Jiro Yura

Percutaneous transhepatic cholangiography (PTC) in biliary atresia with special reference to the structure of the intrahepatic bile ducts

Percutaneous transhepatic cholangiography (PTC) was carried out in 30 cases of biliary atresia, 19 prior to surgery, and 11 following hepatic portoenterostomy. The intrahepatic biliary system was demonstrated in 47% of the patients prior to surgery and in all cases following surgery. Two distinct patterns of intrahepatic bile ducts were noted. The first shows changes similar to those noted by intrahepatic cholangiography in patients with choledochal cyst, as in type A. The second pattern shows collections of numerous narrow proliferated bile ducts that constitute the ducts within and outside the liver as in type B. In patients with recurrent ascending cholangitis or symptoms suggestive of stenosis of the hepatointestinal anastomosis following Kasai-type operations for biliary atresia, PTC is useful in determining the structure of the hepatobiliary ductal system prior to reexploration procedures.

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.

Localization of endothelin-1 and its binding sites to the nervous system of the human colon

Endothelin-1 (ET-1) has been reported to possess a wide variety of biological activities, including neurotransmission. Our aim was to demonstrate ET-like immunoreactivity (ET-LI) and its binding sites in human enteric nervous system using immunohistochemistry and in vitro autoradiography. ET-LI was displayed in nerve bundles and most of the ganglion cells in both myenteric and submucous plexuses, many of which costored VIP. [125I]ET-1 binding sites were identified, especially to plexuses, mucosa, and blood vessels. High-affinity (Kd = 0.35 +/- 0.014 nM; mean +/- SEM) binding sites, with a maximum binding capacity (Bmax) of 92 +/- 6.3 amol/mm2, were demonstrated in the myenteric plexus. This study provides evidence that ET-1 is a neuropeptide in the human colon with binding sites on neural plexuses and mucosa, indicating a possible role in the modulation of motility and secretion in the human intestine.

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.

A bacteriological study of perforated duodenal ulcers

Peritoneal fluid sampling and bacteriological examination were performed in 63 patients with perforated duodenal ulcers, and the results compared with those in 175 patients with other perforations. Bacterial culture was positive in 100 per cent of the patients whose perforations occurred in the colon, whereas it was positive in only 44.4 per cent of those with duodenal perforations, being negative in many cases when the interval from perforation to surgery was short. A mixed contamination with both aerobes and anaerobes was usually found in the cases of lower digestive tract perforation, and the isolates from duodenal perforations were uniquely aerobes in most cases. It is suggested that bacteria play a minor role in the pathogenesis of early stage duodenal perforation, which supports the technique of primary closure without indwelling drainage tubes during early stage operations following sufficient peritoneal lavage. Moreover, if the stomach is empty at the time of perforation and the peritonitis is localized, even conservative therapy seems possible, provided it is begun shortly after the perforation.

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.

The relationship between juxtapapillary duodenal diverticula and the presence of bacteria in the bile

A total of 432 patients with gallstone disease were studied with respect to the existence of juxtapapillary duodenal diverticula and their relationship to the presence of bacteria in the bile. A total of 63 patients were found to have diverticula with an incidence of 14.6 per cent, being significantly higher in the elderly group aged 60 years or older (p<0.01), and no sex difference was noted. Among the patients with diverticula, positive bacterial cultures of bile were recognized at a significantly higher frequency, being found in 49 of the 63 patients (77.8 per cent; p<0.01), and the probability of bilirubinate stones was also higher, being found in 35 of 37 patients (94.6 per cent; p<0.01). The presence of a diverticulum bore significant relation to a higher positive bile bacterial culture (p<0.05), dilatation of the common bile duct (p<0.05), and elevation of the bile duct pressure (p<0.05), even when the conditions were divided into cholecystolithiasis or choledocholithiasis. It was suggested that the presence of a diverticulum affected the flow in the bile duct by narrowing it from the outside and chronically stimulating the papilla, inducing biliary tract infection and/or the formation of gallstones. As the surgical procedures for juxtapapillary duodenal diverticula, including its indications, have not been established, long term follow up investigations seem necessary.

ARGYROPHILIC THYMIC CARCINOID - CLINICOPATHOLOGIC STUDY OF FOUR CASES

Four cases of carcinoid tumor resting on the superior mediastinum were concluded to be of thymic origin by detecting thymic remnants, occasionally containing normal argyrophil cells, either attaching to tumor capsule or buried in the tumor tissue, and by denying possible mediastinal metastasis from bronchial carcinoid, except for one metastatic case. All the tumors were regarded as argyrophilic non‐argentamn carcinoid and had a tendency of invasive growth, though they grew slowly with clinical courses of long duration. From ultrastructural and biochemical analyses of one case, the carcinoid tumor occurring in thymus did not seem to produce any of the amines such as serotonin, histamine and dopamine, but may be possible to elaborate yet unrecognized endocrine substances relevant to inherent thymic functions. The twenty‐two cases previously recorded in the literature were reviewed and discussed, together with four cases presented here.

Thromboxane as a possible hepatotoxic factor increased by endotoxemia in obstructive jaundice

In a study using rats, we investigated whether liver damage induced by endotoxemia in obstructive jaundice is associated with thromboxane (TX) in order to acertain whether its vasoconstrictive and platelet aggregating properties play a role in reducing liver blood flow. The rats were divided into the following 5 groups; a control group, an endotoxin (Et) group, a bile duct ligation (BDL) group, a bile duct ligation and endotoxin (BDL+Et) group and an OKY046 (Thromboxane synthetase inhibitor) treated bile duct ligation+endotoxin (OKY-BDL+Et) group. The blood TXB2 levels in the Et, BDL and BDL+Et groups were higher than those in the control group. The liver TXB2 levels in the Et and BDL+Et groups were also higher than those in the control group. Liver phospholipids and liver blood flow decreased in the BDL+Et group, whereas in the OKY-BDL+Et group they returned close to the control group levels by decreasing the TXB2 levels in both the liver and blood to normal. These results suggest that the high level of TX in the blood and liver tissue may further aggrevate the liver during endotoxemia in obstructive jaundice by inhibiting liver blood flow.

Guidelines for the Assessment of the Therapeutic Efficacy of Antibiotics for Postoperative Infections in Japan (1997)

7Second Department of Surgery, Wakayama Medical School, Wakayama 2Digestive Center, Matsunami General Hospital, Gifu 3Department of Obstetrics and Gynecology, Kohtoh Hospital, Tokyo 4Department of Urology, National Hospital Kyushu Medical Center, Fukuoka SGeneral Surgery, Saitama National Hospital, Saitama 6Department of Mathematics, Kansai Medical University, Moriguchi ZDepartment of Clinical Pathology, School of Medicine, Juntendo University, Tokyo 8Third Department of Surgery, School of Medicine, Nihon University, Tokyo 9Institute of Medical Science, School of Medicine, St. Marianna University, Kawasaki 1~ of Surgery, Tokyo Dental College, Ichikawa General Hospital, Ichikawa ~Nagoya Municipal Kosei Hospital, Nagoya ~2Second Department of Surgery, Medical School, Osaka City University, Osaka 73Department of General Medicine, School of Medicine, Hiroshima University, Hiroshima, Japan