Nobuo Baba

High dose, external beam and intraoperative radiotherapy in the treatment of resectable and unresectable pancreatic cancer

Ninety patients with pancreatic cancer were treated by external beam radiotherapy (EBRT) and/or intraoperative radiotherapy (IORT) with or without surgical resection of the tumor, and the results were compared with those of a historical control comprising 112 patients treated by surgery alone. At an early stage of this study, postoperative EBRT (50-60 Gy) or IORT (25-33 Gy) was given alone, but recently the two modalities have been combined. The combination of high doses of EBRT and IORT was well tolerated provided that the gastrointestinal tract was not irradiated during IORT. Although EBRT plus IORT appeared to yield better results than either EBRT or IORT alone, the difference was not significant on multivariate analysis, and patients receiving EBRT, IORT, or EBRT + IORT were grouped together. Patients receiving radiotherapy in addition to macroscopically curative surgery had a slightly longer median survival time (14 months) than those receiving curative surgery alone (10 months), but the 3-year survival rate was similar (21% vs. 19%). In patients who underwent noncurative resection, the median survival time was significantly longer for the irradiated group (12 months) than for the control group (6.5 months). Also, in patients with unresectable lesions but no distant metastases, irradiation prolonged the median survival time significantly (8 vs. 3.5 months). In this group, there was one 5-year survivor, who received EBRT of 55 Gy plus IORT of 30 Gy to his unresectable pancreatic body lesion. Patients with metastases were also treated for palliation of symptoms, but it was found that irradiation prolonged the median survival time even in such cases (4.5 vs. 2.5 months). Based on these results, we plan to use EBRT plus IORT in all pancreatic cancer patients with no metastases.

Unresponsiveness of insulinoma cells to secretin: significance of the secretin test in patients with insulinoma.

Summary It is well known that B cells in the pancreas release insulin when stimulated by secretin, but there have been few reports on the response of insulinoma cells to secretin. In five patients with insulinoma, changes in serum immunoreactive insulin (IRI) concentration were measured after the intravenous injection of secretin into the peripheral vein before and after extirpation of the insulinoma. The extirpated insulinomas were cultured and tested for their response to secretin. The rise in serum IRI in response to secretin in patients with insulinoma was significantly slower and smaller than in normal volunteers. After removal of the insulinoma, the response to secretin became prompt and increased with time. Cultured insulinoma cells did not release insulin when stimulated by secretin. Therefore, it is concluded that the response of insulinoma cells to secretin is quite different from that of normal β cells, and that the function of β cells in the insulinoma-bearing pancreas is suppressed by the autonomous hypersecretion of insulin by the insulinoma. The extent of the decrease in function of the β cells in patients with insulinoma can be estimated by the intravenous secretin test. Thus, the secretin test is sometimes useful in the differentiation of hypoglycemia due to insulinoma from that due to β cell hyperplasia or alimentary hyperinsulinemia.

Venous bypass grafting for celiac occlusion in radical pancreaticoduodenectomy.

Radical pancreaticoduodenectomy was performed for cancer of the head of the pancreas in a 65-year-old male patient with congenital celiac occlusion. Preoperative angiography revealed that the arterial flow to the liver, spleen, and stomach was supplied via the pancreaticoduodenal arcade and that the dorsal pancreatic artery arose from the superior mesenteric artery. In order to perform radical pancreatectomy with sufficient clearance of lymph nodes and soft tissues around the pancreas, the celiac arterial circulation was reconstructed. The restoration of flow was effected via a saphenous vein graft between the common hepatic artery and the aorta. Postoperative angiography demonstrated patency of the graft. The patients postoperative course was uneventful.

Influence of obstructive jaundice on pancreatic growth and on basal plasma levels of cholecystokinin and gastrin in rats.

Obstructive jaundice was produced in rats by ligation and transection of bile duct outside the liver; the control group underwent laparotomy alone. Pancreatic wet weight, amylase, lipase, protein, DNA, RNA, RNA/DNA ratio, and weight/100 μg DNA were significantly increased in jaundiced rats when compared to control rats. Histologic evaluation of pancreatic tissue obtained from jaundiced rats revealed the appearance of large or multiple nuclei in pancreatic acinar cells. Basal plasma levels of immunoreactive CCK were significantly increased in haundiced rats at two weeks and four weeks but, when compared to the levels obtained in laparotomized controls at those time intervals, CCK levels were not significantly different. In jaundiced rats, plasma immunoreactive gastrin was found to be significantly decreased at two and four weeks. Plasma gastrin levels were also found significantly decreased when the jaundiced group was compared with laparotomized control group. The results suggest that obstructive jaundice induced enlargement of the pancreas, probably due to hyperplasia and hypertrophy of pancreatic cells. Whether or not this phenomenon is related to changes in gastrin and CCK is not known.

