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At least 91 records · Page 5Linked to original sources

PubMed2001

Early detection of pancreatic cancer in patients with chronic pancreatitis: diagnostic utility of a K-ras point mutation in the pancreatic juice.

OBJECTIVE: Point mutations of the K-ras oncogene at codon 12 have been described several months before the onset of pancreatic cancer in isolated cases of chronic pancreatitis (CP). The aim of this study was to evaluate the interest of a prospective follow-up of patients with CP and K-ras mutations at codon 12 in the detection of early pancreatic cancer. METHODS: From February 1996 to March 1998, 36 patients (mean age 52.6 yr, 31 men, five women) with CP (alcoholic: 61.1%, pancreas divisum: 5.6%, autoimmune: 5.6%, unknown origin: 27.7%) were included and then prospectively monitored (median duration of 22 months) for detection of pancreatic carcinoma. K-ras point mutations were examined by two-step polymerase chain reaction combined with restriction enzyme digestion in pancreatic juice collected during endoscopic retrograde pancreatography. RESULTS: Ten patients (27.8%) were positive for K-ras mutation. Patients with and without the mutation were not different with respect to age and sex ratio. K-ras mutations were homogeneously distributed according to the etiology (alcoholic vs nonalcoholic) and morphological characteristics (ductal stricture or mass vs none) of CP. A pancreatic carcinoma was discovered at an invasive stage in two patients, respectively at 7 and 17 months after disclosure of a K-ras mutation, versus none in patients without the mutation (p < 0.02). CONCLUSIONS: Presence of a K-ras gene mutation is not rare in patients with CP and represents an increased risk of developing pancreatic cancer. However, its utility for the detection of early pancreatic cancer remains doubtful in clinical practice.

Adenocarcinoma↗

PubMed2004

Protein expression profiles in pancreatic adenocarcinoma compared with normal pancreatic tissue and tissue affected by pancreatitis as detected by two-dimensional gel electrophoresis and mass spectrometry.

Pancreatic cancer is a rapidly fatal disease, and there is an urgent need for early detection markers and novel therapeutic targets. The current study has used a proteomic approach of two-dimensional (2D) gel electrophoresis and mass spectrometry (MS) to identify differentially expressed proteins in six cases of pancreatic adenocarcinoma, two normal adjacent tissues, seven cases of pancreatitis, and six normal pancreatic tissues. Protein extracts of individual sample and pooled samples of each type of tissues were separated on 2D gels using two different pH ranges. Differentially expressed protein spots were in-gel digested and identified by MS. Forty proteins were identified, of which five [i.e., alpha-amylase; copper zinc superoxide dismutase; protein disulfide isomerase, pancreatic; tropomyosin 2 (TM2); and galectin-1] had been associated previously with pancreatic disease in gene expression studies. The identified proteins include antioxidant enzymes, chaperones and/or chaperone-like proteins, calcium-binding proteins, proteases, signal transduction proteins, and extracellular matrix proteins. Among these proteins, annexin A4, cyclophilin A, cathepsin D, galectin-1, 14-3-3zeta, alpha-enolase, peroxiredoxin I, TM2, and S100A8 were specifically overexpressed in tumors compared with normal and pancreatitis tissues. Differential expression of some of the identified proteins was further confirmed by Western blot analyses and/or immunohistochemical analysis. These results show the value of a proteomic approach in identifying potential markers for early diagnosis and therapeutic manipulation. The newly identified proteins in pancreatic tumors may eventually serve as diagnostic markers or therapeutic targets.

Biomarkers, Tumor↗

PubMed1986

Elevated pancreatic oncofetal antigen levels measured by enzyme immunoassay in pure pancreatic juice of patients with pancreatic cancer.

Pancreatic oncofetal antigen (POA) was measured by enzyme immunoassay in pancreatic juice from patients with pancreatic cancer, chronic pancreatitis, or other diseases. POA levels in pancreatic cancer were significantly higher than in other disorders, and POA was seen by immunofluorescence to be in the cancerous tissues of pancreatic cancer. Assay of POA in the pancreatic juice may be more reliable than serum POA, and could contribute to the diagnosis of pancreatic cancer.

Antigens, Neoplasm↗

PubMed1988

CA 19-9 in serum and pancreatic juice: its role in the differential diagnosis of resectable pancreatic cancer from chronic pancreatitis.

