Isamu Mizuno

Chemotherapy Targeting Regional Lymph Nodes by Gastric Submucosal Injection of Liposomal Adriamycin in Patients with Gastric Carcinoma

We investigated the delivery of adriamycin (ADR) to the regional lymph nodes of the stomach following the gastric submucosal injection of liposomal adriamycin (Lipo‐ADR) in 34 gastric carcinoma patients, as well as following intravenous administration of free ADR (F‐ADR) in another 18 patients. Prior to radical gastrectomy, Lipo‐ADR was endoscopically injected into the gastric submucosa adjacent to the primary tumor via a needle‐tipped catheter. After Lipo‐ADR injection, the ADR concentration in the primary and secondary drainage lymph nodes was higher than in the other regional lymph nodes. Thus, the regional nodes more susceptible to metastasis showed higher levels of ADR. In contrast, the intravenous administration of F‐ADR produced a similar and far lower ADR concentration in all the nodes. Delivery of ADR to the primary drainage lymph nodes following injection of 5 ml of Lipo‐ADR was compared with delivery to the left gastric artery lymph nodes after intravenous administration of an equal dose of F‐ADR. The ADR levels (μg/g) after gastric submucosal injection were 15.1±8.30 on day 1 (n = 4); and 11.9±4.80 on day 4 (n = 6). Those after intravenous administration were 0.29±0.10 on day 1 (n = 4); and 0.36±0.0 on day 4 (n = 2). The differences between the two groups were significant (P<0.05). The ADR levels after the gastric submucosal injection were far higher than those after intravenous administration. These findings indicate that the gastric submucosal injection of Lipo‐ADR can specifically deliver ADR to the regional lymph nodes at high concentrations. Such preoperative adjuvant chemotherapy targeting the regional lymph nodes may be useful for preventing the lymph node recurrence of gastric carcinoma.

Antitumor effect of liposome-entrapped adriamycin administered via the portal vein

We examined the distribution in tissues and antitumor effect of freeze‐dried liposome‐entrapped adriamycin (Lipo‐ADM) administered via the portal vein to rabbits bearing VX2 tumors. Liposomes composed of egg phosphatidylcholine (cholesterol 50 mol%) were used as drug carriers. The liver concentration of ADM increased after delivery and cardiac uptake decreased compared with free drug treatment. The in vivo antitumor effect of Lipo‐ADM was determined in rabbits inoculated with VX2 tumor. Repeated injections of free ADM via the portal vein prolonged the life span of tumor‐bearing rabbits. The life span was further prolonged by Lipo‐ADM treatment compared with the control group and the free ADM group. Histological examination revealed that the damage to the liver caused by Lipo‐ADM administered via the portal vein did not differ from that observed in animals treated with free ADM. These results indicate that portal vein administration of Lipo‐ADM may be more effective in dealing with liver metastases than treatment with free ADM and may be therapeutically useful without toxic side effects.

Delivery of Lymph Node‐targeted Adriamycin by Gastric Submucosal Liposomal Injection in Rabbits

We investigated the feasibility of specifically delivering adriamycin (ADR) to the regional lymph nodes via gastric submucosal injection of liposomal adriamycin (Lipo‐ADR) in a rabbit model. We determined the tissue distribution of ADR for up to 7 days after the gastric submucosal injection of Lipo‐ADR (0.4 nag/kg of ADR potency) and i.v. administration of an equal dose of free adriamycin (F‐ADR). The area under the ADR concentration‐time curve (AUC) of the regional lymph nodes was 85.4 μg‐day/g after gastric submucosal injection of Lipo‐ADR and 8.44 μg‐day/g after i.v. administration of F‐ADR. The targeting index of the regional lymph nodes, defined as the ratio of the AUC after gastric submucosal injection of Lipo‐ADR to the AUC after i.v. administration of F‐ADR, was 10.1. Gastric submucosal injection of Lipo‐ADR enhanced lymph node‐specific delivery of ADR compared with i.v. administration of F‐ADR. The targeting index was 0.47 for the heart, 0.25 for the bone marrow, and 0.41 for the spleen, indicating that gastric submucosal injection of Lipo‐ADR reduced delivery of ADR to these organs, as compared with i.v. administration of F‐ADR. These data demonstrate that gastric submucosal injection of Lipo‐ADR is well suited for specific delivery of ADR to the regional lymph nodes, suggesting that this method of administration may be useful in delivering preoperative adjuvant chemotherapy for preventing gastric cancer recurrence.

Perforated acute appendicitis in a patient with AIDS/HIV infection: report of a case.

We report herein the case of a 40-year-old man with AIDS who was admitted to hospital with severe abdominal pain, fever, and chills. He underwent an emergency laparotomy which revealed a perforated appendix with suppurative peritonitis. An appendectomy with peritoneal drainage was carried out, but the postoperative course was complicated by fever without leukocytosis; however, he gradually improved following treatment with intravenous antibiotics, granulocyte colony-stimulating factor (G-CSF) and immunoglobulins, and made a complete recovery. His postoperative course demonstrates the effectiveness of this treatment regimen for patients with AIDS complicated by infection without an increase in the white blood cell count (WBC).

