ulcers that present with haemorrhage or perforation is high (33% and 8%, respectively). Truncal vagotomy plus drainage (TV+D) and highly selective vagotomy (HSV) are associated with recurrence rates of 9% and 12%, respectively, but ulcer recurrences following these operations are less frequently accompanied by complications then recurrences after gastric resection and, as a result, the risks of haemorrhage (1.7% for TV+D; 1.3% for HSV) are similar to the risks after gastric resection. During long term (five years or more) maintenance treatment with H2-receptor antagonists, the risks of haemorrhage and perforation are < 2% and < 0.5%, respectively. It appears, therefore, that the likelihood of developing haemorhage or perforation following gastric surgery is of the same order as that during maintenance treatment with H2-receptor antagonists, at least during the first decade of follow-up.     

Peptic ulcer and gastritis in uraemia, with particular reference to the effect of Helicobacter pylori infection

AIMS: To determine: (i) the prevalence of histological gastritis and peptic ulcer; and (ii) the clinical features of peptic ulcer, in patients with end-stage renal failure. METHODS: Upper endoscopy was performed by a single observer in 268 patients with end-stage renal failure over a 6-year period. Gastric histology and Helicobacter pylori status were studied in 40 consecutive subjects in whom there were no contraindications for gastric biopsy and who had not used antibacterial drugs in the preceding 4 weeks. As there are only limited data for healthy volunteers in Singapore, 33 age-, sex- and race-matched patients with functional dyspepsia from an earlier drug trial and 18 healthy volunteers who were not age-matched were used as controls. The clinical features of 43 consecutive uraemic patients with peptic ulcer were compared with those of 118 consecutive non-uraemic peptic ulcer patients seen by the same author. RESULTS: Among uraemic patients, histological gastritis was less common, compared with healthy volunteers and functional dyspepsia patients. Helicobacter pylori infection as assessed by histology was also less common among uraemic patients compared with functional dyspepsia patients, but the difference was not statistically significant on serological assessment. Uraemic patients with ulcer had an equal sex ratio, in contrast to a male preponderance among peptic ulcer patients with normal renal function. Uraemic patients with ulcer were more likely to be pain-free, to present with haemorrhage, to have multiple ulcers and postbulbar duodenal ulcers, but were less likely to have H. pylori infection. Among uraemic subjects, the prevalence of H. pylori infection was similar whether or not peptic ulcer was present. CONCLUSIONS: The prevalence of histological gastritis was lower in uraemic patients when compared with patients with functional dyspepsia and healthy volunteers. Peptic ulcers in uraemic subjects have different clinical characteristics from peptic ulcer in non-uraemic subjects.     

Peptic ulcer bleeding: accessory risk factors and interactions with non-steroidal anti-inflammatory drugs

AIMS: To determine risk factors for peptic ulcer bleeding other than non-steroidal anti-inflammatory drugs (NSAIDs). Methods-Data on possible antecedent risk factors obtained in a large case control study of 1121 patients admitted to hospitals in Glasgow, Newcastle, Nottingham, Oxford, and Portsmouth with bleeding peptic ulcers were compared with the same information obtained in 989 population controls. Data were analysed by logistic regression with the calculation of odds ratios (OR) and 95% confidence intervals (CI). RESULTS: From a logistic regression model, oral anticoagulants (OR 7. 8; 95% CI 2.8-21.5), previous peptic ulcer (3.8; 2.6-4.9), treatment for heart failure (5.9; 2.3-13.1), oral corticosteroid use (2.7; 1. 3-4.5), treatment for diabetes (3.1; 1.2-4.3), and current smoking (1.6; 1.2-2.0) were all independent risk factors. No association was found with use of calcium channel antagonists. Odds ratios for concomitant NSAID usage were multiplicative with the exception of current smoking. CONCLUSIONS: Some 45% of admissions for peptic ulcer bleeding in England and Wales in those aged 60 or more are calculated to be attributable to, or associated with, these accessory risk factors, which, together with those associated with aspirin or other NSAID use will account for over 80% of predisposing factors to ulcer bleeding.     

