Pancreatic abscess following acute pancreatitis.

Pancreatic abscess is probably the most serious complication of acute pancreatitis. During the ten-year period from 1966 to 1975, twenty-eight patients with pancreatic abscess following acute pancreatitis were treated by surgical drainage. A review of these cases revealed that there was a lull in the clinical course of the antecedent pancreatitis prior to the time of surgical drainage in 70% of the cases. Despite an aggressive surgical approach, there were major postoperative problems in 26 patients. Sepsis persisted in 14 patients. Major gastrointestinal hemorrhage occurred in seven, intra-abdominal bleeding in nine, and fistulization in 13. Fourteen patients died (a mortality of 50%). The operative treatment of pancreatic abscess must be aggressive and persistent. In addition to extensive drainage with soft sump drains, vigilance must be exercised to avoid pressure against bowel or major vessels. Reoperation should be considered if postoperative improvement is not sustained.     

Selective arterial perfusion with antienzymes in experimental acute pancreatitis. Preliminary experience]

Authors analyze some results obtained treating, with selective arterial perfusion (using antienzymes), experimental acute pancreatitis in dogs (fifteen). The first dogs' group was used to perform several experimental acute pancreatitis; the second group was treated by selective arterial perfusion and was related to group of dogs treated by i.v. antienzymes drugs. Histological and biochemical data are discussed. The results obtained with arterial perfusion are preliminary referred as better than classic i.v. antienzymes drugs therapy.     

Pancreatic microcirculation in acute pancreatitis

We present a review of the microvascular morphology of the pancreas and microstructure of the pancreatic lobule, and report our experimental results of the investigation of pancreatic microcirculation following acute pancreatitis. Impairment of pancreatic microcirculation in the early phase of acute pancreatitis may play a key role in the progression of this disease. Possible contributory mechanisms include increased vascular permeability, reduced blood flow, leukocyte-endothelial cell interaction and intravascular thrombus formation. Using an in-vivo microscope system and off-line computer analysis, we achieved direct visualization and quantification of changes in microvascular permeability and leukocyte behavior in pancreas with acute pancreatitis. Bradykinin and oxygen radicals have been demonstrated to be involved in the increase of vascular permeability in the early stage of caerulein pancreatitis. Leukocyte adherence to the vessels in the pancreatic microcirculation is a secondary event following permeability changes in acute pancreatitis. Leukocyte infiltration during exacerbation of acute pancreatitis is mediated by leukocyte-endothelial cell interaction via leukocyte integrin CD11b/18. Received for publication on Jan. 29, 1997; accepted on April 24, 1997     

Pancreatic ischaemia in experimental acute pancreatitis: mechanism, significance and therapy

Much clinical and experimental evidence suggests that pancreatic ischaemia in the early phase of acute pancreatitis is important in the development of pancreatic necrosis. While depletion of intravascular volume has often been assumed to be the main circulatory defect, an additional disturbance of pancreatic microcirculation has been demonstrated experimentally. Possible contributory mechanisms include chemical-induced vasoconstriction, direct injury of vessel wall, intravascular coagulation and increased endothelial permeability resulting in pancreatic oedema, haemoconcentration and impaired venous drainage. Pancreatic ischaemia as a consequence of these local effects seems to be responsible for the transition of mild pancreatitis to parenchymal necrosis. In experimental models the beneficial effect of various drugs and of sympathetic blockade has been ascribed to an improvement in pancreatic perfusion. Although effective volume therapy is generally accepted as the mainstay of conservative treatment in acute pancreatitis, the efficacy of different fluid preparations is still controversial, and simple fluid resuscitation has not been shown to prevent the development of parenchymal necrosis. The specific impairment of pancreatic microcirculation cannot be prevented merely by replenishment of intravascular volume with crystalloids, albumin or plasma despite normalization of macrohaemodynamics. In contrast, partial replacement of blood by dextran preparations has been shown to increase pancreatic perfusion by improving blood fluidity. Isovolaemic haemodilution in conjunction with conventional fluid therapy may provide a new and effective means of protecting the pancreas from secondary injury due to the early ischaemic phase of acute pancreatitis.     

