Interleukin 10 reduces the severity of acute pancreatitis in rats

BACKGROUND & AIMS: Previous studies have documented the effectiveness of interleukin (IL)-10 if given before the onset of experimental acute pancreatitis. This study examined whether IL-10, a cytokine that inhibits macrophage release of inflammatory mediators, would alter the severity of acute pancreatitis if given before or after the induction of disease. METHODS: Eighty-four Sprague-Dawley rats were divided into four groups. Group 1 received intravenous saline, and groups 2, 3, and 4 received intravenous cerulein (8.5 microg x kg(-1) x h(-1)). Group 3 was also given 150,000 U of intraperitoneal IL-10 1 hour before cerulein infusion and every 3 hours thereafter. Group 4 received 150,000 U intraperitoneal IL-10 2 hours after cerulein infusion and every 3 hours thereafter. Serum amylase and tumor necrosis factor (TNF)-alpha levels were measured before and 3, 9, or 15 hours after induction of pancreatitis. Animals were killed at these time points. Pancreata were analyzed for edema and TNF-alpha mRNA and TNF-alpha protein concentrations and were graded histologically. RESULTS: Serum amylase, TNF-alpha mRNA, and TNF-alpha protein levels, pancreatic edema, and histological score were significantly reduced when IL-10 was administered either before or after induction of pancreatitis. Serum TNF-alpha levels were undetectable. CONCLUSIONS: IL-10 attenuated the severity of experimental acute pancreatitis if given either before or after the induction of the disease. These results are consistent with the hypothesis that the macrophage is important in determining the severity of acute pancreatitis in this model.     

Chemokine gene expression in rat pancreatic acinar cells is an early event associated with acute pancreatitis

BACKGROUND & AIMS: The molecular mechanisms underlying pancreatitis are largely unknown. The goal of this study was to identify an early genetic event that correlated with pancreatitis. METHODS: Differential display of messenger RNAs (mRNAs) was conducted on normal pancreas vs. those of animals with secretagogue-induced pancreatitis. Northern blots from normal animals and animals with experimental acute pancreatitis were probed with cloned complementary DNAs for chemokines. Pancreatitis was induced with cerulein and by retrograde injection of bile salts. Immunocytochemistry was used to identify the source of chemokine expression. Pyrrolidine dithiocarbamate was tested for effects on chemokine expression and pancreatitis. RESULTS: A differentially amplified band was consistently observed early after cerulein hyperstimulation. This band was identified as a portion of the mob-1 gene, an alpha-chemokine. Northern analysis indicated that mRNAs for mob-1 and another chemokine, mcp-1, were induced after cerulein hyperstimulation in vivo. mob-1 mRNA was also induced by retrograde injection of bile salts and by cerulein in acinar cells in vitro. mob-1 protein was localized to exocrine cells in pancreata of diseased animals. Pyrrolidine dithiocarbamate inhibited both chemokine gene expression and early inflammatory characteristics of pancreatitis. CONCLUSIONS: Chemokines are induced in acinar cells by treatments that induce pancreatitis and may play an important role in the early stages of the disease.     

Glutamine stabilizes intestinal permeability and reduces pancreatic infection in acute experimental pancreatitis

