Identification of immunoreactive pancreatic stone protein in pancreatic stone, pancreatic tissue, and pancreatic juice

We first examined whether pancreatic stone protein (PSP) was present in pancreatic stone and normal pancreatic tissue. By using HPLC and Western blotting, a protein of Mr 13.5 kDa that reacted with monoclonal antibody against PSP was detected as a major component in EDTA-soluble fractions of pancreatic stone. In an in vitro experiment, this protein dose-dependently suppressed CaCO3 precipitation. PSP was immunohistochemically stained in the acinar cells of normal pancreatic tissue. Based on these findings, it seemed that PSP in pancreatic stone is probably a physiological secretory protein of the pancreas. We subsequently examined immunoreactive PSP in normal pancreatic juice by the Western blotting method. In all of the specimens, the band for immunoreactive PSP in pancreatic juice was found to correspond to 13.5 kDa, which thus agreed with that of purified PSP from a stone.     

Interdigestive canine pancreatic juice composition and pancreatic reflux and pancreatic sphincter anatomy

Canine and human exocrine pancreatic secretion into the duodenum during fasting is cyclical and related to intestinal motility. To characterize the composition of pure pancreatic juice during the cyclically recurring sequence of propagated motor events (interdigestive motor complex) and to establish whether pancreatic reflux occurs, dogs were prepared with three permanent indwelling duodenal catheters and a pancreatodochal cutaneous catheter. The duodenal catheters were used to record duodenal pressures and measure pancreatic secretion of trypsin, lipase, and bicarbonate, based on the recovery of a constantly perfused marker, [¹⁴C]PEG. Pancreatic duct pressures or pancreatic juice concentrations of [¹⁴C]PEG, trypsin, lipase, or bicarbonate (done separately in each of five dogs throughout one interdigestive cycle on 4 different days) were related to duodenal motor activity. Finally, the pancreatic duct orifice of freshly sacrificed dogs was examined by light and electron microscopy. During fasting, (1) pancreatic volume secretion increased 10-fold during phases II, III, and IV (P<0.001), and bicarbonate concentration increased during phases III and IV (P<0.05) compared with phase I, while trypsin and lipase concentrations did not change; (2) reflux of duodenally perfused [¹⁴C]PEG into the pancreatic duct occurred in two of five dogs and was minimal (<0.1%); and (3) a positive mean pressure gradient from duodenum to pancreatic duct occurred only during phase III (7.4±4.1 cm H₂O). Anatomic studies of the pancreatic duct opening showed a specialized papillary mucosa and an independent crescentic sphincter muscle. We conclude that during fasting, pancreatic juice composition is intimately linked to the different phases of interdigestive intestinal motor activity and that an efficient antireflux mechanism exists.Supported in part by contract CP 55660 and grant CA 25064 from the National Institutes of Health, U.S. Public Health Service, Bethesda, Maryland.     

Serum pancreatic stone protein in pancreatic diseases

Summary Serum pancreatic stone protein (PSP) was determined in sera of pancreatic and nonpancreatic diseases using enzyme immunoassay specific to human PSP to study the diagnostic and pathophysiological significance of PSP. Serum PSP in acute pancreatitis (mean±SD=1075.4±2849.1 ng/mL,n=33) was significantly higher than that in controls (78.6±31.8 ng/mL,n=37,p<0.01), chronic pancreatitis (156.8±82.8 ng/mL,n=32,p<0.05), and pancreatic cancer (148.468.8 ng/mL,n=26,p<0.05). No significant difference was found between noncalcified and calcified chronic pancreatitis. Serum PSP levels were significantly higher in chronic renal failure under hemodialysis (1796.0±1492.9 ng/mL) than in other diseases such as peptic ulcer, liver cirrhosis, gallstone, and diabetes mellitus. Low but significant correlation was obtained between serum PSP and serum immunoreactive trypsin (r=0.22,p<0.05). Increased serum PSP levels in acute pancreatitis and chronic renal failure suggest that serum PSP levels reflect reflux from pancreatic secretion, release from damaged pancreatic acinar cells, or retention in circulation, and can be useful for diagnosis of acute pancreatitis, but not chronic calcified pancreatitis.     

Solitary pancreatic tuberculosis mimicking advanced pancreatic carcinoma

A 40-year-old woman was referred for pancreatic head carcinoma invading the portal vein. The dichotomy between the radiological findings and the general condition of the patient, as well as the laboratory results (no evidence of cholestasis), cast doubt on the diagnosis. There was no history of tuberculosis. The chest radiograph revealed no pathological findings. The anatomic relationships of the lesion entailed a high risk of vascular injury if tissue biopsy were to be done; therefore, diagnostic laparotomy was performed. Biopsy revealed granulomas with caseous necrosis, consistent with tuberculosis. After 6 months of antituberculosis treatment, the lesions had completely resolved. Tuberculosis should be considered in the differential diagnosis of pancreatic masses, particularly in regions where the disease is endemic. The condition usually resembles an advanced pancreatic tumor. Performing a biopsy of inoperable lesions and maintaining a reasonable skepticism in regard to the evaluation of operable lesions (attention to nonexclusive but helpful clues, such as young patient age, history of tuberculosis, absence of jaundice) will lead to the diagnosis in most patients. Diagnostic laparotomy may be required in a small subset of patients. The response to antituberculosis treatment is very favorable. The role of resection (e.g., pancreatoduodenectomy) is very limited.     

