Clinical significance of cathepsin E in pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma

BACKGROUND: It has been reported that cathepsin E (CTSE) is a non-secretory and intracellular aspartic proteinase found in the superficial epithelial cells of the stomach and that it is also expressed in pancreatic ductal adenocarcinoma. We evaluated the diagnostic value of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma compared with that of CA19-9, carcinoembryonic antigen (CEA) and K-ras mutations. METHODS: One hundred and one patients (25 with pancreatic ductal adenocarcinoma and 76 with chronic pancreatitis) were examined for the diagnostic significance of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma. Forty of 101 patients (15 with pancreatic ductal adenocarcinoma and 25 with chronic pancreatitis) were examined to compare the diagnostic value of various tumor markers in the pancreatic juice, namely CA19-9, CEA, K-ras mutations and CTSE. RESULTS: The detection frequency of CTSE was significantly higher in patients with pancreatic ductal adenocarcinoma (64.0%) than in patients with chronic pancreatitis (7.9%; chi2 = 34.76; P < 0.0001). The sensitivity, specificity and diagnostic accuracy of CTSE in the pancreatic juice for pancreatic ductal adenocarcinoma was 66.7, 92.0 and 82.5%, respectively. These values were more efficient in comparison with those of CA19-9, CEA and K-ras mutations. The main cause of the detection failure of CTSE in pancreatic ductal adenocarcinoma was obstruction of the main pancreatic duct. Sensitivity was 85.7% in patients without obstruction of the main pancreatic duct. CONCLUSIONS: Cathepsin E in the pancreatic juice is a novel marker for a definitive diagnosis of pancreatic ductal adenocarcinoma.     

Diagnosis of pancreatic cancer by cytology and measurement of oncogene and tumor markers in pure pancreatic juice aspirated by endoscopy

BACKGROUND/AIMS: Cytological examination of pancreatic juice is useful in the diagnosis of an occult cancer of the pancreas. The early diagnosis of pancreatic carcinoma using traditional radiographic or ultrasonographic methods is extremely difficult. METHODOLOGY: In order to detect an early pancreatic cancer, cytological examination, measurement of tumor marker, and detection of K-ras point mutation were performed using the samples of pure pancreatic juice aspirated endoscopically in patients who had symptoms or findings that suggested pancreatic disease. RESULTS: By routine ERP-cytology, positive cytologic results were obtained in 15 (4%) out of 359 patients without a mass. With the aid of intra-operative cytodiagnosis, all 15 occult neoplasms of the pancreas were successfully resected. One patient died from another disease without evidence of recurrence. However, the other patients were alive with no evidence of recurrence for an average of 5.5 years following surgery. The patients who had negative ERP-cytology results were observed, but no further cases of pancreatic cancer were found. The CEA levels in the pure pancreatic juice were significantly higher in patients with pancreatic cancer than in those with pancreatitis. K-ras point mutation at codon 12 was detected not only in cases of pancreatic cancer, but also in cases of chronic pancreatitis as well as control subjects. CONCLUSIONS: Cytological examination of pancreatic juice is useful in the diagnosis of an early and potentially curable in situ cancer of the pancreas. The CEA levels in the pure pancreatic juice provided useful information for differentiating the pancreatic cancer from chronic pancreatitis. K-ras point mutation at codon 12 in pancreatic juice was considered to be useful in identifying patients at high risk for the development of pancreatic cancer.     

