Cigarette smoking accelerates progression of alcoholic chronic pancreatitis.

BACKGROUND: Smoking is a recognised risk factor for pancreatic cancer and has been associated with chronic pancreatitis and also with type II diabetes. AIMS: The aim of this study was to investigate the effect of tobacco on the age of diagnosis of pancreatitis and progression of disease, as measured by the appearance of calcification and diabetes. PATIENTS: We used data from a retrospective cohort of 934 patients with chronic alcoholic pancreatitis where information on smoking was available, who were diagnosed and followed in clinical centres in five countries. METHODS: We compared age at diagnosis of pancreatitis in smokers versus non-smokers, and used the Cox proportional hazards model to evaluate the effects of tobacco on the development of calcification and diabetes, after adjustment for age, sex, centre, and alcohol consumption. RESULTS: The diagnosis of pancreatitis was made, on average, 4.7 years earlier in smokers than in non-smokers (p = 0.001). Tobacco smoking increased significantly the risk of pancreatic calcifications (hazard ratio (HR) 4.9 (95% confidence interval (CI) 2.3-10.5) for smokers v non-smokers) and to a lesser extent the risk of diabetes (HR 2.3 (95% CI 1.2-4.2)) during the course of pancreatitis. CONCLUSIONS: In this study, tobacco smoking was associated with earlier diagnosis of chronic alcoholic pancreatitis and with the appearance of calcifications and diabetes, independent of alcohol consumption.

Neural network analysis of EUS images to differentiate between pancreatic malignancy and pancreatitis.

BACKGROUND: The differentiation of focal pancreatitis and pancreatic adenocarcinoma is problematic and often resolved only by pancreaticoduodenectomy. EUS is the most sensitive imaging modality for both conditions, yet ultrasonic criteria for distinguishing the two have not been described and differentiation remains difficult. The aims of this study were to develop a self-learning computer program that can analyze EUS images and differentiate malignancy from pancreatitis, and to compare results obtained with this system with EUS interpretation by experienced endosonographers. METHODS: Twenty-one patients with pancreatic cancer and 14 with focal pancreatitis were included. The diagnosis was confirmed histologically in all cases and each patient had undergone EUS. A single EUS image from each procedure was used for computer analysis. The results were compared with the EUS diagnosis reported at the actual procedure as well that of an endosonographer who reviewed videotapes of the procedures. RESULTS: The software program differentiated focal pancreatitis from malignancy with a maximal 89% accuracy. With sensitivity set at 100% for malignancy, the program was 50% specific and accuracy was 80%. Sensitivity and accuracy of the endosonographer's impression at the time of EUS were, respectively, 89% and 85%. A sensitivity of 73% and accuracy of 83% were achieved with blinded interpretation of EUS videotapes. CONCLUSIONS: Analysis of EUS images with computer software programs is feasible and compares favorably with human interpretation. The application of this technology to EUS and other imaging scenarios could be a useful adjunct to diagnostic endoscopy and warrants further investigation.

Utility of endoscopic ultrasonography in endoscopic drainage of pancreatic pseudocysts in selected patients.

OBJECTIVES: To determine the effect of endoscopic ultrasonography (EUS) on endoscopic drainage of pancreatic pseudocysts and to determine patency with fistula dilation and placement of multiple stents. PATIENTS AND METHODS: Between September 1995 and January 1999, 19 patients underwent endoscopic drainage of pancreatic pseudocysts, 17 of whom were assessed by EUS before drainage. Radial EUS scanning was used to detect an optimal site of apposition of pseudocyst and gut wall, free of intervening vessels. A fistula was created with a fistulatome, followed by balloon dilation of the fistula tract. Patency was maintained with multiple double pigtail stents. The primary goal of this retrospective study was to determine whether EUS affected the practice of endoscopic drainage of pancreatic pseudocysts. RESULTS: In 3 patients, drainage was not attempted based on EUS findings. In the other 13 patients (14 pseudocysts), creation of a fistula was successful on 13 occasions, and no immediate complications occurred. However, 1 patient subsequently developed sepsis that required surgery. All other patients were treated with balloon dilation, multiple stents, and antibiotics, with no septic complications. Of 14 pseudocysts (in 13 patients), 13 (93%) resolved. CONCLUSIONS: Results of EUS may alter management of patients considered for endoscopic drainage of pancreatic pseudocysts. Endoscopic ultrasonography was useful for selecting an optimal and safe drainage site. The combination of balloon dilation, multiple stents, and antibiotics appears to resolve pancreatic pseudocysts without septic complications.

