Paul Georg Lankisch

Pancreatitis and the Risk of Pancreatic Cancer

Background The results of case-control studies and anecdotal reports suggest that pancreatitis may be a risk factor for pancreatic cancer, but there have been no studies of sufficient size and power to assess the magnitude of the relation between these two diseases. Methods and Results We undertook a multicenter historical cohort study of 2015 subjects with chronic pancreatitis who were recruited from clinical centers in six countries. A total of 56 cancers were identified among these patients during a mean (±SD) follow-up of 7.4 ±6.2 years. The expected number of cases of cancer calculated from country-specific incidence data and adjusted for age and sex was 2.13, yielding a standardized incidence ratio (the ratio of observed to expected cases) of 26.3 (95 percent confidence interval, 19.9 to 34.2). For subjects with a minimum of two or five years of follow-up, the respective standardized incidence ratios were 16.5 (95 percent confidence interval, 11.1 to 23.7) and 14.4 (95 percent confidence interval, 8...

Natural course in chronic pancreatitis : pain, exocrine and endocrine pancreatic insufficiency and prognosis of the disease

The natural course of the classical symptoms of chronic pancreatitis, i.e. pain, exocrine and endocrine pancreatic insufficiency, was followed up in 335 patients over a median of 9.8 years (mean 11.3 +/- 8.3 years). Pain relief was not obtained in the majority of patients, even after a longterm observation of > 10 years, and severe exocrine and/or endocrine insufficiency, severe duct abnormalities and pancreatic calcifications developed. Alcohol abstinence failed to have a significant beneficial effect on pain. Pancreatic surgery led to pain relief immediately after operation, but later on the pain course between operated and nonoperated patients was not significantly different. Repeated exocrine pancreatic function tests in 143 patients showed that functional exocrine impairment came to a standstill (46%), or improved (11%). At the end of the observation, 22% of 335 patients still had normal endocrine function and only 40% required insulin treatment. Alcohol abstinence had a significant beneficial effect on endocrine, but not on exocrine pancreatic insufficiency. Chronic pancreatitis led to a sharp increase in unemployment and retirement. Pancreatic carcinoma occurred in 3% and extrapancreatic carcinoma in 4%. The mortality rate within the observation period was 22%, pancreatitis-induced complications accounted for 13% of these deaths.

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.

Acute pancreatitis in five European countries: etiology and mortality.

Introduction In recent years, many advances have been made in the diagnosis and treatment of acute pancreatitis that have lead to a significant reduction in both morbidity and mortality; however, knowledge of the etiology and of the relation between etiology and mortality is far from complete. Aim To obtain a more comprehensive view of the etiology and mortality of acute pancreatitis in Europe than has been given by previous single-center studies. Methodology The study comprised 1,068 patients in five European countries who were admitted to hospitals for acute pancreatitis from January 1990 to December 1994. Data for each patient were collected on a standardized form. Results Of the 1,068 patients (692 men, 376 women; mean age, 52.8 years; range, 10–95 years), 589 had edematous pancreatitis, and 479 the necrotic form. Cholelithiasis (37.1%) and alcohol (41.0%) were the most frequent etiologic factors. In Germany, cholelithiasis and alcohol occurred with similar frequency (34.9 and 37.9%, respectively); in Hungary, alcohol predominates over cholelithiasis (60.7 vs. 24.0%); in France, a small predominance of alcohol was seen (38.5 vs. 24.6%); and in Greece and Italy, there was a clear predominance of cholelithiasis over alcohol (71.4 vs. 6.0% and 60.3 vs. 13.2%, respectively). The differences in the frequency of cholelithiasis and alcohol between Greece and Italy and the other countries were statistically significant (p < 0.01). Eighty-three patients (7.8%) died of acute pancreatitis; 77 (16.1%) had necrotic disease and 6 (1.0%) edematous. There was no statistically significant difference in mortality among the etiologic groups, and no relation was found between mortality and age. Conclusion Both cholelithiasis and alcohol were main etiologic factors in the more northern countries studied, whereas cholelithiasis alone predominated in the more southern ones. Mortality was high for necrotic pancreatitis; it was similar among the various etiologic groups, and there was no relationship between mortality and age.

Natural history of acute pancreatitis: a long-term population-based study.