Endoscopic pancreatic stenting in pancreatic cancer.

Most pancreatic carcinomas are unresectable at the time of diagnosis; therefore, palliative treatment is very often the main concern of clinicians in this setting. The main symptoms resulting in the need for palliation in pancreatic cancer are obstructive jaundice, duodenal obstruction and pain. Therapeutic endoscopy plays a major role in the palliation of obstructive jaundice by stent placement into the biliary ducts. Initial experience has also been gained recently with endoscopic placement of expandable metallic stents to treat gastric outlet obstruction. Much less is known about the possible role of endoscopic pancreatic stenting in patients with unresectable pancreatic carcinoma. The main indication for pancreatic ductal stenting is 'obstructive' pain related to meals in patients with dilated main pancreatic duct beyond the stricture and intraluminal brachyradiotherapy. The technique of endoscopic pancreatic stenting does not substantially differ from that applied on the biliary tree. When technically possible, placement of 10 French plastic stents is preferred. According to the authors' indications, only about 15% of patients with advanced pancreatic cancer (55 of 355 in the present study) may potentially benefit from this technique. Pancreatic stenting may be obtained in more than 80% of these selected patients, with low morbidity (less than 10%) and no procedure-related mortality. According to the authors of the present and other studies reported in the literature, about 60% of patients treated because of 'obstructive' pain become symptom-free, and another 20% to 25% significantly reduce the amount of analgesic drugs required. Intraluminal brachyradiotherapy with 192iridium in the main pancreatic duct is a feasible and safe method to deliver high radiation doses to the tumour while sparing adjacent organs. Brachyradiotherapy may be performed alone or in conjunction with external beam radiotherapy. Because of the small number of patients suitable for this treatment, only a multicentre study will be able to detect whether intraluminal brachyradiotherapy in pancreatic cancer may have any positive impact on survival.     

Immunoneutralization of circulating pancreatic polypeptide and pancreatic secretion

To determine the role of endogenous pancreatic polypeptide (PP) as a physiological inhibitor of pancreatic secretion, normal rabbit serum (control) or rabbit PP-antiserum was administered intravenously to dogs with chronic esophageal, gastric, and pancreatic fistulas. In all dogs tested, sham-feeding and ordinary feed with a meat meal resulted in a marked rise in the plasma level of immunoreactive PP that coincided with an increase in the exocrine pancreatic secretion of HCO3- and protein. After intravenous administration of PP antiserum, endogenous plasma PP was almost completely bound by infused antibodies to PP, whereas no such binding was detected after infusion of normal rabbit serum. In contrast, plasma gastrin remained unchanged both under basal and stimulated conditions. Immunoneutralization of PP, released endogenously, failed significantly to affect gastric acid and pancreatic protein responses to sham-feeding and the pancreatic HCO3- and protein responses to feeding a meat meal in chronic pancreatic fistula dogs. However, the PP antiserum abolished, in part, the inhibitory effect of exogenous PP on pancreatic secretion stimulated by exogenous hormones. We conclude that endogenous PP is not a physiological inhibitor of exocrine pancreatic secretion, as has been suggested previously.     

Serum pancreatic isoamylase activity in pancreatic disease.

The diagnostic value of serum amylase determination for pancreatic disease has been questioned due to its lack of specificity. Several methods have been developed to separate the tissue-unspecific salivary fractions from the tissue-specific pancreatic fractions. Agarose or cellulose acetate gel electrophoresis are most suitable for clinical practice. The isoamylase patterns were studied by agarose electrophoresis in 55 patients with known pancreatic diseases (acute pancreatitis, pancreatic pseudocysts, exocrine pancreatic insufficiency and pancreatic carcinoma). Increased P-type isoamylase seems to be more sensitive than total amylase in diagnosing acute pancreatitis, while identification of the minor isoamylase P3 is more specific and could have a prognostic value. Detection of low P-type isoamylase levels is an easy method to diagnose exocrine pancreatic insufficiency. Furthermore, a group of patients with pancreatic disease (Pa), was compared with a group of patients with biliary disease without clinical evidence of pancreatic involvement (Bi), and patients with abdominal pain, without evidence of biliary or pancreatic disease (Ab). More than half of the Bi patients presented with abnormal P isoenzyme patterns, whereas 72% of the Ab patients had a normal pattern. Only P3 could distinguish between the Bi and Ab group. This might point to pancreatic involvement in patients presenting with biliary disease, only detected by isoamylase analysis.     

