Showing papers on "Pancreatitis published in 1998"

Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis.

Abstract: Background It is unknown whether genetic factors predispose patients to idiopathic pancreatitis. In patients with cystic fibrosis, mutations of the cystic fibrosis transmembrane conductance regulator (CFTR ) gene typically cause pulmonary and pancreatic insufficiency while rarely causing pancreatitis. We examined whether idiopathic pancreatitis is associated with CFTR mutations in persons who do not have lung disease of cystic fibrosis. Methods We studied 27 patients (mean age at diagnosis, 36 years), 22 of whom were female, who had been referred for an evaluation of idiopathic pancreatitis. DNA was tested for 17 CFTR mutations and for the 5T allele in intron 8 of the CFTR gene. The 5T allele reduces the level of functional CFTR and is associated with an inherited form of infertility in males. Patients with two abnormal CFTR alleles were further evaluated for unrecognized cystic fibrosis–related lung disease, and both base-line and CFTR-mediated ion transport were measured in the nasal mucosa. Results Ten...

Mutations of the Cystic Fibrosis Gene in Patients with Chronic Pancreatitis

Abstract: Background The pancreatic lesions of cystic fibrosis develop in utero and closely resemble those of chronic pancreatitis. Therefore, we hypothesized that mutations of the cystic fibrosis transmembrane conductance regulator (CF TR ) gene may be more common than expected among patients with chronic pancreatitis. Methods We studied 134 consecutive patients with chronic pancreatitis (alcohol-related disease in 71, hyperparathyroidism in 2, hypertriglyceridemia in 1, and idiopathic disease in 60). We examined DNA for 22 mutations of the CF TR gene that together account for 95 percent of all mutations in patients with cystic fibrosis in the northwest of England. We also determined the length of the noncoding sequence of thymidines in intron 8, since the shorter the sequence, the lower the proportion of normal CFTR messenger RNA. Results The 94 male and 40 female patients ranged in age from 16 to 86 years. None had a mutation on both copies of the CF TR gene. Eighteen patients (13.4 percent), including 12 withou...

The Role of Cytokines in the Pathogenesis of Acute Pancreatitis

Abstract: Background: The systemic manifestations of acute pancreatitis are responsible for the majority of pancreatitis-associated morbidity and mortality and are now believed to be due to the actions of specific inflammatory cytokines. This report summarizes what is known about the role of cytokines in the pathogenesis of acute pancreatitis. Methods: Comprehensive literature review of experimental pancreatitis as well as all reports of cytokine involvement during clinical pancreatitis. Results: Several cytokines and other noncytokine inflammatory mediators are produced rapidly during pancreatitis. These mediators arise in many tissues in a predictable fashion independent of the animal model used or the underlying etiology in human disease. Preventing the activities of these mediators has a profound beneficial effect in experimental animals. Conclusions: A few recently described inflammatory mediators are believed to be primarily responsible for the systemic manifestations of acute pancreatitis and its associated distant organ dysfunction. The predictable nature in which they are produced may allow for novel approaches to treating this disease.

Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis

Abstract: Background—In patients with major trauma and burns, total enteral nutrition (TEN) significantly decreases the acute phase response and incidence of septic complications when compared with total parenteral nutrition (TPN).Poor outcome in acute pancreatitis is associated with a high incidence of systemic inflammatory response syndrome (SIRS) and sepsis. Aims—To determine whether TEN can attenuate the acute phase response and improve clinical disease severity in patients with acute pancreatitis. Methods—Glasgow score, Apache II, computed tomography (CT) scan score, C reactive protein (CRP), serum IgM antiendotoxin antibodies (EndoCAb), and total antioxidant capacity (TAC) were determined on admission in 34 patients with acute pancreatitis. Patients were stratified according to disease severity and randomised to receive either TPN or TEN for seven days and then re-evaluated. Results—SIRS, sepsis, organ failure, and ITU stay, were globally improved in the enterally fed patients. The acute phase response and disease severity scores were significantly improved following enteral nutrition (CRP: 156 (117‐222) to 84 (50‐ 141), p<0.005; APACHE II scores 8 (6‐10) to 6 (4‐8), p<0.0001) without change in the CT scan scores. In parenterally fed patients these parameters did not change but there was an increase in EndoCAb antibody levels and a fall in TAC.Enterally fed patients showed no change in the level of EndoCAb antibodies and an increase in TAC. Conclusion—TEN moderates the acute phase response, and improves disease severity and clinical outcome despite unchanged pancreatic injury on CT scan. Reduced systemic exposure to endotoxin and reduced oxidant stress also occurred in the TEN group. Enteral feeding modulates the inflammatory and sepsis response in acute pancreatitis and is clinically beneficial. (Gut 1998;42:431‐435)