Typical fibrolamellar hepatocellular carcinoma in Japanese patients: Report of two cases

We report herein the cases of two Japanese patients with typical fibrolamellar hepatocellular carcinoma treated at our institute. The first patient was a 19-year-old man with no hepatitis B or C viral infection and a normal, noncirrhotic liver in the nontumorous area. The second was a 36-year-old woman with no viral infection and a noncirrhotic liver in the nontumorous area. The clinicopathology, imaging appearances, and histology of both cases were similar to reports from the United States.

Factors influencing prognosis and indications for curative pancreatectomy for ductal adenocarcinoma of the head of the pancreas

SummaryThe factors influencing prognosis and the indications for curative resection by radical pancreatectomy were evaluated in 74 patients treated with pancreatectomy for ductal cell carcinoma of the head of the pancreas. The 5-yr survival rates for patients without lymph node metastasis, capsular invasion, portal system involvement, or retroperitoneal invasion were 21.2, 20.2, 25.5, and 19.6%, respectively; the 5-yr survival rate for patients with lymph node metastasis or capsular invasion was 5.3% and 6.4%, respectively, and the 2-yr survival rate for patients with portal system involvement or retroperitoneal invasion was 0%. The 5-yr survival rate for 32 patients treated with radical pancreatectomy was 33.4%, and the 3-yr survival rate for 42 patients treated with nonradical pancreatectomy was 0%. Our results suggest that, in patients with ductal adenocarcinoma of the pancreas without factors limiting prognosis, curative resection by radical pancreatectomy is feasible; however, in patients with positive factors, particularly portal system involvement or retroperitoneal invasion, a comprehensive therapeutic program combining extensive surgery, radiation, chemotherapy and/or immunotherapy is necessary to obtain better results.

Pharmacokinetics of intratumoral RK-28, a new hypoxic radiosensitizer

RK-28 is one of the new hypoxic cell radiosensitizers being developed in Japan and has been tested clinically. To reduce its toxicity and increase its sensitizing activity, intratumoral injection of RK-28 was performed during intraoperative radiation therapy for pancreatic cancer. This report presents the results of pharmacokinetic studies performed in 10 of the 17 patients who were administrated intravenous or intratumoral RK-28 during intraoperative radiation therapy. No adverse effects were noted following intravenous or intratumoral injection of the drug. Pharmacokinetic studies demonstrated several metabolites of RK-28 in both serum and tumor tissues. After intratumoral injection, the tumor drug concentration ranged from 123 micrograms/g to 9,292 micrograms/g just after intraoperative radiation therapy (30-50 min after injection of the compound), while the serum concentration ranged from 4.1 to 9.8 micrograms/ml. The tumor drug concentration was 23.3 micrograms/g at 45 min after intravenous injection of RK-28. Thus, intratumoral injection of RK-28 was superior to intravenous administration in this pharmacokinetic study. The combination of intraoperative radiation therapy and intratumoral injection of RK-28 appears to be a feasible treatment method.

Effects of Trypsin Inhibitor on the Remant Pancreas after 85 Percent Pancreatectomy in Rats

Major resection of the pancreas leads to disorders of the endocrine and exocrine pancreas. The effect of a trypsin inhibitor on the remnant pancreas was studied in rats after 85 percent pancreatectomy. Impairments of the glucose elimination rate and the integrated insulin response after 85 percent pancreatectomy were improved by means of oral administration of a synthetic trypsin inhibitor for 4 and 12 weeks. The pancreatic insulin content in the animals treated with trypsin inhibitor for 13 weeks increased to about 1.3 times than that obtained in control animals. The exocrine pancreatic function in 85 percent pancreatectomized rats treated with trypsin inhibitor for 4 weeks and 12 weeks showed substantial improvement as shown by the test with N-benzoyl-L-tyrosil-p-aminobenzoic acid (BT-PABA). The pancreatic amylase, lipase, and protein contents in the animals treated with trypsin inhibitor were increased to 1.9, 1.7 and 2.1-fold, respectively, as compared to control animals for 13 weeks. Histologic examination showed a decrease in abnormal islets of Langerhans, and a tendency toward hypertrophy of the acinar cells. These results suggest that oral administration of a trypsin inhibitor to rats is effective in improving pancreatic endocrine and exocrine functions after 85 percent pancreatectomy.