Peptic ulcer in hepatic cirrhosis and renal failure

Abstract The prevalence of peptic ulcer in cirrhotic patients is similar to that reported for the general population. Although gastric acid outputs ar normal or lower in cirrhotic subjects compared with non-cirrhotics, the frequency of non-response to histamine H₂-receptor antagonists is higher. Peptic ulcer disease in the cirrhotic seems to pursue a more virulent course compared with that in the non-cirrhotic subject.
Peptic ulcer prevalences in patients dying of uraemia or in uraemic patients on maintenance dialysis treatment are comparable with those in the general population. However, the frequency of peptic ulcer, especially complicated ulcer, is increased following renal transplantation. Ulcer complications in this context are associated with a high mortality rate. Pre-transplant risk factors for subsequent development of peptic ulcer remain to be identified and the value of histamine H₂-receptor antagonists in prophylaxis is as yet unproven.     

Factors affecting mortality and morbidity in patients with peptic ulcer perforation

BACKGROUND AND AIM: With the introduction of H2 receptor antagonists and proton pump inhibitors, the incidence of elective surgery for peptic ulcer (PU) diseases has decreased, although complications of PU such as perforation and bleeding have remained fairly constant. The purpose of this study was to identify the risk factors that predict morbidity and mortality in patients with perforated PU. METHODS: The records of 269 patients who were operated on for perforated PU were reviewed retrospectively. The following factors were analyzed in terms of morbidity and mortality: age >65 years; gender; associated medical illness; chronic ingestion of non-steroidal anti-inflammatory drugs, aspirin, corticosteroids or immunosuppressants; alcohol ingestion and smoking habits; American Society of Anesthesiologist (ASA) status; season; delayed operation; site of ulcer perforation; and shock on admission and type of operation. RESULTS: There were 30 female (11.16%) and 239 male (88.84%) patients. Seventy-one (26.4%) patients had associated diseases. Simple closure was performed in 257 (95.5%) patients; 12 patients (4.5%) underwent definitive operations. A total of 108 postoperative complications were present in 65 (24.2%) patients. Twenty-three patients died (8.55%). Multivariate analysis showed that only age, ASA score, treatment delay, presence of shock and definitive operation were independent predictors of mortality. Significant risk factors that led to morbidity were ASA status, time of surgery, season, presence of shock and type of surgery. There was a significant difference concerning morbidity and mortality between simple closure of the perforation and definitive surgery. CONCLUSIONS: Age, delayed surgery, presence of shock, ASA risk and definitive surgery are factors significantly associated with fatal outcomes in patients undergoing emergency surgery for perforated PU. Therefore, proper resuscitation from shock, improving ASA grade, decreasing delay and reserving definitive surgery for selected patients is needed to improve overall results.     

Lansoprazole Capsules and Amoxicillin Oral Suspension in the Treatment of Peptic Ulcer Disease

Background: Lansoprazole is a potent antisecretory drug also possessing anti-Helicobacter pylori activity in vitro. It is a candidate drug for combination regimens with antibiotics for treating H. pylori infections. Methods: In a semiblind study, 65 patients with duodenal and/or gastric ulcer and pathologic ¹⁴C urea breath test results were treated with either 60 mg lansoprazole every morning only for 14 days or combined with 500 mg amoxicillin oral suspension four times daily between meals, given for 11 days. Endoscopy and breath test were repeated after 6 weeks and 6 months. Patients with unhealed ulcers were withdrawn. Results: Eradication of H. pylori infection was attained in 46% of patients receiving lansoprazole and amoxicillin but in no patient receiving lansoprazole alone. Ulcers healed significantly more often in those who were H. pylori-negative (18 of 19 (95%)) than in those who were H. pylori-positive (20 of 41 (49%)). Adverse events, particularly stomatitis/sore throat and diarrhea, occurred significantly more often when amoxicillin was combined with lansoprazole. Conclusions: Lansoprazole eradicated H. pylori infection only when combined with amoxicillin. Eradication rates in this study are hardly acceptable, and further studies are necessary to define optimal doses and duration of treatment. Using amoxicillin as an oral suspension may not be of any substantial benefit and may cause stomatitis and sore throat.     