Percutaneous CT-guided catheter drainage of infected acute necrotizing pancreatitis: techniques and results.

Abstract: The objective of this paper was to assess the safety and efficacy of percutaneous catheter drainage for initial treatment of infected acute necrotizing pancreatitis.Thirty-four patients with acute necrotizing pancreatitis shown with contrast-enhanced CT were treated for sepsis with percutaneous catheter drainage. Extent of necrosis was less than 30% in 10 cases, 30-50% in 10 cases, and greater than 50% in 14 cases. Fourteen patients had central necrosis. Eighteen patients were critically ill with multiorgan failure.Sixteen (47%) of the 34 patients were cured with only percutaneous catheter drainage, including four (29%) of the 14 patients with central gland necrosis and 12 (60%) of the 20 with body-tail necrosis. Sepsis was controlled (defervescence of fever and return of WBC to normal) in an additional nine patients, allowing elective pancreatic surgery for control of pancreatic duct fistula. Eight patients failed to show clinical improvement after drainage and required necrosectomy. No patient experienc...

Early NF-κB activation is associated with hormone-induced pancreatitis

Abstract: Inflammation and cell death are critical to pathogenesis of acute pancreatitis. Here we show that transcription factor nuclear factor-κB (NF-κB), which regulates these processes, is activated and p...

Extended drainage versus resection in surgery for chronic pancreatitis: a prospective randomized trial comparing the longitudinal pancreaticojejunostomy combined with local pancreatic head excision with the pylorus-preserving pancreatoduodenectomy.

Abstract: OBJECTIVE: To analyze the efficacy of extended drainage--that is, longitudinal pancreaticojejunostomy combined with local pancreatic head excision (LPJ-LPHE)-and pylorus-preserving pancreatoduodenectomy (PPPD) in terms of pain relief, control of complications arising from adjacent organs, and quality of life. SUMMARY BACKGROUND DATA: Based on the hypotheses of pain origin (ductal hypertension and perineural inflammatory infiltration), drainage and resection constitute the main principles of surgery for chronic pancreatitis. METHODS: Sixty-one patients were randomly allocated to either LPJ-LPHE (n = 31) or PPPD (n = 30). The interval between symptoms and surgery ranged from 12 months to 10 years (mean 5.1 years). In addition to routine pancreatic diagnostic workup, a multidimensional psychometric quality-of-life questionnaire and a pain score were used. Endocrine and exocrine functions were assessed in terms of oral glucose tolerance and serum concentrations of insulin, C-peptide, and HbA1c, as well as fecal chymotrypsin and pancreolauryl testing. During a median follow-up of 24 months (range 12 to 36), patients were reassessed in the outpatient clinic. RESULTS: One patient died of cardiovascular failure in the LPJ-LPHE group (3.2%); there were no deaths in the PPPD group. Overall, the rate of in-hospital complications was 19.4% in the LPJ-LPHE group and 53.3% in the PPPD group, including delayed gastric emptying in 9 of 30 patients (30%; p < 0.05). Complications of adjacent organs were definitively resolved in 93.5% in the LPJ-LPHE group and in 100% in the PPPD group. The pain score decreased by 94% after LPJ-LPHE and by 95% after PPPD. Global quality of life improved by 71% in the LPJ-LPHE group and by 43% in the PPPD group (p < 0.01). CONCLUSIONS: Both procedures are equally effective in terms of pain relief and definitive control of complications affecting adjacent organs, but extended drainage by LPJ-LPHE provides a better quality of life.

