Surveillance for pancreatic cancer in high-risk individuals.

Background: Surveillance of individuals at high risk of pancreatic ductal adenocarcinoma (PDAC) and its precursors might lead to better outcomes. The aim of this study was to determine the prevalence and outcomes of PDAC and high-risk neoplastic precursor lesions among such patients participating in surveillance programmes. Methods: A multicentre study was conducted through the International CAncer of the Pancreas Screening (CAPS) Consortium Registry to identify high-risk individuals who had undergone pancreatic resection or progressed to advanced PDAC while under surveillance. High-risk neoplastic precursor lesions were defined as: pancreatic intraepithelial neoplasia (PanIN) 3, intraductal papillary mucinous neoplasia (IPMN) with high-grade dysplasia, and pancreatic neuroendocrine tumours at least 2 cm in diameter. Results: Of 76 high-risk individuals identified in 11 surveillance programmes, 71 had undergone surgery and five had been diagnosed with inoperable PDAC. Of the 71 patients who underwent resection, 32 (45 per cent) had PDAC or a high-risk precursor (19 PDAC, 4 main-duct IPMN, 4 branch-duct IPMN, 5 PanIN-3); the other 39 patients had lesions thought to be associated with a lower risk of neoplastic progression. Age at least 65 years, female sex, carriage of a gene mutation and location of a lesion in the head/uncinate region were associated with high-risk precursor lesions or PDAC. The survival of high-risk individuals with low-risk neoplastic lesions did not differ from that in those with high-risk precursor lesions. Survival was worse among patients with PDAC. There was no surgery-related mortality. Conclusion: A high proportion of high-risk individuals who had surgical resection for screening- or surveillance-detected pancreatic lesions had a high-risk neoplastic precursor lesion or PDAC at the time of surgery. Survival was better in high-risk individuals who had either low- or high-risk neoplastic precursor lesions compared with that in patients who developed PDAC.

Antecedentes: Se podrían obtener mejores resultados con el seguimiento de individuos de alto riesgo para adenocarcinoma ductal pancreático (pancreatic ductal adenocarcinoma, PDAC) y lesiones precursoras. El objetivo de este estudio fue determinar la prevalencia y los resultados del PDAC y de las lesiones precursoras de alto riesgo neoplásico en pacientes que participaron en programas de seguimiento. Métodos: Se llevó a cabo un estudio multicéntrico a través del registro internacional del consorcio CAPS (Common Automotive Platform Standard) para identificar a las personas de alto riesgo que se habían sometido a una resección pancreática o habían progresado a PDAC avanzado mientras estaban en seguimiento. Se definieron como lesiones neoplásicas precursoras de alto riesgo la neoplasia intraepitelial pancreática de tipo 3 (PanIN­3), la neoplasia papilar mucinosa intraductal (intraductal papillary mucinous neoplasia, IPMN) con displasia de alto grado y los tumores neuroendocrinos pancreáticos (pancreatic neuroendocrine tumours, PanNET) de ≥ 2 cm de diámetro. Resultados: De 76 individuos con lesiones de alto riesgo identificados en 11 programas de seguimiento, 71 fueron tratados quirúrgicamente y 5 fueron diagnosticados de un PDAC inoperable. De las 71 resecciones, 32 (45%) tenían PDAC o una lesión precursora de alto riesgo (19 PDAC, 4 IPMN de conducto principal, 4 IPMN de rama secundaria y 5 PanIN­3). Los otros 39 pacientes tenían lesiones que se consideraron asociadas con un menor riesgo de progresión neoplásica. La edad ≥ 65 años, el sexo femenino, el ser portador de una mutación genética y la localización de la lesión en la cabeza/proceso uncinado fueron factores asociados a las lesiones precursoras de alto riesgo o al PDAC. No hubo diferencias en la supervivencia de individuos de alto riesgo con lesiones neoplásicas de bajo riesgo frente a aquellos que presentaron lesiones precursoras de alto riesgo. La supervivencia fue peor en los pacientes con PDAC. No hubo mortalidad relacionada con la cirugía. Conclusión: Un elevado porcentaje de individuos de alto riesgo que se sometieron a resección quirúrgica tras la detección de lesiones pancreáticas en el seguimiento tenían una lesión precursora neoplásica de alto riesgo o un PDAC. La supervivencia fue mejor en individuos de alto riesgo que tenían lesiones precursoras neoplásicas de bajo o alto riesgo en comparación con aquellos pacientes que habían desarrollado un PDAC.

Endoscopic pH monitoring for patients with suspected or refractory gastroesophageal reflux disease.

