Compartment syndrome in experimental chronic obstructive pancreatitis: effect of decompressing the main pancreatic duct

Chronic pancreatitis is characterized by persistent and severe pain, which can be relieved by decompression of the main pancreatic duct (MPD). Both ductal and interstitial pressures have been shown to be increased in chronic pancreatitis in patients. A study was carried out of pancreatic interstitial pressure and pancreatic blood flow in normal cats and those in which chronic obstructive pancreatitis had been induced 5 weeks earlier to determine the effect of decompression of the MPD. In the normal pancreas, median(interquartile range (i.q.r.)) basal interstitial pressure was 0.05(1.2) mmHg and median(i.q.r.) basal pancreatic blood flow 58.3(24.3) ml per min per 100 g. Secretory stimulation did not change the interstitial pressure significantly, but was associated with a 40 per cent increase in median(i.q.r.) blood flow to 81.8(45.8) ml per min per 100 g. In contrast, in chronic obstructive pancreatitis, the median(i.q.r.) basal interstitial pressure was 2.0(1.5) mmHg, which was significantly higher than in the normal gland, and median(i.q.r.) pancreatic blood flow was 38.3(9.8) ml per min per 100 g, significantly lower than in the normal pancreas. Furthermore, secretory stimulation was associated with a significant increase in median(i.q.r.) interstitial pressure to 3.3(1.6) mmHg and a simultaneous decrease in median(i.q.r.) blood flow to 31.5(13.7) ml per min per 100 g. After decompression of the MPD in cats with chronic obstructive pancreatitis, the median(i.q.r.) basal interstitial pressure was 2.0(1.4) mmHg and on secretory stimulation 1.8(1.5) mmHg. Decompression thus prevented the increase in interstitial pressure seen in the animals with obstruction. In contrast, ductal decompression improved the median(i.q.r.) basal pancreatic blood flow to 45.9(38.4) ml per min per 100 g and, furthermore, this increased significantly on secretory stimulation to a median(i.q.r.) of 81.4(47.8) ml per min per 100 g. Decompression thus restored the normal pattern of secretory hyperaemia. Within the confines of this model, these observations demonstrate that chronic obstructive pancreatitis exhibits a compartment syndrome that is relieved by duct drainage.     

Absence of pancreatic duct dilation in chronic pancreatitis: surgical significance

Of 22 patients treated surgically for intractable pain from chronic alcoholic pancreatitis, eight did not show notable dilation of the main pancreatic duct by endoscopic retrograde cholangiopancreatography (ERCP), operative pancreatography, and/or operative and microscopical studies of the pancreas after subtotal pancreatectomy. In all patients, far advanced parenchymal pancreatitis was evident at operation and by microscopical study of the removed portion of the pancreas. These findings indicate that the basic problem in a considerable number of patients with symptomatic alcoholic chronic pancreatitis is not related primarily to obstruction with dilation of the major pancreatic duct, but to intrinsic changes in the parenchymal pancreas. The preoperative use of ERCP and individualization of operative procedures with a preference for subtotal or partial pancreatectomy for symptomatic chronic alcoholic pancreatitis are supported.     

Resolution of panniculitis after placement of pancreatic duct stent in chronic pancreatitis

The association of panniculitis and pancreatitis is well described. However, panniculitis remains a relatively uncommon manifestation of pancreatic inflammation. We report a case in which treatment of pancreatitis by the placement of a pancreatic stent led to simultaneous resolution of both the pancreatitis and the associated panniculitis. There are no other reports in the literature demonstrating resolution of panniculitis subsequent to stent placement or definitive surgery.     

Wirsung's duct and chronic pancreatitis. Changes in the morphology of the pancreatic ducts after pancreatic duct shunts. 23 cases followed-up

The authors study in chronic pancreatitis the morphology of Wirsung's duct in 31 patients who had undergone repeated operations, 23 of them were submitted in a first stage to an anastomosis between the pancreatic duct and the digestive tract. The main causes of failure were obstructions of the anastomosis, biliary complications and continuation of the pancreatic disease. The difference in prognosis between pancreatitis with a dilated pancreatic duct, and those with a filiform duct, is perhaps due to lesions of different histological appearance and course. The best results were obtained in patients able to give up alcohol and in whom it was possible to carry out a broader anastomosis on a dilated and unobstructed pancreatic duct.     