Débridement and closed packing for the treatment of necrotizing pancreatitis.

Abstract: Objective To evaluate the results of debridement and closed packing for necrotizing pancreatitis and to determine the optimal timing of surgical intervention based on patient outcomes. Methods Between February 1990 and November 1996, 64 consecutive patients with necrotizing pancreatitis were treated with necrosectomy followed by closed packing of the cavity with stuffed Penrose and closed suction drains. The mean APACHE II score immediately before surgery was 9, and 31% of the patients had organ failure. Patients were stratified with an outcome score based on death and major complications; this was correlated with the timing of surgical intervention. The data were then subjected to cut-point analysis by sequential group comparison. Results Patients underwent surgery a median of 31 days after diagnosis. Fifty-six percent had infected necrosis. The mortality rate was 6.2% and was no different in infected or sterile necrosis. Eleven patients required a second surgical procedure and 13 required percutaneous drainage; a single surgical procedure sufficed in 69%. Enteric fistulae occurred in 16% of patients. The mean hospital stay after surgery was 41 days, and the interval until return to regular activities was 147 days. A significant negative correlation between duration of pancreatitis and outcome scores was found, and sequential group comparison demonstrated that the change point at which significantly better outcomes were encountered was day 27. Conclusion Debridement of pancreatic necrosis followed by closed packing and drainage is accomplished with a low mortality rate and reduced rates of complications and second surgical procedures. Although intervention is best deferred until the demarcation of necrosis is complete, delay beyond the fourth week confers no additional advantage.

Autoimmune pancreatitis: CT and MR characteristics.

Abstract: OBJECTIVE: Our goal was to elucidate the CT and MR imaging characteristics in patients with autoimmune pancreatitis, which is a reversible chronic pancreatitis with an autoimmune cause. CONCLUSION: On CT and MR imaging, a capsulelike rim, which is thought to correspond to an inflammatory process involving peripancreatic tissues, appears to be a characteristic finding of autoimmune pancreatitis. Also, diffuse pancreatic enlargement along with hypointensity on T1-weighted MR images and delayed enhancement on dynamic CT and MR studies are other features of this disorder.

Progression of pancreatic intraductal neoplasias to infiltrating adenocarcinoma of the pancreas.

Abstract: Pancreata with cancer also frequently have intraductal proliferative lesions, suggesting an association between pancreatic cancer and these lesions. We present three cases in which atypical papillary hyperplasia of the pancreas was documented 17 months to 10 years before the development of an infiltrating adenocarcinoma of the pancreas. The first patient was a 70-year-old woman who underwent pancreaticoduodenectomy for adenocarcinoma of the pancreas. Atypical papillary duct hyperplasia extended to the pancreatic neck margin of resection, but the margin was negative for infiltrating carcinoma. Nine years later, an infiltrating adenocarcinoma developed in the remaining pancreas. The second patient was a 58-year-old man who underwent distal pancreatectomy for chronic pancreatitis with pseudocyst. Histologic examination showed chronic pancreatitis and multiple foci of atypical papillary duct hyperplasia. Ten years later, the patient underwent a Whipple procedure for infiltrating adenocarcinoma of the pancreas. The third patient was a 46-year-old woman with recurrent pancreatitis who underwent a Whipple procedure. Histologic examination showed atypical papillary duct hyperplasia and chronic pancreatitis but no infiltrating carcinoma. At the time of surgery, the tail of the pancreas was grossly and radiographically normal. Seventeen months later, a malignant pleural effusion developed, and postmortem examination showed infiltrating adenocarcinoma in the tail of the pancreas. In the cases presented, atypical papillary hyperplasia was documented 17 months, 9 years, and 10 years before the development of infiltrating adenocarcinoma of the pancreas, supporting the concept that there is a progression from intraductal hyperplasia to infiltrating carcinoma of the pancreas, just as there is a progression from adenoma to infiltrating carcinoma in the colorectum. Based on evidence that these intraductal lesions are precursor lesions to infiltrating adenocarcinoma of the pancreas, we suggest that the term "hyperplasia" be replaced by the more specific term "pancreatic intraepithelial neoplasia."

Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury

Abstract: Substance P, acting via the neurokinin 1 receptor (NK1R), plays an important role in mediating a variety of inflammatory processes. However, its role in acute pancreatitis has not been previously described. We have found that, in normal mice, substance P levels in the pancreas and pancreatic acinar cell expression of NK1R are both increased during secretagogue-induced experimental pancreatitis. To evaluate the role of substance P, pancreatitis was induced in mice that genetically lack NK1R by administration of 12 hourly injections of a supramaximally stimulating dose of the secretagogue caerulein. During pancreatitis, the magnitude of hyperamylasemia, hyperlipasemia, neutrophil sequestration in the pancreas, and pancreatic acinar cell necrosis were significantly reduced in NK1R−/− mice when compared with wild-type NK1R+/+ animals. Similarly, pancreatitis-associated lung injury, as characterized by intrapulmonary sequestration of neutrophils and increased pulmonary microvascular permeability, was reduced in NK1R−/− animals. These effects of NK1R deletion indicate that substance P, acting via NK1R, plays an important proinflammatory role in regulating the severity of acute pancreatitis and pancreatitis-associated lung injury.

United Kingdom Guidelines for the management of acute pancreatitis

Abstract: Preface These guidelines on the management of acute pancreatitis were commissioned by the British Society of Gastroenterology. They have been endorsed by the Clinical Services Committee of the British Society of Gastroenterology, the Association of Upper Gastro-Intestinal Surgeons of Great Britain and Ireland, the Pancreatic Society of Great Britain and Ireland, and the Association of Surgeons of Great Britain and Ireland. The guidelines address the initial steps in diagnosis, investigation and treatment of acute pancreatitis, but stop short of the specific surgical management of complex cases. The nature of acute pancreatitis with its wide variation of severity and complications means that rigid guidelines may be inappropriate and diYcult to apply. Thus, although these guidelines attempt to describe the highest standard of care and set audit goals, a large element of independent clinical decision making is still required. A further factor relates to the availability of local resources and expertise in the management of acute pancreatitis and this is addressed with reference to specialist units. The list of clinicians from diVerent specialities who are directly responsible for these guidelines together with those who were consulted at a later stage of their production is given at the beginning of this supplement. The modus operandi of the group is given within the text. These guidelines were finalised in April 1997 and will need to be revised in two years time.

Acute pancreatitis: the substantial human and financial costs

Abstract: A greater understanding of the natural history of acute pancreatitis combined with greatly improved radiological imaging has led to improvement in the hospital mortality from acute pancreatitis, from around 25-30% to 6-10% in the past 30 years. Moreover, it is now recognised that the first phase of severe acute phase pancreatitis is a systemic inflammatory response syndrome (SIRS), during which multiple organ failure and death often supervene. Survival into the second phase may be accompanied by local complications, such as infected pancreatic necrosis, which may be prevented by prophylactic antibiotics and treated by judicious surgery. Intensive care unit costs can be substantial, but might be justified because of the excellent quality of life of survivors. Reduction in multiple organ failure by agents such as lexipafant, an antagonist of platelet activating factor (PAF) (which plays a critical role in generating the SIRS), may contribute to intensive care unit cost containment, as well as reducing the incidence of local complications and deaths from acute pancreatitis. A further improvement in the human and financial costs also requires the centralisation of the management of patients with severe acute pancreatitis, to single hospital units whose concentrated expertise equips them to intervene most effectively in what is still recognised as a highly complex disease.