The diagnostic role of serum and pancreatic juice CA 19-9 determination in discriminating surgically resectable pancreatic cancer from chronic pancreatitis was investigated. Only in about one third of cancer patients the serum assay was diagnostic versus subjects with chronic pancreatitis. None of 5 patients with 'early' pancreatic cancer had a diagnostic score [greater than 120 U/ml]. Conversely, the determination of CA 19-9 content in pure pancreatic juice, expressed as Units per microgram of protein, discriminated all the 15 patients with operable tumors, including those with early carcinoma, from subjects with chronic pancreatitis. The CA 19-9 assay of pancreatic juice is proposed as a reliable marker of cancer in those patients in whom the ERCP pattern is not definitive for malignancy.

Adenocarcinoma↗

PubMed1994

Pancreatic duct mucosa following bile salt injury in cats. Morphology, barrier function to pancreatic exocrine proteins and vulnerability by activated pancreatic juice.

We studied pancreatic duct mucosal morphology and barrier function to both activated and nonactivated pancreatic exocrine proteins following bile salt injury in cats. Prograde pancreatic duct perfusion with 15 mM glycodeoxycholate caused epithelial disruption with focal epithelial loss in the majority of animals. In these cats, flow of preanalyzed nonactivated rat pancreatic juice along the duct resulted in a selective loss of zymogens from the duct lumen as determined by two-dimensional isoelectric focusing-sodium dodecyl sulfate gel electrophoresis and reversed-phase high-performance liquid chromatography. Proteins lost had a low isoelectric point (< or = 5.7) and a molecular weight as large as 47,000 Da and included chymotrypsinogen 1, trypsinogens 1 and 2, and procarboxypeptidases B. Proteins with a high isoelectric point (> 5.7), a high molecular weight (> 47,000 Da), or both, were completely recovered from the duct lumen. Flow of activated rat pancreatic juice along a pancreatic duct with bile salt-induced epithelial disruptions caused additional morphologic alterations including an increase in epithelial destruction and occasional necrosis of the duct interstitial and vascular tissue. In some cats, in which the integrity of the ductal epithelium remained preserved following exposure to the bile salt, neither loss of rat pancreatic exocrine zymogens from the duct lumen nor degradation of the duct mucosa by activated rat pancreatic juice was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1997

Pancreatic enzyme secretion and pancreatic pseudocysts in patients with chronic pancreatitis.

CONCLUSIONS: Pseudocyst contents are not indicative of pancreatic function. We presume that the nonresolving pseudocysts did not resolve because they were noncommunicating. The question of the kinetics of secretion into pancreatic pseudocysts is still unresolved. BACKGROUND: Pseudocysts are one of the complications of chronic pancreatitis. We wanted to investigate whether it is of any value to measure enzyme activities (amylase and lipase) in pseudocyst contents, in order to answer the following questions: Is the enzymatic activity: 1. Reproducible in consecutive punctures of the same cyst; 2. Related to cyst age; 3. Indicative for the risk of relapse; and 4. Representative of exocrine pancreatic function. METHODS: In a retrospective study we examined 28 patients with chronic pancreatitis complicated with pancreatic pseudocysts. RESULTS: Reproducibility of enzyme activity in cyst juice in consecutive punctures of the same cyst was poor. We did not observe any correlation between enzyme activity and cyst age defined as the time between two cyst punctures. Enzyme activity in cyst juice was without indication for the risk of relapse. No correlation between enzyme activity and exocrine pancreatic function was found. The pseudocyst contents are not pancreatic juice in the common sense of the word

Adult↗

PubMed2001

Internal pancreatic fistulas with pancreatic ascites and pancreatic pleural effusions: recognition and management.

BACKGROUND: Internal pancreatic fistulas are well recognized complications of chronic pancreatitis. METHODS: Six patients with internal pancreatic fistulas were treated over a period of 5 years from 1995 to 1999. Four patients presented with ascites, one patient presented with ascites and bilateral pleural effusion and the sixth patient presented with left-sided pleural effusion. Five patients were chronic alcoholics and in one patient the cause of pancreatitis was not clear. Although the serum amylase was mildly elevated the levels of amylase in the aspirated fluid were consistently elevated (more than 800 Somogyi units/100 mL), along with the level of proteins (> or = 3 g/100 mL), and on this basis the diagnosis was made. Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated pancreatic ductal disruption in four cases. Initial treatment was conservative, consisting of nasogastric aspiration, nil per oral, antisecretory drugs, repeated paracentesis or thoracocenthesis and total parenteral nutrition (TPN). In two patients naso-pancreatic drains (NPD) were placed across the disrupted pancreatic duct. RESULTS: In one patient conservative treatment with NPD was successful, and the remaining five patients required surgical intervention. There was no mortality. Two patients developed surgery-related complications that were successfully managed, but they required an extended hospital stay. CONCLUSION: Internal pancreatic fistulas should be treated initially non-operatively; if this is not effective, operative therapy should be considered without delay.