Pancreatic Sphincterotomy and Pure Pancreatic Juice Collection for Treatment of Chronic Pancreatitis

Abstract: After our introduction of endoscopic pancreatic sphincterotomy for treatment of chronic pancreatitis in 1985, our interest has been focused to the value of pure pancreatic juice collection with or without pancreatic sphincterotomy for management of chronic pancreatitis. Through pancreatic sphincterotomy, pain relief was obtained in 13 out of 16 cases with moderate and marked chronic pancreatitis. After pancreatic sphincterotomy extraction of pancreatic calculi using basket forceps was done successfully in 2 of these cases, Spontaneous stone passage occured in the other 2. In pure pancreatic juice collection without pancreatic sphincterotomy, pain relief was seen in 6 out of 13 cases with mild and moderate chronic pancreatitis. The protein plug was simultaneously aspirated during the procedure in 3 cases. Recently, we have indicated in these patients both pancreatic sphincterotomy and pure pancreatic juice collection and noted pain relief was obtained in all of the 8 cases with this approach. With an improvement in the technology of pancreatic drainage, these endoscopic treatment modalities may be possibly useful to stop the progression of chronic pancreatitis.     

Measurement of sialylated stage-specific embryonic antigen-1 in pure pancreatic juice for the diagnosis of pancreatic cancer

The diagnostic significance of measuring sialylated stage-specific embryonic antigen-1 (SLX) in pure pancreatic juice was evaluated in 20 patients with pancreatic cancer, 43 with chronic pancreatitis, 13 with cholecystolithiasis, and 15 control individuals. Four fractions of pure pancreatic juice were collected sequentially from the pancreatic duct by endoscopic cannulation. The SLX levels in all four fractions of pure pancreatic juice were significantly higher in patients with pancreatic cancer than in controls. On the other hand, patients with chronic pancreatitis or cholecystolithiasis did not have SLX levels that significantly differed from those of controls in any fraction. When the cut-off value was set as the mean concentration + 2 times the standard deviation of the control values, the positive rates of SLX in the first fraction (washout phase) and the third fraction (secretory phase) of pure pancreatic juice from pancreatic cancer were 55% (11/20) and 40% (8/20), respectively. Although the false positive rates in the first fraction were high in chronic pancreatitis (30%) and cholecystolithiasis (31%), such high SLX levels in the third fraction were found only in one (2%) patient with chronic pancreatitis and in one (8%) with cholecystolithiasis. The specificities of the test for pancreatic cancer in the first fraction and the third fraction were 70% (39/56) and 96% (54/56), respectively. These results indicate that the measurement of SLX in the third fraction of pure pancreatic juice is useful as a specific marker for pancreatic cancer.     

胰腺癌内镜超声引导下细针穿刺活检物中肿瘤标志物检测价值研究

目的 探讨检测内镜超声引导下细针穿刺(EUS-FNA)活检物中CEA、CA19-9常用肿瘤标志物对胰腺癌诊断的价值.方法 2004年6月至2006年1月间的65例胰腺癌患者和25例慢性胰腺炎患者行EUS-FNA,采用电化学发光法对EUS-FNA活检物的离心上清进行CEA、CA19-9检测,并与该患者外周静脉血清中的CEA、CA19-9进行对比和分析.随后对临床可疑胰腺癌而EUS-FNA病理学检测阴性的12例的病例进行随访,观察该方法诊断胰腺癌的敏感性.结果 (1)胰腺癌患者中EUS-FNA标本中CEA和CA19-9均高于血清(P＜0.01).慢性胰腺炎患者EUS-FNA标本与血清中的CEA(P=0.122)和CA19-9(P=0.035)都没有明显差别.(2)对于EUS-FNA标本,胰腺癌中的CEA、CA19-9高于慢性胰腺炎(P＜0.01).对于血清标本,慢性胰腺炎与胰腺癌中的CEA没有明显差别(P=0.079),胰腺癌中的CA19-9高于慢性胰腺炎患者(P＜0.01).(3)12例可疑胰腺癌随访后确诊10例为胰腺癌,2例为慢性胰腺炎.对于胰腺癌的诊断,血清CEA的敏感性为30%,血清CA19-9为70%;EUS-FNA活检物中CEA和CA19-9的预测敏感性均为90%.结论 胰腺癌EUS-FNA活检物中的CEA、CA19-9对提高胰腺癌诊断的敏感性具有较高的临床实用价值,为提高胰腺癌的诊断率提供了一种新的方法.     