Intra-acinar cell activation of trypsinogen during caerulein-induced pancreatitis in rats

Abstract: Supramaximal stimulation of the pancreas with the CCK analog caerulein causes acute edematous pancreatitis. In this model, active trypsin can be detected in the pancreas shortly after the start of supramaximal stimulation. Incubation of pancreatic acini in vitro with a supramaximally stimulating caerulein concentration also results in rapid activation of trypsinogen. In the current study, we have used the techniques of subcellular fractionation and both light and electron microscopy immunolocalization to identify the site of trypsinogen activation and the subsequent fate of trypsin during caerulein-induced pancreatitis. We report that trypsin activity and trypsinogen-activation peptide (TAP), which is released on activation of trypsinogen, are first detectable in a heavy subcellular fraction. This fraction is enriched in digestive enzyme zymogens and lysosomal hydrolases. Subsequent to trypsinogen activation, both trypsin activity and TAP move to a soluble compartment. Immunolocalization studies indicate that trypsinogen activation occurs in cytoplasmic vacuoles that contain the lysosomal hydrolase cathepsin B. These observations suggest that, during the early stages of pancreatitis, trypsinogen is activated in subcellular organelles containing colocalized digestive enzyme zymogens and lysosomal hydrolases and that, subsequent to its activation, trypsin is released into the cytosol.

Intraductal neoplasms of the pancreas

Abstract: background Since 1980 a group of pancreatic tumors have been termed intraductal papillary mucinous tumors (IPMT). Because these tumors occupy an intraductal position they are demonstrated by pancreatography to reside in the main pancreatic duct (MPD) or side branch ducts (SBD). Lesions of IPMT result in abdominal pain or pancreatitis symptoms because mucin production or papillary growth results in ductal obstruction. Only 104 cases had been reported in the literature by 1996 but more are being presented in abstract form. We reviewed our own 33 cases to assist defining operative decision-making criteria. methods All cases of IPMT between 1989 and 1997 were reviewed for clinical presentation, anatomy by endoscopic retrograde cholangiopancreatography and computed tomography, histologic findings, and long-term outcomes. results Our cases were older (65 years) and presented with disease centered mainly in the head of the gland. Clinical presentation was epigastric pain (82%), pancreatitis (56%), weight loss (36%), diabetes (27%), and jaundice (9%). Operations were pancreatectomy in 31 (Whipple n = 15, total n = 5, distal n = 10, local n = 1), bypass only (n = 1), and no operation (n = 1). Malignancy was found in 14 of 33 (42%). Factors significantly associated (P conclusion Malignancy is common with IPMT and is more likely to be present with the clinical history of alcohol abuse or jaundice and if the tumor involves both the MPD and the SBD. The prognosis after resection is better than pancreatic cancer but the 19% recurrence of symptoms was equally seen with benign or malignant cases owing to residual disease in pancreatic remnants. The amount of resection should be extensive in patients likely to have malignancy (alcohol, jaundice, MPD + SBD). In those likely to redevelop symptoms, ie, those with preoperative pain, a careful assessment should be made via imaging studies for extent of disease.

A prospective study of K-ras mutations in the plasma of pancreatic cancer patients.

Abstract: K-ras mutations are frequently found in primary pancreatic adenocarcinomas. In this prospective study, we looked for K-ras mutations in the plasma of patients with pancreatic cancer. We isolated plasma DNA from 21 pancreatic cancer patients using a simple and rapid extraction technique and detected K-ras alterations with a PCR assay and subsequent product sequencing. Patients were followed up to determine their clinical outcome. We found K-ras mutations in the plasma of 17 patients (81%). In cases in which both plasma and pancreatic tissue were available, DNA mutations were similar in corresponding plasma and tissue samples. Plasma DNA alterations were found 5-14 months before clinical diagnosis in four patients. Mutant DNA was not found in the plasma of two patients with chronic pancreatitis or in five healthy controls. Our results indicate that K-ras mutations are often found in DNA isolated from the plasma of pancreatic cancer patients and that a noninvasive plasma-based assay may provide qualitative diagnostic information to clinicians in the future. Larger studies are required to further assess the relevance of our findings to clinical practice.