Islet amyloid polypeptide is not a satisfactory marker for detecting pancreatic cancer.

BACKGROUND & AIMS: Islet amyloid polypeptide (IAPP) levels are elevated in pancreatic cancer and may be a useful marker of pancreatic cancer-associated diabetes. The aim of this study was to compare the sensitivity and specificity for pancreatic cancer of IAPP with that of CA19-9, examine clinical characteristics of diabetes in pancreatic cancer, and define the relationship of IAPP to diabetes of pancreatic cancer. METHODS: Fasting serum glucose, IAPP, and CA 19-9 were measured in 130 subjects with pancreatic cancer, 250 subjects with other pancreatic and peripancreatic diseases, and 116 controls. In pancreatic cancer patients, we noted tumor stage and the presence and duration of diabetes. RESULTS: IAPP was markedly elevated in pancreatic cancer, especially in patients with diabetes. However, the sensitivity of IAPP for pancreatic cancer was less than that of CA 19-9 (40% vs. 75%; P < 0.001). Diabetes was present in 46% of pancreatic cancers and 55% of resectable tumors. In pancreatic cancer with diabetes, the sensitivity of IAPP was only 50%. In resectable cancer it was 27%. CONCLUSIONS: IAPP is elevated in pancreatic cancer but is not sensitive enough to replace or complement existing tests. Diabetes occurs early and frequently in pancreatic cancer. Development of a sensitive and specific marker for pancreatic-associated diabetes might lead to diagnosis of resectable pancreatic cancer.

Gastric acid suppression and treatment of severe exocrine pancreatic insufficiency.

Adding either H(2)-receptor antagonists (cimetidine or ranitidine) or proton pump inhibitors to an adequate amount of lipolytic activity improves fat malabsorption in most cases and abolishes steatorrhoea in up to 40% of children and adults with cystic fibrosis and in adults with chronic pancreatitis. Acid suppression improves fat absorption because the resultant increase in pH within the upper gastrointestinal tract improves the survival of lipolytic activity, reduces duodenal volume flow and prevents the precipitation of bile acids. These effects increase the concentration of intraduodenal lipolytic activity and promote the aggregation of bile acids and the micellar solubilization of lipid. The amount of lipase that should be recommended is controversial, but we interpret our studies as indicating that at least 90 000 United States Pharmacopeia (USP) units should be ingested with meals. This amount of lipolytic activity taken with an agent that suppresses gastric acid secretion improves fat absorption in most patients and may even abolish steatorrhoea.

Protection of research subjects with emphasis on protocols involving radiation.

Approval by an institutional review board (IRB) or human studies committee must be obtained prior to conducting human subject research. Historically this was not the case, and human subjects were injured as a result. Because there has been and still remains an inevitable conflict of interest for researchers, instititions that perform human research must follow regulations designed to protect human subjects contained in the Code of Federal Regulations, if the research is federally funded. Two federal agencies provide oversight for IRB activities: the Food and Drug Administration (FDA) and a National Institutes of Health Office for Human Research Protection (OHRP), formerly the Office for Protection from Research Risks (OPRR). These agencies are charged with the implementation of rules related to ethical and legal obligations of researchers and their institutions. The institution's role, by means of an IRB, is to adhere to principles of the Belmont Report and to set forth ethical principles, policies, and procedures for protecting the rights and welfare of human subjects. The researchers' role is to conduct their research ethically while maximizing benefits and minimizing harm. Studies involving radiation exposure of human subjects add another level of risk that must be evaluated by an IRB with assistance of a radiation expert or radiation safety committee (RSC). This paper will look at regulatory aspects of human research, IRB responsibilities overall and as they relate to radiation exposure of subjects, and the role of the RSC.

The effect of small amounts of alcohol on the clinical course of chronic pancreatitis.

