Clinical significance of dihydropyrimidine dehydrogenase in adjuvant 5-fluorouracil liver perfusion chemotherapy for pancreatic cancer.
OBJECTIVE
To clarify the relationship between intratumoral dihydropyrimidine dehydrogenase (DPD) expression and response to 5-fluorouracil (5-FU) liver perfusion chemotherapy (LPC) in pancreatic cancer patients, we evaluated DPD expression immunohistochemically in resected pancreatic cancer tissues.


BACKGROUND
Pancreatic cancer is considered a disease with a poor prognosis even if aggressive resection is performed. One of the main causes of death is hepatic metastasis soon after surgery. As a treatment, we have assessed adjuvant LPC via the portal vein using 5-FU just after pancreatectomy for advanced pancreatic cancer since 1994. However, the results remain unsatisfying.


METHODS
Sixty-eight resected specimens were obtained from patients with pancreatic cancer from 1988 to 2000. Formalin-fixed paraffin-embedded tissues were immunostained with polyclonal anti-DPD antibody. The relation between intratumoral DPD expression and the prognoses of pancreatic cancer patients was investigated statistically.


RESULTS
Of the 68 tumors studied, 27 carcinomas (39.7%) were DPD(+), and 41 (60.3%) were DPD(-). In the DPD(+) group, there was no significant difference between the LPC(+) and LPC(-) subgroups, whereas in the DPD(-) group the LPC(+) subgroup showed a significantly higher survival rate than the LPC(-) subgroup. Moreover, in the LPC(+) group, overall survival in the DPD(-) subgroup was significantly better than in the DPD(+) subgroup.


CONCLUSIONS
An immunohistochemical evaluation of intratumoral DPD expression might be useful in predicting responsiveness to 5-FU-based chemotherapy in pancreatic cancer patients. In the DPD(-) group, liver perfusion chemotherapy using 5-FU via the portal vein is effective adjuvant therapy for pancreatic cancer once pancreatectomy has been performed.
Nakayama
Shigeki
S
Department of Surgery II, Nagoya University School of Medicine, Nagoya, Japan.
Takeda
Shin
S
Kawase
Yoshihisa
Y
Inoue
Soichiro
S
Kaneko
Tetsuya
T
Nakao
Akimasa
A
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D010478:Chemotherapy, Cancer, Regional Perfusion; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000032:analysis*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007150:Immunohistochemistry; D008102:Liver Circulation; D008113:Liver Neoplasms / Q000517:prevention & control / Q000556:secondary; D008297:Male; D008875:Middle Aged; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D011169:Portal Vein; D011379:Prognosis; D015996:Survival Rate
D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil