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.     

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.     

Effects and mechanism of emodin and sandostatin on pancreatic ischemia in acute haemorrhagic necrotizing pancreatitis

We hypothesized that maternal serum levels of the isoenzyme creatine kinase (CK)-BB, which is highly expressed in the placenta, may be elevated during the early second trimester in gestations destined to deliver prematurely or of a small-for-gestational-age infant (birthweight below 10th percentile). To test this hypothesis, we compared maternal serum CK-BB levels and percentage of CK-BB over total CK, in 69 normal pregnancies (delivering at term of appropriate-for-gestational-age infants) with those of 25 cases complicated by preterm delivery at < or = 34 weeks (n = 14), of a small-for-gestational-age infant (n = 8), or both (n = 3). No differences were present in maternal serum CK BB levels between normal and complicated pregnancies. Moreover, no correlation was found between gestational age at delivery and CK BB levels (r = 0.03; p = 0.7).     

Beneficial effects of pentoxifylline treatment of experimental acute pancreatitis in rats

BACKGROUND: Apolipoprotein E (apo E) is a protein associated with plasma lipoproteins. Apo E polymorphism has been related to significant modifications of lipoprotein profile, as well as to the incidence of different pathologies including cardiovascular disease, Alzheimer's disease, and vascular dementia. Furthermore, it was proposed that apo E polymorphism might be involved in the aging selection process. OBJECTIVE: The purposes of the present study were the following: (1) to evaluate apo E polymorphism in 'successful' and 'unsuccessful' aging, defined as the absence or presence of disability and severe chronic diseases (mainly cardiovascular disease and dementia), respectively; (2) to evaluate the impact of apo E polymorphism on plasma lipids in very old individuals free of or affected by disability. METHODS: 253 Italian subjects including 100 free-living healthy octo- and nonagenarians, 62 disabled octo- and nonagenarians, and 91 healthy adult controls, all matched for origin were studied. Apo E phenotypes were determined by PhastSystem (Pharmacia). Lipoprotein parameters (total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, lipoprotein (a), and apoprotein A-I and B) were measured by standardized methods. ADL were evaluated by the Katz index. RESULTS: The frequency of sigma2, sigma3, and sigma4 alleles was 0.062, 0.887, and 0.051 respectively in the entire sample; no differences in alleles distribution were found between the three groups. When the subjects were divided according to the E type (E2 type: E2/E2 and E2/E3; E3 type: E3/E3; E4 type: E3/E4 and E4/E4), no differences in lipoprotein parameters emerged, but a trend toward higher total and LDL-cholesterol from the E2 to the E4 type was observed. The sigma4 allele had a raising effect, while sigma2 had a lowering effect on total cholesterol levels, but these effects were much less profound in the disabled octo- and nonagenarians. CONCLUSIONS: We conclude that (1) the frequency of the sigma4 allele is very low in this sample of subjects from central Italy; (2) no differences emerged in sigma4 distribution between healthy and disabled octo- and nonagenarians, and adult controls; the very low frequency of sigma4 allele might contribute to this finding; (3) our data do not support the hypothesis of a possible association between apo E polymorphism and longevity or disability in this population.     

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.     

Inhibition of TNF alpha improves survival in an experimental model of acute pancreatitis

The best method for the diagnosis of osteoporosis and assessment of fracture risk is currently considered to be bone densitometry. The most commonly used dual-energy X-ray absorptiometry (DXA) methods may sometimes not predict bone mass accurately in every skeletal site, are expensive and not widely available. The recent development of computed analysis of a plain radiograph of the hand might provide a practical, inexpensive and rapid method for evaluation of bone mineral status. In this study we evaluated 20 healthy premenopausal and 660 postmenopausal women. In 36 of these subjects a second evaluation was carried out after 2 years of therapy with calcium supplements. The internal and external diameters of the second metacarpal and the metacarpal and ultradistal radial bone density were evaluated using a technical device developed in our laboratory and marketed by NIM, Verona, Italy (Osteoradiometer). The radiographic images, captured by a video camera, were digitized and studied by computed analysis. In 150 subjects bone density at the level of the lumbar spine, femur, and ultradistal and proximal radius was also measured by DXA techniques. Both external (D) and internal (d) diameters increase significantly with age and years since menopause (YSM), whereas metacarpal index (D--d/D) and metacarpal and ultradistal radial bone density decrease significantly with age and YSM. The ratio between metacarpal bone mineral content and the cortical area (volumetric metacarpal bone density) did not change with age. Significant correlations were found between radiometric findings and DXA measurements. The best correlation coefficients were between bone density measured at the level of the ultradistal radius by DXA and radiographic absorptiometry. In the 2-year follow-up study, a 4.9% and 6.2% decline in radial metacarpal bone density respectively were observed, but the difference was statistically significant only for the latter. In conclusion, computed radiogrammetry is closely correlated with all DXA measurements and may be useful in screening of large populations, providing a simple, inexpensive and sufficiently precise method for evaluation of bone mineral status. Further studies are warranted for assessing the accuracy of radiogrammetry for longitudinal investigations and its capacity to predict fracture risk.     

