Postoperative pancreatitis, hyperamylasemia and amylase isoenzymes after parathyroidectomy for primary hyperparathyroidism

Recent studies have cast doubt on the concept of causative association between parathyroidectomy for primary hyperparathyroidism and postoperative pancreatitis. The present study indicated that the relationship was real and that the development of acute pancreatitis after parathyroid surgery was not purely incidental. Acute pancreatitis was observed postoperatively in 3 p. 100 of cases after parathyroidectomy (6/196 cases), in 37 p. 100 after pancreatic surgery (19/51 cases), but never after thyroidectomy (100 cases) or other extra-abdominal operations (100 cases). During the first five postoperative days, the incidence of hyperamylasemia was 16 p. 100 after parathyroidectomy, 47 p. 100 after pancreatic surgery, 3 p. 100 after thyroidectomy, 2 p. 100 after other extra-abdominal operations. During the same period, the frequency of hyperlipasemia was similar: 20 p. 100 after parathyroidectomy, 54 p. 100 after pancreatic surgery, 1 p. 100 after thyroidectomy, 0 p. 100 after other extra-abdominal operations. In all cases with hyperamylasemia after parathyroidectomy, the pancreatic fractions of amylase isoenzymes were abnormally elevated.     

Comparison of serum amylase pancreatic isoamylase and lipase in patients with hyperamylasemia

We compared results of measurements of total serum amylase, pancreatic isoamylase, and lipase measurements in patients with hyperamylasemia. Serial measurements of these three enzyme levels in patients recovering from acute pancreatitis indicated that pancreatic isoamylase and lipase were elevated above normal to a greater extent and remained elevated much longer than did the total amylase. This finding indicates an appreciable sensitivity advantage of the pancreatic isoamylase and lipase over total amylase measurement during the recovery phase of pancreatitis. Comparison of pancreatic isoamylase and lipase levels in selected sera indicated a good correlation (r=0.84) between these two measurements in patients who did not have macroamylasemia. Lipase was normal in sera with amylase elevations due solely to salivary isoamylase. Thus, in nonmacroamylsemic sera, pancreatic isoamylase and lipase appear to be roughly interchangeable markers of the level of pancreatic enzymes in the blood. An advantage of the lipase assay is that this enzyme is normal in hyperamylasemia caused by macroamylasemia, whereas the inhibitor assay indicates that the pancreatic isoamylase is elevated. Development of automated assays for either pancreatic isoamylase or lipase should lead to the routine use of one of these assays in place of the present reliance on total amylase measurements in the diagnosis of pancreatitis.Supported by Veterans Administration Research Funds and National Institutes of Health grant 13309-15.     

Serum apolipoprotein A-I in alcoholic patients with chronic calcifying pancreatitis

Serum apolipoprotein A-I measurement was compared in alcoholic patients according to presence or absence of chronic pancreatitis and liver fibrosis. Among alcoholic patients without liver disease, apolipoprotein A-I was significantly lower in patients with chronic pancreatitis (157 +/- 70 mg/dl) than in patients without pancreatitis (209 +/- 74 mg/dl, p less than 0.001). In cirrhotic patients, apolipoprotein A-I was lower in patients with chronic pancreatitis (82 +/- 35 mg/dl) than in patients without pancreatitis (102 +/- 45 mg/dl), but this difference was not significant. The decrease of serum apolipoprotein A-I was independent of nutritional parameters whether or not there was cirrhosis. Immunohistochemical study of pancreatic samples with chronic pancreatitis showed that apolipoprotein A-I was located in the pancreatic fibrosis whereas lobules were unstained. This study suggests that apolipoprotein A-I is trapped by the pancreatic extracellular matrix and that this sequestration might explain, in part, the decrease of the serum apolipoprotein A-I.     

Serum cytokine profiles in patients with pancreatic cancer and chronic pancreatitis

BackgroundChronic pancreatitis (CP) may cause tumor-like lesions, creating a challenge in distinguishing between CP and pancreatic ductal adenocarcinoma (PDAC) in a patient. Given that invasive surgery is a standard cancer treatment, we aimed to examine whether a noninvasive diagnostic tool utilizing serum cytokines could safely differentiate between PDAC and CP.MethodsA pre-operative serum panel comprising 48 inflammatory cytokines, CA19-9, and C-reactive protein (CRP) was analyzed, consisting of 231 patients, 186 with stage I–III PDAC and 45 with CP. We excluded PDAC patients who underwent neoadjuvant therapy and those CP patients with other active malignancies. The laboratory variables most associated with PDAC diagnosis were assessed using logistic regression and selected using the lasso method.ResultsThe cytokines CTACK, GRO-α, and β-NGF were selected alongside CA19-9 and CRP for our differential diagnostic model. The area under the curve (AUC) for our differential diagnostic model was 0.809 (95% confidence interval [CI] 0.738–0.880), compared with 0.791 (95% CI 0.728–0.854) for CA19-9 alone (not significant).ConclusionsWe found that inflammatory cytokines CTACK, GRO-α, and β-NGF alongside CA19-9 and CRP may help distinguish PDAC from CP.     

