Kenichi Tsushima

Patency of the Human Accessory Pancreatic Duct as Determined by Dye-Injection Endoscopic Retrograde Pancreatography

The accessory pancreatic duct (APD) is the smaller and less constant pancreatic duct. The patency of the APD was investigated clinically in an effort to determine its role in pancreatic pathophysiology. Dye-injection endoscopic retrograde pancreatography (ERP) was performed in 190 cases. In the patients who exhibited filling of the fine branches of the ducts on ERP, contrast medium with indigo carmine was injected into the major duodenal papilla. The patency of the APD was determined by observing the excretion of the dye from the minor duodenal papilla. Of the 123 control cases studied, 41% had a patent APD. According to the shape of the terminal portion of the APD on accessory pancreatogram, it was classified as either the stick type (n = 63), branch type (n = 15), saccular type (n = 15), spindle type (n = 11), or cudgel type (n = 8). In these groups, 49, 0, 27, 82, and 87% of the APD were patent, respectively. The patency of the APD in the patients with acute pancreatitis was 6% (1 of 17). The difference in patency between this group and the control group was significant (p < 0.01). The patency of the APD varies with the shape of the terminal portion of the APD. A patent APD may prevent acute pancreatitis by lowering the pressure in the main pancreatic ducts.

Randomized controlled study of mitomycin C/carboquone/5-fluorouracil/OK-432 (MQ-F-OK) therapy and mitomycin C/5-fluorouracil/doxorubicin (FAM) therapy against advanced liver cancer.

SummaryWe have previously reported that the combination of mitomycin C, carboquone, 5-fluorouracil and OK-432, including the intra-arterial administration of mitomycin C and carboquone (MQ-F-OK therapy), was effective in the treatment of advanced liver cancer. The Cooperative Study Group conducted a controlled study on MQ-F-OK therapy and the combination of mitomycin C, 5-fluorouracil and doxorubicin, including the intra-arterial administration of mitomycin C and doxorubicin (FAM therapy), against advanced liver cancer. Forty patients with advanced primary or secondary liver cancer were enrolled in this study and randomized into the MQ-F-OK group and the FAM group. Seventeen of the 21 cases in the MQ-F-OK group and 16 of the 19 cases in the FAM group were eligible for response evaluation in accordance with the criteria of the Japan Society for Cancer Therapy. There was no significant difference in the patient characteristics between the two groups. Three cases in the MQ-F-OK group and two in the FAM group showed partial response. There was, however, no significant difference in the response rates and the prolongation of life between the two groups. As for the side-effects, only anemia was observed more frequently in the FAM group than in the MQ-F-OK group. In conclusion, we could not preferentially recommend either MQ-F-OK therapy or FAM therapy for advanced liver cancer. The performance status of the patient was one of the most important factors in the treatment of advanced liver cancer because patients with poor performance status showed poorer results.

Long-term Survivors with Adult Acute Leukemia in Complete Remission: Complications and Return to Work

For addressing, and eventually being able to predict and prevent, both disease-related complications and changes in social status in long-term acute leukemia survivors, the follow-up is the most important factor after treatment. To this end, we assessed the complications following the attainment of complete remission in adult acute leukemia patients and the changes in social status of patients surviving more than 5 years after disease onset. In our study population of 42 survivors, 24 (57.1%) suffered from various combinations of 18 types of identified complications including posttransfusion hepatitis, diabetes mellitus, and idiopathic osteonecrosis. Regarding fertility, 9 live births were recorded in this cohort, from 2 female patients and the partner of a male patient. Of these 42 long-term survivors, at the time of this report 48.5% were working full- or part-time, 9.0% were unemployed, 30.3% were homemakers, and 12.2% were retired.