Pure pancreatic juice from patients with chronic pancreatitis has an impaired antibacterial activity

Summary Conclusion These data show that pure pancreatic juice of AICP patients has a markedly defective antibacterial activity. This finding might be of potential clinical interest in the understanding of the pathophysiology of the disease. Background The aim of the present study was to test the antibacterial activity of pure pancreatic juice in patients with chronic pancreatitis. Methods The study group consisted of ten patients with ethanol-induced chronic pancreatitis (AICP) and seven control patients free of pancreatic disease. All subjects had recently undergone a secretin-pancreozymin pancreatic function test. After an overnight fast, through a side-viewing endoscope, selective pancreatic duct cannulation was performed. After secretin stimulation, pure pancreatic juice was obtained. Three fractions of different molecular weights were separated. Samples were incubated with 1-mL suspension of 10⁵ Escherichia coli ATCC 25922, and log₁₀ of colony-forming units were counted. Experiments were repeated by grading pancreatic juice concentration, pH of the medium, and inoculum size. Results No significant change of pH of pure pancreatic juice appeared between AICP and controls. Starting from 6-h observation, pure pancreatic juice of AICP patients showed a significant bacterial colonization vs controls (p<0.01). A direct correlation appeared between bacterial colonization and either pH and dilution of pancreatic juice (p<0.001). Antibacterial activity was independent of inoculum size, enzymatic activation or inhibition, and heat treatment. The fraction with 1000–10,000 molecular weight was the one endowed with antibacterial activity.     

Significance of adenocarcinoma-associated antigen YH206 levels in the pancreatic juice

We measured the pancreatic juice levels of antigen YH206, which is a new tumor marker of adenocarcinomas detected by monoclonal antibody YH206 (Hinoda et al., Int. J Cancer 24(5):653-658, 1988). Sandwich enzyme imunoassay revealed that samples from patients with pancreas cancer (n=21) showed significantly higher values (P<0.01) than those of healthy controls (n=15). Eight out of 21 (38.1%) samples from patients with pancreas cancer showed more than 100 U/ml, whereas only one out of 20 (5.0%) from patients with chronic pancreatitis exhibited more than 100 U/ml of antigen YH206. Simultaneous measurement of antigen YH206 and CA19-9 demonstrated that although a higher incidence of positivity in the case of pancreas cancer was obtained for both antigens, antigen YH206 showed much lower incidence of positivity (14%) than CA19-9 (57%) in patients with chronic pancreatitis. Therefore, the measurement of antigen YH206 in the pancreatic juice could be of use for the diagnosis of pancreas cancer. This work was supported by Grants for Cancer Reserch from the Ministry of Education, Science and Culture and by Grants from the Ministry of Health and Welfare for Comprehensive 10-year Strategy for Cancer Control, Japan.     

Cu/Zn-SOD in human pancreatic tissue and pancreatic juice

Summary Conclusion Cu/Zn-SOD is present in pancreatic juice and tissue. Immunohistochemical studies reveal a localization of this enzyme in islet, duct, and centroacinar cells, but to a much lower extent in pancreatic acinar cells. Background It is generally accepted that oxygen radicals are involved in the pathogenesis of acute and chronic pancreatitis. An imbalance of radical-generating and radical-scavenging processes is thought to lead to the damage of pancreatic acinar cells that initiate the autodigestion of the whole organ. Methods We investigated the distribution pattern of the cytosolic radical-scavenging enzyme, copper/zinc-superoxide dismutase (Cu/Zn-SOD), in pancreatic juice and tissue. In patients with chronic pancreatitis or pancreatic malignancies, Cu-Zn-SOD was quantitated in different fractions of pancreatic juice by means of an enzyme immunoassay using two Cu/Zn-SOD-specific monoclonal antibodies. Cryostat or paraffin sections of pancreatic tissue were analyzed by immunohistochemical techniques. Results We found this enzyme to be present in the first secretin-triggered fraction of endoscopically obtained pancreatic juice in concentrations similar to serum. In contrast, after cholecystokinin stimulation, only low levels could be found in pancreatic juice, indicating that this enzyme is not actively secreted. Interestingly, pancreatic juice of patients with chronic pancreatitis or pancreas tumor contained higher levels (25–29 ng/mL) of Cu/Zn-SOD than juice of controls without pancreatic diseases (15 ng/mL). Immunohistochemical studies of Cu/Zn-SOD in pancreatic tissue revealed a more intense staining of duct cells, islet cells, and centroacinar cells, whereas acinar cells showed almost no staining for Cu/Zn-SOD.     