Occurrence of oxidatively modified proteins: an early event in experimental acute pancreatitis

Major recent advances in hardware performance, sample-handling procedures and software algorithms now allow reliable and sensitive mass spectrometric identification of proteins. Mass spectrometry vastly outperforms traditional sequencing technologies and thereby greatly facilitates the elucidation of the functions of individual proteins as well as multiprotein complexes and larger protein assemblages.     

Sodium fusidate and the cytokine response in an experimental model of acute pancreatitis

Previously, we described cloning of three alternatively spliced mRNA forms of human FGF8, a, b, and e, of which the b form is the major expressed species in both normal and tumor prostatic epithelial cells. In this report, we describe construction and overexpression of sense and antisense sequences of either the full length FGF8b coding region (215-amino acids or 215aa), 103aa N-terminal part or a smaller N-terminal region (34aa), each including the 23aa putative signal peptide domain, via a retrovirus system. While the morphologic transforming activities of the sense 215aa and 103aa constructs were similar in NIH3T3 cells, 103aa displayed reduced soft agar clonogenic activity. The 34aa construct was practically inert in these assays, although its expression could mimic the ability of 215aa or 103aa in conferring cell growth under reduced serum condition. Overexpression of any of the three constructs in antisense orientation, however, was similarly effective in reversing the morphology and anchorage-independent growth property of FGF8b-transfected NIH3T3 cells. The expression of the antisense 215aa construct significantly reduced the growth rate of the human prostatic carcinoma DU145 cells and inhibited their soft agar clonogenic activity and in vivo tumorigenicity in nude mice. Taken together, these results identify N-terminal portions of FGF8 protein isoform for having the domains necessary for one or more of the biologic effects examined, and suggest that low levels of FGF8 expressed in prostatic epithelial cells may contribute significantly to their growth and tumorigenic properties.     

Clinical value of pancreatitis-associated protein in acute pancreatitis

OBJECTIVES: Pancreatitis-associated protein (PAP) is a secretory protein that is overexpressed by the pancreas during acute pancreatitis. This study was carried out to assess the clinical value of PAP in acute pancreatitis, particularly its ability to indicate the severity of the disease. METHODS: Twenty-one healthy subjects, 58 patients with acute pancreatitis, and 20 patients with nonpancreatic acute abdomen were studied. In addition to serum PAP concentration, serum concentrations of amylase, lipase, and C-reactive protein (CRP) were measured at admission and, in patients with acute pancreatitis, during the following 5 days. RESULTS: On admission, serum PAP concentrations were abnormally high in 46 of the 58 patients with acute pancreatitis (79%); serum amylase, in 57 patients (98%); serum lipase, in all patients (100%); and serum CRP, in 40 patients (69%). During the subsequent days of the study, PAP and CRP tended to increase, whereas amylase and lipase decreased. No significant differences in PAP or amylase and lipase concentrations were found between patients with mild pancreatitis and those with severe pancreatitis during the entire study period, whereas from the third day to the sixth day, CRP concentrations were significantly higher in patients with severe pancreatitis than in those with mild pancreatitis. Among the 20 patients with nonpancreatic acute abdomen, PAP concentrations were abnormally high in 10 (50%), whereas amylase concentrations were abnormally high in five (25%), and lipase concentrations were high in two (10%). CONCLUSIONS: Our results indicate that the clinical value of PAP in acute pancreatitis is quite limited and, in particular, that PAP is not a useful marker for determining the severity of the disease.     

Analysis of the surgical treatment results in patients with acute pancreatitis

The results of treatment of 248 patients with an acute pancreatitis (AP) are analyzed. Conservative therapy was effective in 178 of them. Mortality was 0.3%. Surgical intervention was done in 64 patients, including 25 with AP, of them 2 (8%) have died; 27--with destructive AP, after cholecystectomy, drainage of bursa omentalis and abdominal cavity 15 (55.5%) died. Pancreatic resection, necrotomy, programmed relaparotomy with permanent necrotomy of pancreas and retroperitoneal cellular tissue were conducted in 17 patients, 3 (17.6%) died.     

Induction of apoptosis in pancreatic acinar cells reduces the severity of acute pancreatitis

1-Cyano-2-hydroxy-3-butene (CHB) has been reported to cause cell death in rat pancreatic acini. In this report, we describe the time-dependent effects of CHB on mouse acinar cell apoptosis and the effects of CHB-induced acinar cell apoptosis on the severity of secretagogue-induced acute pancreatitis in mice. CHB administration to mice resulted in a time-dependent increase in pancreatic apoptosis, which was maximal 12 hours after CHB administration. The severity of pancreatitis was significantly reduced by prior CHB administration and maximal protection was observed when the caerulein injections were started 12 hours after CHB administration. These observations indicate that induction of apoptosis can reduce the severity of pancreatitis and they suggest that induction of pancreatic acinar cell apoptosis may be beneficial in the clinical management of acute pancreatitis.     

The effect of hemodilution with stroma-free hemoglobin and dextran on collateral perfusion of ischemic myocardium in the dog

The effect of hemodilution with stroma-free hemoglobin (SFH) solution was assessed on the collateral perfusion of acutely ischemic myocardium in anesthetized dogs. A similar protocol was used in three groups: one hour following occlusion of the LAD coronary artery, a rapid exchange-transfusion was performed and the changes were followed for the subsequent two hours. Group I was hemodiluted with SFH, in Group II whole blood was reinfused, and Group III was hemodiluted with dextran 70. Following the exchange-transfusions, blood flow to the ischemic zone (15 +/- 3 micrometer microspheres) increased in all groups, but only marginally so in Group II (23 +/- 17%). The greatest increments were seen in the SFH-hemodiluted group (Group I) in which endocardial flow increased by 83 +/- 29% (p less than .05) and epicardial flow increased by 45 +/- 21%; these resulted in the greatest improvements in oxygen delivery. Significant increments in blood flow were seen in Group III, as well, but oxygen delivery was less adequate. Group I also exhibited the lowest output of CPK from the heart and was the only one in which indices of left ventricular performance (dP/dt and EDP) were returned to the pre-occlusion level. these findings suggest the possibility that reduction of blood viscosity by dilution with SFH improves collateral perfusion of the ischemic myocardium.     

Enhancement of survival in acute experimental fowl typhoid in chicks by the administration of iron dextran

Chicks aged 15 days were infected orally with 10(6-4) living Salmonella gallinarum. Iron from iron dextran or ferric ammonium citrate (DFe and CFe respectively), in doses of 2-0 or 0-4 mg/kg given intramuscularly at the time of infection, had no effect on subsequent mortality compared with infected controls. Increasing the amount of CFe to the maximum (20 mg/kg) that was non-toxic intramuscularly was also ineffective but when the dose of DFe was increased to 20 or 50 mg/kg the survival rate rose sharply. If given at other times in relation to the time of infection, or more frequently, 50 mg/kg or more of DFe was less active. The increased survival rate among infected chicks given 50 mg/kg of DFe at the time of infection was accompanied by decreases in the severity of the morbid changes in the disease, and by reductions of between c 10- to 100-fold in the numbers of viable S gallinarum in the liver, spleen or blood at the height of the acute infection. DFe (50 mg/kg) given at the time of infection also eliminated the difference in the survival rate noted previously between infected chicks fed respectively with diets containing fish or meat meal as the sole source of supplementary protein.     

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.     

Staging and treatment for patients with pancreatic cancer. How small is an early pancreatic cancer?

We report a case of a 66-yr-old woman with progressive hair balding, hirsutism and virilization. Gonadotropins and estradiol levels were in the postmenopausal range; total testosterone (TT), free testosterone (FT) and 17-hydroxyprogesterone (17-OHP) were elevated with dehydroepiandrosterone sulphate, androstendione and cortisol serum levels in the normal range, as 24-hr free urinary cortisol. TT, FT and 17-OHP were normalized, and FSH and LH fell to premenopausal levels on 18th day after a single i.m. injection of the GnRH analogue (GnRHa), triptorelin. Then, a diagnosis of hyperandrogenism of ovarian origin was made and bilateral ovariectomy was performed. Histological study of gonadal tissue revealed diffuse stromal hyperplasia of both ovaries with occasional nests of luteinized cells. With immunoperoxidase techniques these cells stained positively for testosterone and progesterone. One month after surgery, androgen levels were normalized together with regression of most of the clinical signs of virilization. In conclusion, our patient showed a severe virilization developed after menopause; hormonal investigations suggested a gonadotropin dependent ovarian hyperandrogenism, confirmed by histological examination; the presence of luteinized cells in the ovarian stroma was responsible for hyperandrogenism, as confirmed by the immunoperoxidase technique.     

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.     

Role of surgery in the treatment of severe acute necrotic pancreatitis

Between May 1975 and December 1991, a total of 208 patients were operated upon for severe acute necrotic pancreatitis. The decision whether to operate on patients with clinical and biologic aggravation despite particularly sustained intensive care was taken after evaluation of ultrasound and CT scan images. Combining pancreatic body resections and necrotic tissue excision with laparostomy and staged lavage drainage reduced global mortality rate from 49.2 to 16.4 p. cent. The criteria used for determining the indication for surgical intervention, and the technical and tactical operative procedures applied allowing this improvement, are described and discussed.     

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.