Pancreatic necrosis and acute pancreatitis

The surgeon should take pains to section and study himself the operative specimen after excision for acute pancreatitis, in order to understand the true nature of the lesions, which the most attentive and competent pathological examination cannot describe as vividly as direct examination by the operator. Often he will be surprised to find that the lesions, predominant in the capsule, are less profound and less severe than he had thought at first sight. The necrosis, which is sometimes limited to the peripheral and interstitial tissue, sparing the gland itself (its prognosis is less serious and has led many surgeons to perform surgical excision). However the problems encountered postoperatively have given rise to doubts a posteriori as to whether this is legitimate. Reference is made to the decapsulation of the pancreas described by Romanian authors, and a method for future operative diagnosis of glandular necrosis is proposed.     

Pancreatic abscess following acute pancreatitis

Without surgical treatment, pancreatic abscess remains a highly lethal complication of acute pancreatitis. Many surgical series have reported mortality rates of 32 to 65 per cent in treated cases. Although pancreatic abscess is a rare condition, it is more common in patients with severe pancreatitis. A retrospective study of 130 patients admitted to our unit with severe acute pancreatitis during the period from 1965 to 1987 revealed 18 cases of pancreatic abscess. All pancreatic abscesses were primary in nature, and no infected pseudocysts were included in the series. Clinical surveillance, repeated laboratory tests, conventional radiology, and especially ultrasonography and CT scan all contributed to the preoperative diagnosis. The applied treatment was surgical debridement of all necrotic tissue and either local or extensive external drainage. In 12 cases this procedure was combined with other surgical interventions. The recorded mortality rate was 16.66 per cent. Factors adversely affecting survival include: 1) severity of precipitating pancreatitis; 2) difficulty in making early and accurate diagnosis of the pancreatic abscess; 3) marked tendency for recurrence of sepsis; and 4) life-threatening associated complications and/or diseases.     

Pancreatic cationic elastase in porcine experimental pancreatitis

A radioimmunoassay for porcine, cationic, pancreatic elastase (irPE) is described. Normal porcine serum contains only small amounts of irPE (less than 3 micrograms/l). IrPE in serum and peritoneal exudate from 6 pigs with experimental pancreatitis was found mainly in a molecular form corresponding to free pro-enzyme. The presence of alpha 1-, alpha 2-macroglobulin-bound elastase-like enzymatic activity in the peritoneal exudates from pigs with pancreatitis, however, indicates that the proteinase is to some extent released as the active enzyme. In some pigs with pancreatitis, the elastase-like activity against Succ(Ala) in the peritoneal exudates increased during the experiment, arguing for a progressive activation of pro-elastase. Free proteolytic activity was not observed in any of the peritoneal exudates. This low degree of activation of elastase and the fact that the elastase inhibiting capacity is substantially larger than the trypsin inhibiting capacity in serum and biological fluids, leads us to the conclusion that active elastase is not a factor of principal importance in the pathogenesis of proteinase inhibitor consumption and tissue damage in our experimental pancreatitis model.     

Central haemodynamics in experimental acute pancreatitis.

OBJECTIVE: To investigate central haemodynamics in severe and mild acute pancreatitis in pigs. DESIGN: Randomised controlled experiment. SETTING: Animal laboratory, Finland. SUBJECTS: 24 domestic pigs weighing 21-27 kg. INTERVENTIONS: In 8 anaesthetised and mechanically ventilated pigs the pancreatic duct was cannulated and taurocholic acid was infused to induce severe acute pancreatitis. Eight animals received intraductal saline infusion and developed mild acute pancreatitis. Eight pigs were cannulated alone and served as controls. MAIN OUTCOME MEASURES: Cardiac index, heart rate, mean arterial pressure, central venous pressure, mean pulmonary arterial pressure, pulmonary arterial occlusion pressure, haemoglobin, arterial blood gases and acid base balance. RESULTS: Intraductally infused taurocholic acid rapidly induced severe necrotising acute pancreatitis as assessed both macroscopically and histologically. Histological changes of mild acute pancreatitis were seen in animals after intraductal saline infusion. Central haemodynamics, arterial blood gases, and acid base balances were stable throughout the study period in all groups. The main finding was haemoconcentration as indicated by the increase in arterial haemoglobin concentration in pigs with mild and severe acute pancreatitis. CONCLUSION: Haemoconcentration precedes central haemodynamic alterations in experimental acute pancreatitis.     

