Clinical significance of the tests used in the diagnosis of pancreatic diseases

Different methods available for investigating patients for pancreatic disease are discussed. They first include measurement of pancreatic enzymes in biological fluids. Basal amylase and/or lipase in blood are truly diagnostic in acute pancreatitis but their utility is low in chronic pancreatic diseases. Evocative tests have been performed to increase the sensitivity of blood enzyme measurement. The procedure is based on enzyme determination following administration of pancreozymin and secretin, and offers a valuable aid in diagnosis of chronic pancreatitis and cancer of the pancreas. They are capable of discerning pancreatic lesions but are not really discriminatory because similar changes are observed in both diseases. The measurement of urinary enzyme levels in patients with acute pancreatitis is a sensitive indicator of disease. The urinary amylase excretion rises to abnormal levels and persists at significant values for a longer period of time than the serum amylase in acute pancreatitis. The fractional urinary amylase escretion seems to be more sensitive than daily urinary measurement. The pancreatic exocrin function can be assessed by examining the duodenal contents after intravenous administration of pancreozymin and secretin. Different abnormal secretory patterns can be determinated. Total secretory deficiency is observed in patients with obstruction of excretory ducts by tumors of the head of the pancreas and in the end stage of chronic pancreatitis. Low volume with normal bicarbonate and enzyme concentration is another typical pattern seen in neoplastic obstruction of escretory ducts. In chronic pancreatitis the chief defect is the inability of the gland to secrete a juice with a high bicarbonate concentration; but in the advanced stage diminution of enzyme and volume is also evident. Diagnostic procedures for pancreatic diseases include digestion and absorption tests. The microscopic examination and chemical estimation of the fats in stool specimens in different conditions of intake are still important screening tests. Isotopic estimates of steatorrhea and distinction between labeled triolein and oleic acid absorption do not provide greater diagnostic discrimination than traditional procedures. 131I labeled proteins permit a good evaluation of a negative nitrogen balance. Sophisticated procedures to estimate exocrine pancreatic insufficiency are based on the study of endoluminal digestive processes at several times and different level of the small intestine. They permite esclusion of extrapancreatic factors interfering in digestion and absorption functions. The endocrin pancreatic function is evaluated by mean of oral tolerance test an radioimmunoassay of blood insulin. It is generally agreed that "diabetes" caused by insulin deficiency and digestion and absorption defects are the result of diffuse pancreatic destruction. Many methods are now available investigating patients with pancreatic disease but the single use of one of them is never satisfactory...     

Endoscopic therapy of chronic pancreatitis

BACKGROUND/AIMS: Endoscopic therapy of chronic obstructive pancreatitis is an indubitable contribution to patients which brings immediate pain relief, enables an increased caloric food intake and improves the quality of patient's life. The authors describe their experience in a set of 42 subjects, in whom endoscopic papillotomy of the pancreatic duct was carried out after diagnosis of chronic obstructive pancreatitis. MATERIAL AND METHODS: Endoscopic papillotomy was performed in 42 patients. In 17 patients, papillotomy was followed by the drainage of the pancreatic duct. RESULTS: The treatment led to disappearance or significant decrease of the epigastric pain in 85.7% patients shortly after the treatment; in 47.1% of patients the painless period lasted for further 24 months after the therapy. Increase in body weight of about 2 kg occurred in 53% of treated subjects during the 2 years since the therapy. Complications in treatment, such as acute pancreatitis in 3 patients and bleeding in 2 were mastered conservatively. CONCLUSION: Endoscopic therapy of chronic pancreatitis is an alternative approach of managing the algic form of chronic obstructive pancreatitis. Changes in the area of Vater papilla, pathological content of pancreatic duct, structure or complications of chronic pancreatitis could be solved endoscopically with a minimum burden on patient. According to the experience of the authors, endoscopic papillotomy of pancreatic duct with contingent drainage led to the pain disappearence nearly in 50% of patients in the set of 42 subjects 24 months after the performance. This fact was followed with an increase in body weight in more than 50% of treated subjects. Minimum of complications put the endoscopic therapy among relatively safe and at the same time effective approach to chronic pancreatitis.     