Intestinal barrier failure and subsequent translocation of bacteria from the gut play a decisive role in the development of systemic infections in severe acute pancreatitis. Glutamine (GLN) has been shown to stabilize gut barrier function and to reduce bacterial translocation in various experimental settings. The aim of this study was to evaluate whether GLN reduces gut permeability and bacterial infection in a model of acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced in 50 rats under sterile conditions by intraductal infusion of glycodeoxycholic acid and intravenous infusion of cerulein. Six hours after the induction of pancreatitis, animals were randomly assigned to one of two groups: standard total parental nutrition (TPN) or TPN combined with GLN (0.5 g/kg(-1)/day(-1)). After 96 hours, the animals were killed. The pancreas was prepared for bacteriologic examination, and the ascending colon was mounted in a Ussing chamber for determination of transmucosal resistance and mannitol flux as indicators of intestinal permeability. Transmucosal resistance was 31% higher in the animals treated with GLN- supplemented TPN compared to the animals given standard TPN. Mannitol flux through the epithelium was decreased by 40%. The prevalence of pancreatic infections was 33% in animals given GLN-enriched TPN as compared to 86% in animals receiving standard TPN (P < 0.05). Adding GLN to standard TPN not only reduces the permeability of the colon but decreases pancreatic infections in acute necrotizing pancreatitis in the rat. This confirms previous reports that GLN decreases bacterial translocation by stabilizing the intestinal mucosal barrier. The present findings provide the first evidence suggesting that stabilizing the intestinal barrier can reduce the prevalence of pancreatic infection in acute pancreatitis and that GLN may be useful in preventing septic complications in clinical pancreatitis.     

Gabexate mesilate improves pancreatic microcirculation and reduces lung edema in a rat model of acute pancreatitis

We evaluated the effects of a protease inhibitor on the progression of acute pancreatitis in rats. The model was selected and modified to mimic an intermediate stage of the disease. The degree of microcirculatory derangement in the pancrease and of lung edema was determined to assess the effects of gabexate mesilate (ethyl-4-(6-guanidinohexanoyloxy) benzoate methane sulfonate), a synthetic antiprotease, in acute pancreatitis. Male Sprague-Dawley rats (225-275 g) were used. Experimental pancreatitis was established by four intramuscular injections of cerulein (50 micrograms/kg) at 1 hour intervals. Lipopolysaccharide (10 mg/kg) was injected intraperitoneally as an acute septic challenge. Gabexate mesilate was infused intravenously 6 hours after the initiation of induction of acute pancreatitis at doses of 0.01, 0.1, 1, or 10 mg/kg/h. Microcirculatory changes in the pancreas were studied using in vivo microscopy. All animals survived until the end of the experiments. Gabexate mesilate significantly improved pathologic criteria and decreased serum lipase levels at doses of 1 and 10 mg/kg/h. It significantly lessened the severity of lung edema and improved the microcirculatory environment in the pancreas by increasing flow velocity and reducing leukocyte sticking. These results indicate the beneficial effects of gabexate mesilate on pancreatic microcirculation and lung edema in the progression of acute pancreatitis with septic challenge in rats.     

Induction of apoptosis in human pancreatic carcinoma cells by a synthetic bleomycin-like ligand

The increased polylactosamine glycosylation of LAMP-2 in MDCK cells cultured for 1 day relative to cells cultured for 3 days has been correlated with its slower rate of Golgi transit (Nabi and Rodriguez-Boulan, 1993, Mol. Biol. Cell., 4, 627-635). To determine if the differential polylactosamine glycosylation of LAMP-2 is a consequence of glycosyltransferase expression levels, the activities of beta1-6GlcNAc-TV, beta1-3GlcNAc-T(i), beta1-2GlcNAc-TI, beta1, 4Gal-T, alpha2-6sialyl-T, and alpha2-3sialyl-T were assayed and no significant differences in the activities of these enzymes in 1 and 3 day cell extracts were detected. During MDCK epithelial polarization, the Golgi apparatus undergoes morphological changes and apiconuclear Golgi networks were more evident in 3 day cells. Treatment with nocodazole disrupted Golgi networks and generated numerous Golgi clusters in both 1 day and 3 day cells. In the presence of nocodazole the differential migration of LAMP-2 in 1 and 3 day MDCK cells was maintained and could be eliminated by treatment with endo-beta-galactosidase, indicating that gross Golgi morphology did not influence the extent of LAMP-2 polylactosamine glycosylation. Nocodazole treatment did, however, result in the faster migration of LAMP-2 which was not due to modification of core N-glycans as the precursor form of the glycoprotein migrated with an identical molecular size. Following incubation at 20 degrees C, which prevents the exit of proteins from the trans-Golgi network, the molecular size of LAMP-2 increased to a similar extent in both 1 and 3 day MDCK cells. Extending the time of incubation at 20 degrees C did not influence the size of LAMP-2, demonstrating that its glycosylation is modified not by its retention within the Golgi but rather by its equivalent slower Golgi passage at the lower temperature in both 1 and 3 day cells. An identical effect was observed in nocodazole treated cells, demonstrating that Golgi residence time determines the extent of LAMP-2 polylactosamine glycosylation, even in isolated Golgi clusters.     

