Hepatobiliary and Pancreatic Oncology

Introduction
The Division of Hepatobiliary and Pancreatic Oncology deals with cancers in the liver, the biliary system,and the pancreas. Various combination therapies are often required in these tumors and the strategies of treatment are fully discussed by surgeons, radiologists and our medical oncologists. We are trying to establish new modalities of treatment and techniques in diagnosis with ultrasonography.

Routine Activities　
Abdominal ultrasonography is performed for both screening malignancies and thorough examination. We have performed contrast-enhanced ultrasound in diagnosis of the liver and pancreatic tumors, since contrast agent of Levovist was approved for the clinical use in 1999. This new modality is useful for differentiating hepatocellular carcinoma (HCC), hemangioma and focal nodular hyperplasia from the other hepatic nodules. In 2001, we mainly used this technique to evaluate blood flow signals from tumor of the pancreas, and now we are studying these results in association with several clinicopathological factors in patients with pancreatic tumor. A total of patients examined by abdominal ultrasonography were 5,597 in 2001, and out of the 5,597 the contrastenhanced ultrasound was applied for 210 patients with hepatic or pancreatic tumors.
Percutaneous transhepatic biliary drainage, cholangiography and cholangioscopy are indicated for the patients with obstructive jaundice to improve a morbid state and examine the cause of obstruction in the bile duct.
Percutaneous ablation therapy including ethanol injection (PEI) and radio-frequency ablation (RFA) is indicated for HCC when the number of tumors is 3 or less and each of them is smaller than 3 cm in diameter as a standard treatment. In 2001, RFA was came to be a first choice of the treatment for small HCC, because it enables to obtain a wide necrotic area by a session of the treatment and shorten the duration of hospitalization, compared with PEI. As a result, PEI is selected when RFA is difficult to perform technically.
Transcatheter arterial chemo-embolization is indicated for patients with advanced or recurrent HCC,which is not suitable for hepatectomy or percutaneous ablation therapy, as a practical setting.

Research Activities
Phase I/II study of hepatic arterial infusion (HAI) with styrene maleic acid neocarzinostatin (SMANCS) alone for patients with far advanced HCC, which started in 2000, is still ongoing. We completed a phase II study of proton beam radiotherapy for HCC in June 2001. A total of 25 patients were enrolled in this study.
Patients with unresectable advanced bile duct cancer receive radiation therapy consisting of external beam radiation therapy (EBRT) and intraluminal radiotherapy. Patients with locally advanced pancreatic cancer (PC) receive EBRT combined with sequential Gemcitabine chemotherapy.Systemic chemotherapy is performed as a clinical trial or a practical treatment in patients with biliary and pancreatic cancer with distant metastases. In 2001, we completed a phase II study of HAI with 5-FU for isolated hepatic metastases from PC. The HAI therapy was active and well tolerated, but resulted in a poorer prognosis, in spite of its high response rate (41%).

New Developments
1. Hypofractionated radiotherapy
We proposed a protocol of hypofractionated radiotherapy for locally advanced PC in phase I setting.According to this, a dose per fraction escalates from 3 to 8 Gy. If the treatment schedule were feasible, full doseof Gemcitabine could be administrated much earlier than that in conventional EBRT schedule. This protocol wasalready submitted to Institutional Review Board (IRB) in August 2001, though we do not have the final approval from IRB at present.
2. Other early clinical trials
Since late 2001, we have taken a part in 3 clinical trials, i.e. late phase II study of CPT-11 for metastatic PC, early phase II study of FTB-8127 for relief of cancer pain and phase II s cancer.
In early 2002, we are going to start 2 clinical trials, i.e. late phase II study of SM11355 (liposoluble platinum complex) for unresectable HCC and phase I study of BAY43-9006 (Raf kinase inhibitor) for advanced HCC.

H. ISHII

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