Absence of K-ras mutations in the pancreatic parenchyma of patients with chronic pancreatitis

BACKGROUND: Human pancreatic cancers exhibit a high frequency of K-ras mutations. METHODS: In this study we used oligonucleotide specific hybridization to compare the frequency of K-ras mutations in genomic DNA samples prepared from 21 normal pancreatic tissues, 26 chronic pancreatitis tissues, and 24 pancreatic cancers. RESULTS: None of the DNA samples from normal or chronic pancreatitis tissues exhibited a K-ras mutation at codons 12 or 13 of K-ras. In contrast, 17 of 24 DNA pancreatic cancers harbored a K-ras mutation. Validity of the methodology was confirmed by genotyping 7 human pancreatic cancer cell lines. Analysis of focal areas of proliferation from 5 chronic pancreatitis and 5 pancreatic cancer samples processed by selective ultraviolet radiation fractionation (SURF), a procedure used to enrich DNA isolation from foci of proliferating cells, revealed complete concordance with total genomic DNA analysis. CONCLUSIONS: These findings indicate that the pancreatic parenchyma in patients with chronic pancreatitis most frequently does not possess a K-ras mutation.     

Retrograde pancreatography. Technical tips and spectrum of pathology

ERP is an important technique in the diagnosis of diseases involving the pancreatic ducts, in determining therapeutic strategy, and in assessing the results of surgical bypass procedures. ERP facilitates the diagnosis of the majority of pancreatic tumors at a stage when they normally present to the clinician. It assists the diagnosis of small tumors in the ampullary region at an early stage when other tests are negative. In cases of obscure recurrent pancreatitis, ERP may identify a mechanical cause (e.g., stone, stricture). ERP is useful in the diagnosis of CCP only in the precalcified stage. If histologic confirmation already has been obtained at surgery, ERCP is not required. Compared with noninvasive techniques, ERP provides additional information: It enables a concomitant examination of the gastroduodenal tract and opacification of the bile ducts; additional procedures may be performed, such as intraductal cytologic brushings, biochemical and cytologic analysis of pancreatic juice, endoscopic manometry, and pancreatoscopy. The diagnostic yield is increased if these procedures are performed during ERCP. Because ERP outlines the ductal anatomy, it is of great value in assessing therapeutic strategy. In cases of acute recurrent pancreatitis or chronic pancreatitis, ERP provides an important baseline for performing procedures such as ductal drainage and therefore reduces the inappropriate use of exploratory laparotomy. In cases of necrotic pancreatitis or pancreatic trauma, ERP enables accurate localization of a pancreatic fistula and facilitates any subsequent surgical procedure. Finally, ERP is the method of choice when assessing the patency of pancreatic-digestive anastomosis.     

Longitudinal changes of plasma pancreatic enzymes and hormones in experimental pancreatolithiasis in dogs

Plasma pancreatic enzymes and hormones were longitudinally observed after producing partial obstruction of the major pancreatic duct in dogs to study an initial state of chronic pancreatitis or pancreatolithiasis. Fasting plasma immunoreactive cationic trypsin was elevated during the first six months and then decreased in a subgroup with pancreatic calculi, marked fibrosis, or duct dilatation when compared with the corresponding opposite at the end of the 12-month period. Similar but less prominent changes were found in fasting plasma immunoreactive pancreatic polypeptide (IRPP). Plasma amylase, glucose, or immunoreactive insulin or glucagon (IRG) show no significant variation. Plasma IRG and IRPP responses to intravenous insulin were reduced in the subgroups with marked pancreatic changes towards the end of the 12-month period. These results suggest that plasma pancreatic enzymes and hormones remain elevated as long as pancreatic damage is mild and then start to decline as the damage progresses in chronic pancreatitis or pancreatolithiasis.     