Diagnostic features of chronic pancreatitis distal to benign and to malignant pancreatic duct obstruction

Differentiation between diffuse chronic pancreatitis and pancreatitis distal to a malignant or benign stenosis has important prognostic and therapeutic implications. We examined the retrograde pancreatograms of 64 patients with histologically confirmed diagnosis of diffuse chronic pancreatitis, chronic pancreatitis distal to a benign tumor and chronic pancreatitis distal to a malignant tumor. The nature of the stenosis was often difficult to determine from the shape of the pancreatic duct only. By using discriminant analysis it was possible to determine an allocation rule based on 8 criteria mainly derived from changes in the pancreatic ductuli. This allocation rule allowed the correct diagnosis to be made in 24 out of 26 patients with diffuse chronic pancreatitis (92%), 19 out of 20 patients with pancreatitis distal to a benign tumor (95%) and all 18 patients (100%) with pancreatitis distal to a malignancy.     

Clinical assessment of pancreatic diabetes caused by chronic pancreatitis

OBJECTIVE: To describe the epidemiologic features of women with extraovarian primary peritoneal carcinoma and compare them with those of women with primary epithelial ovarian cancer. METHODS: The epidemiologic features of 50 women with extraovarian primary peritoneal carcinoma were compared with those of 503 women with primary epithelial ovarian cancer. We included all women with the respective diagnoses admitted to the Roswell Park Cancer Institute between October 1982 and October 1996 who returned an epidemiologic questionnaire. Epidemiologic features of the study and control groups were extracted from a database compiled from a self-administered questionnaire that has been given to patients as part of the admission process since 1982. Individual variables between the study and control groups were compared using Student t test, chi2 analysis, and Wilcoxon nonparametric test. Two-tailed P < .05 was considered significant. RESULTS: We found few significantly different epidemiologic features between women with extraovarian primary peritoneal carcinoma and those with primary epithelial ovarian cancer. Women with extraovarian primary peritoneal carcinoma were significantly older (mean age 63.8 versus 55.0 years, P < .001), had later menarche (13.3 versus 12.8 years, P = .024), and were less likely to have used perineal talc powder (26.0% versus 48.1%, P = .003). There were no significant differences with respect to reproductive history, contraceptive use, or use of hormone replacement therapy. A larger proportion of ovarian cancer patients reported a family history of breast cancer, but the numbers were too small to reach statistical significance. CONCLUSION: The epidemiologic features of women with extraovarian primary peritoneal carcinoma compared with women with primary epithelial ovarian cancer show few differences. The observed areas of difference warrant further research to determine whether they suggest the occurrence of distinct disease entities.     

Role of endogenous and exogenous cholecystokinin in experimental acute pancreatitis induced in rats by the duodenal loop technique

The role of endogenous cholecystokinin (CCK) release and exogenous CCK-8 administration in the development and progression of acute pancreatitis and in the early recovery phase of acute pancreatitis were investigated in rats with closed duodenal loop (CDL)-induced pancreatitis. The subcutaneous injection of CCK-8 (2 micrograms/kg) stimulated a physiological level of pancreatic enzyme secretion in normal control rats, but did not lead to any biochemical or histological evidence of acute pancreatitis. A higher dose of CCK-8 (8 micrograms/kg), however, did produce both biochemical and histological evidence of acute pancreatitis in the normal control rats. When 2 micrograms/kg of CCK-8 was injected subcutaneously in rats 6 and 12 h after the creation of the CDL, neither the biochemical nor the histological findings of acute pancreatitis showed any progression compared with the changes in controls given no CCK-8. Serum CCK levels, measured by radio-immunoassay, increased significantly from mean levels of 5.39 pg/ml (+/- 0.95 SD) before creation of the CDL to 42.06 pg/ml (+/- 2.27 SD) 6 h after, and 41.95 pg/ml (+/- 1.88 SD) 12 h after its creation (P < 0.01). The difference between serum CCK levels at 6 and 12 h was not statistically significant. Following the release of the loop, serum CCK levels decreased gradually, especially in rats in which the loop was released 6 h after being created. Although no marked biochemical and histological changes of acute pancreatitis were observed following the administration of 2 micrograms/kg of CCK-8 to rats upon release of the loop 6 h and 12 h after its creation, a higher dose of CCK-8 (8 micrograms/kg) in these rats adversely affected both the biochemical and histological findings of acute pancreatitis. Based on these findings, it was concluded that neither endogenous CCK release, as a result of the CDL, nor physiological stimulation of the pancreas by exogenous CCK-8 administration, caused progression from edematous to hemorrhagic acute pancreatitis, and neither CCK treatment had any adverse effect on the early recovery phase of CDL-induced acute pancreatitis. A pharmacological dose of CCK, however, exacerbated the acute pancreatitis, even in the early recovery stage.     