Abdominal Pain↗

PubMed1993

Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group.

BACKGROUND: The results of case-control studies and anecdotal reports suggest that pancreatitis may be a risk factor for pancreatic cancer, but there have been no studies of sufficient size and power to assess the magnitude of the relation between these two diseases. METHODS AND RESULTS: We undertook a multicenter historical cohort study of 2015 subjects with chronic pancreatitis who were recruited from clinical centers in six countries. A total of 56 cancers were identified among these patients during a mean (+/-SD) follow-up of 7.4 +/- 6.2 years. The expected number of cases of cancer calculated from country-specific incidence data and adjusted for age and sex was 2.13, yielding a standardized incidence ratio (the ratio of observed to expected cases) of 26.3 (95 percent confidence interval, 19.9 to 34.2). For subjects with a minimum of two or five years of follow-up, the respective standardized incidence ratios were 16.5 (95 percent confidence interval, 11.1 to 23.7) and 14.4 (95 percent confidence interval, 8.5 to 22.8). The cumulative risk of pancreatic cancer in subjects who were followed for at least 2 years increased steadily, and 10 and 20 years after the diagnosis of pancreatitis, it was 1.8 percent (95 percent confidence interval, 1.0 to 2.6 percent) and 4.0 percent (95 percent confidence interval, 2.0 to 5.9 percent), respectively. CONCLUSIONS: The risk of pancreatic cancer is significantly elevated in subjects with chronic pancreatitis and appears to be independent of sex, country, and type of pancreatitis.

Adult↗

PubMed2002

Outcome differences after endoscopic drainage of pancreatic necrosis, acute pancreatic pseudocysts, and chronic pancreatic pseudocysts.

BACKGROUND: Comparative outcomes after endoscopic drainage of specific types of symptomatic pancreatic fluid collections, defined by using standardized nomenclature, have not been described. This study sought to determine outcome differences after attempted endoscopic drainage of pancreatic fluid collections classified as pancreatic necrosis, acute pseudocyst, and chronic pseudocyst. METHODS: Outcomes were retrospectively analyzed for consecutive patients with symptoms caused by pancreatic fluid collections referred for endoscopic transmural and/or transpapillary drainage. RESULTS: Complete endoscopic resolution was achieved in 113 of 138 patients (82%). Resolution was significantly more frequent in patients with chronic pseudocysts (59/64, 92%) than acute pseudocysts (23/31, 74%, p = 0.02) or necrosis (31/43, 72%, p = 0.006). Complications were more common in patients with necrosis (16/43, 37%) than chronic (11/64, 17%, p = 0.02) or acute pseudocysts (6/31, 19%, p = NS). At a median follow-up of 2.1 years after successful endoscopic treatment (resolution), pancreatic fluid collections had recurred in 18 of 113 patients (16%). Recurrences developed more commonly in patients with necrosis (9/31, 29%) than acute pseudocysts (2/23, 9%, p = 0.07) or chronic pseudocysts (7/59, 12%, p = 0.047). CONCLUSIONS: Successful resolution of pancreatic fluid collections may be achieved endoscopically by an experienced therapeutic endoscopist. Outcomes differ depending on the type of pancreatic fluid collection drained. Further studies of endoscopic drainage of pancreatic fluid collections must use defined terminology to allow meaningful comparisons.

Acute Disease↗

PubMed2002

Effects of acute pancreatic duct obstruction on pancreatic perfusion: implication of acute pancreatic duct decompression.