Pancreatic microcirculation in acute pancreatitis of dogs

Pancreatic microcirculation in acute pancreatitis and the effect of dopamine and pancreatic protease inhibitor were investigated in 35 mongrel dogs. Acute pancreatitis was induced by the injection of autologous bile added trypsin into pancreatic duct. In acute pancreatitis dogs femoral artery pressure and pulse pressure gradually decreased and pancreatic microflow in basal state temporarily increased immediately after bile injection, however, thereafter continuously decreased during the experiments. Portal flow severely decreased just after onset of acute pancreatitis. By administration of dopamine femoral artery pressure was maintained during the first 90 minutes of experiments, however, thereafter decreased until the end of experiments. Pancreatic microflow, 56.1 +/- 15.3 ml/min/100g in basal level was shown 66.1 +/- 13.7 and 60.3 +/- 10.3 ml/min/100g at 1 and 2 hours, respectively, after bile injection, which were significantly high values as compared with those of non dopamine administration. However those values decreased at 5 hours of both experiments. Portal flow whose basal level was 237 +/- 67 ml/min was maintained during the first 1 hour however it decreased to 139 +/- 25 ml/min at 5 hours. By administration of pancreatic protease inhibitor femoral artery pressure and pulse pressure, temporarily decreased immediately after bile injection, however, they were maintained thereafter. Pancreatic microflow, 57.1 +/- 18.3 ml/min/100g in basal level, was maintained during the first 2 hours, however significantly decreased to 27.6 +/- 9.7 ml/min/100g at 5 hours. Portal flow significantly increased to 442 +/- 115 ml/min at 2 hours, however, thereafter decreased 219 +/- 93 ml/min at 5 hours.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pancreatic resection for severe acute pancreatitis

Non-operative management of acute necrotizing pancreatitis carries a mortality of up to 80 per cent. Over the last 6 years we have pursued an aggressive policy of intensive supportive therapy followed by pancreatic resection in those patients with this severe form of the disease. We have managed 15 patients in this way, 14 by subtotal pancreatic resection (usually body and tail of the gland) and one by total pancreatectomy; 7 had early overwhelming multi-system failure with a median of 4 positive prognostic factors whilst 8 were operated on later between 3 and 8 weeks (plus one at 32 weeks) and had varying clinical pictures. Eight patients had ischaemia of the transverse colon which was noted at operation in four, and presented postoperatively in the remainder. Re-operation was necessary in 13 patients to remove further slough or resect ischaemic bowel. Five patients (33 per cent) died between 10 days and 4 weeks postoperatively, death being due to sepsis and multi-system failure in four and a massive retroperitoneal haemorrhage in one. Of the ten survivors, four require insulin. Timely excision of necrotic pancreatic tissue combined with intensive supportive therapy may help reduce the high mortality in this condition.     

Pancreatic tissue and ductal pressures in chronic pancreatitis

To assess the contribution of parenchymal hypertension to pain, pancreatic tissue pressures were measured intraoperatively in 17 patients with chronic pancreatitis and in four other patients undergoing pancreatic surgery (reference group). The technique involved direct fine needle cannulation of the pancreas using a flow infusion system, which measured parenchymal resistance to this infusion. Three to six recordings were obtained at each site. In chronic pancreatitis the pressure (mean +/- s.e.m.) was substantially elevated in all regions of the pancreas compared with reference subjects: head (257 +/- 59 versus 19 +/- 5 mmHg, P less than 0.05); body (201 +/- 51 versus 13 +/- 6 mmHg, P less than 0.05) and tail (161 +/- 45 versus 11 +/- 3 mmHg, P less than 0.05). Elevation was greater in areas of calcific disease (281-383 mmHg) than in non-calcific disease (81-120 mmHg, P less than 0.05). Mean pancreatic ductal pressure in 10 patients (seven with calcific disease) was 20 +/- 4 mmHg. Differential pressure measurements within the pancreas helped determine the extent of resection in six patients with diffuse disease. The greatly increased tissue pressures in chronic pancreatitis, especially in the presence of calcification, suggest a possible 'compartment syndrome'.     

