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Background: To evaluate the immunogenicity of MUC1 peptide vaccine in advanced pancreatic and bile duct cancers, a phase I clinical trial was conducted., Materials and Methods: A 100-mer MUC1 peptide consisting of the extracellular tandem repeat domain and incomplete Freund's adjuvant were subcutaneously administered to 6 pancreatic and 3 bile duct cancer patients at weeks 1, 3 and 5 and doses ranging from 300 to 3000 microg. Circulating intracytoplasmic cytokine-positive CD4+ T cells and anti-MUC1 IgG antibodies were measured before and after vaccination., Results: There were no adverse events, except for mild reddening and swelling at the vaccination site. In 8 patients eligible for clinical evaluation, 7 had progressive disease and 1 stable disease with a tendency for increased circulating anti-MUC1 IgG antibody after vaccination., Conclusion: This phase I clinical trial revealed the safety of a vaccine containing 100-mer MUC1 peptides and incomplete Freund's adjuvant.

Background: MUC1 is associated with tumor invasion and metastasis, and is expressed in pancreatic cancer with a high frequency. This study explored whether MUC1 expression affected the survival of patients with pancreatic cancer., Methods: Tissue specimens obtained from 70 patients with invasive ductal carcinoma of the pancreas, in pTNM stage III or IV, were immunostained with the anti-MUC1 monoclonal antibody DF3. The results of immunostaining were determined to be positive when more than 50% of the total cancer cells were positively stained. Association of the expression of the DF3 epitope with clinicopathological parameters or patients' survival was statistically evaluated., Results: The incidence of positivity of MUC1 expression was 55.7% (39/70) and this incidence was significantly higher in pTNM stage IV than in stage III (odds ratio [OR], 4.015; 95% confidence interval [CI], 1.459-11.0541; P = 0.0076). As there was a clear difference in overall survival between pTNM stages III and IV ( P = 0.0016), the effect of MUC1 expression on survival was separately evaluated in each stage. It was shown that the expression of MUC1 was associated with unfavorable overall survival in stage IV ( P = 0.0197)., Conclusions: Our data suggest that the expression of MUC1 may be related to the progression of pancreatic cancer.

MUC1 is immunogenic in vivo and humoral and cellular immune responses against MUC1 have been detected in cancer patients. Our study explored the association of circulating anti-MUC1 antibodies with clinicopathological parameters or patients' survival of pancreatic cancer. Serum specimens from 36 patients with invasive ductal carcinoma of the pancreas were subjected to enzyme immunoassay for anti-MUC1 IgG or IgM antibodies. Serum levels of anti-MUC1 IgG antibodies were significantly correlated with survival time (p = 0.0004), whereas neither those of anti-MUC1 IgM nor anti-Galalpha(1,3)Gal IgG antibodies, the latter known as natural antibodies cross-reactive with MUC1, showed a given tendency. Some patients' sera with the higher antibody titer showed the reactivity with MUC1-transfectants of cultured pancreatic cancer cells, but not with MUC1-negative parental cells. When the samples were tentatively divided into 2 groups by the serum level of anti-MUC1 IgG antibodies, the survival of patients was significantly longer in the group with optical density >or=0.3 than in that with optical density <0.3 (p = 0.008). Circulating anti-MUC1 IgG antibody levels remained significant (HR, 0.03; 95% CI, 0.003-0.289; p = 0.0024) after multivariate analysis for pTNM stage, patient age and gender. These data suggest that circulating anti-MUC1-IgG antibody levels may be predictive for survival of pancreatic cancer patients., (Copyright 2002 Wiley-Liss, Inc.)

Background/aims: Periampullary cancer frequently metastasizes to the lymph nodes around the superior mesenteric artery. Simultaneous dissection of the nerve plexus around the SMA, however, often results in intractable diarrhea. This study was performed to examine the extent to which regional lymph nodes may be dissected while preserving the superior mesenteric nerve plexus during radical surgery for periampullary cancer., Methodology: The pancreas and surrounding tissue from ten adult autopsied subjects were sectioned at 5 mm intervals. The structure of the nerve plexus and the distribution of the lymph nodes were analyzed, and the anatomical relationship between the nodes and the nerve plexus was investigated., Results: The average thickness of the PLsma was 4.2 +/- 1.3 mm, becoming thinner from the root to the periphery. The lymph nodes were distributed uniformly on the right and left hemicircles of the superior mesenteric artery and along its longitudinal axis. The average number of lymph nodes was 14.2 +/- 7.5 per subject, and the average maximum node diameter was 3.3 +/- 2.3 mm. The distance from the adventitia of the superior mesenteric artery to the node was 5.5 +/- 2.0 mm. Of a total of 142 lymph nodes, 134 (94.4%) were located outside of the nerve plexus., Conclusion: Dissection of the superior mesenteric lymph nodes while preserving the superior mesenteric nerve plexus is theoretically possible.