Hemorrhage after pancreatoduodenectomy.

Abstract: OBJECTIVE: The authors reviewed the hemorrhagic complications of patients who underwent pancreatoduodenectomies between 1972 and 1996. SUMMARY BACKGROUND DATA: Although recent studies have demonstrated a reduction in the mortality of pancreatic resection, morbidity is still high. Bleeding is a close second to anastomotic dehiscence in the list of dangerous postoperative complications. METHODS: The medical records from a prospective data bank of 559 patients who underwent pancreatic resection at the Surgical Clinic of Mannheim (Heidelberg University) were analyzed in regard to postoperative hemorrhagic complications. Differences were evaluated with the Fisher exact test. RESULTS: The overall mortality rate was 2.7%. Postoperative bleeding occurred in 42 patients (7.5%), with 6 episodes ending fatally (14.3%). Erosive bleeding after pancreatic leak was noted in 11 patients (26.2%), 4 of whom died. Gastrointestinal hemorrhage occurred in 22 patients, and operative field hemorrhage was present in 20 cases. Relaparotomy was necessary in 29 patients. An angiography with interventional embolization for recurrent bleeding was performed in three patients. Seven hemorrhages (4.6%) occurred after pancreatectomy for chronic pancreatitis and 35 episodes of bleeding (8.6%) were encountered after pancreatectomy for malignant disease. Obstructive jaundice was present in 359 patients (63.9%). In this group of patients, 32 (8.9%) postoperative hemorrhages occurred. Preoperative biliary drainage did not influence the type and mortality rate of postoperative hemorrhage in jaundiced patients. CONCLUSION: The prevention of these bleeding complications depends in the first place on meticulous hemostatic technique. Preoperative biliary drainage does not lower postoperative bleeding complications in jaundiced patients. Continuous, close observation of the patient in the postoperative period, so as to detect complications in time, and expeditious hemostasis are paramount.

Endoscopic papillary balloon dilation for the management of common bile duct stones: experience of 226 cases.

Abstract: Background and Study Aims: Endoscopic sphincterotomy is a widely accepted technique for the treatment of patients with common bile duct stones. However, it is still associated with occasional complications. The recently developed technique of endoscopic papillary balloon dilation seems to be a safe and effective procedure, and to have great potential for replacing endoscopic sphincterotomy. However, few reports have been published on the use of this technique for bile duct stones. The present study was undertaken to evaluate its safety and efficacy. Patients and Methods: Endoscopic papillary balloon dilation was used to remove common bile duct stones in 226 consecutive patients including 41 patients of ASA classification III/IV, 41 elderly patients (>80 years) 24 with liver cirrhosis, and 86 with periampullary diverticulum. After dilation of the papilla with a balloon diameter of 8 mm, the stones were retrieved. Results: In conjunction with the use of a mechanical or/ and electrohydraulic lithotriptor in 79 patients (35%) with large stones (>10 mm in diameter), clearance of the common bile duct was achieved in 225 of 226 patients (99%) without serious complications, such as hemorrhage or severe pancreatitis; mild (n=13) or moderate (n = 2) pancreatitis occurred in 7 % of cases. Conclusions: Endoscopic papillary balloon dilation is a safe and effective technique for the treatment of common bile duct stones, even in high-risk patients.