OBJECTIVE: To investigate the hypothesis that an increasing intake of alcohol accelerates the course of chronic pancreatitis. PATIENTS AND METHODS: In this retrospective record analysis and subsequent prospective follow-up of 372 patients with chronic pancreatitis, we separately compared the clinical course of chronic pancreatitis among the following patients: those with early-onset idiopathic chronic pancreatitis and no alcohol intake (group A [n=25]) and those with late-onset idiopathic chronic pancreatitis and no alcohol intake (group B [n=41]), low alcohol intake (< 50 g/d) (group C [n=57]), and high alcohol intake (> or = 50 g/d) (group D [n=249]). From medical records, physical examinations, questionnaires, death certificates, or autopsy reports, we obtained information on sex, age, signs and symptoms (pain severity, calcification, endocrine and exocrine insufficiency), complications, surgery, and survival. RESULTS: Group D had the highest percentage of men (72%). At the onset of chronic pancreatitis, patients in group A were significantly younger than those in groups B, C, and D (P<.05), and severity of pain was significantly greater in patients in group A than in groups B, C, and D (P<.05). The percentage of patients who eventually developed endocrine or exocrine insufficiency was similar in all groups. Among patients in groups B, C, and D, an increasing intake of alcohol from zero to less than 50 g/d to more than 50 g/d was associated with earlier inception of disease (P<.001). Pain prevalence at onset was less in group B patients than in patients in groups C and D (P<.05). Intake of a large amount of alcohol (group D) shortened time to calcification and survival (P<.05). In addition, patients in group D had more complications (fistulas, pseudocysts, abscesses, and biliary obstruction) (P<.05) than those in groups A and B. More patients in group A underwent pancreatic surgery compared with patients in groups B and C. CONCLUSIONS: Among patients with onset of chronic pancreatitis after age 35 years, alcohol intake, even less than 50 g/d, induced earlier disease characterized by more frequent severe pain, calcification, and complications. Intake of large amounts of alcohol (> or = 50 g/d) reduced time to calcification and death.

Chronic pancreatitis.

An increasing number of novel mutations are associated with chronic pancreatitis. Some cause a high-penetrance, autosomal dominant type of clinical picture (eg, mutations at codons 29 and 122 of the cationic trypsinogen gene), whereas others have a low penetrance or are frequent in the general population (eg, mutations in Kazal type 1 [SPINK1] and in codons 16, 22, and 23 of the cationic trypsinogen gene) and act as disease modifiers. The results of recent studies indicate that smoking adversely affects the course and complications of chronic pancreatitis (more frequent and faster rate of calcification and higher risk of development of pancreatic cancer). Thus, regardless of the cause of chronic pancreatis, patients with this condition should not smoke. Using current diagnostic criteria, the accuracy of endoscopic ultrasound for the diagnosis of chronic pancreatitis is not good. For example, 39% of dyspeptic persons without any other evidence of chronic pancreatitis fulfilled the endoscopic ultrasound criteria for chronic pancreatitis. Diabetes frequently occurs in chronic pancreatitis, but it is not prevented or increased by pancreatic surgery. Islet cell autotransplantation holds promise for the prevention of diabetes in patients requiring total pancreatectomy if the pancreas is not extensively fibrotic. Splenic vein occlusion is present in 7% of patients undergoing surgery for chronic pancreatitis, but fewer than one fifth of these patients have variceal bleeding before or after surgery.

Cigarette smoking increases the risk of pancreatic calcification in late-onset but not early-onset idiopathic chronic pancreatitis.

An association exists between cigarette smoking and pancreatitis owing to alcohol. We determined whether cigarette smoking affected the course of pancreatic calcification and insufficiency in idiopathic chronic pancreatitis. Medical records were analyzed of 24 persons with early- and 42 with late-onset idiopathic chronic pancreatitis who were diagnosed between 1976 and 1982 and then followed prospectively until 1985. Smoking equaled >5 pack-years before calcification or insufficiency or last follow-up. Mean follow-up after onset of chronic pancreatitis was 27 and 13 years in early- and late-onset idiopathic chronic pancreatitis, respectively. Incidence of calcification in the two groups was 58 and 43%, respectively. In early-onset idiopathic chronic pancreatitis, smokers and nonsmokers developed calcification at a similar rate and frequency (58%). In late-onset idiopathic chronic pancreatitis, smokers developed pancreatic calcifications faster (p < 0.001) and more frequently (83 vs. 13%, p < 0.001) than nonsmokers. The association between smoking and pancreatic calcification was independent of gender, body mass index, and exocrine or endocrine insufficiency. Smoking did not affect development of exocrine or endocrine insufficiency. Cigarette smoking increases the risk of pancreatic calcification of late- but not of early-onset idiopathic chronic pancreatitis. These data support encouraging cessation of smoking in chronic pancreatitis.

Acute pancreatitis in the postpartum period: a population-based case-control study.