Prolonged hyperamylasemia following acute pancreatitis

Summary A case of prolonged hyperamylasemia of record length following typical acute pancreatitis of idiopathic etiology is presented, and 40 cases from the literature are summarized. The observed relationship of exacerbations to generalized premenstrual edema bears further study. The apparent benign nature and final spontaneous resolution is demonstrated by the patient's excellent health for the subsequent 4 years, with no evidence of relapse or pancreatic insufficiency.The incidence of prolonged hyperamylasemia approximated 3.4% of cases of acute pancreatitis. It is more likely to occur in patients with chronic alcoholism or biliary tract disease than in those with idiopathic pancreatitis. Two-thirds of reported cases were managed medically, and one-third with definitive surgery. Although prolonged hyperamylasemia frequently indicates a complication of acute pancreatitis, it does not yield the high fatality rate one would expect.I am indebted to Dr. Gordon McHardy, and to Dr. Henry L. Bockus for their incomparably experienced counseling with respect to the late clinical course of this patient, and to Dr. David A. Dreiling for suggestions contributing to the preparation of this paper.     

Use of amylase isoenzymes in laboratory evaluation of hyperamylasemia

Amylase isoenzyme analysis by agarose gel electrophoresis and lipase concentration by radioimmunoassay were performed in 98 consecutive hyperamylasemic patients. Total pancreatic (P-type) isoamylase was elevated in 89% of patients with clinical evidence of pancreatitis, and in only 11% of those without pancreatitis. Of 43 patients in whom the clinical diagnosis was obscure, 44% demonstrated an increase in pancreatic amylase and three (7%) had an increase in salivary (S-type) amylase. Lipase concentration by radioimmunoassay correlated well with lipase activity (r=+0.69,P<0.05) and was as effective as amylase isoenzymes in distinguishing patients felt likely to have pancreatitis from those who were unlikely. Amylase isoenzymes or serum lipase concentration may be useful tests in the laboratory evaluation of hyperamylasemia when the etiology is obscure.Supported by a grant from the Office of Consolidated Laboratory Services, Rush Medical Center.     

Detection of painless pancreatitis by computed tomography in patients with post-endoscopic retrograde cholangiopancreatography hyperamylasemia

ObjectivesPost-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is diagnosed on the basis of pancreatic pain and hyperamylasemia. However, because the diagnosis of abdominal pain is not objective, there may be some cases of painless pancreatitis among patients with post-ERCP hyperamylasemia (PEH). We reviewed the computed tomography (CT) findings of PEH cases to determine the incidence of painless pancreatitis.MethodsBetween July, 2005 and December, 2011, CT was performed in 91 patients with hyperamylasemia 18 h after ERCP. We reviewed the CT findings and graded the severity of pancreatitis according to the Balthazar grading system. Grades C, D, and E were defined as pancreatitis.ResultsThirty-four patients (37%) had pancreatitis according to the CT findings. There was a significant difference in the serum amylase levels between the positive- and negative-CT finding groups (1306 ± 833 vs. 786 ± 315 IU/L, respectively; p = 0.0012). Receiver operating characteristic curve analysis showed that the amylase cut-off value for discriminating between the 2 groups was 795 IU/L (6.36 times the upper normal limit).ConclusionsThirty-seven percent of PEH patients had painless pancreatitis. CT is useful to determine pancreatitis in patients taking analgesics, steroids, or anti-immunological drugs and those with diabetes mellitus and 18-h serum amylase levels of >6 times the normal upper limit.     

Pancreatic and salivary amylase/creatinine clearance ratios in normal subjects and in patients with chronic pancreatitis.

The clearance of pancreatic and salivary amylase relative to creatinine was measured in 26 control subjects and 22 patients with chronic pancreatitis. Control values for pancreatic amylase clearance (+/- SD) were 2.64 +/- 0.86% compared with 1.54 +/- 0.95% for salivary amylase. In chronic pancreatitis, pancreatic amylase clearance ratios were significantly higher than controls (P less than 0.0005, mean 4.09 +/- 1.63 SD). The difference in clearance rate of salivary amylase did not reach a level of significance when compared with the control group. Twelve of the 22 patients showed pancreatic amylase clearance values above the normal limit of 4.4, while only five were abnormal when the clearance of total amylase was measured. The patients also showed statistically higher (P less than 0.0005) levels of serum salivary amylase when compared with 69 control sera. No such difference was found for the pancreatic component of serum amylase. Comparison of beta2-microglobulin clearance values showed no statistical difference between patients and controls.     