BACKGROUND: Acute pancreatitis can result in pancreatic ischaemia and necrosis. Pancreatic duct (PD) obstruction may be the first step causing ischaemia in acute pancreatitis. Nitric oxide donors can attenuate acute pancreatitis through improvement in compromised pancreatic perfusion (PP). In this study, we determined if (1) PD obstruction altered PP and (2) PD decompression or L-arginine administration reversed this change. METHODS: Fifteen Australian possums were randomly assigned to two groups: Animals in group A (n = 6) were subjected to 30 min of PD obstruction and 60 min of PD decompression. Animals in group B (n = 9) were subjected to 120 min PD ligation and 60 min PD decompression. A subset group B (n = 6) were subjected to intravenous L-arginine (100 microg/kg) at the end of 120 min of ligation and at the end of PD decompression. The PP (Laser Doppler fluxmetry), PD pressure and blood pressure were continuously monitored. RESULTS: PD pressure increased from 2.9 +/- 2.5 to 18.1 +/- 4.9 mmHg following PD ligation. PP was reduced to 67.1% +/- 4.5% (P<0.01) and 46.2% +/- 7.5% (P<0.001) of baseline following 30 and 120 min of PD ligation, respectively. Following 60 min of PD decompression, PP was restored to 89.1% +/- 13.4% (P<0.02) of the baseline in the 30-min group. However, following 120 min PD ligation, PP remained depressed. L-arginine administration after 120 min of PD ligation transiently increased PP from 46.2% +/- 7.5% to 81.1% +/- 8.6% (P<0.03) of baseline. This effect was reproduced if L-arginine was administered at the end of decompression (P<0.05). CONCLUSION: In patients with acute pancreatitis due to obstructive causes, early decompression of the PD may prevent early pancreatic ischaemia.

Acute Disease↗

PubMed1997

Change of pancreatic enzymes, pancreatic stone protein (PSP), and plasma alpha(2)-macroglobulin-trypsin complex-like substance (MTLS) in the activation of pancreatic juice.

To characterize the activation of pancreatic zymogens (trypsinogen, chymotrypsinogen, and proelastase 1) in acute pancreatitis, we studied the activation of pancreatic juice with porcine enteropeptidase in vitro, and then enzymatic activities and the generation of pancreatic stone protein (PSP) S1 form in pancreatic juice were investigated. Further, we determined immunoreactive trypsin, immunoreactive elastase 1, PSP, and alpha(2)-macroglobulin-trypsin complex-like substance (MTLS) levels in plasma to which the activated juice was added. In the present report, we demonstrate that the plasma MTLS level reflected the activation of pancreatic trypsinogen in pancreatic juice. Further, the generation of PSP S1 form was found at an early stage of activation. Therefore, the plasma MTLS level and the generation of PSP S1 form may offer new diagnostic information on the amounts of activated proteases and subsequently on the severity of acute pancreatitis.

Animals↗

PubMed1989

CT-guided pancreatic percutaneous fine-needle biopsy in differential diagnosis between pancreatic cancer and chronic pancreatitis.

Differential diagnosis between pancreatic cancer and chronic pancreatitis is still difficult to establish. In 63 patients with suspected pancreatic neoplasm we performed: serum CA 19-9 assessment, abdominal ultrasound. CT scan and CT-guided pancreatic percutaneous fine-needle biopsy. The conclusive diagnosis was pancreatic cancer in 40 patients and chronic pancreatitis in 23 patients. With regard to the differential diagnosis, sensitivity and specificity were respectively 80% and 78% for serum CA 19-9, 75% and 65% for abdominal US. 85% and 70% for CT scan. 00% and 87% for percutaneous fine-needle biopsy. We conclude that CT-guided percutaneous fine-needle biopsy is the most reliable method for differential diagnosis between pancreatic cancer and chronic pancreatitis.

Adenocarcinoma↗

PubMed2001

Pancreatic polypeptide secretion in patients with chronic pancreatitis and after pancreatic surgery.

AIM: We investigated polypeptide (PP) secretion under basal conditions, in response to bombesin infusion and to meal ingestion in patients with chronic pancreatitis (CP) and patients after different types of pancreatic surgery. METHODS: Included were patients with CP without (n = 20) and with (n = 30) exocrine pancreatic insufficiency, patients after duodenum preserving resection of the head of the pancreas (DPRHP; n = 20), after Whipple's procedure (n = 19), following distal pancreatectomy (DP; n = 12), and healthy controls (n = 36). RESULTS: In CP patients basal and bombesin stimulated PP levels were significantly (p<0.01) reduced compared to controls only when exocrine insufficiency was present. Meal-stimulated PP secretion was significantly (p<0.01-0.05) reduced in CP patients both with and without exocrine insufficiency. Plasma PP peak increments after bombesin and meal ingestion correlated significantly with exocrine function. Basal PP, meal, and bombesin-stimulated PP secretion had low sensitivities of 22%, 42%, and 60% respectively, in detecting chronic pancreatitis. In patients after pancreatic surgery that included pancreatic head resection (DPRHP or Whipple operation) basal and stimulated PP secretion were significantly (p<0.01-0.05) reduced. CONCLUSION: Basal and meal or bombesin-stimulated PP levels are significantly reduced in patients with CP only when exocrine insufficiency is present. Determination of plasma PP levels has low sensitivity and is not useful in detecting chronic pancreatitis without exocrine insufficiency. In patients after pancreatic surgery, PP secretion is dependent on the type of operation (head vs tail resection).