Genetic diagnosis of pancreatic cancer

Genetic analysis of pancreatic juice is a promising aid for the accurate and early diagnosis of pancreatic cancer. K‐ras mutation is frequently observed in pancreatic cancer; however, it is not specific for carcinoma because pancreatic adenoma and pancreatitis also show this mutation. Overexpression of p53 protein is solely detected in pancreatic juice from pancreatic cancer patients, but the positivity rate differs among various reports. Telomerase activity in pancreatic juice was detected in 20 of 24 (83.3%) pancreatic cancer patients and in only 1 of 23 (4.3%) pancreatic adenoma patients, while none of 23 (0%) pancreatitis patients showed evident telomerase activity. The relative value for telomerase activity was significantly higher in parcreatic cancer than in adenoma and pancreatitis. Centrosome abnormalities are very frequently seen in pancreas cancer tissues and the detection of these abnormalities is expected to be a potent new diagnostic tool for the genetic analysis of pancreatic juice. Genetic analysis of pancreatic juice will improve the sensitivity and specificity of pancreatic cancer diagnosis.     

Significance of K-ras mutation and CEA level in pancreatic juice in the diagnosis of pancreatic cancer

The early diagnosis of pancreatic carcinoma is essential for increasing patient survival rates. In this study, 52 patients with suspected pancreatic diseases were examined to investigate the value of K‐ras codon 12 point mutation, levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19‐9), and cytology of pancreatic juice in the diagnosis of pancreatic carcinoma. Pancreatic juice was taken without secretin stimulation. K‐ras mutation was detected by enriched polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). K‐ras mutation in pancreatic juice was more frequent in carcinoma than in benign diseases (P = 0.0448). The positive predictive value of K‐ras mutation for the diagnosis of neoplastic disease was 83%. The CEA level in pancreatic juice in carcinoma was significantly greater than that in benign disease (P < 0.0001). When the cutoff level of CEA was set at 50 ng/ml, its accuracy for the diagnosis of carcinoma was 85%. A multivariate analysis showed that K‐ras mutation and CEA level in pancreatic juice, as well as serum CA19‐9 level and age of the patient were independent variables for the diagnosis of carcinoma, and the accuracy of diagnosis by this analysis was increased to 90%. In conclusion, both K‐ras mutation and CEA level in pancreatic juice may be valuable for the diagnosis of carcinoma. Better discrimination was possible with a multivariate analysis.     

Intraductal carcinoma in a surgically resected pancreas with chronic pancreatitis

A 59-yr-old Japanese male presented with epigastralgia. Endoscopic retrograde cholangiopancreatography (ERCP) revealed narrowing of the inferior common bile duct and protein plugs in the main pancreatic duct. He was diagnosed as suffering from chronic pancreatitis with suspicion of a pancreatic head tumor, and a pancreatoduodenectomy was performed. Histologically, a diffuse chronic pancreatitis was evident in the resected pancreas. Although no tumors were seen in the head portion of the pancreas around the inferior common bile duct, an intraductal carcinoma was found in the second branch of Santorini’s duct. Precancerous alteration of the duct epithelium, presenting papillary hyperplasia, and atypical hyperplasia were observed in areas continuous with the intraductal carcinoma. Immunohistochemically, carcinoembronic antigen (CEA) was specifically expressed in atypical hyperplasia and intraductal carcinoma, but not in papillary hyperplasia.     