OBJECTIVE: To determine relationships among pregnancy (during and postpartum), acute pancreatitis, and gallstones. PATIENTS AND METHODS: In this retrospective population-based case-control study, we identified all 12- to 50-year-old Rochester, Minn, females diagnosed between 1976 and 1991 as having acute pancreatitis (cases). For each case, we matched 4 women of the same age (+/- 6 years) with no history of acute pancreatitis (controls). Acute pancreatitis was defined as associated with pregnancy if it occurred from 10 months prior to delivery to delivery and with the postpartum period if it occurred within 10 months of the date of delivery. Logistic regression was used to assess associations between pregnancy-related acute pancreatitis, age, gallstone occurrence, and alcohol use. RESULTS: In a cohort of 61 women who developed acute pancreatitis and 244 controls, the relative risk for acute pancreatitis associated with pregnancy was 1.43 (95% confidence interval, 0.61-3.40). All 10 cases of acute pancreatitis associated with pregnancy occurred in the postpartum period. Gallstones were present in 6 of them compared with 13 of 51 women with non-pregnancy-related acute pancreatitis (P < .05). Women with postpartum-related pancreatitis were younger than those with non-pregnancy-related pancreatitis (mean, 28 vs 36 years; P < .05). Alcohol was not associated with pregnancy-related pancreatitis. CONCLUSIONS: Acute pancreatitis during the postpartum period is not directly related to pregnancy but is associated with gallstones and occurs in younger women.

Clinical and pathologic correlation of 84 mucinous cystic neoplasms of the pancreas: can one reliably differentiate benign from malignant (or premalignant) neoplasms?

OBJECTIVE: To determine whether the long-term behavior of cystic mucinous neoplasms of the pancreas could be predicted using a novel, precisely defined classification of benign mucinous cystadenomas, noninvasive proliferative cystic mucinous neoplasms, and invasive mucinous cystadenocarcinomas. The primary interest was to obtain long-term follow-up after complete resection to determine the recurrence rates based on this objective classification. BACKGROUND: Current understanding is that all cystic mucinous neoplasms of the pancreas are potentially malignant and that mucinous cystadenomas, when completely removed, are biologically benign. Cystadenocarcinomas are thought to be less aggressively malignant than ordinary ductal adenocarcinoma, but reported recurrence rates vary widely and are unpredictable. METHODS: All patients who underwent "curative" resection for cystic mucinous neoplasms at Mayo Clinic Rochester from 1940 to 1997 were identified. All available pathology slides, gross specimens, and clinical records were reviewed, eliminating patients with inadequate documentation. Neoplasms were reclassified as mucinous cystadenomas, noninvasive proliferative mucinous cystic neoplasms, or invasive cystadenocarcinomas based on specific histologic criteria. RESULTS: Of 84 patients (70 women, 14 men) with cystic mucinous neoplasms of the pancreas, 54 were classified as cystadenomas, 23 as noninvasive proliferative cystic mucinous neoplasms, and only 7 as cystadenocarcinomas. Recurrent disease developed in none of the 77 patients without invasion, but 5 of the 6 patients surviving resection for cystadenocarcinomas died of recurrent cystadenocarcinoma within 5 years. CONCLUSIONS: When the neoplasm is completely resected and subjected to adequate histopathologic examination based on these objective criteria, absence of tissue invasion predicts a curative operation and detailed follow-up may be unnecessary. In contrast, a histologic diagnosis of invasive cystadenocarcinoma portends a dismal prognosis, similar to that of typical ductal adenocarcinoma of the pancreas.

Chronic pancreatitis.

In the past year, there has been at least one important clinical paper that sheds light on the character and natural history of painful chronic pancreatitis, which has important clinical implications. In addition, several novel mutations have been described in the cationic trypsinogen gene in patients with hereditary pancreatitis. The mechanism by which these mutations cause pancreatic disease remains speculative. The diagnosis of early chronic pancreatitis is controversial. A novel noninvasive pancreatic function test (measurement of postprandial APOB-48) was reported but is unlikely to be a sensitive test of pancreatic function. Pancreatic fibrosis is frequently seen in alcoholics without chronic pancreatitis, and this makes it difficult to interpret the findings on endoscopic ultrasonogram. Recent studies highlight the difficulty in abolishing pancreatic steatorrhea. Recently fibrosing colonopathy in adult patients has been reported. Extracorporeal shockwave lithotripsy combined with endoscopic therapy failed to benefit patients with calcific chronic pancreatitis.

AGA technical review on the epidemiology, diagnosis, and treatment of pancreatic ductal adenocarcinoma. American Gastroenterological Association.

This literature review and the recommendations therein were prepared for the American Gastroenterological Association Clinical Practice and Practice Economics Committee. The paper was approved by the Committee in March 1999 and by the AGA Governing Board in May 1999.

Early and late onset in idiopathic and alcoholic chronic pancreatitis. Different clinical courses.