4-Aminobenzoic Acid↗

PubMed1984

Chronic pancreatitis: long-term surgical results of pancreatic duct drainage, pancreatic resection, and near-total pancreatectomy and islet autotransplantation.

Severe abdominal pain was the major indication for operation in 85 patients with chronic pancreatitis. Preoperative endoscopic retrograde cholangiopancreatography (50 patients) or intraoperative pancreatic ductograms (44 patients) demonstrated dilated or obstructed major pancreatic ducts in 50 patients (59%), nonvisualization of the distal duct in 10 patients (12%), and normal or small sized ducts in 34 patients (40%). Operative procedures, tailored according to duct morphology, included pancreatic duct drainage (46 patients), subtotal (40% to 80%) pancreatectomy (21 patients), near-total (85% to 95%) pancreatectomy alone (eight patients), and near-total or total pancreatectomy and intrahepatic islet autotransplantation (10 patients). Pancreatic duct drainage resulted in pain relief in 37/46 patients (80%) followed for 6 years. However, 20/46 patients (43%) had continued loss of pancreatic function after duct drainage as measured by the development of insulin-dependent diabetes (16 patients) or steatorrhea (seven patients). Seven years after subtotal pancreatectomy, pain relief was partial in 9/21 patients (43%) and complete in five patients (24%). A higher incidence of hypoglycemic or ketoacidotic complications was noted in patients treated by subtotal pancreatectomy (three patients, 14%) than by duct drainage (one patient, 2%). Near-total pancreatectomy was the most effective surgical procedure in relieving pain, but late sequelae in three patients (38%) included one hypoglycemic death and two ketoacidotic episodes. Five years after near-total pancreatectomy and islet autotransplantation, one patient remained permanently insulin independent; three patients were insulin independent for 4, 5, and 15 months, respectively, but subsequently developed nonketosis-prone diabetes (tested by insulin withdrawal) and require 15 to 30 U of insulin daily; three patients had immediate insulin requirements and currently need 20 to 30 U of insulin per day but are nonketosis prone; and two patients are ketosis prone and require 30 to 60 U of insulin daily. Our analysis suggests that 5-year survival of patients undergoing operation for chronic pancreatitis is similar after treatment by duct drainage, subtotal pancreatectomy, or near-total pancreatectomy, regardless of duct morphology. Five years after duct drainage or subtotal pancreatic resection, a high incidence of diabetes (59% and 48%) and/or continued pain (20%) and (35%) can be expected.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMedDate not supplied

Pancreatic head carcinoma: is pancreatic resection indicated for patients with stage III pancreatic duct cancer?.

BACKGROUND/AIMS: This paper examines factors influencing the outcome of patients suffering from unresectable pancreatic carcinoma. MATERIALS AND METHODS: One hundred forty-three patients with pancreatic carcinoma were placed into three groups. Group A (n = 56) received pancreatic resection. Group B (n = 30) included patients deemed ineligible for pancreatic resection. Group C (n = 57) was made up of patients deemed ineligible for pancreatic resection who received combined locoregional immuno-chemotherapy. RESULTS: Twenty-two patients (36%) from Group A are still living. Average survival is 18.6 months. Survival was dependent on the stage of the disease, the site of origin, and the type of resection. All Group B patients are dead with an average survival of 4.5 months and poor quality of life. Thirty-two patients (56%) from Group C are alive. Average survival is 21 months and they have a much greater quality of life index compared to Group A or B. CONCLUSION: Based on the above results, we believe that for patients with Stage III Pancreatic Duct Carcinoma, pancreatic resection should not be the initial treatment option. These patients should be treated first with Locoregional Combined Immunochemotherapy. Then depending upon their response, should be assigned to a subsequent pancreatic resection.

Adult↗

PubMedDate not supplied

Pancreatic head enlargement associated with a pancreatitis- induced intrasplenic pseudocyst in a patient with chronic pancreatitis: organ preserving surgical treatment.

