title: Intra-arterial infusion chemotherapy with angiotensin-II for locally advanced and nonresectable pancreatic adenocarcinoma: further evaluation and prognostic implications.
abstract: BACKGROUND
  For locally advanced and nonresectable cancer of the pancreas, we performed intra-arterial infusion chemotherapy with angiotensin-II (AT-II). In our preliminary report, this treatment resulted in a median of 14 months of survival without objective adverse effects. This study was designed to clarify the prognostic factor in this chemotherapy by using a larger number of cases.
  
  
  METHODS
  For 32 patients, intra-arterial chemotherapy was performed: 1 or 2 catheters were intraoperatively placed into the pancreas-supplying arteries. The tissue blood flow and its change by AT-II infusion were determined. For intra-arterial chemotherapy, a mixture of methotrexate (50 or 100 mg/m(2)) and AT-II (.4 microg/kg/hour) was repeatedly infused from the catheter, mainly at our outpatient clinic.
  
  
  RESULTS
  With our intra-arterial chemotherapy, the median survival period was 13 months. The median survival period was 19 months in patients without coexisting pancreatitis but was only 9 months in those with it (P =.0003). The presence or absence of coexisting fibrosis in the neighboring uninvolved pancreas offered the only prognostic indicator. The blood flow in cancerous tissue was increased during AT-II infusion, and this was characteristic in the patients whose neighboring uninvolved pancreas had normal parenchyma (nonatrophic) or higher blood flow before AT-II infusion.
  
  
  CONCLUSIONS
  Because the AT-II infusion played a role in shifting the blood flow from the surrounding uninvolved pancreas to the cancer tissues, we can speculate that cancer tissues might have thereby received a higher dose of anticancer drugs if the surrounding uninvolved pancreas had been nonfibrotic and more rich in tissue blood flow.
authors.affiliation: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. oohigasi-hi@mc.pref.osaka.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohigashi
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishikawa
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Yokayama
authors.forename: Yo
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Terumasa
authors.initials: T
authors.lastname: Yamada
authors.forename: Shingi
authors.initials: S
authors.lastname: Imaoka
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nakaizumi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uehara
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000008:administration & dosage / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D008727:Methotrexate