Nagao Shinagawa

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.

ORAL VANCOMYCIN HYDROCHLORIDE THERAPY FOR POSTOPERATIVE METHICILLIN-CEPHEM-RESISTANT STAPHYLOCOCCUS AUREUS ENTERITIS

The postoperative development of methicillincephem-resistantStaphylococcus aureus (MRSA) enteritis can be fatal unless it is detected at an early stage and treated with effective antibacterial agents. We report herein a Japanese multicenter collaborative clinical study on the efficacy and safety of oral vancomycin hydrochloride (VCM) in the treatment of MRSA enteritis. A total of 49 patients who had been diagnosed as having, or were strongly suspected of having, MRSA enteritis during the early postoperative period, were given oral VCM as four standard doses of 0.5g per day. The VCM concentrations in the blood, urine, and feces were then measured. No side effects were observed and the clinical efficacy of oral VCM in the 31 evaluable patients was excellent. There was a 100% clinical response rate and a 95.8% bacterial elimination rate in the feces. The clinical complete response (CR) rate to oral VCM differed significantly between patients in whom MRSA was detected only in the feces (100%) and those in whom MRSA was isolated from an additional source (57%) (P<0.01). Although VCM concentrations in the stools were extremely high, the levels in the blood and urine were very low. These results demonstrate that oral VCM should be the treatment of choice for postoperative MRSA enteritis due to its safety and efficacy.

Changes in arginine carboxypeptidase (CPR) activity in stressed rats

Abstract An arginine carboxypeptidase (CPR) is generated from its precursor (ProCPR) by proteolytic enzyme and may function in vivo in the removal of C-terminal arginine from inflammatory peptides such as C3a and C5a. We studied changes in this enzyme activity in rats submitted to liver cirrhois, hepatectomy, splenectomy, burning or endotoxin challenge. It is suggested that this enzyme could be activated with simultaneous generation of active peptides such as C3a and C5a at inflammatory sites to prevent their excess activity and inactivated due to its instability.

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.

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.

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

Bacterial adherence to human gallbladder epithelium

The adherence of Escherichia coli and Pseudomonas aeruginosa to the epithelium of the gallbladders obtained from 32 patients with negative bile culture was quantified by a scanning electron microscope. Of the gallbladders, 5 were histologically normal (group A), 21 had chronic calculus cholecystitis (group B), and 6 had acute calculus cholecystitis (group C). The data were expressed as the mean±S.D. of the numbers of adherent bacteria to 1,000 μm2 of the gallbladder epithelium. The number of adherent E. coli were 0.1±0.2 in group A, 4.2±2.8 in group B, and 9.2±3.3 in group C. A similar result was also observed with P. aeruginasa. The number of adherent bacteria, both of E. coli and P. aeruginosa were significantly higher in group C than in groups A and B, and were also significantly higher in group B compared to group A. The amount of bacterial adherence paralleled that of the degree of epithelial damage, and the normal epithelium proved to have an inhibiting ability. Thus, a secondary bacterial infection is more likely to happen in patients with contaminated bile, and therefore, the treatment for acute cholecystitis should be based either on the results of a bile culture or according to predictive factors for bactibilia.

The operative risk factors of cholelithiasis in the elderly

A total 725 patients with cholelithiasis were divided into three groups according to age, and the risk factors and morbidity rates compared. Group 1 consisted of those aged younger than 49 years, group 2 of those aged between 50 to 69 years, and group 3 of those aged over 70 years. In group 3, the incidence of caliculi in the common bile duct was significantly higher than in the other two groups (p<0.05), and therefore, choledochotomy accompanying cholecystectomy was performed more often in this group (p<0.01). The rate of complications related to calculi and the presence of underlying disease were also higher in this group than in the two younger groups (p<0.05), as were preoperative abnormal liver or renal function tests, anemia and hypoproteinemia (p<0.05). The rate of positive bile cultures in group 3 was 75.6 per cent which was again significantly higher than in groups 1 and 2 (p<0.01). Postoperative complications appeared in 14.3 per cent of the group 3 patients, which was not statistically higher than in group 2 (9.7 per cent), but the percentages of both groups 2 and 3 were high compared to the 4.3 per cent of group 1 (p<0.01). The rates of complications directly attributable to the surgical procedures were 2.0 per cent in group 1, 4.8 per cent in group 2, and 5.1 per cent in group 3 with no significant differences between the three groups. There was no increase in the technical problems associated with the surgical procedures performed on the elderly patients and thus, if the operative risks are precisely evaluated and treated cautiously elderly patients should tolerate surgery for cholelithiasis well.

Prophylactic antibiotics for patients undergoing elective biliary tract surgery: A prospective randomized study of cefotiam and cefoperazone

Cefotiam, a second generation cephalosporin and cefoperazone, a third generation cephalosporin have a broad spectrum of activity against a majority of organisms commonly found in the bile. Although cefoperazone is excreted into the human bile to a greater extent than is cefotiam, there are no comparative data available that cefoperazone prophylaxis is safer and more effective than cefotiam for patients undergoing biliary tract surgery. A prospective randomized study was performed to compare the safety and efficacy of cefotiam with those of cefoperazone for prophylaxis in patients undergoing elective biliary tract surgery. The incidence of postoperative infection was not significantly different between the cefotiam group (n=86) and the cefoperazone group (n=86). The rate of side effects, however, was significantly different. In the cefotiam group, only one patient had diarrhea whereas in the cefoperazone group, eight had diarrhea and one skin eruption.Clostridium difficile cytotoxin was nil in those with diarrhea. Diarrhea in all patients was mild and recovery was rapid. Cefotiam is thus safer and as effective as cefoperazone in preventing postoperative infections following biliary tract surgery. We suggest that cefotiam is the first choice antibiotic for prophylaxis in biliary tract surgery.

Antimicrobial-susceptible patterns of Staphylococcus aureus isolated from surgical infections: A new approach

Our goal was to analyze minimum inhibitory concentration (MIC) data for Staphylococcus aureus isolated from surgical infections (SIs) and to look for correlations among the clinically available antimicrobials that were tested. Clinical isolates from SIs were collected by a multicenter surveillance group involving 34 institutions in Japan. During the period April 1998 to March 2007, 312 strains of S. aureus [71 methicillin susceptible (MSSA) and 241 methicillin resistant (MRSA)] were consecutively obtained from these institutions. MIC data for 18 clinically available antimicrobial agents [ABPC, CEZ, CTM, CMX, CPR, FMOX, CFPM, CZOP, IPM, MEMP, GM, ABK, MINO, CLDM, FOM, LVFX, VCM, and TEIC (abbreviations defined in Tables 2 and 3)] against these isolates was analyzed using a principal component analysis (PCA). PCA revealed that four principal components explained 71.1% of the total variance. The first component consisted of major contributions from MEPM and IPM. The second component consisted of major contributions from MINO. These two-first axes, which were strong and explained 54.2% of the total variance, were able to classify the clinical isolates into four clusters. Furthermore, the proportion of the four clusters provided the characteristics of the S. aureus that were clinically isolated at each institute. PCA is a clinically applicable method for analyzing MIC patterns. Such analyses might contribute to the establishment of a practical classification of antimicrobial agents and to the identification of the characteristic antimicrobial resistance patterns at each institute.