BACKGROUND: Wireless pH studies can offer prolonged pH monitoring, which may potentially facilitate the diagnosis and management of patients with gastroesophageal reflux disease (GERD). The aim of the present study was to evaluate the detection rate of abnormal esophageal acid exposure using prolonged pH monitoring in patients with suspected or refractory GERD symptoms. METHODS: Patients undergoing prolonged ambulatory pH studies for the evaluation of GERD-related symptoms were assessed. Patients with a known diagnosis of GERD were tested on medical therapy, while patients with suspected GERD were tested off therapy. The wireless pH capsules were placed during upper endoscopy 6 cm above the squamocolumnar junction. RESULTS: One hundred ninety-one patients underwent a total of 198 pH studies. Fifty ambulatory pH studies (25%) were excluded from the analysis: 27 patients (14%) had insufficient data capture (less than 18 h on at least one day of monitoring), 15 patients had premature capsule release (7%), seven were repeat studies (3.5%) and one had intolerable pain requiring capsule removal (0.5%). There were 115 patients undergoing pH studies who were off medication, and 33 patients were on therapy. For the two groups of patients, results were as follows: 32 (28%) and 22 (67%) patients with normal studies on both days; 58 (50%) and five (15%) patients with abnormal studies on both days; 18 (16%) and three (9%) patients with abnormal studies on day 1 only; and seven (6%) and three (9%) patients with abnormal studies on day 2 only, respectively. CONCLUSIONS: Prolonged 48 h pH monitoring can detect more abnormal esophageal acid exposure but is associated with a significant rate of incomplete studies.

Endoluminal gastroplication for treatment of patients with classic gastroesophageal reflux symptoms and borderline 24-h pH studies.

BACKGROUND: Patients with classic gastroesophageal reflux disease (GERD) symptoms and borderline 24-h pH studies are not considered to be good candidates for surgical fundoplication. Endoluminal gastroplication (ELGP) is a new endoscopic treatment for patients with GERD. The aim of this study was to evaluate the efficacy of ELGP in these patients. METHODS: Patients with heartburn, regurgitation symptoms and a DeMeester score of less than 30 were studied. ELGP involved placement of two or three plications within 2 cm of the gastroesophageal junction. Clinical outcomes measured were heartburn symptom score (HSS), regurgitation frequency score (RFS) and medication use. RESULTS: Twenty-five patients (11 M, 14 F, mean age of 51 years) had a medication use of 11.5 doses of proton-pump inhibitors per week prior to ELGP. Average lower esophageal sphincter pressure measured 15 +/- 8 mmHg, and average DeMeester score was 18 +/- 8. Nine patients had hiatal hernias and 11 had esophagitis. Twenty-four patients were available for a mean follow-up of 12 months. HSS significantly decreased from 48 to 17 (P < 0.01) and RFS was reduced from 1.8 to 0.7 (P < 0.01). Proton-pump inhibitor use was 5.3 doses per week (P < 0.01) post-ELGP; 12 patients (50%) were off medications, 3 (13%) had a 50% reduction in medication use, and in 9 (37%) there was no change. Complications were bleeding in one patient and aspiration pneumonia in another patient. CONCLUSIONS: Endoluminal gastroplication provides symptomatic relief for patients with classic GERD symptoms despite medical therapy and borderline 24-h pH studies.

Clinical outcome of the use of enteral stents for palliation of patients with malignant upper GI obstruction.

BACKGROUND: The endoscopically placed enteral stent has emerged as a reasonable alternative to palliative surgery for malignant intestinal obstruction. This is a report of our experience with the use of enteral stents for nonesophageal malignant upper GI obstruction. METHODS: Data on all patients who had undergone enteral stent placement were reviewed. Those with a diagnosis of pancreatic cancer were compared with another similar cohort of patients who underwent palliative gastrojejunostomy. RESULTS: Thirty-one procedures were performed on 29 patients (mean age 67.7 years). Thirteen (45%) were men and 16 (55%) women. The diagnoses were gastric (13.8%), duodenal (10.3%), pancreatic (41.4%), metastatic (27.6%), and other malignancies (6.9%). Malignant obstruction occurred at the pylorus (20.7%), first part of duodenum (37.9%), second part of duodenum (27.6%), third part of duodenum (3.5%), and anastomotic sites (10.3%). Twenty-nine (93.5%) procedures were successful and good clinical outcome was achieved in 25 (80.6%). Re-obstruction by tumor ingrowth occurred in 2 patients after a mean of 183 days. The median survival time for patients with pancreatic cancer who underwent enteral stent placement compared with those who underwent surgical gastrojejunostomy was 94 and 92 days, charges were $9921 and $28,173, and duration of hospitalization was 4 and 14 days, respectively (latter 2 differences with p value < 0.005). CONCLUSION: Endoscopic enteral stent placement of nonesophageal malignant upper GI obstruction is a safe, efficacious, and cost-effective procedure with good clinical outcome, lower charges, and shorter hospitalization period than the surgical alternative.