Endoscopic therapy of a pancreatic effusion caused by chronic pancreatitis

A 36-year-old patient was hospitalized because of an extensive right pleural effusion. He complained of increasing dyspnea, moderate weight loss and night sweats. The pleural aspirate was hemorrhagic and, surprisingly, excessively elevated lipase activity (57,000 U/L) was measured. An ultrasound examination of the epigastric area revealed several cystic structures in the upper retroperitoneum, and CT scan additionally showed diffuse pancreatic calculi. After conservative treatment had failed, ERCP was performed. A pseudocyst and the indistinct outline of a stenosis of the pancreatic duct could be seen. A few fragments of calculi were removed and a pancreatic duct stent was positioned. Because of stent occlusion ERCP was repeated and some more calculi were extracted, after which the pleural effusion and the pseudocysts completely regressed. In cases of pleural effusion on unclear etiology, a pancreatic pleural effusion should be included in the differential diagnosis. In patients with this clinical picture ERCP can provide not only diagnostic information, but also opportunities for new modes of treatment.     

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.     

Bacterial renal infection in rats produced by direct injection of bacteria into renal tissue--an experimental model

A new method for producing an experimental model of renal infection in rats is described. It is based on a direct injection of a concentrated E. coli suspension either into both kidneys or only one of them. The method is simple and takes little time; the mortality of experimental animals is low. A focal acute purulent renal inflammation is elicited which tends to propagate towards the papilla. A significant renal infection persists at least over six weeks. The renal infection model is suitable for testing the antibacterial activities of drugs, as documented by the results of a therapeutical experiment with gentamicin and other agents.     

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.     

Contribution of pancreatic scintiscanning to the diagnosis of chronic pancreatitis

1. Ferritin has been isolated from the serum of four patients with iron overload by using two methods. 2. In method A, the serum was adjusted to pH 4.8 and heated to 70 degrees C. After removal of denatured protein, ferritin was concentrated and further purified by ion-exchange chromatography and gel filtration. In most cases, only a partial purification was achieved. 3. In method B, ferritin was extracted from the serum with a column of immuno-adsorbent [anti-(human ferritin)] and released from the column with 3M-KSCN. Further purification was achieved by anion-exchange chromatography followed by the removal of remaining contaminating serum proteins by means of a second immunoadsorbent. Purifications of up to 31 000-fold were achieved, and the homogeneity of the final preparations was demonstrated by polyacrylamide-gel electrophoresis. 4. Serum ferritin purified by either method has the same elution volume as human spleen ferritin on gel filtration on Sephadex G-200. Serum ferritin has a relatively low iron content and iron/protein ratios of 0.023 and 0.067 (mug of Fe/mug of protein) were found in two pure preparations. On anion-exchange chromatography serum ferritin has a low affinity for the column when compared with various tissue ferritins. Isoelectric focusing has demonstrated the presence of a high proportion of isoferritins of relatively high pI. 5. Possible mechanisms for the release of ferritin into the circulation are briefly discussed.     

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.     