Rupture of an abnormal pulmonary artery with a flow-directed pulmonary artery catheter

Most authors believe that biliary pancreatitis rarely progresses to chronic pancreatitis. Here, we present a case of an 18-yr-old white male with a history of gallstone pancreatitis and pancreatic pseudocyst resulting in radiographic and pathologic evidence of pancreatic calcification over a 16-mo period.     

Effect of oral protease inhibitor administration on gallbladder motility in patients with mild chronic pancreatitis

Oral administration of a protease inhibitor (camostat) induces pancreatic hypersecretion via hormonal and neural systems in humans. Camostat may also affect gallbladder motility via these systems. The aim of this study was to evaluate the effect of camostat on gallbladder function. Gallbladder emptying in response to caerulein administration and to egg yolk ingestion was examined ultrasonographically in 15 patients with mild chronic pancreatitis before and after 6 months of camostat treatment, and in 10 control subjects. The plasma cholecystokinin concentration after yolk ingestion was measured by radioimmunoassay. Fasting gallbladder volume and contractile function, whether stimulated by caerulein or yolk, did not differ between pancreatitis patients before camostat treatment and controls. Plasma cholecystokinin levels, basal and yolk-stimulated, did not differ between nontreated pancreatitis patients and control subjects. Fasting volume had decreased significantly by 1, 3, and 6 months of camostat treatment, while contractile function was not affected. Camostat did not influence plasma cholecystokinin levels. Oral administration of a protease inhibitor appears to decrease fasting gallbladder volume via a mechanism other than cholecystokinin release.     

Bayou virus-associated hantavirus pulmonary syndrome in Eastern Texas: identification of the rice rat, Oryzomys palustris, as reservoir host

OBJECTIVE: To validate the safety of gadolinium-diethylenetriamine pentaacetic acid (GD-DTPA) by measuring its effect on pancreatic capillary perfusion and acinar injury in acute pancreatitis. BACKGROUND: Contrast-enhanced computed tomography (CECT) is proposed as a gold standard for early evaluation of acute necrotizing pancreatitis. However, iodinated contrast media used for CECT have been shown in these circumstances to reduce pancreatic capillary flow and increase necrosis and mortality. Recent reports suggest that post-GD MRI provides images comparable to CECT in the assessment of severe acute pancreatitis. METHODS: Necrotizing pancreatitis was induced in 14 Wistar rats by intraductal glycodeoxycholic acid (10 mM/L) and intravenous caerulein (5 microg/kg/h) over 6 hours. Intravital microscopic quantitation of pancreatic capillary blood flow was performed using fluorescein isothiocyanate-labeled erythrocytes after induction of pancreatitis and 30 and 60 minutes after an intravenous bolus of either Ringer's solution or GD-DTPA (0.2 mL/kg). RESULTS: The two study groups were comparable with regard to mean arterial pressure, heart rate, arterial blood gases, hematocrit, amylase, lipase, and trypsinogen activation peptide production throughout the experiment. GD-DTPA did not reduce capillary flow (1.93 +/- 0.05 nL/capillary/min) compared to animals infused with Ringer's solution (1.90 +/- 0.06 nL/capillary/min). CONCLUSIONS: Intravenous injection of GD-DTPA does not further impair pancreatic microcirculation or increase acinar injury in acute necrotizing pancreatitis. Because of this advantage over CT contrast medium, further development of MRI as a staging tool in acute pancreatitis seems desirable.     

Effect of granulocyte colony-stimulating factor on the course of infection with gram-positive bacteria in mice during granulocytopenia induced by sublethal irradiation or cyclophosphamide