Serum levels of interleukin-1β and interleukin-6 in patients with chronic pancreatitis

To investigate the role played by cytokines in chronic pancreatitis, we examined serum levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6) by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) in 33 patients with definitively diagnosed chronic pancreatitis. All the patients, who had received either no treatment or only digestive enzyme products for their chronic pancreatitis, had significantly elevated serum IL-1β levels (38.5±28.8pg/ml, mean ± SD), compared to normal controls (16.0±6.7pg/ml;P<0.01); however they showed no changes in serum IL-6 levels. Changes in IL-1β and IL-6 serum levels were not correlated with the etiological features of pancreatitis or with complications due to liver diseases. Serum IL-1β and IL-6 levels were also not correlated with the activity of any pancreatic enzymes in blood or urine. However, in the patients with chronic pancreatitis, serum IL-6 levels were correlated with C-reactive protein (CRP), whereas serum IL-1β levels were not correlated with CRP or with erythrocyte sedimentation rate. These results suggest that serum IL-1β is involved in the progression and reduction of chronic inflammation of the pancreas, and that the serum IL-1β level may be useful as a marker for chronic pancreastitis.     

Prevalence of normal serum amylase levels in patients with acute alcoholic pancreatitis

Acute alcoholic pancreatitis is uncommonly diagnosed when the serum amylase level is normal. We defined acute alcoholic pancreatitis as a clinical syndrome in which hyperamylasemia was not a necessary component and sought support for the diagnosis by ultrasonography and computed tomography of the pancreas. In 68 episodes of acute alcoholic pancreatitis identified in a one-year period, the serum amylase level was normal at the time of hospital admission in 32%. In 40 episodes, we performed ultrasonography and computed tomography within 48 hr of admission. The diagnosis was supported by ultrasonography in 43%, by computed tomography in 68%. Ultrasonography and computed tomography supported the diagnosis as frequently in patients with normal serum amylase levels as in patients with hyperamylasemia. We conclude that patients with acute alcoholic pancreatitis frequently have normal serum amylase levels. The widespread clinical practice of relying solely on hyperamylasemia to establish the diagnosis of acute alcoholic pancreatitis is unjustified and should be abandoned.     

Serum endocannabinoids in assessing pain in patients with chronic pancreatitis and in those with pancreatic ductal adenocarcinoma

Background: The endocannabinoid system plays a substantial role in analgesia.

Aim: To analyze N-arachidonoylethanolamine (AEA), N-oleoylethanolamine (OEA), linoleoyl ethanolamide (LEA), α-linoleoyl ethanolamine (α-LNEA), N-palmitoylethanolamine (PEA) and N-stearoyl ethanolamine (SEA) in two groups of patients having chronic pancreatic diseases.

Patients and methods: Twenty-six patients with chronic pancreatitis, 26 patients with pancreatic ductal adenocarcinoma and 36 healthy subjects were studied. The visual analogic scale (VAS) was used for assessing pain immediately before the venipuncture to obtain blood in all subjects. Six endocannabinoids were measured in serum of the patients enrolled.

Results: Only OEA, LEA and PEA serum levels were significantly higher in patients with pain as compared to those without. Using the cutoff values, the sensitivity and specificity of the various endocannabinoids in evaluating pain in patients with chronic pancreatitis and in those with pancreatic ductal adenocarcinoma were: 44.2% and 95.6% for AEA, 83.7% and 73.3% for LEA, 88.4% and 91.1% for LNEA, 81.4% and 82.2% for OEA, 81.4% and 88.9% for PEA, 86.0% and 88.9% for SEA, respectively.

Conclusion: Endocannabinoids are not useful in assessing pain in patients with chronic pancreatic diseases and they cannot replace a simple method such as VAS for assessing the pain and its intensity.     

Serum trypsinogen in diagnosis of chronic pancreatitis

A new radioimmunoassay to serum trypsinogen (Cis Trypsik) was tested in several patient populations. A low serum trypsinogen level (<10 ng/ml) was found in 69.2% of 13 patients with chronic pancreatic insufficiency (CPI), in 100% of 10 patients with 95–100% pancreatectomy but only in 14% of 14 patients with cancer of the pancreas. A low trypsinogen level was not found in any of 68 control subjects or 10 patients with nonpancreatic steatorrhea. Nine patients with CPI or 95% pancreatectomy were retested a mean of six months after initial testing. Four of these nine (44.4%) had a significant variation in serum trypsinogen which would have led to a different diagnostic interpretation (two went from low to normal levels and two from normal to low levels). A mixed meal had little effect on serum trypsinogen levels in five of six patients with CPI, and pancreatic enzyme replacement therapy had no consistent effect on the serum trypsinogen level in seven patients with CPI or 95% pancreatectomy. It is speculated that minor subclinical episodes of focal pancreatitis may effect the serum trypsinogen level. Although there can be considerable variability using this assay, it still offers important clinical utility. A low trypsinogen level points to a chronic pancreatic process with excellent specificity. A normal trypsinogen level is of no help and should be repeated if clinical suspicion of chronic pancreatitis remains high.     