胃克星抗消化性溃疡的药理研究

目的：探讨胃克星抗消化性溃疡的药理作用。方法：观察药物对小鼠水浸应激性溃疡，无水乙醇性溃疡，慢性乙酸烧灼性溃疡模型和大鼠胃蛋白酶、胃酸活性的影响。结果：胃克星对小鼠水浸应激性胃溃疡，无水乙醇性溃疡的形成有显著预防作用（P＜0．05，＜0．01）；对乙酸烧灼性溃疡等有显著治疗作用（P＜0．05，＜0．01），并可显著抑制胃酸和胃蛋白酶分泌（P＜0．05，＜0．01）。结论：胃克星具有抗消化性溃疡的作用。     

The effect of platelet–albumin ratio on mortality and morbidity in peptic ulcer perforation

Background:The aim of our study was to investigate the prognostic role of platelet/albumin ratio in patients treated under emergency conditions for peptic ulcer perforation (PUP).Methods:A retrospective study involving emergency patients who were operated for PUP was carried out. The patients were divided into 2 groups: PUP patients who died after surgical treatment (PUP-M) and PUP patients who survived after surgical treatment (PUP-S). The laboratory values of the patients were compared statistically. A P value of <.05 was considered statistically significant.Results:This cohort study consisted of 171 patients treated between June 2013 and December 2019. The mean age of the patients was 46.3 ± 20.5 years; and 33 (19.3%) patients were women. The age (P ≤ .001), platelet/lymphocyte ratio (P = .02), lactic dehydrogenase to albumin ratio (P ≤ .001), and platelet/albumin ratio (PAR; P ≤ .001) values were high and lymphocyte count was low (P = .006) in the PUP-M group. A positive correlation was determined between length of stay in hospital and age (P ≤ .001), lactic dehydrogenase/albumin ratio (P ≤ .001), platelet count (P = .044), and PAR (P ≤ .001). A substantial negative correlation was determined between length of stay in hospital and albumin count (P ≤ .001).Conclusions:We determined a high preoperative PAR level in PUP patients who had undergone surgery as a negative prognostic parameter. PAR is a candidate biomarker for clinical practice.     

Cost-effectiveness of strategies for primary prevention of nonsteroidal anti-inflammatory drug-induced peptic ulcer disease

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of peptic ulcer disease by 5- to 7-fold in the first 3 months of treatment. This study examined the relative cost-effectiveness of different strategies for the primary prevention of NSAID-induced ulcers in patients that are starting NSAID treatment. MEASUREMENTS AND MAIN RESULTS: A decision analysis model was developed to compare the cost-effectiveness of 6 prophylactic strategies relative to no prophylaxis for patients 65 years of age starting a 3-month course of NSAIDs: (1) testing for Helicobacter pylori infection and treating those with positive tests; (2) empiric treatment of all patients for Helicobacter pylori; (3) conventional-dose histamine2 receptor antagonists; (4) high-dose histamine2 receptor antagonists; (5) misoprostol; and (6) omeprazole. Costs were estimated from 1997 Medicare reimbursement schedules and the Drug Topics Red Book. Empiric treatment of Helicobacter pylori with bismuth, metronidazole, and tetracycline was cost-saving in the baseline analysis. Selective treatment of Helicobacter pylori, misoprostol, omeprazole, and conventional-dose or high-dose histamine2 receptor antagonists cost $23,800, $46,100, $34,400, and $15,600 or $21,500 per year of life saved, respectively, relative to prophylaxis. The results were sensitive to the probability of an ulcer, the probability and mortality of ulcer complications, and the cost of, efficacy of, and compliance with prophylaxis. The cost-effectiveness estimates did not change substantially when costs associated with antibiotic resistance of Helicobacter pylori were incorporated. CONCLUSIONS: Several strategies for primary prevention of NSAID-induced ulcers in patients starting NSAIDs were estimated to have acceptable cost-effectiveness relative to prophylaxis. Empirically treating all patients for Helicobacter pylori with bismuth, metronidazole, and tetracycline was projected to be cost-saving in older patients.