Intrasplenic pseudocyst is a rare form of a late complication of chronic pancreatitis. We report the case of a 30-year-old man with an intrasplenic pseudocyst associated with chronic alcoholic pancreatitis. The patient was admitted with the third acute phase of chronic relapsing pancreatitis. Abdominal US and CT showed a large cyst in the pancreatic tail with involvement of the spleen. ERCP revealed marked irregularities of the main pancreatic duct without communication to the large cyst and a narrowing of the distal common bile duct by chronic pancreatitis of the head of the pancreas. Organ preserving surgical treatment with duodenum- preserving resection of the head of the pancreas combined with distal pancreatectomy and splenectomy was performed. This procedure may be indicated in selected patients to preserve functional pancreatic tissue and prevent diabetes. It should be in the armamentarium of the specialized pancreatic surgeon.

Adult↗

PubMed2005

Quantification of pancreatic exocrine function with secretin-enhanced magnetic resonance cholangiopancreatography: normal values and short-term effects of pancreatic duct drainage procedures in chronic pancreatitis. Initial results.

The aim of this study was to quantify pancreatic exocrine function in normal subjects and in patients with chronic pancreatitis (CP) before and after pancreatic duct drainage procedures (PDDP) with dynamic secretin-enhanced magnetic resonance (MR) cholangiopancreatography (S-MRCP). Pancreatic exocrine secretions [quantified by pancreatic flow output (PFO) and total excreted volume (TEV)] were quantified twice in ten healthy volunteers and before and after treatment in 20 CP patients (18 classified as severe, one as moderate, and one as mild according to the Cambridge classification). PFO and TEV were derived from a linear regression between MR-calculated volumes and time. In all subjects, pancreatic exocrine fluid volume initially increased linearly with time during secretin stimulation. In controls, the mean PFO and TEV were 6.8 ml/min and 97 ml; intra-individual deviations were 0.8 ml/min and 16 ml. In 10/20 patients with impaired exocrine secretions before treatment, a significant increase of PFO and TEV was observed after treatment (P<0.05); 3/20 patients presented post-procedural acute pancreatitis and a reduced PFO. The S-MRCP quantification method used in the present study is reproducible and provides normal values for PFO and TEV in the range of those obtained from previous published intubation studies. The initial results in CP patients have demonstrated non-invasively a significant short-term improvement of PFO and TEV after PDDP.

Adult↗

PubMed2004

p-[123I]iodo-L-phenylalanine for detection of pancreatic cancer: basic investigations of the uptake characteristics in primary human pancreatic tumour cells and evaluation in in vivo models of human pancreatic adenocarcinoma.

Pancreatic cancer is associated with the worst 5-year survival rate of any human cancer. This high mortality is due, in part, to difficulties in establishing early and accurate diagnosis. Because most tumours share the ability to accumulate amino acids more effectively than normal tissues and any other pathology, assessment of amino acid transport in tumour cells using radiolabelled amino acids has become one of the most promising tools for tumour imaging. This study investigated the potential of p-[(123)I]iodo-L-phenylalanine (IPA) for detection of pancreatic cancer by single-photon emission tomography. IPA affinity for pancreatic tumour was investigated in human pancreatic adenocarcinoma PaCa44 and PanC1 cells, followed by analysis of the underlying mechanisms of tracer accumulation in neoplastic cells. Thereafter, IPA was evaluated for targeting of pancreatic tumours using SCID mice engrafted with primary human pancreatic adenocarcinoma cells, as well as in acute inflammation models in immunocompetent mice and rats. IPA accumulated intensively in human pancreatic tumour cells. Radioactivity accumulation in tumour cells following a 30-min incubation at 37 degrees C/pH 7.4 varied from 41% to 58% of the total loaded activity per 10(6) cells. The cellular uptake was temperature and pH dependent and predominantly mediated by specific carriers for neutral amino acids, namely the sodium-independent and L-leucine-preferring (L-system) transporter and the alanine-, serine- and cysteine-preferring (ASC-system) transporter. Protein incorporation was less than 8%. Biodistribution studies showed rapid localization of the tracer to tumours, reaching 10%+/-2.5% to 15%+/-3% of the injected dose per gram (I.D./g) in heterotopic tumours compared with 17%+/-3.5% to 22%+/-4.3% I.D./g in the orthotopic tumours, at 60 and 240 min post injection of IPA, respectively. In contrast, IPA uptake in the gastrointestinal tract and areas of inflammation remained moderate and decreased with time. Excellent tumour detection was obtained by gamma camera imaging. The specific and high-level targeting of IPA to tumour and the negligible uptake in the gastrointestinal tract and areas of inflammation indicate that p-[(123)I]iodo-L-phenylalanine is a promising tracer for differential diagnosis of pancreatic cancer.

Adenocarcinoma↗