Endogenous glucocorticoids decrease the acinar cell sensitivity to apoptosis during cerulein pancreatitis in rats

BACKGROUND & AIMS: We recently showed that activation of the hypothalamus-pituitary-adrenal axis may mitigate the progress of acute pancreatitis. To clarify the mechanism, the role of endogenous glucocorticoids in pancreatic acinar cell death was examined. METHODS: The occurrence of apoptosis was studied in adrenalectomized or sham-operated rats with or without cerulein-induced pancreatitis. The effects of RU38486, a glucocorticoid-receptor antagonist, on the survival of cultured acinar cells (AR42J) were also examined. RESULTS: Adrenalectomy caused increases in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) of acinar nuclei depending on the time after adrenalectomy but not of other cell types in the pancreas and in other digestive organs. Electron microscopy showed the characteristic features of apoptosis in the TUNEL-labeled acinar cells. In cerulein pancreatitis of adrenalectomized rats, the TUNEL-labeled acinar nuclei increased remarkably depending on the time after cerulein infusion. Replacement of glucocorticoids blocked the occurrence of apoptosis in these experiments. RU38486 induced dose dependently the apoptosis of AR42J cells. CONCLUSIONS: These results provide evidence that endogenous glucocorticoids are an important factor for acinar cell survival. Endogenous glucocorticoids may protect acinar cells by decreasing their sensitivity to the induction of cell death during acute pancreatitis.     

Messenger role of calcium in function of pancreatic acinar cells

Enzyme secretion from the exocrine pancreas is elicited by a) cholinergic stimulants, b) hormones belonging to the family of pancreozymin, c) some amphibian peptides such as bombesin, eledoisin, and physalaemin, and d) secretin and vasoactive intestinal polypeptide. Whereas the mechanism of the group d hormones in stimulating enzyme secretion involves adenosine 3',5'-cyclic monophosphate, the others seem to use a common pathway involving Ca2+ as intracellular messenger and probably guanosine 3',5'-cyclic monophosphate as modulator of their action. Their effects can be ascribed to two processes. One pathway involves release of Ca2+ from an intracellular store that is most likely located in the plasma membrane. This phase is independent of extracellular Ca2+ and leads to a rise of guanosine 3',5'-cyclic monophosphate. The other pathway is characterized by an increased permeability of the plasma membrane for Ca2+ and is necessary for sustained secretion. Both pathways lead to an increase cytosolic-free Ca2+ concentration. Ca2+ is either directly involved in fusion of zymogen granules with the luminal cell membrane or triggers events that lead to exocytosis. Furthermore, augmented cytosolic-free calcium concentration a) increased the plasma membrane permeability for Na+, Cl-, and K+, which leads to depolarization of the cell, and b) induces uncoupling of neighboring acinar cells.     