Pancreatic response to crystalloid resuscitation in experimental pancreatitis

Restoration and maintenance of intravascular volume is crucial in acute pancreatitis to prevent hypotension and ensure normal organ perfusion. This study evaluated the hemodynamic and metabolic effects of adequate versus inadequate fluid replacement on the pancreas in a canine model of acute experimental pancreatitis. Bile-trypsin pancreatitis (BTP) was induced in 14 conditioned mongrel dogs. Lactated Ringer's solution was administered intravenously at high (HIR) and low (LIR) infusion rates (6.5 and 1.75 ml/kg/hr, respectively) to 7 dogs each for 4 h. Seven sham-operated controls (CON) received lactated Ringer's at 6.5 ml/kg/hr for 3 hr. Mean arterial pressure remained unchanged in all groups. Central venous pressure decreased in the LIR group (P < 0.05) and remained unchanged in the other groups. Cardiac index fell uniformly (P < 0.05) in all groups. Pancreatic blood flow (Q_P) decreased in the LIR group (73%) to a significantly greater extent than in the HIR (23%) and CON (8%) groups, and in the HIR group significantly more than in the CON group. The fall in pancreatic oxygen consumption (O₂C_P) in both the pancreatitis groups was significant compared to the rise in the CON group. Final changes in Q_P and O₂C_P from baseline were significant only in the LIR group. We conclude that inadequate crystalloid replacement after BTP results in a progressive fall in Q_P and O₂C_P. Vigorous fluid replacement incompletely prevents these effects.     

Effect of spore-free anaerobic microorganisms of pancreatic tissue in experimental acute pancreatitis

The simulation model of an acute pancreatitis (AP), using translocation of microorganisms from intestine to ductal system and pancreatic tissue, was created in experiment on dogs. Interrelationships between pancreatic tissue and anaerobic microorganism in an AP were studied, using electron microscopy. Possibility of the microorganisms migration to pancreas from ductal system in early stage of AP due to enhanced reproduction of anaerobic microorganisms in duodenum was established. It is impossible to exclude the possibility of their invasion via the lymph and the blood flow into destructively changed pancreatic tissue in late terms of the disease.     

Protease inhibitors and experimental acute hemorrhagic pancreatitis.

Proteolytic enzyme inhibitors have been reported to decrease morbidity and mortality from certain types of experimental pancreatitis, although recent randomized trials have been unable to demonstrate that they are of benefit in the treatment of clinical acute pancreatitis. We have evaluated the effect of two proteolytic enzyme inhibitors (trasylol and chlorophyll-a, on experimental acute pancreatitis induced in mice by the feeding of a choline-deficient ethionine-enriched diet. The mortality rate and the biochemical and morphological severity of pancreatitis were not altered by either trasylol or chlorophyll-a administration. Thus, in this respect, diet-induced pancreatitis appears to resemble clinical acute pancreatitis. The reasons for the lack of effectiveness of proteolytic enzyme inhibitors in the treatment of both forms of pancreatitis are discussed.     

Lipid metabolism in experimental acute pancreatitis

In order to study the changes of lipid metabolism in acute pancreatitis, the following experiments were performed in monogrel dogs. Bile-induced pancreatitis (severe type) and collagenase-induced pancreatitis (mild type) were prepared, and changes of FFA, TG, IRI and IRG were determined for one week. In addition, IVFTT and PHLA were determined at 24th hour, on the 3rd day and 7th day. A rise of FFA was observed during the first 24 hours, which was considered the lypolytic stage. On the 3rd day TG reached the maximal level, while K values in IVFTT and PHLA showed the lowest levels. The above results suggest that the elimination mechanism of TG was impaired on the 3rd day. Changes of FFA, TG, IRI and IRG showed marked differences between the two groups. Therefore it is thought that lipid metabolism in acute pancreatitis is regulated by balance of endogenous pancreatic hormones.     

Pancreatic endocrine function in patients with acute pancreatitis]

The secretory function of the pancreas is also impaired in acute destructive pancreatitis. A four- to five-fold increase of serum insulin and glucagon concentrations during the development of the disease is evidence in favor of the development of pancreonecrosis. Diabetic, type disorders of glucose tolerance were encountered in 38% of patients with acute pancreatitis, the clinical form of diabetes mellitus was found in 8.3% of the examined patients.