Exocrine pancreatic function in patients with end-stage renal disease.

AIM: malnutrition is a common problem in patients with end-stage renal disease (ESRD). Several studies showed 30 years ago that more than half of patients with ESRD suffered from exocrine pancreatic insufficiency. However, the studies never investigated whether the functional impairments led to morphological changes of the pancreas or to steatorrhea and thus indicating the need for lifelong pancreatic enzyme substitution. Our goal was therefore not only to establish the frequency but also the severity of exocrine pancreatic insufficiency in hemodialysis patients. METHODS: the study included 50 hemodialysis patients with no history of acute or chronic pancreatitis or upper abdominal symptoms of uncertain origin. All patients with hyperthyroidism, status post-gastrectomy or (partial) small bowel resection, or chronic inflammatory bowel disease were excluded. In all 50 patients, fecal elastase-1 was determined using two different methods (Bioserv Diagnostics and ScheBo Biotech) and fecal fat content and fecal weight were measured. RESULTS: mild to moderate exocrine pancreatic insufficiency (elastase-1 100 - 200 microg/g stool) was found in 10% of patients. It was not correlated with age, sex, and underlying renal disease, duration of hemodialysis, or diarrhea and steatorrhea. In no patient was the enzyme content < 100 microg/g stool, i.e., it never sank to a level at which pancreatic enzyme substitution would have been recommended. Nine patients (18%) had mild diarrhea (200 - 300 g stool/ day), and 10 (20%) had mild steatorrhea (7 - 15 g fat/day in the stool). Five patients had both diarrhea and steatorrhea. CONCLUSIONS: mild to moderate but not severe exocrine pancreatic insufficiency is not infrequent in patients on hemodialysis but unlikely to be responsible for malnutrition in ESRD. Non-pancreas-related steatorrhea is also not uncommon. This finding requires further analysis because steatorrhea might influence nutrition, thus potentially opening the way to new therapeutic approaches.

Acute and chronic pancreatitis. An update on management.

Therapeutic measures for acute pancreatitis depend on the severity of the disease and its complications. Since complications of acute pancreatitis may develop at any time, patients should be admitted to an intensive care unit for assessment (and frequent reassessment) of the severity of the disease and the development of complications. Basic therapy should include relief of pain, total fasting, nasogastric suction, parenteral replacement of fluids, electrolytes, albumin and blood, and antibiotics. Hyperglycaemia should be corrected and heparin should be given in cases of disseminated intravascular coagulation. In renal insufficiency, peritoneal dialysis is important, and in respiratory complications, humidified oxygen or artificial ventilation including positive and expiratory pressure therapy should be applied. Although the effect of peritoneal dialysis has been proven only in animal experiments and in retrospective studies in man, it is recommended in severe cases for shock therapy and for correction of electrolyte imbalance when ascites is present, even before anuria occurs. Conservative treatment measures in chronic pancreatitis are limited to the management of pain and of exocrine and endocrine pancreatic insufficiency.

Increased body weight as a prognostic parameter for complications in the course of acute pancreatitis.

To evaluate whether obesity is a negative prognostic parameter in the course of acute pancreatitis, we examined 149 patients and divided them into four weight groups. Single (methemalbumin) and multiple (Ranson's signs) prognostic parameters were found to be independent of increased body weight in all groups, although the incidence of patients with more than six Ranson's signs or a positive methemalbumin test was highest in the most obese group. There was also no direct positive correlation between increased body weight and the incidence of mortality and late complications such as pseudocysts and abscesses. However, when compared with patients of normal weight, the obese groups showed a slight increase in the incidence of early complications such as shock and renal insufficiency and a significant increase in respiratory insufficiency necessitating artificial ventilation. Thus, increased body weight was associated with increased incidence of early extrapancreatic complications.

Acute pancreatitis and hyperamylasaemia in pancreatic carcinoma.

To determine the incidence of acute pancreatitis in pancreatic carcinoma, a retrospective study was performed in 174 patients. Acute pancreatitis was found in 24 (13.8%), and hyperamylasaemia, but no clinical manifestation of acute pancreatitis, was found in 17 (9.8%) of these patients. The incidence of acute pancreatitis was higher when the papilla of Vater or the head of the pancreas was involved. Clinically, pancreatitis was slight to moderate, and the underlying disease was soon diagnosed with invasive procedures. Pancreatic carcinoma should be considered an etiological factor in patients with relapsing and/or unexplained pancreatitis of long duration.