A severity score for spontaneous canine acute pancreatitis

OBJECTIVE: To derive a severity score for spontaneous canine acute pancreatitis applicable to general practice. DESIGN: Cohort study of canine pancreatitis cases. PROCEDURE: Cases (n = 68) of spontaneous canine acute pancreatitis presented to general practitioners were identified among accessions to Veterinary Pathology Services Brisbane. The primary veterinarian was surveyed by telephone to ascertain the outcome of each case. Scores were assigned for extent of hyperamylasaemia, hyperlipasaemia and number of organ systems other than the pancreas compromised. The probability of mortality with each score of each analyte was calculated. The strength of interaction between scores for each analyte and mortality rate was assessed by chi-square analysis where appropriate. Relationships between the organ system score, other physiological variables and likelihood of euthanasia were analysed. RESULTS: Scores derived mathematically from analysis of enzyme activities had poor abilities to predict mortality. The score based upon the number of organ systems compromised showed good ability to predict mortality and the interaction between the organ system score and mortality rate was significant by chi-square analysis (P < 0.01). Distribution of data within the amylase and lipase scores was not compatible with chi-square analysis. CONCLUSION: Assessment of severity of spontaneous canine acute pancreatitis using pancreatic enzyme activities is potentially inaccurate. The use of a severity score based upon organ system compromise was more accurate in determining the likelihood of mortality in spontaneous canine acute pancreatitis. This is compatible with the hypothesis that severe canine acute pancreatitis is a multiple organ failure syndrome.     

A voltage-sensitive transient potassium current in mouse pancreatic acinar cells

We describe, for the first time, a potassium current in acutely isolated mouse pancreatic acinar cells. This current is activated by depolarization and has many of the characteristics of the fast transient potassium current of neurones where roles in shaping action potential duration and frequency have been proposed. Although acinar cells do not carry action potentials, our experiments indicate that the primary regulator of the current in these cells is the membrane potential. In whole-cell patch-clamped cells we demonstrate an outward current activated by depolarization. This current was transient and inactivated over the duration of the pulse (100-500 ms). The decay of the inactivation was adequately fitted by a single exponential. The time constant of decay, tau, at a membrane potential of +20 mV was 34 +/- 0.6 ms (mean +/- SEM, n = 6) and decreased with more positive pulse potentials. The steady-state inactivation kinetics showed that depolarized holding potentials reduced the amplitude of the current observed with a half-maximal inactivation at a membrane potential of -40.6 +/- 0.33 mV (mean +/- SEM, n = 5). These activation and inactivation characteristics were not affected by low intracellular calcium (10(-10) mol.l-1) or by an increase in calcium (up to 180 nmol.l-1). In addition we found no effect on the current of dibutyryl cyclic adenosine monophosphate (db-cAMP) or the agonist acetylcholine. The current was blocked by 4-aminopyridine (Kd approximately 0.5 mmol.l-1) but not affected by 10 mmol.l-1 tetraethylammonium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Foreign serum-induced pancreatitis in mice. II. Secretory disturbances of acinar cells

As previously reported, pancreatic acinar cell necrosis and inflammation develop in mice a few hours after one intraperitoneal injection of foreign serum. However, sublethally injured acinar cells exhibited notable increases in both zymogen granule numbers and amylase activity, observed within 3 hours and increasing with time. These two changes were coupled with a progressive decrease in the secretory response to pilocarpine and were preceded by significant disturbances in pancreatic tissue concentrations of sodium and potassium. We conclude that (1) the granule increase results from an induced disturbance of the granule exocytosis mechanism while granule formation continues and, therefore, (2) the granule secretory process is more sensitive to the serum injury mechanism than is the zymogen synthesis process. Although the granule increases developed in acinar cells throughout most of the nonnecrotic gland and persisted for at least 24 hours, acinar cell necrosis was maximal in extent--approximately 25% of the gland in severest form--by 12 to 15 hours. We conclude, therefore, that the increase in granules is neither the primary determinant nor initiator of acinar cell death. The latter is likely caused by disturbed plasma membrane functions, sufficient in some cells to result in lethal changes in ion and fluid composition. The injury mechanism, which permits granule formation to go on in the face of impaired granule exocytosis, is yet to be worked out. The possibilities are discussed in relationship to the reactivity of foreign sera for target cell plasma membranes.     