Gastrointestinal stromal sarcoma--a case report of palliative enteral stenting.

We report a case of metastatic gastrointestinal stromal sarcoma (GISS) in a 33-year-old man who subsequently underwent successful palliative endoscopically-placed enteral stenting for duodenal stenosis secondary to extrinsic compression. Enteral stenting for palliative relief of malignant gastrointestinal obstruction is recommended for its safety, efficacy and cost-effectiveness.

The value of intravenous heme-albumin and plasmapheresis in reducing postoperative complications of orthotopic liver transplantation for erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is marked by a deficiency of ferrochelatase, which occurs in all cells and tissues, preventing effective conversion of proto porphyrin IX to heme and thereby blocking effective feedback inhibition of heme synthesis. The major source of the excess protoporphyrin is the bone marrow. Protoporphyrin IX may accumulate, with resultant toxicity chiefly of the marrow, skin, nervous system, and liver. Orthotopic liver transplantation (OLT) is, at present, the only adequate intervention for severe liver compromise secondary to protoporphyrin deposition, but it has been complicated by severe photosensitivity and polyneuropathy. Intravenous heme and plasmapheresis have been proposed but not previously reported as means to reduce the protoporphyrin burden before liver transplantation. We report a man with EPP who underwent preoperative heme-albumin administration and plasmaphereses that led to marked reductions in plasma and erythrocyte protoporphyrin levels. His OLT was uneventful, and he developed neither polyneuropathy nor exacerbation of photosensitivity.

A randomized trial of Lactobacillus acidophilus BG2FO4 to treat lactose intolerance.

BACKGROUND: Lactose intolerance is the most common disorder of intestinal carbohydrate digestion. Lactobacillus acidophilus BG2FO4 is a strain of lactobacilli with properties of marked intestinal adherence and high beta-galactosidase activity. OBJECTIVE: This study was designed to determine whether oral feeding of Lactobacillus acidophilus BG2FO4 leads to a lactose-tolerant state. DESIGN: We studied 42 subjects with self-reported lactose intolerance and performed breath-hydrogen tests to determine whether they were lactose maldigesters. Subjects with established lactose maldigestion (n = 24) were invited to be randomly assigned to an omeprazole-treated (hypochlorhydric) group or a non-omeprazole-treated group, but 6 subjects chose not to participate. All randomly assigned subjects (n = 18) ingested Lactobacillus acidophilus BG2FO4 twice per day for 7 d and stool samples were collected. Breath-hydrogen tests were performed and symptom scores were recorded at baseline and after lactobacilli ingestion. RESULTS: Lactose maldigestion was established in 24 of 42 subjects (57%) with self-reported lactose intolerance. In 18 lactose-maldigesting subjects, overall hydrogen production and symptom scores after ingestion of Lactobacillus acidophilus BG2FO4 were not significantly different from baseline values. Live Lactobacillus acidophilus BG2FO4 was recovered in stool samples from 7 subjects. CONCLUSIONS: Lactose intolerance is overreported in subjects with gastrointestinal symptoms after lactose ingestion. Treatment of lactose-maldigesting subjects with and without hypochlorhydria with Lactobacillus acidophilus BG2FO4 for 7 d failed to change breath-hydrogen excretion significantly after lactose ingestion.

Lactose intolerance and irritable bowel syndrome.

A recent study on lactose intolerance and irritable bowel syndrome has shown that subjective lactose intolerance is increased in patients with irritable bowel syndrome, despite no increase in the prevalence of lactose maldigestion.

The aging gut. Nutritional issues.