Ligation of the common bile-pancreatic duct induces hyperamylasemia and acute pancreatitis in rats. Pancreatic morphologic changes include edema, acinar cell damage, and mild inflammation. The pathogenesis of acute pancreatitis in this model is not understood, but may involve altered secretion and intrapancreatic activation of acinar proteases. We hypothesized that trypsinogen activation, measured by the production of plasma and pancreatic trypsinogen activation peptides (TAP), occurs early in this model. We performed the following experiments: rats were prepared with (1) bile-pancreatic ducts ligated and (2) ducts dissected but not ligated (sham). Rats were killed after 6, 24, and 48 hr. Serum amylase was measured and histologic sections were analyzed for morphologic changes. TAP was measured in both serum and pancreatic tissue homogenates using a specific polyclonal. anti-TAP antibody in an enzyme-linked immunosorbant assay. After 6, 24, and 48 hr of bile-pancreatic duct ligation, hyperamylasemia and acute morphologic changes of acute pancreatitis were observed. Evidence of acinar cell destruction was not evident until 48 hr after ligation. Levels of serum and pancreatic tissue TAP were significantly elevated at both 24 and 48 hr after ligation compared to those of sham. We conclude that increased intrapancreatic trypsinogen activation occurs early in this form of experimental acute pancreatitis and that it occurs prior to evidence of acinar cell destruction. These data and observations support the possibility that intrapancreatic protease activation contributes to the pathogenesis of ligation-induced acute pancreatitis.     

Transduodenal sphincteroplasty and transampullary septectomy for papillary stenosis

Twenty patients received transduodenal sphincteroplasty and transampullary septectomy between 1987 and 1993. Seven patients had post-cholecystectomy pain which was much improved or abolished in 5 of 7 patients at a mean follow-up of 4 years and 5 months. Four of five patients with chronic pancreatitis were improved at 3 years and 2 months. Three of five patients with recurrent acute pancreatitis were improved at 4 years and 5 months. One of three patients with chronic abdominal pain of hepatobiliary origin was improved at 3 years. Transduodenal sphincteroplasty and transampullary septectomy can relieve pain in patients with post-cholecystectomy pain, recurrent acute pancreatitis, chronic pancreatitis, and chronic abdominal pain of hepatobiliary origin, presumably by improving drainage of the obstructed ducts.     

Clinical effects of anticancer drugs to pancreatic diseases as protein synthesis inhibitors

The anticancer drugs, like 5-Fluorouracil, which are believed to interfere with enzyme protein synthesis in the exocrine cells of pancreas were administered intravenously to fifteen patients with various pancreatic diseases. The improvement of clinical symptoms and the diminution of serum and urinary amylase levels were observed in four cases with acute pancreatitis and two cases with chronic relapsing pancreatitis. The postoperative complications, namely the formation of pancreatic fistula and the rupture of pancreaticojejunostomy, or the aggravation of concomitant pancreatitis were not observed in three cases with benign surgical pancreatic diseases and six cases with pancreatic carcinoma. Furthermore, the diminution of amylase and protein output of pancreatic juice from canulae inserted into pancreatic ducts were observed.     

Chronic advanced pancreatitis--diagnosis, biochemical and ultrastructural changes and surgical procedures

On the basis of 162 cases of chronic advanced pancreatitis seen at our Department during the last 15 years the diagnosis, indications and surgical procedures are described in this paper. Quantitative and qualitative changes of pancreatic collagen in chronic inflammation were also analysed. Results of these investigations were compared with histological and ultrastructural pictures of pancreatic tissue. Amongst 162 patients, 142 (88%) were operated upon. 71 underwent pancreatectomy or pancreatoduodenectomy, 14 anastomotic procedures and rest of them various operation of the bile ducts. Overall, 18 (13%) patients experienced significant complications after resectional procedures and 6 (4%) died as well after anastomotic procedures.     

Peak oxygen uptake and maturation in 12-yr olds

OBJECTIVE: The purpose of this study is to report a new sign, "acinar filling," observed on dynamic MR pancreatography after secretin stimulation in patients with suspected early chronic pancreatitis. CONCLUSION: Acinar filling might reflect tissue hypertension or loss of pancreatic parenchyma compliance or both. This finding is probably an insensitive but specific sign of early chronic pancreatitis.     