Evaluation of Cancer-Associated Carbohydrate Antigen (NCC-ST-439) Measurement in Pure Pancreatic Juice Collected by Endoscopic Aspiration

Abstract: This study was undertaken to elucidate the diagnostic significance of the measurement of a cancer-associated carbohydrate antigen, NCC-ST-439 (ST-439), in pure pancreatic juice collected by endoscopic cannulation, chiefly from patients with pancreatic diseases. The mean concentrations of ST-439 in each of the 4 fractions collected were significantly higher in patients with pancreatic cancer than in controls, but patients with chronic pancreatitis or cholecystolithiasis did not have higher levels. Similarly, a significant increase in the mean output of ST-439 was observed only in patients with pancreatic cancer. When the cut-of value was set at the mean concentration+ 2 X the standard deviations of the controls, significant concentrations of ST-439 were found, in the first fraction (washout phase) in 56% of the pancreatic cancer cases, 31% of the chronic pancreatitis cases and 0% of the cholecystolithiasis cases; in the third fraction (secretory phase) results were 50%, 7% and 0%, respectively. Furthermore, when the cut-of value was set at the highest concentration found among patients with chronic pancreatitis (to enhance the specificity for pancreatic cancer), the prevalence of significant ST-339 levels among Pancreatic cancer patients was 50% in the first fraction and 44% in the third fraction. These results indicate that the measurement of ST-439 in pancreatic juice is useful as a specific marker for pancreatic cancer, although its sensitivity is less than was initially hoped,     

Argyrophilic Nucleolar Organizer Regions May Help the Differential Diagnostic Distinction between Chronic Pancreatitis and Pancreatic Ductal Adenocarcinoma

Mäkinen K, Eskelinen M, Lipponen P, Pasanen P, Nuutinen P, Alhava E. Argyrophilic nucleolar organizer regions may help the differential diagnostic distinction between chronic pancreatitis and pancreatic ductal adenocarcinoma. Scand J Gastroenterol 1994;29:1029-1033.

Background: The aim of this study was to determine whether the number of argyrophilic nucleolar organizer regions (AgNORs) could be of diagnostic significance in differentiating between chronic pancreatitis and pancreatic ductal adenocarcinoma.

Methods: The number of AgNORs was enumerated in biopsy specimens of normal pancreas, chronic pancreatitis, and pancreatic ductal adenocarcinoma.

Results: The number of AgNORs was lower in patients with normal pancreas than in patients with chronic pancreatitis or pancreatic adenocarcinoma. In addition, the number of AgNORs was significantly lower in chronic pancreatitis than in pancreatic ductal adenocarcinoma (p < 0.001).

Conclusions: The diagnosis of pancreatic adenocarcinoma is usually clear. Difficulties can be encountered, however, in cases of chronic pancreatitis, specially when biopsy material is small. Our results suggest that the number of AgNORs may help in distinguishing between chronic pancreatitis and pancreatic ductal adenocarcinoma, especially in diagnostically difficult specimens.     

Immunolocalization of pS2, a putative growth factor, in pancreatic carcinoma

pS2 is a 60 amino acid secretory polypeptide which belongs to a newly described family of trefoil-shaped growth factors. It is widely distributed throughout the gastrointestinal tract, particularly adjacent to damaged mucosa, and is also expressed by some epithelial tumours such as breast carcinoma. The aim of this study was to examine the expression of pS2 in pancreatic cancer. The presence of pS2 was analysed immunohistochemically using two antibodies, a polyclonal (pNR-2) and a monoclonal (pS2^TM) in 42 cases of pancreatic adenocarcinoma and 10 cases of ampullary carcinoma. The findings were compared with chronic pancreatitis and normal pancreas. No immunostaining was seen in normal pancreas, with the exception of one area of ductular proliferation, and although 8/10 cases of chronic pancreatitis expressed pS2, it was focal and confined to the occasional duct. In contrast, a significant proportion of malignant cells in 23/42 (55%) of pancreatic adenocarcinoma and 8/10 (80%) of ampullary tumours expressed immunoreactive pS2. The finding of pS2 expression in more than 50% of pancreatic and ampullary carcinomas in contrast to the findings seen in chronic pancreatitis and normal pancreas suggests that pS2 may play an important role in the growth of these highly malignant tumours.     