Zinc deficiency in patients with chronic pancreatitis

BACKGROUND Zinc is a key element in numerous proteins and plays an important role in essential cell functions such as defense against free radicals and DNA damage repair. Chronic pancreatitis(CP) is a chronic inflammation with progressive fibrosis of pancreas ultimately resulting in pancreatic exocrine insufficiency(PEI),which is associated with malnutrition. Studies analyzing zinc levels in patients with CP are sparse and lead to conflicting results.AIM To investigate serum zinc levels in patients with CP of various etiologies.METHODS Between October 2015 and March 2018, patients with a diagnosis of CP were identified and recruited from the Pancreatic Outpatient Clinic at the Karolinska University Hospital in Stockholm, Sweden. Demographic, clinical and laboratory data were analyzed. Etiology of CP was determined according to the MANNHEIM classification system into the following etiological subcategories:alcohol consumption, nicotine consumption, hereditary factors, efferent pancreatic duct factors and immunological factors. Pancreatic exocrine function was defined as normal(fecal elastase 1 > 200 μg/g), mildly reduced(100-200μg/g) and severely reduced(fecal elastase 1 < 100 μg/g).RESULTS A total of 150 patients were included in the analysis. Zinc deficiency(< 11μmol/L) was present in 39(26.0%) of patients: 22 females and 17 males. In the group of patients with zinc deficiency, 76.7% of patients had an exocrine pancreatic insufficiency(FE-1 < 200 μg/g). Older age was significantly associated with low zinc levels. Following a univariate analysis, patients aged 60-69 and patients ≥ 70 years of age had a significantly higher prevalence of zinc deficiencies compared to patients < 40 years of age [OR: 3.8, 95%CI(1.08-13.4); P= 0.04]; [OR 6.26, 95%CI(1.94-20.2), P > 0.002]. Smoking and number of packyears were additionally associated with low zinc levels. The risk of zinc deficiency in current smokers and smokers with ≥ 20 pack-years was approximately three times higher compared to those who had never smoked.Gender, body mass index, etiology of CP, presence of diabetes mellitus, levels of glycated hemoglobin(HbA1 c), bone mineral density, alcohol intake and presence of PEI were not associated with low zinc levels.CONCLUSION Zinc deficiency is common in patients with CP and is significantly associated with age ≥ 60, smoking and the number of pack-years, but not with PEI.     

Lipase/amylase ratio in biliary acute pancreatitis and alcoholic acute/acutized chronic pancreatitis

BACKGROUND: Alcoholic or biliary acute pancreatitis may need different therapeutic approaches. AIM: Assessing the validity of lipase/amylase ratio in differentiating biliary from alcoholic acute pancreatitis/acutized chronic pancreatitis. METHODS: Nine male patients (mean age and standard deviation: 39.8 +/- 7.0 years) with alcoholic acute pancreatitis/acutized chronic pancreatitis (group I) and 29 patients, 8 male and 21 female (mean age: 43.6 +/-19.9 years), with biliary acute pancreatitis (group II) were evaluated. Serum lipase and amylase levels were measured in patients with symptoms for no more than 48 hours. The lipase/amylase ratio was calculated based on serum lipase and amylase levels and expressed as multiples of their respective superior reference values. RESULTS: Mean levels of serum lipase (4,814 +/- 3,670 U/L) and amylase (1,282 +/- 777 U/L) in patients of group I were comparable to group II (2,697 +/- 2,391 and 1,878 +/- 1,319 U/L, respectively), but the mean lipase/amylase ratio was significantly higher in group I (4.4 +/- 3.6) than in group II (2.2 +/- 2.2). Lipase/amylase ratio >3 occurred at significantly higher proportions in patients of group I (66.7%) than of group II (24.1%), differentiating the two groups with sensitivity of 67% and specificity of 76%. CONCLUSIONS: 1) Amylase and lipase serum levels did not differ in the two groups evaluated; 2) the lipase/amylase ratio >3 was more often seen in alcoholic acute pancreatitis/acutized chronic pancreatitis than biliary acute pancreatitis, and it may be useful in differentiating these two causes of pancreatitis.