Endoscopic pancreatic duct stenting to treat pancreatic ascites

BACKGROUND: Management of pancreatic ascites with conservative medical therapy or surgery has met with limited success. Decompression of the pancreatic ductal system through transpapillary stent placement, an alternative strategy, has been reported in only a handful of cases of pancreatic ascites. METHODS: We reviewed all cases from 1994 to 1997 in which patients with pancreatic ascites underwent an endoscopic retrograde pancreatogram documenting pancreatic duct disruption with subsequent placement of a transpapillary pancreatic duct stent. Clinical end points were resolution of ascites and need for surgery. RESULTS: There were 8 cases of pancreatic ascites in which a 5F or 7F transpapillary pancreatic duct stent was placed as the initial drainage procedure. Pancreatic ascites resolved in 7 of 8 patients (88%) within 6 weeks. Ascites resolved in the eighth patient, a poor candidate for surgery, following placement of a 5 mm expandable metallic pancreatic stent. No infections, alterations in ductal morphology, or other complications related to stent placement were noted. There was no recurrence of pancreatic ascites or duct disruption at a mean follow-up of 14 months. CONCLUSIONS: Our experience doubles the number of reported cases in which transpapillary pancreatic stent placement safely obviated the need for surgical intervention in the setting of pancreatic ascites. This therapeutic endoscopic intervention should be seriously considered in the initial management of patients with pancreatic ascites.     

Relationship between pancreatic secretion and pancreatic blood flow

An indicator fractionation technique using radioactive rubidium has been used to measure pancreatic blood flow after infusions of secretin, pancreozymin, urecholine, and pentagastrin.Secretin resulted in the production of a large volume of low viscous pancreatic juice and was associated with an increase in the cardiac output. Duodenal and pancreatic blood flow and perfusion rate were increased significantly. Blood flow to the remainder of the gastrointestinal organs was only marginally increased but the perfusion rate in each organ was increased significantly.Infusion of pancreozymin, urecholine, and pentagastrin resulted in the output of a small volume of viscous juice and was associated with no increase in cardiac output but with an increase in both pancreatic blood flow and perfusion rate.     

Serum pancreatic secretory trypsin inhibitor in pancreatic diseases

To elucidate the diagnostic significance of serum pancreatic secretory trypsin inhibitor (PSTI) in pancreatic diseases, organ distribution of PSTI and abnormalities in serum PSTI were studied. The pancreas showed the highest content of PSTI, which was five times that of the stomach and almost 40 times that of the other organs. Serum PSTI and amylase were elevated in eight patients with acute pancreatitis, 27 and 11 patients of 47 with chronic pancreatitis, 31 and 13 of 36 with pancreatic cancer, and 67 and 62 of 109 with non-pancreatic disease, respectively. PSTI levels were more sensitive to the presence of pancreatic disease than were amylase levels. The specificities in serum of healthy controls and patients with non-pancreatic disease were similar for PSTI and amylase (69% vs 71%). In chronic pancreatitis and pancreatic cancer patients the efficiency of the PSTI assay was higher (P < 0.02) than the amylase assay (67% vs 63% for pancreatitis and 71% vs 66% for cancer). The sensitivity and efficiency of serum PSTI assay in chronic pancreatic diseases were superior to those of amylase.     

胰腺星状细胞与胰腺癌的相互关系

胰腺癌是一种恶性程度极高的消化系肿瘤,其生长速度快、转移早,对放射和化学治疗不敏感.胰腺癌重要的病理特征是癌组织周围有大量以成纤维细胞、胶原和纤维黏连蛋白等结缔组织聚集.目前已有文献报道,活化的胰腺星状细胞在其中起着重要的作用:更有研究认为,胰腺星状细胞在胰腺癌的发生、发展和转移中亦可能起到一定的作用.本文就胰腺星状细胞和胰腺癌细胞之间的相互关系及其在胰腺癌发展和转移中的作用作一综述.     

Treatment of pancreatic exocrine insufficiency after pancreatic resection

Summary Background  Steatorrhea following major pancreatic resection can be difficult to control, requiring high doses of pancreatic enzyme supplements. The aim of this study was to demonstrate equivalent efficacy of high-dose and standard-dose pancreatin in treating steatorrhea after pancreatectomy. Methods  A randomized, double-blind, crossover study was conducted with a 2-wk run-in period for stabilization on a suitable dose of standard-dose pancreatin and two 14-d treatment periods using either high-dose or standard-dose pancreatin at this dosage. Parameters used to demonstrate efficacy of treatment were stool fat excretion, stool volume, and clinical symptoms. Results  Thirty-nine patients who had undergone total or partial pancreatectomy were randomised; 37 completed all parts of the study. During stabilization, the mean daily capsule intake was 19.4 (range 9-54); even so, 22 (56%) patients had stool fat excretion > 7 g/d. There were significant correlations between stool fat excretion and stool volume (p < 0.0001) and stool frequency (p < 0.01), but not with indices of abdominal pain and global symptoms. Both high-dose and standard-dose pancreatin demonstrated statistically similar efficacy in the treatment period. Conclusion  The use of high-dose pancreatin for the treatment of pancreatic insufficiency in patients following pancreatectomy should significantly reduce capsule intake with increased convenience and greater compliance rate. Our results, however, indicate that further progress is needed to resolve steatorrhea following pancreatic resection. Abstract published in Digestion 1997: 58 (suppl 2): 54