Intra-abdominal manifestations of Henoch-Schönlein Purpura

Abstract: Gastrointestinal involvement occurs in approximately two thirds of children with Henoch-Schonlein Purpura (HSP) and usually is manifested by abdominal pain. Abdominal symptoms precede the typical purpuric rash of HSP in 14-36%; the symptoms may mimic an acute surgical abdomen and result in unnecessary laparotomy. Major complications of abdominal involvement develop in 4.6% (range 1.3-13.6%), of which intussusception is by far the most common. The intussusceptum is confined to the small bowel in 58%; its frequent inaccessibility to demonstration by contrast enema means that ultrasonography is the investigation of choice. Ultrasonography complements serial clinical assessment, clarifies the nature of the gastrointestinal involvement and reduces the likelihood of unnecessary surgery. Bowel ischaemia and infarction, intestinal perforation, fistula formation, late ileal stricture, acute appendicitis, massive upper gastrointestinal haemorrhage, pancreatitis, hydrops of the gallbladder and pseudomembranous colitis are seen infrequently. Earlier diagnosis and prompt treatment of intra-abdominal complications has reduced the mortality from 40% to almost zero.

Management of necrotizing pancreatitis by repeated operative necrosectomy using a zipper technique.

Abstract: methods From 1983 to 1995, 72 patients with necrotizing pancreatitis were treated with a general approach involving planned reoperative necrosectomies and interval abdominal wound closure using a zipper. results Hospital mortality was 25%. Multiple organ failure without sepsis caused early mortality in 3 of 4 patients and sepsis caused late mortality in 11 of the remaining 14. The mean number of reoperative necrosectomies/debridements was 2 (0 to 7). Fistulae developed in 25 patients (35%); 64% were treated conservatively. Recurrent intraabdominal abscesses developed in 9 patients (13%) but were drained percutaneously in 5. Hemorrhage required intervention in 13 patients (18%). Prognostic factors included APACHE-II score on admission P = 0.005), absence of postoperative hemorrhage ( P = 0.01), and peripancreatic tissue necrosis alone ( P conclusions The zipper approach effectively maximizes the necrosectomy and decreases the incidence of recurrent intraabdominal infection requiring reoperation. APACHE-II score ≥13, extensive parenchymal necrosis, and postoperative hemorrhage signify worse outcome.

Involvement of matrix metalloproteinase-2 activity in invasion and metastasis of pancreatic carcinoma.

Abstract: BACKGROUND Activation of matrix metalloproteinase-2 (MMP-2) has been implicated in the progression, invasion, and metastasis of various cancers, but little information is available with regard to its role in pancreatic carcinoma with poor prognosis. METHODS Gelatin zymography was used for the detection of latent and activated forms of MMP-2 and MMP-9 in 13 normal pancreatic tissue specimens, 14 chronic pancreatitis tissue specimens, and 33 pancreatic carcinoma tissue specimens. The gelatinase activity was quantified by densitometer, and the 66-kilodalton (kDa)/(66-kDa + 72-kDa) ratio was calculated as the MMP-2 activation ratio. Western blot analysis was performed to confirm the zymographic profile. RESULTS Latent forms of MMP-2 and MMP-9 were detected in all samples of pancreatic carcinoma, chronic pancreatitis, and normal pancreatic tissue. The expression rate of the MMP-2 activated form in pancreatic carcinoma tissue specimens was 100% (33 of 33) but that of MMP-9 was 21%. The MMP-2 activation ratio in pancreatic carcinoma tissue specimens was significantly higher than that of chronic pancreatitis and normal pancreatic tissue specimens. The MMP-2 activation ratio in pT3 tumors was significantly higher than that in pT1 tumors. The MMP-2 activation ratio also was significantly higher in pancreatic carcinoma specimens with histologically positive regional lymph node metastasis and distant metastasis than those without metastasis. The MMP-2 activation ratio observed in patients who developed postresection recurrence within 6 months was significantly higher than that in patients without recurrence at 6 months. CONCLUSIONS The results of the current study indicate that MMP-2 activation plays a significant role in tumor invasion and metastasis in pancreatic carcinoma. Cancer 1998;82:642-50. © 1998 American Cancer Society.