The surgical treatment of pancreatic pseudocysts following acute pancreatitis

The tactics and results of the operative treatment of pancreatic cysts, complicating severe destructive pancreatitis in a series of thirteen patients, are discussed. The following operative methods are made use of: marsupialization (1), Yurash (10), cystojejunoanastomosis with Braunova (2). The character and scope of surgical intervention are determined intraoperatively, depending on the anatomical situation faced. In pancreatic cysts operated according to Yurash (cystogastroanastomosis), an original drainage method with two probes introduced nasally is used--one wider into the anastomosis, and a narrower one into the duodenum for feeding. The probes are retained for periods ranging from 9 to 35 days. No relapse of the cysts operated by different methods are registered, with the exception of a female patient undergoing marsupialization. In one case operated according to Yurash where no preoperative preparation is done the outcome is fatal, with the patient dying of hemorrhage on the third postoperative day. All patients are operated within 3 months after the formation of cysts. The preoperative preparation includes Kontrikal, Petphtoruracil, atropine, heparin and antibiotic; in some patients the listed drugs are introduced intraarterially into truncus celiacus. A number of inferences are reached and recommendations made: 1. Waiting for the generally accepted 3-month term is unnecessary. 2. In cysts involving the head of the pancreas, tightly adherent to the posterior wall of the stomach, the method of Yurash with the modification suggested for probing should be given preference. 3. In cysts of the body region and tail cystojejunoanastomosis with Braunova is practicable. 4. Proceeding with the preoperative medication in the postoperative period is advisable.     

Brefeldin A inhibits the constitutive-like secretion of a sulfated protein in pancreatic acinar cells

Sulfation is a common posttranslational modification of secretory proteins and serves as a valuable marker of constitutive and regulated secretory pathways. We investigated the cellular localization and the secretory behavior of sulfated macromolecules in the mouse pancreatic acinar cell. The major sulfated proteins of the cell were present in isolated zymogen granules, as determined by metabolic labeling with [35S]sulfate and subcellular fractionation. The sulfated proteins fell into three groups: gp300 is not secreted and is a component of the zymogen granule membrane; pancreatic lipase (56 kDa) and a 40 kDa protein are soluble and exhibit regulated secretion kinetics; and p82 is initially granule membrane associated, but is released from the cell with constitutive-like kinetics as a 75 kDa protein (p75). Secretion of p75 could be stimulated for up to 4 h after pulse labeling, presumably from immature secretory granules, but not after 6 h of chase. Treatment of cells with brefeldin A (BFA) at the start of the [35S]sulfate pulse resulted in almost total inhibition of sulfation. Addition of BFA during the chase (0-2 h) allowed normal basal and stimulated secretion of regulated secretory proteins, but reversibly inhibited the constitutive-like secretion of p75. In this case, the behavior of p75 was maintained as that of a regulated secretory protein for up to 6 h of chase. In untreated cells, immunofluorescence of p82/p75 was along the acinar lumen, and in small punctate structures in the apical cytoplasm. In BFA-treated cells, immunolabeling of p82/p75 was lost from the acinar lumen, and cytoplasmic labeling was finer and appeared to be associated with the secretory granule membranes. These data suggest a role for brefeldin A-sensitive coat formation in maturation of secretory granules after they bud from the TGN.     

Hepatic Kupffer cell blockade reduces mortality of acute hemorrhagic pancreatitis in mice

BACKGROUND: Recovery of upper aerodigestive tract function after reconstruction of segmental oromandiblectomy defects is frequently incomplete. The purpose of this study was to quantitate postreconstruction function and define variables that predict functional outcome in this population. METHODS: A prospective study of 21 patients who underwent microvascular free tissue transfer reconstruction of segmental oromandibular defects was performed. Measures of swallowing, speech, bite, and oral intake were performed preoperatively and at 1, 3, 6, and 12 months postoperatively or until plateau. Preoperative versus maximal postoperative measures were compared and correlated with nine potentially predictive variables. Univariate and multivariate analyses were performed to determine the most significant predictive factors. RESULTS: Baseline function in the study population was abnormal. Postoperative bite force improved, but swallowing, speech, and oral intake were worse than preoperative. Significant (univariate) predictors of outcome included diagnosis of cancer, tongue resection, pharynx resection, and flap skin paddle area. Only tongue resection remained significant in multivariate analysis. CONCLUSIONS: Increasing need for oropharyngeal lining replacement, especially after tongue resection, is the most important predictor of functional outcome in reconstruction of segmental mandible defects.     