Publication rates following pancreas meetings.

Publication rates and determinants of publication were studied based on abstracts presented at pancreatic meetings. All abstracts presented at the 1994 and 1995 annual meetings of the European Pancreatic Club (EPC) and the American Pancreatic Association (APA) were followed up by searching MEDLINE. Publication rates were compared using log-rank tests and multiple logistic regression. The prestige of the publishing journals was compared using Kruskal-Wallis tests on scientific impact factors (SIF). Overall, 340 abstracts were presented at the EPC, and 254 were presented at the APA. Of these, 203 (59.7%, EPC) and 138 (54.3%, APA) were later published in peer-reviewed journals. Publication rates did not differ by study type or country region of origin. In addition, median SIFs were similar by conference (APA vs. EPC) and research type (basic science vs. clinical studies) (overall, 1.7). However, North American and North/West European articles were published in higher impact journals as compared with those from other countries. Publication rates and median journal SIFs in pancreas research are similar to those reported from other medical specialty meetings. There is no difference by conference, type of research, or origin (North American vs. European).

No parallel between the biochemical course of acute pancreatitis and morphologic findings.

The clinical, biochemical (serum enzymes), and morphologic course of acute pancreatitis was studied in 83 consecutive patients from time of admission until 3 months after discharge. At discharge, all 75 surviving patients had no more symptoms of acute pancreatitis, even though amylase (in 11%) and lipase (in 25%) were still elevated, computed tomography (CT) findings still abnormal (in 81%), and necrosis amounting up to 50% of the gland still present (in 24%). There was no significant correlation between serum enzymes and CT findings at discharge. Three months later, with the exception of one patient with an acute relapse of the disease, all followed-up patients were free of symptoms and had normal serum amylase, whereas lipase was still elevated in 10%, and CT findings abnormal in 23%. Subsiding symptoms provided a more accurate picture of the patients' recovery than the biochemical markers, and even more so that the morphologic findings.

No strict correlation between necrosis and organ failure in acute pancreatitis.

The aim of this study was to determine the relationship between pancreatic necrosis and organ failure in acute pancreatitis. Two hundred seventeen patients with acute pancreatitis were prospectively included. All of them had been examined by computed tomography (CT) within 72 hours of admission. Initial organ failure was defined according to the Atlanta classification (arterial pO2 <60 mm Hg, serum creatinine >2 mg/dL after rehydration). Organ failure during the total hospital stay was defined as necessity for artificial ventilation and/or dialysis treatment, independent of initial organ failure. One hundred seventy-five (81%) patients had interstitial and 52 (19%) necrotizing pancreatitis. Forty-two (19%) had initial organ failure and 54 (25%) organ failure during the total hospital stay. There was a significant correlation between the incidence of initial pancreatic necrosis and initial organ failure as well as initial pancreatic necrosis and organ failure during hospital stay (p < 0.001). However, 24 (57%) of the 42 patients with pancreatic necrosis had no initial organ failure, and 19 (45%) no organ failure during hospital stay, and vice versa, 24 (14%) patients had initial and 31 (18%) organ failure during the total hospital stay in the absence of pancreatic necrosis. Initial organ failure and organ failure during the total hospital stay were independent of the extent of pancreatic necrosis. The incidence of initial organ failure and organ failure during the total hospital stay increased significantly with the CT score (p < 0.001). However, 24 (15%) and 31 (18%) of the patients with interstitial pancreatitis had initial organ failure and organ failure during the total hospital stay, respectively. Patients with pancreatic necrosis are not necessarily at risk of having initial organ failure or organ failure during the total hospital stay and vice versa. Thus, these groups should be considered separately in therapy studies.

The calendar and acute pancreatitis.