Antitumor effect of combination of murine recombinant interferon β, murine recombinant interferon γ and human recombinant interleukin-2 in methA-bearing mice

SummaryWe have previously reported that the combination of murine recombinant interferon β (Mu-rIFNβ) with murine recombinant interferon γ (Mu-rIFNγ) provided greater inhibition of tumor growth than did each one alone in MethA-bearing mice. In the present study the effect of addition of human recombinant interleukin-2 (Hu-rIL-2) to the combination of Mu-rIFNβ with Mu-rIFNγ on tumor growth in BALB/c mice bearing syngeneic MethA fibrosarcoma was examined. Low doses of Hu-rIL-2 (5 × 103 U or 5 × 104 U at 3-day intervals) showed no antitumor activity, while a high dose of Hu-rIL-2 (5 × 105 U) showed profound growth inhibition. The administration of IL-2 (ranging between 5 × 103 U and 5 × 105 U) in addition to the combination of IFNβ and IFNγ showed more augmented antitumor effects in a dose-dependent manner. Furthermore, the simultaneous administration of IL-2, IFNβ and IFNγ had more effective therapeutic activity, compared with the sequential administration of interferons and IL-2. These findings indicated that IL-2 in combination with IFNβ and γ was effective for cancer treatment.

Correlation between augmentative effects of leucovorin on 5-fluorouracil and thymidylate synthase inhibition

BackgroundWe studied the relationship between the augmentative effects of leucovorin (LV) on 5-fluorouracil (5-FU) and the inhibition rate of thymidylate synthase (TS) activity in Colon 26 murine colon carcinoma cells and L1210 murine leukemia cells.MethodsIn cytotoxic and TS inhibition studies, cells were exposed for 24 hours to varied concentrations of 5-FU alone or in combination with 1 or 10 μmol/L LV. Cytotoxicity was determined by colony forming efficiency or trypan blue dye exclusion, and TS inhibition rate was determined by [6-3H]-5-FdUMP binding assay. A growth inhibition curve was constructed for longer exposures.ResultsFor tumor cell growth inhibition and cytotoxicity, the augmentative effect was observed when the lower 5-FU concentrations (0.1 μg/mL) were used. There was no difference in the effects between the low (1 μmol/L) and high (10 μmol/L) LV doses. Normally, TS enzyme levels rise acutely when cells are exposed to 5-FU. Both cell lines displayed an increase in TS after exposure to 5-FU. This exposure to 5-FU resulted in the maintenance of free enzyme. LV was able to increase the ternary complex and TS inhibition rate with little induction of TS, however, the inhibition rate was not dependent on doses of LV.ConclusionsIt was concluded that the augmentative effect of LV at a concentration of 0.1 μg/mL 5-FU occurred at the clinically achievable levels of 1 μmol/L of LV, and there was no difference in the effect between the low and high doses. TS was inhibited effectively by 5-FU and the addition of LV, without a marked induction of TS.

A novel model of solitary hepatic tumor in rats using ascites hepatoma AH13: suitability for chemotherapeutic studies.

A highly reproducible model of a solitary hepatic tumor in rats using ascites hepatoma AH13 has been developed using a two‐step method which was suitable for quantitative chemotherapeutic studies. Diffuse hepatic metastases were induced first by inoculation of three different ascites hepatomas, AH13, AH130 and AH7974 into the portal vein in a dose‐dependent fashion. Second, the induced hepatic tumor (3×107 cells) was minced into 1×1×4 mm fragments and implanted in the liver of normal rats. In this procedure, the AH13 strain proved best suited for the generation of a solitary hepatic tumor. The growth of the solitary liver tumor using AH13 was highly reproducible. To demonstrate the suitability of this solitary hepatic tumor model for the evaluation of chemotherapy, the tumor‐burdened rats were treated with adriamycin (ADR) and mitomycin C (MMC). The reduction in tumor size was proportional to dosage, and the statistical significance of the differences between the treatment group and control group was proportional to dosage. A synergistic effect of ADR and MMC on the tumor also was demonstrated. This model should prove to be a useful tool for the testing of newly developed treatments of hepatic cancer.