In summary, a prerequisite for the development of alcoholic pancreatitis would be the specific individual predisposition present in patients with late-onset idiopathic chronic pancreatitis. Furthermore, because the reported prevalence of chronic pancreatitis in patients with heavy alcohol consumption is markedly higher than the prevalence of late-onset idiopathic pancreatitis in the general population, the authors conclude that, in predisposed patients, alcohol consumption promotes the development of pancreatitis and accelerates the manifestation of symptoms and complications. This concept explains the observation that only a minority of severe alcoholics develop chronic pancreatitis. Conversely, in postmortem studies, a substantial proportion of older individuals without premortem evidence of pancreatic disease and no excessive alcohol history have pancreatic morphologic alterations resembling chronic pancreatitis. Thus, in the general population, a considerable number of asymptomatic "carriers," together with an undetected high prevalence of late-onset idiopathic chronic pancreatitis, may exist. In these persons, alcohol consumption might amplify and accelerate preexisting asymptomatic idiopathic pancreatic damage. As a consequence, in a dose-dependent manner, alcohol may lead to an earlier onset of or induce clinically apparent pancreatitis in persons who otherwise might never have had symptoms during their lives.

Pancreatic cancer: clinical presentation, pitfalls and early clues.

The diagnosis of pancreatic cancer usually depends upon symptoms; consequently it is late when there is no chance for cure. At this point, pain, anorexia, early satiety, sleep problems and weight loss are present. Back pain also may be prominent, which predicts unresectability and shortened survival after resection. However, earlier recognition of symptoms of pancreatic cancer might improve early detection of the cancer. For example, 25% of patients have symptoms compatible with upper abdominal disease up to 6 months prior to diagnosis and 15% of patients may seek medical attention more than 6 months prior to diagnosis. These symptoms erroneously may be attributed to problems such as irritable syndrome. Symptoms, however, may be less common. For example a quarter of patients with pancreatic cancer may have no pain at diagnosis, and half, particularly those with pancreatic head tumors, may have little pain compared with patients with body-tail tumors. However, if the tumor is suspected because of predisposing conditions, earlier diagnosis may be possible. These conditions include diseases such as chronic pancreatitis, intraductal papillary mucinous tumor (IPMT), and recent onset of diabetes mellitus, particularly if the diabetes occurs during or beyond the sixth decade. In addition inherited syndromes also are associated with an increased risk of pancreatic cancer including familial pancreatic cancer, hereditary pancreatitis, familial adenomatous polyposis syndrome (FAP) and familial atypical multiple mole melanoma (FAMMM) syndrome (hereditary dysplastic nevus syndrome). Of these conditions, recent onset of diabetes may be the best clue and should be included in a clinical profile of patients prior to the onset of symptoms to identify a high-risk group to apply screening strategies for detection of early disease. Contrary to a clinical aphorism that pancreatic cancer patients are elderly, lean and recently may have developed diabetes, we found that patients who develop pancreatic cancer are overweight prior to onset of symptoms compared to controls (body mass index, 28 vs 25). Forty percent had the diagnosis of diabetes made at the time of diagnosis of pancreatic cancer and more patients with a resectable tumor had diabetes (58%) compared to patients with locally unresectable or metastatic disease (37%). Perhaps, screening overweight persons who have new-onset diabetes may lead to a diagnosis of asymptomatic, early, resectable pancreatic cancer.

Effect of prolonged intraluminal alpha-amylase inhibition on eating, weight, and the small intestine of rats.

Effects of chronic intraluminal amylase inhibition on eating and the digestive system are unclear. In growing rats, we determined the effect of ingesting a wheat amylase inhibitor (AI) on eating, weight, small intestinal mucosal growth, and disaccharidases. Three groups of 12 rats received AI, were pair-fed controls (PFC), or had free access to food (FAC). After measuring food intake and body and stool weight for 21 d, rats were decapitated and the small intestine was divided into four segments. AI and PFC rats had similar food intake, weight gain, and stool output, but these were less than FAC rats (P < 0.005). AI rats ate less (P < 0.001) than PFC during the light cycle and less than FAC rats during darkness. Mucosal DNA and RNA were reduced (P < 0.05) in the upper small intestine of AI and PFC rats compared with FAC rats. Mucosal weight, RNA, and disaccharidase activities were greater (P < 0.01) in the ileum of AI rats compared with PFC and FAC rats. AI alters the amount and pattern of food intake, reduces weight gain, upper small intestinal mucosal weight, protein and DNA, and increases distal small intestinal mucosal weight, RNA, and disaccharidases. AI likely causes these effects by inducing satiety and increasing carbohydrate delivery to the distal intestine.