OBJECTIVES:It is unknown whether after an initial attack of acute pancreatitis, the inflamed gland heals completely, or whether and under what circumstances the disease progresses to chronic pancreatitis. Therefore, the aim of this study was to investigate the progression of disease from acute to chronic pancreatitis.METHODS:During a 20-year period, 532 patients who were hospitalized after an initial attack of acute pancreatitis were followed up for an average of 7.8 years (range: 1 day to 19.7 years). We used the Kaplan–Meier method to study the frequency of recurrent attacks of pancreatitis, subsequent development of chronic pancreatitis, and all-cause mortality during the follow-up period in patients with pancreatitis due to different causes.RESULTS:During the follow-up period, recurrent pancreatitis developed in 88 (16.5%) patients. The annual relapse rates were 5.3, 1.5, 0.6, and 1.9/100 per year in patients with acute pancreatitis due to alcohol, gallstones (biliary), and other identified causes of unknown origin (idiopathic), respectively. Chronic pancreatitis developed only in alcoholics, independent of the severity of the first attack and also of discontinuation of alcohol and nicotine consumption. The cumulative incidence of chronic pancreatitis was 13% in 10 years and 16% in 20 years. After surviving a second attack, the incidence of chronic pancreatitis increased distinctly to 38% after only 2 years of follow-up. Smoking significantly enhanced the risk of progression from acute to chronic alcoholic pancreatitis.CONCLUSIONS:The progression from acute to chronic pancreatitis occurred only in alcoholics. In this group, a substantial number of patients developed chronic pancreatitis in a short period of time after surviving a second attack of acute pancreatitis. Both alcohol consumption and smoking at this time are risk factors for the transition from acute to chronic pancreatitis.

Epidemiology of Pancreatic Diseases in Lüneburg County

Background/Aims: Worldwide, the incidence of pancreatic cancer is very well known, that of acute pancreatitis and chronic pancreatitis not. Our study sought to determine the incidence of all three pancreatic diseases in a well-defined population in Germany. Methods: Records of all patients treated for acute (first attacks only) and chronic pancreatitis as well as pancreatic cancer from 1988 to 1995 and who resided in the county of Lüneburg were evaluated. Results: The crude incidence rates for acute pancreatitis, chronic pancreatitis and pancreatic cancer per 100,000 inhabitants/year were 19.7, 6.4, and 7.8. In acute and chronic pancreatitis the male gender dominated, whereas in pancreatic carcinoma the gender ratio was almost even. Peak incidence for acute pancreatitis was in the age group of 35–44 years, for chronic pancreatitis 45–54, and for pancreatic cancer 65–75. Etiology of acute pancreatitis was biliary in 40%, alcohol abuse in 32%, unknown in 20%, and other in 8% of the patients. In chronic pancreatitis alcohol abuse was the etiology in 72% and unknown (idiopathic) in 28%. Conclusion: For the first time, epidemiological data obtained in a well-defined German population are being published relating to all three pancreatic diseases: acute pancreatitis (incidence rate, etiology and severity), chronic pancreatitis (incidence rate and etiology), and pancreatic carcinoma (incidence rate). A peak incidence of chronic pancreatitis occurring in an age group 10 years older than the peak age group for acute pancreatitis suggests that chronic pancreatitis develops during this time-frame following first attacks of acute pancreatitis.

Hemoconcentration: an early marker of severe and/or necrotizing pancreatitis? A critical appraisal.

OBJECTIVE:A study was designed to reevaluate hemoconcentration as an early marker of severe and/or necrotizing pancreatitis and compare it against contrast-enhanced CT, the gold standard to diagnose acute necrotizing pancreatitis.METHODS:This prospective study covers the years 1988–1999 for 316 patients (202 male, 114 female) with a first attack of acute pancreatitis. The role of the hematocrit as an early marker of severe and/or necrotizing pancreatitis has been retrospectively evaluated against the prospectively obtained data. They all underwent a CT within 72 h after admission. In addition to the CT-controlled diagnosis of interstitial/necrotizing pancreatitis, the following variables were used to assess severity: initial organ failure according to the Atlanta classification; indication for artificial ventilation and/or dialysis; Ranson score adjusted for etiology; Imrie score; Balthazar score; length of stay in intensive care unit (ICU); total hospital stay; development of pancreatic pseudocysts; indication for operation (necrosectomy); and mortality. Hemoconcentration on admission was defined as a hematocrit level >43.0% for male and >39.6% for female patients. Logistic regression was used to assess the correlation between hemoconcentration and the severity of variables.RESULTS:Hematocrit, as a single parameter measured on admission, had the same sensitivity and negative predictive value as the more complicated Ranson and Imrie scores obtained only after 48 h. However, its specificity, positive predictive value, and total accuracy were lower. Hemoconcentration significantly correlated with the Balthazar score (differential diagnosis between interstitial and necrotizing pancreatitis), stay in ICU, and total hospital stay. Sensitivity and specificity of the hematocrit cut-off level of 43.0% for male and 39.6% for female patients to detect necrotizing pancreatitis were 74% and 45%, respectively. The positive predictive value was 24% and the negative predictive value 88%. Receiver operation characteristics (ROC) curve values for several cut-offs did not result in more ideal levels.CONCLUSION:Hemoconcentration does not significantly correlate with important clinical outcome variables of acute pancreatitis including organ failure and mortality rate. Its prognostic value is comparable to the more complicated Ranson and Imrie scores obtained only after 48 h. The major value of this single easily obtainable and cheap parameter on admission lies in its high negative predictive value. In the absence of hemoconcentration, contrast-enhanced CT may be unnecessary on admission unless the patient does not improve.