Is an elevated concentration of acinar cytosolic free ionised calcium the trigger for acute pancreatitis?

The pathogenesis of acute pancreatitis is poorly understood, despite well-recognised precipitating factors. Current evidence suggests that the earliest abnormalities of acute pancreatitis arise within acinar cells, but the key intracellular trigger has yet to be identified. Within the pancreas, physiological concentrations of secretagogues bind to G-protein-linked cell-surface receptors on acinar cells, evoking short, oscillatory spikes of acinar cytosolic-free ionised calcium ([Ca2+]i), an ubiquitous intracellular messenger. Specific effects within acinar cells include initiation of enzyme release through the phosphorylation cascades of stimulus-secretion coupling. Low resting levels of [Ca2+]i are restored by Ca(2+)-ATPase, which pumps calcium into the endoplasmic reticulum and out of the cell. If high concentrations of [Ca2+]i persist, toxicity results, intracellular signalling is disrupted, and cell damage occurs. Sustained elevations in acinar [Ca2+]i result from exposure to high concentrations of secretagogues, high doses of which also induce acute pancreatitis. Similarly, sustained elevations of [Ca2+]i may result from ductal hypertension, alcohol, hypoxia, hypercalcaemia, hyperlipidaemia, viral infection, and various drugs--all factors known to precipitate acute pancreatitis. We suggest that these factors precipitate acute pancreatitis by causing either excessive release of acinar [Ca2+]i, or damage to the integrity of mechanisms that restore low resting levels of [Ca2+]i, and that the consequent calcium toxicity is the key trigger in the pathogenesis of acute pancreatitis.     

Monoacetyldiglycerides as new Ca2+ mobilizing agents in rat pancreatic acinar cells

OBJECTIVES: To elucidate the effects of hypobaric pressure on cochlear hydrodynamics in patents with well-defined Meniere's disease. DESIGN: Sixteen patients were consecutively selected. Elevated hearing threshold levels and pathological transtympanal electrocochleography (tt-ECOG) were confirmed at the day of trial. The patients were exposed to repeated episodes of hypobaric pressure in a pressure chamber. The rate (20 daPa/s) and magnitude (-285 daPa) of chamber pressure change were low. The induced tympanic overpressure (+185 daPa) was continuously monitored and any tympanic equilibration was avoided. METHODS: The results of Bekesy and speech audiometry as well as tt-ECOG performed immediately before and after exposure were compared. The importance of chamber pressure change, number of hypobaric episodes, duration of exposure, and the induced relative tympanic overpressure was tested. RESULTS: It is shown that the relative tympanic overpressure is the most important factor to affect the cochlear hydrodynamics. Higher relative overpressure was associated with improvement of hearing threshold levels, while the ECOG results tended to improve with lower induced tympanic overpressure. CONCLUSION: The importance of tympanic overpressure shown in this study is in agreement with previous findings from hypobaric animal experiments. The inverse relation of psychoacoustic and ECOG tests suggests that the two methods evaluate different parameters, perhaps contributing differently to the physiology of hearing.     