Cutaneous metastases originating from pancreatic cancer are relatively rare. Five cases of metastatic pancreatic cancer to the skin are presented and discussed with a review of 17 previous case reports. In 20 cases, the cutaneous metastases were present prior to the diagnosis of pancreatic cancer. The most common site of cutaneous metastases originating from pancreatic cancer was the umbilicus. Although such cases are rare, it is important to note that metastatic lesions in the skin may be the first sign and one type of distant metastases originating from pancreatic cancer.

CA 19-9 ganglioside antigen was extracted from the tumors of 16 patients with pancreatic cancer and the antigen was confirmed by mass spectrometry to be a sialyl Lewis(a) ganglioside. Ductal adenocarcinomas from four patients, two whose Lewis blood phenotype was Le(a- b-), one with undifferentiated carcinoma, and one with an acinar cell carcinoma, did not contain detectable amounts of sialyl Le(a) ganglioside. A significant correlation was found between serum CA 19-9 levels and the recovery of ganglioside antigen from respective tumors, but not tumor burden.

Background/aim: The usefulness of magnetic resonance imaging (MR imaging) in the differential diagnosis of cystic lesions of the pancreas was assessed., Methods and Materials: Pseudocyst was present in 9 patients, retention cyst in 4, simple cyst in 2, serous cystadenoma in 1, mucinous cystadenoma in 6, mucinous cystadenocarcinoma in 6. The relative signal intensity (SI) of each cystic lesion on MR imaging was assessed in comparison with that of the liver., Results: It was difficult to distinguish the cystic types from each other based on the SI on MR images. Insofar as mucinous cystic tumors, those containing gelatinous mucin showed higher SI on T1-weighted images than those containing mucinous but watery fluid. five of the 6 mucinous cystic tumors containing gelatinous mucin were histologically malignant, whereas all except one those containing watery fluid were benign., Conclusions: Our results suggest that the SI on T1-weighted images may be useful in distinguishing malignant from benign mucinous cystic tumors.

DU-PAN-2 reactive gangliosides were isolated from the tumor of a patient with pancreatic cancer (duct cell carcinoma, moderately differentiated adenocarcinoma), having a negative Lewis blood phenotype, and were analyzed by means of TLC-immunostaining, enzyme-linked immunosorbent assay (ELISA), permethylation study, 1H NMR spectroscopy and fast atom bombardment mass spectrometry. The structures of the gangliosides were found to be NeuAc alpha 2-3Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer, containing normal and hydroxy fatty acids. By TLC-immunostaining and ELISA with chemically synthesized gangliosides, DU-PAN-2 was demonstrated to react strongly with IV3 alpha NeuAc-Lc4Cer, weakly with IV3 alpha NeuAc-nLc4Cer, and moderately with IV6 alpha NeuAc-Lc4Cer and IV6 alpha NeuAc-nLc4Cer. Thus it was concluded that the DU-PAN-2 reactive ganglioside in the tumor is IV3 alpha NeuAc-Lc4Cer and that DU-PAN-2 has a rather broad specificity.

To assess the treatment effect of pancreatic cancer, thallium 201 chloride (201TlCl) SPECT was performed in three patients. All of the patients before and after treatment showed the same change between the tumor/liver uptake ratio of 201TlCl and the serum level of CA 19-9. In one of the patients, tumor shrinkage was not observed on CT. However, the uptake ratio decreased, accompanying with a reduced serum level of CA 19-9. These results indicate that 201TlCl SPECT is useful to evaluate therapeutic effect of pancreatic cancer.

We studied 428 lymph nodes attached to the head of the pancreas (13,14,17) in 18 patients with ductal carcinoma of the pancreatic head. These were classified into the small size of the lymph nodes less than 5mm (group S), the moderate size of the lymph nodes (group M) and the large size of the lymph nodes more than 10 mm (group L). The metastases were seen in 76 nodes, which consisted of 49 with group S, 14 with group M and 13 with group L. The lymph node involvement in group (14) S was found in 7 of 18 patients (38.9%), that in group (14) M was in 4 (22.2%) and that in group (14) L was in 2 (11.1%). In these involved cases, the primary tumors tended to be locate in the portion near the superior mesenteric artery, such as in the uncinate process. Invasion of extrapancreatic neural plexus was noted in 9 of 18 patients (50%). There was no significant correlation between nerve plexus invasion and lymphatic invasion by Spearman's rank correlation. In addition, any close relationship between plexus invasion and primary tumor location could not be indicated. These results suggested that neural invasion in pancreatic carcinoma is independent of lymphatic invasion, and the routes of cancer spread via the neural plexus are different from those via the lymphatic vessels. Those without liver metastases survived longer than those with liver metastases, which were characteristically multiple.

A tumor in the body of the pancreas was detected in a 31-year-old man who had undergone a resection of a malignant fibrous histiocytoma (MFH) of the left distal femur 2 years before. The patient underwent a distal pancreatectomy with regional lymph node dissection. The surgical specimen revealed MFH metastatic to the pancreas. He is alive without recurrence or metastasis at 1 year after pancreatectomy. This case seems to be the first report of successfully resected pancreatic metastasis of a malignant fibrous histiocytoma in the published literature, as far as we can determine.