Postoperative infection prophylaxis for upper gastrointestinal tract surgery—A prospective and comparative randomized study of cefoxitin and ceftizozime

A prospective and randomized clinical study was conducted in order to compare cefoxitin (CFX) and ceftizoxime (CZX) as prophylactic antibiotics. Two hundred and three consecutive cases of elective upper gastrointestinal tract surgery, performed at our institute between January, 1983, and March, 1986, were entered in the trial. The patients were assigned randomly, before surgery, to the CFX or to the CZX group. Two grams of the assigned antibiotic was first administered during surgery and then continued at a dose of 1 gram, every 8 hrs for a total of 4 days. One patient was withdrawn from the study due to an allergic reaction. Both groups were comparable in sex, age, underlying disease, diagnosis, operation, and preoperative laboratory data. There were 18 infections related to the operation in the CFX group, while there were only 3 in the CZX group (p<0.001). The number of unrelated infections in each group was 6 and 6 respectively (NS). No special differences were found between the two groups regarding the kinds of microorganisms isolated, and no significant differences were seen in the adverse effects of either antibiotic. Our study demonstrated that ceftizoxime was more efficient than cefoxitin in preventing postoperative infection, following upper gastrointestinal tract surgery.

Lymph Node — Targeting Delivery of Adriamycin by Liposomal Administration into Gastric Submucosa in Rabbits

We studied tissue distribution of adriamycin for up to 7 days after gastric submucosal injection of Liposomal adriamycin (Lipo-ADR) (0.4 mg/kg) and i.v. of an equal dose of free adriamycin (F-ADR) in rabbits. The AUC of the regional lymph nodes was 85.4 μg-day/g after the submucosal injection and 8.44 μg day/g after the i.v. The targeting index of the regional lymph nodes, defined as the ratio of the AUC after the submucosal injection to the i.v., was 10.1, and of the bone marrow was 0.25. Gastric submucosal injection of Lipo-ADR enhanced lymph node-specific delivery of ADR.

Prognostic Comparison of Hepatic Resection of Liver Metastases and Chemotherapy via the Portal Vein with Liposome-Entrapped Adriamycin for Unresectable Liver Metastases on Gastric Cancer

The prognoses of hepatic resection of the liver metastases on the gastric cancer were compared with those by chemotherapy via the portal vein with liposome-entrapped adriamycin for unresectable liver metastases. Seven cases of hepatic resection in liver metastases were operated from 1988 to 1992. Postoperative mean survival times were 15.6 months in Hr0(L), 12.7 months in Hr1(L) and 35.4 months in Hr2(AP). To date, 7 cases of unresectable liver metastases have been evaluated via the potal vein with Lipo-ADM(20–30mg/every 2 weeks/body). There were no side effects via the portal vein with Lipo-ADM. As compared with survival time of hepatic resection and unresectable cases with Lipo-ADM for liver metastases, statistically there were no differences between hepatic resection and unresectable cases in the survival time.

A Case of Fulminating Amebic Colitis Presenting as an Acute Abdomen.

アメーバ赤痢は本邦ではまれな疾患であるが, 炎症性大腸疾患の鑑別診断上重要な疾患の1つである. 一般には下痢を主症状とする慢性の経過をとることが多いが, まれには症状が急激に進行して穿孔などの重篤な合併症を併発して不幸な帰転をとることもある.今回, われわれは急性腹症を呈した激症型アメーバ性大腸炎の1例を経験したので報告する.症例は45歳男性で, 主訴は右下腹部痛と水様性下痢. 右下腹部の腹膜刺激症状と強い急性炎症所見があり, 注腸検査で盲腸に潰瘍を認めた. 確定診断には至らなかったが, 症状が進行しており穿孔の危険があるので, 急性腹症と判断し回盲部切除術を施行した. PAS染色で組織学的に栄養型赤痢アメーバを認め本症と確定診断した. 本症は抗アメーバ剤によく反応するが診断が遅れれば死亡率が高いので注意が必要である. 本症例を経験し, 炎症性大腸疾患の鑑別診断には本症を念頭におく必要があると痛感した.

A study on multiple primary gastric carcinoma.

過去18年間に教室で経験した多発胃癌症例について検討した. 多発胃癌の定義はMoertelらの基準によった.胃癌症例692例中同時性多発胃癌は24例 (3.4%) に認められ, 2多発癌22例, 3多発癌2例であった. 主・副病巣とも胃中部領域に存在するものが7例と最も多かった. 副病巣には早期癌が比較的多かった. 多発早期胃癌では陥凹型と隆起型の組み合わせは1例のみであった.組織型の組み合わせでは, 主・副病巣とも分化型を呈するものが14例 (58.3%) に認められた. 副病巣が胃上部領域に存在する6例は, 組織学的に副病巣の方がより低分化であった.中下部領域胃癌に対して幽門側胃亜全摘出術を施行する際には, 術前および術中に胃上部領域の検索を行い, 併存する癌病巣を見逃さないよう十分な注意が必要である.