With improvements in health care, living standards, and socioeconomic status, more adults are living to old age. As the population ages, it is increasingly important to understand the factors that affect the nutritional status and thus the health status of older adults. Many factors contribute to inadequate nutrition, including health status, financial capacities, mobility, exercise, and physiologic needs. This article considered only the potential changes in nutritional needs because of alterations in the gastrointestinal tract owing to aging. One of the most remarkable changes with aging is the frequent development of atrophic gastritis and the inability to secrete gastric acid. This process affects approximately a third of older adults in the United States and only recently was recognized to be due to infection by H. pylori in the majority of cases. The lack of gastric acid in atrophic gastritis may lead to small intestinal bacterial overgrowth and influences the absorption of a variety of micronutrients, including iron, folate, calcium, vitamin K, and vitamin B12. Lactose maldigestion is a frequent condition in older adults and is extremely common worldwide. The intolerance of dairy products leads to avoidance of these foods and likely contributes to the development of osteopenia. Overall, the small intestine and pancreas undergo astonishingly few clinically significant changes with aging. The relative preservation of overall gastrointestinal function with aging is likely due to the large reserve capacity of this multiorgan system. Further research is needed to define the precise nutritional needs for older adults because simple extrapolation of values from younger adults is now recognized to be insufficient. In addition, it is no longer acceptable to define adequate nutriture in terms of amounts of vitamins needed to maintain serum levels of a nutrient. Further RDAs must consider the functional implications of adequate nutrition. Nutrients in the elderly will be measured as to whether they result in improvements in markers of chronic disease such as homocysteine or, most importantly, in the prevention of chronic disease such as osteoporosis and cardiovascular disease.

Utility of hepatic iron index in American patients with hereditary hemochromatosis: a multicenter study.

BACKGROUND & AIMS: A hepatic iron index (hepatic iron concentration divided by age) of more than 1.9 has been proposed as useful to identify patients with homozygous hereditary hemochromatosis (HHC). There are limited data on the diagnostic use of the hepatic iron index in patients with HHC in the United States. This study evaluated the hepatic iron index in the diagnosis of HHC in a multicenter U.S. study. METHODS: Hepatic iron concentration was measured in 509 patients undergoing liver biopsy. The diagnosis of HHC was made using clinical, biochemical, and histopathologic criteria. RESULTS: Fifty-five patients met criteria for HHC; hepatic iron index was > 1.9 in 51 of 55 (93%) patients with HHC but in none of 454 patients with other liver diseases; hepatic iron concentration was > 71 mumol/g dry weight in 54 of 55 patients with HHC but only 1 of the other 454 patients. CONCLUSIONS: A hepatic iron index of > or = 1.9 can identify most U.S. patients with HHC but is < or = 1.9 in 7%. A "threshold" hepatic iron concentration of 71 mumol/g can almost always distinguish patients with HHC from patients with other liver diseases and may be a useful adjunct to the hepatic iron index in the diagnosis of HHC in the diverse U.S. population.

Enteral nutrition in acute pancreatitis.

A recent prospective and randomized study comparing enteral nutrition with total parenteral nutrition has shown that enteral nutrition may be a cost-effective alternative to total parenteral nutrition in patients with acute pancreatitis.

Evaluation of the clinical impact of endoscopic ultrasonography in gastrointestinal disease.

BACKGROUND: Outcome studies evaluating the impact of endosonography on patient management are lacking. We conducted a prospective study to assess the overall clinical effectiveness of endosonography as perceived by the requesting physician. METHODS: Physicians requesting endosonography were asked to fill out a questionnaire listing clinical diagnosis, diagnostic certainty, and future management plans. After the procedure, the requesting physicians were asked about changes in diagnosis and management, and the physicians' impressions of how clinically helpful the test was. Comparisons were made between the preprocedure and postprocedure assessment and plans, changes in diagnosis, diagnostic certainty, patient management plans, and if endosonography led to a more or less invasive course of therapy. RESULTS: Sixty-three patients (35 women and 28 men) were evaluated. Management was altered in 30 patients (48%). In 66% of these patients the subsequent course of therapy was less invasive. Diagnostic certainty increased from 2.8 before endosonography to 4.3 after sonography (p = 0.0001). Endosonography was judged to be 4.1 on a "usefulness" score of 1 to 5. CONCLUSIONS: Endosonography is helpful in improving diagnostic certainty, frequently leading to altered patient management, and is perceived to be a helpful test by requesting physicians.

Gastric emptying and first-pass metabolism of ethanol in elderly subjects with and without atrophic gastritis.