The behavior of mucopolysaccharide in the pancreatic juice in chronic pancreatitis

In order to study whether or not mucosubstance increases occur in the pancreatic juice of patients with chronic pancreatitis, hexosamine was measured in duodenal aspirates during the secretin phase (S-40) following pancreozymin-secretin stimulation in 16 normal subjects, 37 patients with chronic pancreatitis, 6 patients with alcoholism, 13 patients with gallstones, and 11 patients with peptic ulcer. The hexosamine concentrations in the pancreatic secretions showed a negative correlation with the bicarbonate concentrations and volume output. Rises in hexosamine concentration were seen in alcoholism and chronic pancreatitis, especially in alcoholic pancreatitis. This is probably intimately related with the repeated ingestion of large amounts of alcohol over long periods of time. Since high hexosamine values are noted in the relapsing type of chronic alcoholic pancreatitis, increases in viscosity due to mucosubstance increases in the pancreatic juice are probably related with the recurrence of acute attacks accompanying ductal stenosis or obstruction.     

Novel post-replicative DNA modification in Streptomyces: analysis of the preferred modification site of plasmid pIJ101

BACKGROUND & AIMS: Chronic alcoholic pancreatitis occurs in only a limited number of heavy drinkers. Other factors than alcohol are necessary for the occurrence of chronic alcoholic pancreatitis. The aim of this study was to examine whether pancreatic duct obstruction resulted in increased alcohol-induced parenchymal cell damage. METHODS: Four groups of adult mongrel dogs were used. In group A, 2. 0 g . kg-1 . day-1 of ethanol was administered via a gastric cannula. In group O, after ligation of the minor pancreatic duct, a polyethylene tube was inserted transduodenally into the major duct. In group AO, the protocols used in groups A and O were combined. Laparotomy was repeated after 3 months in each group. RESULTS: Three of the 9 dogs in group AO had pancreatic calculi in the main pancreatic duct. Moderate interlobular fibrosis, parenchymal cell loss, and inflammatory cell infiltration resembling human chronic alcoholic pancreatitis were observed in group AO. Little change was observed in groups A and O. Exocrine function assessed by secretin test in group AO was significantly reduced. Total protein, hexosamine, and calcium contents of the pancreatic juice in group AO were significantly increased. CONCLUSIONS: Pancreatic duct obstruction is an aggravating factor in chronic alcoholic pancreatitis.     

Gallstone pancreatitis. Exploration of the biliary system in acute and recurrent pancreatitis

During a five-year period, 82 patients were treated for acute pancreatitis, 63 of whom were proved to have associated biliary tract disease. In 18 of the 63, the accepted preoperative diagnostic measures failed to demonstrate pathologic findings in the biliary system. In 16 of the 18 patients, stones were discovered at the time of operation, although in five they were so small as to be demonstrable only filtering the aspirated bile through gauze. In the two of the 18 without stones, cholecystitis was present. In 14 patients the ducts choledochus and the pancreatic duct had a common path. All patients had no further pancreatitis two to eight years cholecystectomy. In Israel, where alcoholism is rare, three fourths of the cases of acute pancreatitis are associated with gallbladder disease.     

Carbohydrate-based probes for detection of cellular lectins

Molecular mechanisms associated with apoptosis in pancreas remain largely unknown. Clusterin mRNA is induced in several tissues in response to most apoptotic stimuli. In these tissues, clusterin has an antiapoptotic activity. The aim of this work was to test whether clusterin, which is not expressed in normal pancreas, was induced in pancreas during pancreatitis and pancreatic development. Clusterin mRNA levels were strongly increased 6 h after pancreatitis induction. Maximal expression happened between 24-48 h and decreased progressively to undetectable levels at day 5. Clusterin mRNA was expressed with similar intensity in oedematous caerulein-induced pancreatitis and in response to various degrees of necrohaemorrhagic taurocholate-induced pancreatitis, indicating a maximal gene activity in all types of pancreatitis; in situ hybridization showed that the acinar cells and some ducts expressed clusterin mRNA. A single band of about 35-38 kDa was detected by western blot in pancreatic homogenates and in pancreatic juice from rats with acute pancreatitis, but not from control rats. Clusterin mRNA expression was strong in late fetal life and remains high until day 11 post-partum, then decreased progressively with a minimum from 35 to 90 days post-partum. Clusterin mRNA levels were strongly induced in pancreatic acinar AR4-2J cells in response to various apoptotic stimuli (i.e., cycloheximide, staurosporine, ceramide and H2O2) but not with interleukin (IL)-1, IL-4 or IL-6 or heat shock, which do not induce apoptosis in AR4-2J cells. In conclusion, we demonstrated that clusterin is synthesized and released by the pancreas. Its strong expression during acute pancreatitis suggests its involvement in the pancreatic response to injury. Clusterin is also induced during pancreatic development. Because these situations are associated with apoptosis and clusterin was shown to protect against apoptosis, we speculate that clusterin could be involved in the control of acinar cell apoptosis.     