Epithelial anomalies in chronic pancreatitis as a risk factor of pancreatic cancer

BACKGROUND/AIMS: The relationship between chronic pancreatitis and the development of pancreatic cancer is still a matter of dispute. Our aim was to determine the frequency of hyperplastic, metaplastic and dysplastic epithelial anomalies in the course of chronic pancreatitis and the potential steps in their development to malignancy. METHODOLOGY: The study was based on biopsy material of 70 patients with clinically diagnosed advanced chronic pancreatitis, who underwent partial or total pancreatectomy, as well as other operations. The patients were assigned to 2 groups: Group I (n = 41) with calcifying chronic pancreatitis; Group II (n = 29) with other forms of the disease. Histological sections were stained with hematoxylin-eosin, Mallory-azan, Gomori's silver method, and glycosaminoglycans (PAS and Alcian blue staining). Special interest was focused on the type and incidence of epithelial ductal and acinar cell anomalies, and on the degree of parenchymal scarring. RESULTS: Hyperplasia of the ductal epithelium was present in 31.4%, focal squamous metaplasia in 21.4%, mucous metaplasia in 11.1%, cellular dysplasia in 8.6%, dysplastic acinar cell nodules in 21.4%, and "tubular complexes" in 30.0% of all cases. The differences in the frequency of these changes, except for ductal epithelial hyperplasia, were not statistically significant in two comparable groups. Advanced pancreatic fibrosis was associated with epithelial anomalies in 65.7% of all cases. CONCLUSIONS: From the morphological point of view, the adequate prerequisites for the consideration of advanced forms of chronic pancreatitis, independent of type, as a risk factor of pancreatic cancer exist, necessitating the surgical removal of pathological lesions.     

Pathophysiologic studies of the pulmonary and coronary circulations in man

Studies of the pulmonary circulation in normal man, performed with external radiation detectors, have shown that pulmonary blood volume is about 10% of total blood volume. Pulmonary blood volume was unchanged in patients with acute or chronic left atrial hypertension and in normal persons during expansion of total blood volume in spite of marked increases in pulmonary vascular pressures. However, pulmonary blood volume was greatly increased in patients with polycythemia rubra vera and a large total blood volume and in patients with a left to right shunt but normal pulmonary intravascular pressure. Studies of regional myocardial perfusion with injection of xenon-133 solution into the left coronary artery revealed localized areas of ischemia distal to stenotic lesions even when the patient was at rest. During angina produced by pacing, more severe ischemia occurred, thus suggesting that functional factors reduce local perfusion below resting levels. In patients with "variant" angina, intravenous injection of thallium-201 chloride during spontaneous attacks has revealed large cold areas in myocardial scintigrams not present under control conditions, thus suggesting severe transmural reduction of perfusion in heart muscle corresponding to S-T segment elevation in the electrocardiogram.     

Pulmonary chemoreflexes elicited by intravenous injection of lactic acid in anesthetized rats

Experiments were carried out to characterize the cardiorespiratory reflex responses to intravenous injection of lactic acid and to determine the involvement of vagal bronchopulmonary C-fiber afferents in eliciting these responses in anesthetized rats. Bolus injection of lactic acid (0.2 mmol/kg i.v.) immediately elicited apnea, bradycardia, and hypotension, which were then followed by a sustained hyperpnea. The immediate apneic and bradycardiac responses to lactic acid were completely abolished by bilateral vagotomy and were absent when the same dose of lactic acid was injected into the left ventricle. The subsequent hyperpneic response was substantially attenuated by denervation of carotid body chemoreceptors. After a perineural capsaicin treatment of both vagus nerves to block the conduction of C fibers, lactic acid no longer evoked the immediate apnea and bradycardia, whereas the hyperpneic response became more pronounced and sustained, presumably because of the removal of the inhibitory effect on breathing mediated by pulmonary C-fiber activation. Single-unit electrophysiological recording showed that intravenous injection of lactic acid consistently evoked an abrupt and intense burst of discharge from the vagal C-fiber afferent endings in the lungs. In conclusion, the cardiorespiratory depressor responses induced by lactic acid are predominantly elicited by activation of vagal pulmonary C fibers.