Fatal Outcome in Acute Pancreatitis: Its Occurrence and Early Prediction

Background/Aims: This study aims to determine predictability of death in acute pancreatitis at a secondary-care hospital in Germany. Methods: This study is part of an ongoing study on the epidemiology of acute pancreatitis and covers 368 patients with a first attack of acute pancreatitis in Lüneburg county from 1988 to 1999. Early and late mortality were defined as ≤1 weeks and >1 week after admission. The following parameters were used to establish on admission likelihood of death: admission within 24 h or later with an acute attack, abdominal tenderness, signs of peritonitis, amylase and lipase in serum, leukocytes, hematocrit, potassium, sodium, calcium, creatinine after rehydration, blood glucose, bilirubin, serum glutamate-oxalacetate transaminase (SGOT), serum lactate dehydrogenase (SLDH), arterial pO2, APACHE II score, Ranson and Imrie scores. Results: Of the 368 patients 17 (5%) died, 7 early because of multiple organ failure and 10 late because of septic complications. Mortality rates in interstitial and necrotising pancreatitis were 3 and 17%, respectively. Only an elevated serum creatinine (>2.0 mg/dl) and a blood glucose >250 mg significantly correlated with mortality. Ranson and Imrie scores were also significantly correlated with mortality; however, they were not obtained on admission, but only after 48 h. In univariate analysis, APACHE II score ≧6 on admission and lipase >1,000 U/l on admission provided a high sensitivity and negative predictive value for early and late mortality patients. Conclusion: Approximately half of the deaths in acute pancreatitis occur because of multiple organ failure or septic complications. New approaches have to be found to counteract these severe complications. A fatal outcome may be predicted by simple laboratory parameters such as a high serum creatinine and blood glucose. An APACHE II score ≧6 and a lipase level on admission ≧1,000 U/l indicate severe pancreatitis.

Underestimation of acute pancreatitis: patients with only a small increase in amylase/lipase levels can also have or develop severe acute pancreatitis

BACKGROUND In most treatment studies on acute pancreatitis, pancreatologists base their diagnosis on amylase/lipase levels more than three times above the upper limit of normal (>3n) and thus exclude patients with smaller enzyme level increases. The recommendations derived from the results of treatment studies do not take into account such patients. Non-pancreatologists frequently believe that only patients with high enzyme levels have a serious prognosis. AIMS To question the assumption that high enzyme levels indicate severe, and conversely low enzyme levels indicate mild, acute pancreatitis. PATIENTS/METHODS This retrospective study includes 284 consecutive patients with a first attack of acute pancreatitis. The cause was biliary in 114 (40%) patients, alcoholism in 83 (29%), other in 21 (7%), and unknown in 66 (23%). Patients were divided into two groups according to their serum enzyme levels (amylase: ⩽3n, n = 88; >3n, n = 196; lipase: ⩽3n, n = 51; >3n, n = 233). Renal impairment, indication for dialysis and artificial ventilation, development of pseudocysts, necessity for surgery, and mortality were taken as parameters of severity. RESULTS The incidence of severity was the same for both the ⩽3n and >3n groups. CONCLUSIONS The severity of acute pancreatitis is independent of the elevation in serum amylase/lipase level (⩽3n or >3n) on admission. Patients with only a slight increase can also have or develop severe acute pancreatitis. Patients with ⩽3n elevated enzyme levels on admission represent a substantial group that treatment studies have frequently overlooked. This is especially true for patients with alcohol induced acute pancreatitis whose amylase levels are lower than in other aetiological groups.

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.