Basic principles of surgical policy in complicated chronic pancreatitis

The paper presents some experience with surgical treatment of 183 patients with complicated forms of chronic pancreatitis. The type of a surgical intervention depended on the pattern of pancreatic morphological changes. Operations of internal drainage of the pancreas in 103 patients with ductal hypertension provide the largest percentage (92.4%) of good and satisfactory results. Resectional methods of surgical treatment for chronic pancreatitis (n = 36) without signs of intraductal hypertension and with the prevalence of predominant lesions in some portions of the gland yield 80% good and satisfactory results. The incidence of postoperative complications following pancreatic resections is higher than those after drainages (16.2 versus 11.6%). The paper gives a concept of combined operations on the pancreas and bile ducts in chronic pancreatitis complicated by stricture of the distal common bile duct, revealed in 24.4% of cases.     

The splice-pattern of CD44 is altered in chronic pancreatitis exhibiting dysplastic changes

Recent studies have shown that several splice variants of CD44, might be involved in tumor progression. Since chronic pancreatitis is suggested to be a risk factor for pancreatic cancer we investigated the splice pattern of CD44 in chronic pancreatitis to elucidate the role of CD44 in pancreas tumorigenesis. The expression of CD44-isoforms was examined in 40 specimens of chronic pancreatitis and 12 specimens of normal pancreas by immunohistochemistry, Westernblotting and exon specific RT-PCR. Pancreatic cancer tissue from two patients who developed pancreatic cancer 2 and 3 years following surgery for chronic pancreatitis were analyzed. Strong expression of CD44s was found in all cells, whereas the expression of CD44v6 was restricted to ductal cells. Westernblotting revealed an overexpression of CD44v6 in chronic pancreatitis as compared to normal pancreas. Exon specific analysis revealed an altered splice pattern of CD44, similar to that in pancreatic cancer, in 12.5% of the chronic pancreatitis specimens. Both patients who developed pancreatic cancer after chronic pancreatitis exhibited this altered splice pattern in both, chronic pancreatitis and pancreatic cancer. These results suggest that variant forms of CD44-mRNA might be expressed in early dysplastic alterations in chronic pancreatitis.     

Are complication rates for elective primary total hip arthroplasty in Ontario related to surgeon and hospital volumes? A preliminary investigation

Eleven specimens of chronic submandibular sialadenitis were examined. A reduction in secretory material in acinar cells was seen with increasing atrophy until the acini resembled intercalary ducts. Myoepithelial cells and basement membrane were sometimes more conspicuous. Striated ducts showed a reduction of the folding of the plasma membranes in the basal part, and striated and excretory ducts showed a reduction in mitochondria. This possibly represents a functional atrophy secondary to reduced salivary flow. Very atrophic parenchyma largely consisted of simple cells. Phagosomes and apoptotic bodies were occasionally seen, and appear to be involved in the atrophy. Thiamine pyrophosphatase in the Golgi apparatus and acid phosphatase in the GERL were demonstrated in moderately atrophic parenchyma. This is similar to normal and indicates continuing synthetic activity. Acid phosphatase was demonstrated in lysosomes, which appear to be involved in the atrophy by their role in phagy. Alkaline phosphatase was occasionally demonstrated at luminal surfaces, and is likely to be involved in resorption of obstructed luminal contents. The changes are similar to those seen in experimentally obstructed glands and indicate that much of the parenchyma survives by adaptation to the altered environment which forms the basis for the successful results following conservative therapy.