Takuya Miyagaki

Hemobilia and cystic artery stump pseudoaneurysm associated with liver abscess after a laparoscopic cholecystectomy: report of a case.

A 63-year-old woman was admitted for cholecystitis and underwent a laparoscopic cholecystectomy (LC). She experienced abdominal pain and hemobilia 11 days after the LC. Angiography was performed but it did not show any source of bleeding. Thereafter, at 27 days after LC, a repeat angiogram was performed which revealed a pseudoaneurysm (PA) arising from a cystic artery stump and an embolized PA sack. However, another PA arising from near the embolized PA and liver abscess was observed 4 days after embolization. The arterial collateral flow was evaluated by endovascular balloon occlusion of the right hepatic artery and it was embolized proximal and distal to the bleeding point. The embolization of the partial hepatic artery was effective for PA when packing the PA sack proved to be insufficient. In patients with liver cirrhosis or liver abscess who require an adequate arterial liver flow, it is important to evaluate the collateral arterial flow before hepatic artery embolization.

The role of monoclonal antibody A7 as a drug modifier in cancer therapy

An anticancer antibiotic, neocarzinostatin (NCS), was covalently conjugated to the murine monoclonal antibody A7 (mAb A7), which recognizes the glycoprotein on the cell surface of human colon cancer. The biological and pharmacological properties of the conjugate (A7-NCS) were examined and compared with those of unconjugated NCS. A7-NCS exhibited a strong binding and cytotoxicity to the cell and an antigen-specific tumor accumulation. Significant tumoricidal effects in vivo were observed in the antigen-positive tumor-bearing mice treated with A7-NCS, whereas NCS mixed with mAb A7 and NCS alone were relatively ineffective. In the antigennegative tumor, the tumoricidal effect of A7-NCS was lower than in the antigen-positive tumor. The NCS concentration in blood and tumor were significantly elevated by conjugation to mAb A7. The NCS localization in tumor was higher in the antigen-positive tumor than in the antigen-negative tumor. Death due to acute toxicity was observed at a dose of 20 units (U) NCS in mice treated with unconjugated NCS, whereas toxicity was seen with a much higher dose of NCS (100 U) if the drug was conjugated to the mAb. These findings show that mAb A7 confers more favorable pharmacological properties on an anticancer drug, making it potentially more useful for cancer chemotherapy.

Efficacy and Specificity of a Monoclonal Antibody‐Drug Conjugate in Chemotherapy by Intratumoral Injection

The murine monoclonal antibody (Mab) A7 conjugated to neocarzinostatin (A7‐NCS) was injected intratumorally (IT) into tumor bearing nude mice. Its pharmacokinetics and tumoricidal effects were compared in the high, moderate and low antigen expressing xenograft for SW1116, WiDr and KB tumor‐bearing nude mice, respectively. When injected IT into nude mice, [125I]A7‐NCS was retained in the tumors according to the degree of antigen expression; it was also disseminated into the blood inverse proportion to the antigen expression. Addition of an excess amount of Mab A7 reduced [125I]‐A7‐NCS accumulation in SW1116 xenograft and elevated the [125I]A7‐NCS concentration in the circulation. Complete tumor reduction was found in all 5 mice with SW1116 tumor, and 2 of 5 mice with WiDr tumor. However, only incomplete tumor suppression was observed in mice with the KB tumor. The significant tumor reduction in SW1116 bearing nude mice was attenuated when excess of Mab A7 was simultaneously administered with A7‐NCS‐ These findings indicate that A7‐NCS was localized in the target tumors and exerted its tumoricidal effects depending on the degree of antigen‐antibody interaction when administered IT. Thus, A7‐NCS can be used successfully in vivo for local therapy, auguring new and promising applications for local cancer therapy.

Efficacy of the modified anvil grasper for laparoscopic intra-corporeal circular stapled anastomosis

The traditional anvil grasper may be difficult to use for connecting the stem of an anvil with the centre rod of a circular stapler because the grasper holds the anvil completely still. In addition, the head angle is fixed and cannot handle the anvil head delicately in a tight pelvic space. Many surgeons use a grasper designed for holding the bowel or a dissector for holding the anvil during intra-corporeal circular stapled anastomosis during low anterior resection, sigmoidectomy, left hemi colectomy and know that it is difficult to connect segments with these instruments due to slipping. A new modified anvil grasper was developed with curved blades that can easily grasp the stem of an anvil and smoothly connect it with the centre rod of the circular stapler. This grasper should be useful for surgeons performing laparoscopic intra-corporeal circular stapled anastomoses, which are the most challenging part of laparoscopic colorectal surgery.

Usefulness of the novel evolutional anvil grasper for laparoendoscopic surgery for intracorporeal circular stapled anastomosis during laparoscopic colorectal surgery.

Traditional anvil graspers cannot delicately handle the anvil head as a result of their unique jaw shape that enhances grip force, and they are not suitable for confined pelvic space. With a manufacturing company, we developed a novel anvil grasper, the evolutional anvil grasper for laparoendoscopic surgery (EAGLE), to ensure more precise and safer anastomosis procedures. The EAGLE has curved blades that create a 6‐mm grasping surface that is the same diameter as the anvil stem and is covered with tungsten carbide tips. When using the EAGLE, a surgeon grasps the anvil stem slightly and easily, handles the anvil head and proximal colon, and smoothly sets the anvil to the center rod of the circular stapler. A surgeon can also securely grasp the stem of the anvil, push it into the center rod of the circular stapler and then perform a sequence of actions in anastomosis procedures smoothly and safely.

Radioimmunoimaging of Local Recurrence of Rectal Cancer by Radiolabeled Mouse Monoclonal Antibody A7

Though the definite diagnosis of local recurrence of rectal carcinoma is still difficult, recent rapid development of new diagnostic tools such as ultrasonography, X-ray CT and MRI brought us many information of mass lesion in the body. One of the most promising approaches to clarify the nature of mass lesion is radioimmunoimaging by radiolabeled tumor specific monoclonal antibody. We had developed mouse monoclonal antibody A7 that is reacted with human adenocarcinoma including colorectal cancer. A7 reacted with glycoprotein that is expressed on the cell surface of cancer. The molecular weight of glycoprotein is 42kD and is proved to be different from CEA and CA19–9. Selective accumulation of 1311-labeled A7 to human cancer tissue was observed in nude mouse model. And 1311-labeled A7 is applied for patients who had mass lesion which suspected to be local recurrence of colorectal carcinoma. Five Mci of radiolabeled A7 diluted in saline was administered intravenously for five patients. One, 2, 3 and 7 days after injection the planner or/and SPECT images of the lesion were obtained by digital gamma camera.

Targeting Chemotherapy for Digestive Cancer Using Monoclonal Antibody Drug Conjugate

Murine monoclonal antibody A7 against human colon cancer was conjugated with the anticancer agent Neocarzinostatin (NCS) to form the conjugate A7-NCS. Using this conjugate, immunotargeted chemotherapy, (missile therapy), was administered to 80 patients with digestive cancers. This missile therapy produced tumor reductions on CT scans in some patients with liver metastasis. In a non-randomized clinical trial, the survival rate for patients with liver metastasis treated with A7-NCS was higher than for patients treated with conventional chemotherapy and was approximately the same for patients receiving chemoembolization. Patients who received A7-NCS experienced no serious adverse effects. Human anti-mouse antibody (HAMA) was detected in all A7-NCS-treated patients. To overcome HAMA, early repeated injections, preparation of human-mouse chimeric antibody, and chemical modification of monoclonal antibody were carried out.