To find out whether a seasonal pattern exists for acute pancreatitis, the weekday and month of admission were retrospectively checked for 263 patients admitted to our hospital from 1987 to 1995 with their first attack of this disease. Etiology was biliary in 105 (40%), alcoholic in 84 (32%), unknown in 54 (21%), and presumed to be other in 20 (7%) patients. Forty-two (16%) patients had necrotizing acute pancreatitis. There was no significant correlation between admission and a specific month or weekday. Furthermore, there was no significant correlation between the etiology or onset of symptoms and a specific weekday. In contrast to other gastroenterological diseases such as peptic ulcer and inflammatory bowel disease, there is no seasonal or weekly pattern for acute pancreatitis.

Acute pancreatitis: which patient is most at risk?

This prospective study aimed to pinpoint acute pancreatic patients who are at a higher risk of clinical deterioration. Once identified, they can be given more costly intensive-care therapy or transferred promptly to hospitals with specialized equipment. Our study included 217 patients with acute pancreatitis. All of them underwent computed tomography within 72 h of admission. Initial organ failure was defined according to the Atlanta classification (arterial pO2, < or = 60 mm Hg; serum creatinine, > 2 mg/dl after rehydration). Forty-two (19%) of the 217 patients had initial organ failure, and 13 (31%) of these deteriorated (i.e., 10 of them needed artificial ventilation, and three, dialysis treatment). Deterioration of initial organ failure was significantly more frequent in alcohol- than in non-alcohol-induced acute pancreatitis (p = 0.005). One hundred seventy-five (81%) patients had no initial organ failure, and 12 (7%) of these deteriorated. All needed artificial ventilation, and two of them dialysis treatment also. There was no significant correlation between etiology and deterioration in these patients. Patients with alcohol-induced acute pancreatitis and initial organ failure represented a major group at risk and should be closely monitored or transferred to specialized units, whereas patients without initial organ failure have a lower risk of later developing organ failure and usually do not need intensive care.

Painless acute pancreatitis mimicking pancreatic carcinoma.

Painful acute pancreatitis masking pancreatic carcinoma and painless acute pancreatitis with shock or coma as leading symptoms have been described before. We report a first case of almost-painless pancreatitis mimicking pancreatic carcinoma with spontaneous normalization of symptoms and biochemical as well as imaging procedure findings.

Acute pancreatitis: induced by heroin intoxication?

Hyperamylasemia has been reported in heroin addicts and ascribed to an increase of salivary isoamylase. Ours is the first report on acute pancreatitis in a heroin user. All prognostic parameters indicating a severe course of the disease were present, and computed tomography showed an edematous pancreatitis, but the acute pancreatitis took a benign clinical course.

Xanthine oxidase inhibitor in acute experimental pancreatitis in rats and mice.

It has been suggested that oxygen-derived free radicals play a decisive role in the pathogenesis of acute experimental pancreatitis in a model of edematous pancreatitis. Accordingly, allopurinol, a xanthine oxidase inhibitor, was shown to mitigate the development of nonfatal acute pancreatitis in ex vivo perfusion models using dogs. For further evaluation of allopurinol, its effect was studied in two forms of fatal necrotizing acute experimental pancreatitis: sodium taurocholate-induced pancreatitis in rats and choline-deficient ethionine-supplemented diet-induced pancreatitis in mice. Allopurinol did not affect the mortality rate, pancreatic enzyme elevation in serum and ascites, the enzyme content of the pancreas, or any parameter indicating histopathological damage in the pancreas. Although these experiments did not determine the role oxygen-derived free radicals play in the development of pancreatitis, they show, none the less, the absence of any beneficial therapeutic effect of a xanthine oxidase like allopurinol on the development of the disease once it has begun.

The course of pain is the same in alcohol- and nonalcohol-induced chronic pancreatitis.

The natural course of pain in chronic pancreatitis was followed up in 318 patients over 10.6 +/- 8.0 years (median, 9.0 years). By the end of our follow-up, a significant decline in pain in alcoholics (n = 228) and nonalcoholics (n = 90) (p < 0.001 and p < 0.03) was marred by the fact that, even after more than 10 years, 50% of alcoholics and 62% of nonalcoholics still reported pain attacks (difference insignificant). Only alcoholics had pain relief with increasing exocrine pancreatic insufficiency (p < 0.02), but 54% of alcoholics and 73% of nonalcoholics still had pain attacks despite severe, enzyme substitution-requiring exocrine pancreatic insufficiency. The development of severe endocrine pancreatic insufficiency did not significantly influence the course of pain. It is concluded that no clinically relevant differences exist in the course of pain in alcoholic and nonalcoholic chronic pancreatitis.