Secretory immunoglobulin A in pancreatic juice and pancreatic tissue of patients with chronic pancreatitis

Background—The predominace of secretory IgA(S-IgA) in intestinal secretions compared with blood is wellestablished, but concentrations of this protein in pancreatic juice andits origin, especially in chronic pancreatitis, are unknown.
Aims—To investigate the role of S-IgA in chronic pancreatitis.
Patients—Twenty one patients with chronicpancreatitis (group I), three patients with proven malignancies (groupII), and 12 patients without pancreatic disease (group III).
Methods—Pure human pancreatic juice was collectedendoscopically in four fractions after consecutive stimulation withsecretin and cholecystokinin (CCK). Samples were analysed for S-IgA,protein, trypsinogen, and proteolytic activity.
Results—The S-IgA level was significant increasedin fraction 1 of pancreatic juice of group I (1210 (1411) ng/ml)compared with controls (33 (70) ng/ml). Protein concentrations andtrypsinogen content were lower in group I than in the other groups.Proteolytic activity could be observed in 53% of all 133 pancreaticjuice samples, but in 87% of fraction 1. In pancreatic tissue of three patients with chronic pancreatitis both IgA and secretory component were detected by immunohistology. Expression of the secretory componentby human pancreatic epithelial cells was increased in patients withchronic pancreatitis compared with normal controls. The concentrationof S-IgA in pancreatic juice did not correlate with the serum S-IgAlevel. In contrast, serum levels of S-IgA were decreased in patientswith chronic pancreatitis.
Conclusion—There are high levels of S-IgA inhuman pancreatic juice following chronic inflammation and a protectiverole is suggested for this immunoglobulin.

Keywords:chronic pancreatitis; pancreatic juice; proteaseactivity; protease inhibitors; secretory IgA; immunohistochemistry

     

Characterization of K-ras gene mutations in association with mucinous hypersecretion in intraductal papillary-mucinous neoplasms

Background/Purpose

Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas have a favorable prognosis. However, invasive ductal carcinomas of the pancreas show a rapid progression. The aim of this study was to investigate gene mutations in pure pancreatic juice from IPMN patients and to define these genetic mutations in relation to the histopathological and clinical features of IPMNs.

Methods

Twenty-two patients with IPMN, 21 patients with ductal carcinoma, and 20 patients with normal pancreas or chronic pancreatitis were recruited for this study. We measured the main pancreatic duct’s largest diameter and the maximum size of a dilated branch was assessed by ultrasonography or endoscopic ultrasonography. Pure pancreatic juice was collected and was investigated for K-ras, p16, and p53 mutations.

Results

Mutant K-ras gene was detected in 13 of the 22 patients (59.1%) with IPMNs. Different kinds of mutations were detected in the same patient in 4 cases. In the 13 patients with mutant K-ras gene, the diameter of the most dilated part of the main pancreatic duct was 2–8 mm (average, 4.5 mm) and in 7 patients with wild-type K-ras gene, the diameter was 2–5 mm (average, 2.7 mm). There was a significant difference in the diameter of the main pancreatic duct between patients with and without the mutant K-ras gene (P = 0.0323).

Conclusions

The incidence of K-ras mutation may be associated with the hypersecretion of mucin.     