Action of cholecystokinin and cholinergic agents on membrane-bound calcium in dispersed pancreatic acinar cells

In dispersed acinar cells prepared from guinea pig pancreas, cellular uptake of 45Ca was moderately rapid and reached a steady state by 60 min. At the steady state, 69% of total cellular 45Ca was membrane-bound. In acinar cells preloaded with 45Ca and then incubated with COOH-terminal octapeptide of cholecystokinin (CCK-OP) or carbamylcholine, total cellular 45Ca decreased by approximately 40% within 5-10 min and then steadily increased to control values by 60 min. Under identical conditions, membrane-bound 45Ca decreased by 40% within 5-10 min and remained constant for the duration of the incubation. Free cellular 45Ca did not change during the initial 30 min but then increased steadily to values three times those in control cells by 60 min. In cells preloaded with 45Ca and then incubated with EDTA, the loss of total cellular radioactivity stimulated by CCK-OP could be accounted for by loss of membrane-bound 45Ca. CCK-OP failed to alter total cellular uptake of 45Ca when both tracer and peptide were added at the beginning of the incubation. Under identical conditions, membrane-bound 45Ca was not altered by CCK-OP during the first 30 min of incubation but was significantly below control values after this time. The effect of CCK-OP on free cellular 45Ca was the same as in cells preloaded with the tracer. These results suggest that CCK-OP causes release of 45Ca from a membrane-bound compartment that equilibrates slowly with extracellular fluid and that the change in free cellular 45Ca is a secondary effect.     

Stimulation of pancreatic growth by cholecystokinin is mediated by high affinity receptors on rat pancreatic acinar cells

Pancreatic acinar cells possess both high low affinity receptors for cholecystokinin. The cholecystokinin analog caerulein, which exerts a trophic effect on the rat pancreas, acts as an agonist at both types of receptors. In contrast, the synthetic analog CCK-JMV-180, which also acts as an agonist at high affinity receptors, opposes the action of caerulein on the low affinity receptors. We report that infusion of either caerulein or CCK-JMV-180 into rats increases [3H]-thymidine incorporation into pancreatic DNA and causes the pancreatic weight as well as content of DNA, RNA, and protein to increase. CCK-JMV-180 also stimulates in-vitro incorporation of [3H]-thymidine into DNA of cultured rat acini. The finding that both caerulein and CCK-JMV-180 exert the same trophic effect on pancreatic acinar cells indicates that this effect is mediated via high affinity acinar cell cholecystokinin receptors.     

Endoscopic fibrin gluing of a pancreatic duct fistula following acute pancreatitis

HISTORY AND CLINICAL FINDINGS: A 45-year-old patient was admitted because of frequent attacks of upper abdominal pain after food intake. The pain episodes had started shortly after a bout of acute pancreatitis. Physical examination was unremarkable except for mild pain on palpation of the left lower abdomen. INVESTIGATIONS: Amylase and gamma-glutamyl transaminase activities as well as inflammatory parameters were slightly raised. Ultrasonography was suggestive of a circumscribed area of necrosis in the tail of the pancreas, a finding confirmed on endoscopic retrograde injection of contrast medium, which passed into the necrotic cavity via a fistula. TREATMENT AND COURSE: The fistula failed to close during 12 days of conservative treatment (total parenteral nutrition; 2 g ceftizoxim twice daily; 1 ampoule somatostatin daily). In three sittings during 6 days, 1-2 ml fibrin glue injections were made by endoscopy retrogradely into the fistular passage resulting in its complete occlusion without any further complications. CONCLUSION: A previously treatment-resistant pancreatic fistula can be successfully occluded by injection of fibrin glue by retrograde endoscopy, obviating surgical intervention with subsequent reduction in glandular capacity.     

Vascular permeability induced by pancreatic exudate formed during acute pancreatitis in dogs

Acute pancreatitis was produced in five dogs by injecting bile into the pancreatic duct. The capillary permeability effects of the exudate formed within the peritoneal cavity were studied by injecting the exudate intradermally into puppies. The amount of radioactively labeled albumin escaping from the circulation and appearing at the intradermal injection site was used as a measure of capillary permeability. It was observed that the peritoneal exudate, especially that produced in the early stage of bile induced pancreatitis, contains one or more substances which result in an increased capillary permeability when injected intradermally into puppies.