Secretin-pancreozymin test (SPT) and endoscopic retrograde cholangiopancreatography (ERCP): both are necessary for diagnosing or excluding chronic pancreatitis.

Results of the SPT and the ERCP staged for their severity were compared in 202 patients. The correlation between both investigations was significant (p < 0.001); however, ERCP showed significantly more severe changes (p = 0.04). Furthermore, we found that 129 (64%) patients had parallel SPT and ERCP results, matching in all four gradings of severity. Forty-three (21%) patients had abnormal results for both SPT and ERCP, but the severity gradings did not parallel. Finally, 30 (15%) patients showed totally nonparallel results, a normal SPT and abnormal ERCP, or vice versa. Abnormal ERCP but normal SPT results were found in 23 of these 30 patients (group 1), and normal ERCP but abnormal SPT results in the seven remaining cases (group 2). In the first group, more patients had a history of acute pancreatitis compared to the second group (19 vs. one, p < 0.005). Based on medical history, laboratory and functional test results, and other morphological tests, chronic pancreatitis was diagnosed in two of 23 patients in group 1 and in all seven patients in group 2. Follow-up interviews (86 +/- 54 months) were possible in 20 of the remaining 21 patients in group 1 and showed definite chronic pancreatitis in one and probable chronic pancreatitis in another two of them, whereas in the other 17 patients no symptoms of acute pancreatitis or abdominal pain suggestive of chronic pancreatitis had occurred. In conclusion, both SPT and ERCP should be used to complement each other when chronic pancreatitis is suspected. ERCP seems to over-diagnose the disease since duct changes may only reflect scars after severe acute pancreatitis, or old age, and are not necessarily a sign of chronic pancreatitis. SPT seems to diagnose chronic pancreatitis with more reliability.

Etiology and age have only a limited influence on the course of acute pancreatitis.

In a retrospective study of 602 patients with a first attack of acute pancreatitis, it was investigated whether the etiology of the disease and age of the patient are negative factors. There was no significant difference concerning hospital stay, respiratory and renal insufficiency, indication for surgery, or mortality rate among the different etiological groups. However, pancreatic pseudocysts developed significantly more frequently in alcoholics than in patients with other etiologies (p < 0.001 to p = 0.007). There was also no difference concerning hospital stay and respiratory insufficiency among the age groups. The increased incidence of renal insufficiency probably is related to physiological alteration with age, but the indication for dialysis did not increase. Pancreatic pseudocysts were more frequent in patients between 31 and 40 years of age, which was also the peak age group of alcoholics. Indication for surgery was the same for all age subgroups. The increase in mortality rate with age was weakly significant (p = 0.049). For the etiological subgroups, an increase in mortality with age was found only for biliary pancreatitis patients (p = 0.003). It is concluded that etiology and age of the patient have only limited influences on the course of acute pancreatitis.

The problem of diagnosing chronic pancreatitis.

High alcohol consumption in Europe makes it necessary to consider chronic pancreatitis when a patient with history of alcohol abuse presents with abdominal pain. Diagnosis should be made on the basis of imaging procedures and function tests. A scoring system for this, together with a short evaluation of the present diagnostic procedures, are presented.

Progression from acute to chronic pancreatitis: a physician's view.

Whether or not AP may progress to the chronic form is controversial. Equally debatable is whether AP caused by alcohol abuse develops in a chronically diseased gland or in a normal pancreas. As for the state of the gland, several postmortem studies have shown that AP may occur after acute alcohol abuse in the normal pancreas. As for progression from acute to chronic pancreatitis, many experimental studies have demonstrated signs of the chronic from of the disease in animals, but these signs were reversible. Some clinical studies have shown that alcohol-induced pancreatitis may progress to chronic pancreatitis. There are, however, presently no predictive parameters indicating when such a progression does or does not occur.

Experimental model for peritoneal dialysis in small laboratory animals.

A simple method of performing peritoneal dialysis in rats and guinea-pigs for 48 hours is described. The method appears to be suitable for the experimental investigation of clinical problems although the long term problem of protein loss should not be forgotten when assessing the results of these short term experiments.