Determination of CA 19-9 antigen in serum and pancreatic juice for differential diagnosis of pancreatic adenocarcinoma from chronic pancreatitis

Serum CA 19-9 levels were measured in 63 patients with ductal pancreatic adenocarcinoma and in 49 patients with chronic pancreatitis. Concentrations were abnormally high (greater than 40 U/ml) in 57 (90%) patients with cancer and only in 5 (10%) patients with chronic pancreatitis. All patients with falsely normal serum values had poorly differentiated carcinomas. Median CA 19-9 concentrations were progressively higher in patients with more advanced cancer. Fifteen of 16 (93%) patients with localized cancer has abnormal serum levels but only 5 (31%) of them had values greater than 120 U/ml, which was the highest score observed in patients with chronic pancreatitis. Pure pancreatic juice was obtained endoscopically from 23 patients with pancreatic cancer and from 20 with chronic pancreatitis. CA 19-9 concentrations in pancreatic juice were significantly higher in patients with cancer than in non-neoplastic patients. All 11 patients with resectable cancer investigated had a ratio of CA 19-9 to secretory protein concentration in pancreatic juice above the range of patients with chronic pancreatitis. We conclude that serum CA 19-9 determination is highly sensitive and specific for the differential diagnosis of pancreatic cancer versus chronic pancreatitis. However, moderately increased values (less than 120 U/ml), as seen in patients with localized pancreatic adenocarcinoma, are not conclusive for malignancy. The measurement of CA 19-9 to total protein ratio in pure pancreatic juice is proposed as an adjunctive, accurate diagnostic marker for early stages of pancreatic adenocarcinoma.     

Morphometric Characteristics in Adenocarcinoma of the Pancreas and Chronic Pancreatitis

Linder S, Weger A-R. Lindholm J, Jui H, Blåsjö M, Sundelin P, von Rosen A. Morphometric characteristics in adenocarcinoma of the pancreas and chronic pancreatitis. Scand J Gastroenterol 1994;29:764-768.

Background: Morphometric analysis whereby size and form of cellular nuclei are transformed into quantities has previously been shown to be a valuable adjunct to the histopathologic differential diagnosis between chronic pancreatitis and pancreatic carcinoma. The present study aims to assess the clinical value of morphometry performed on cytologic material from benign and malignant pancreatic lesions. Methods: Cytologic specimens from 100 patients with the diagnosis of pancreatic carcinoma and 15 patients with chronic pancreatitis were evaluated by interactive morphometry using a digital image analyzer system. Results: There were significant differences (p < 0.001) for all morphometric variables between the malignant and benign groups (mean area p 50,135.41 μm² versus 69.66 um²; anisokaryosis, 0.74 versus 0.41; and polymorphism, 0.13 versus 0.09). Conclusions: Morphometry may be used as a complementary tool in the cytologic diagnosis of pancreatic carcinoma.     

Overexpression of pancreatitis-associated protein (PAP) in human pancreatic ductal adenocarcinoma

Pancreatitis-associated protein (PAP) is almost absent in normal pancreas, but is strongly induced in acute pancreatitis. PAP mRNA is also expressed in cancer cells, including pancreatic ductal adenocarcinoma. However, the clinicopathological significance of PAP in human pancreatic cancer is not clear. We examined PAP expression in pancreatic tissues from individuals with pancreatic ductal adenocarcinoma using immunohistochemistry. PAP was overexpressed in 79% (30 of 38) of pancreatic ductal adenocarcinoma, 19% (7 of 36) of chronic pancreatitis, and 29% (2 of 7) of mucinous cystadenoma. PAP was found in malignant ductular structures in pancreatic carcinomas as well as in benign proliferating ductules and acinar cells in chronic pancreatitis. It was not expressed in normal pancreas. The incidence of PAP overexpression was significantly higher in pancreatic cancer than in the other pancreatic diseases (P < 0.01). PAP overexpression was significantly correlated with nodal involvement, distant metastasis (P < 0.05), and short survival (P < 0.01) in pancreatic cancer. These results suggest that overexpression of PAP in human pancreatic ductal adenocarcinoma indicates tumor aggressiveness.