BACKGROUND: Oral ethanol intake results in lower blood ethanol concentrations than intravenous administration of the same dose of ethanol. This first-pass metabolism is thought to be due to gastric metabolism of ethanol via alcohol dehydrogenase and also to hepatic first-pass metabolism. METHODS: Since a loss of gastric mucosa may decrease first-pass metabolism of ethanol, this metabolism was studied in 10 elderly subjects (6 women and 4 men) with atrophic gastritis and bacterial overgrowth and in 17 control subjects with normal gastric secretory function. Atrophic gastritis was verified by means of the serum pepsinogen I to pepsinogen II ratio and the hypochlorhydria occurring after pentagastrin stimulation. Bacterial overgrowth was assessed by bacteria. In addition, gastric emptying rates of ethanol solution with technetium-99m sulfur colloid were calculated from scintigraphic images. Furthermore, gastric biopsy specimens were taken from 12 female patients with atrophic gastritis and from 12 controls for determination of alcohol dehydrogenase activity. RESULTS: Neither gender (female versus male, 28 +/- 5% versus 42 +/- 5%), atrophic gastritis (normal versus atrophic gastritis, 35 +/- 4% versus 32 +/- 6%), nor tetracycline treatment in atrophic gastritis subjects (before versus after, 32 +/- 6% versus 41 +/- 5%) had a statistically significant effect on the first-pass metabolism of ethanol in the elderly. Gastric alcohol dehydrogenase activity was significantly lower in atrophic gastritis subjects than in controls (p < 0.01). A significant correlation was found between the first-pass metabolism of ethanol in healthy controls and gastric half-emptying time (p = 0.032). CONCLUSIONS: We conclude from these data that the rate of gastric emptying modulates first-pass metabolism of ethanol in elderly individuals.

Nutrition status predicts survival in cirrhosis.

Nutrition assessments using anthropometric, visceral, and immunologic measurements were performed to determine the prevalence, characteristics, and clinical importance of nutrition disorders in patients with liver cirrhosis from alcohol or viral hepatitis. Severely malnourished patients, as determined by triceps skinfold thickness or midarm muscle circumference, had significantly poorer survival rates.

Rice inhibits intestinal secretions.

Rice-based oral rehydration solutions have been found to be effective in decreasing stool output and improving intestinal absorption in acute infectious diarrhea. Recent tests of the ability of a rice extract to inhibit intestinal secretions were undertaken, and it was shown that an isolated fraction of rice extract decreased intestinal losses by actively inhibiting the chloride channel.

Breast carcinoma metastatic to the esophagus: clinicopathological and management features of four cases, and literature review.

Dysphagia due to esophageal metastases from primary breast carcinoma is an unusual entity. In this series of cases, we describe the clinical features of dysphagia due to metastatic esophageal lesions in four patients (with a primary diagnosis of breast cancer made 8-22 yr previously). We provide the first endoscopic ultrasound characterization of metastatic lesions to the esophagus from breast carcinoma. Endoscopic management of these strictures with both bougienage and balloon dilation techniques resulted in esophageal perforation in three of our four patients. We believe that endoscopic ultrasound is helpful in the diagnosis of metastatic breast cancer to the esophagus. However, endoscopic dilation of these strictures should be done gently and only after other treatment options have been carefully considered.

Hypochlorhydria from short-term omeprazole treatment does not inhibit intestinal absorption of calcium, phosphorus, magnesium or zinc from food in humans.

OBJECTIVE: Low gastric pH is generally believed to be an important factor in intestinal mineral absorption. Thus, hypochlorhydria could be an important risk factor for mineral malabsorption and the development of marginal mineral status. We studied whether the hypochlorhydria associated with treatment with the anti-ulcer medication omeprazole, a potent gastric proton pump inhibition, would affect intestinal calcium, phosphorus, magnesium, or zinc absorption from food. METHODS: Thirteen normal, healthy adults were assigned to either a control group (n = 5) receiving no drug treatment or an omeprazole treatment group (n = 8) to produce increased gastric pH. Omeprazole treatment of normal volunteers resulted in a significant change in postprandial gastric pH (pH 6.4 +/- 0.3 vs. 3.6 +/- 0.5 in control subjects, p < 0.01) and baseline fasting pH (pH 5.8 +/- 0.5 vs. pH 1.8 +/- 0.3 in controls, p < 0.01) after an overnight fast. Net mineral absorption from a standard test meal was measured using a whole gut lavage technique. Mineral absorption was measured twice in each subject, once with 120 mL of 0.1 mol/liter hydrochloric acid and a second time with 120 mL of distilled water alone. RESULTS: We found that despite marked changes in gastric pH due to drug treatment or administration of exogenous HCl, no change in the intestinal absorption of calcium, phosphorus, magnesium or zinc from a standard test meal was evident. CONCLUSIONS: These findings suggest that changing the gastric pH alone does not modify the net intestinal absorption of several minerals from food. Therefore, it is unlikely that moderate hypochlorhydria resulting from short-term omeprazole treatment substantially increases the risk for developing calcium, phosphorus, magnesium, or zinc deficiencies due to mineral malabsorption.