Inflammation-Induced Attenuation of Prostaglandin D2 Elimination across Rat Blood-Brain Barrier: Involvement of the Downregulation of Organic Anion Transporter 3 and Multidrug Resistance-Associated Protein 4.

Prostaglandin (PG) D2 is a lipid mediator, and in the brain, overproduction of PGD2 is reportedly involved in the progression and exacerbation of neuroinflammation. The objective of this study was to elucidate PGD2 efflux transport, under normal and inflammatory conditions, across the blood-brain barrier (BBB), which is formed by brain capillaries. Elimination of [3H]PGD2 across the BBB of normal and lipopolysaccharide (LPS)-induced inflammatory rats was examined by the intracerebral microinjection technique. After intracerebral injection, the percentage of [3H]PGD2 remaining in the ipsilateral cerebrum decreased with time, with a half-life of 13 min. This [3H]PGD2 elimination across the BBB was significantly inhibited by the co-administration of unlabeled PGD2, which suggests carrier-mediated PGD2 efflux transport at the BBB. In isolated rat brain capillaries, mRNA expression of organic anion transporter (Oat) 3, organic anion-transporting polypeptide (Oatp) 1a4, and multidrug resistance-associated protein (Mrp) 4 was observed. In addition, co-administration of substrates/inhibitors for Oat3, Oatp1a4, and/or Mrp4, such as benzylpenicillin and cefmetazole, reduced [3H]PGD2 elimination across the BBB. Data suggest that Oat3 and Mrp4, but not Oatp1a4 are involved in PGD2 elimination across the BBB, as Oatp1a4-expressing Xenopus (X.) oocytes did not show the significant [3H]PGD2 uptake compared with water-injected X. oocytes. In LPS-treated rats, [3H]PGD2 elimination across the BBB and mRNA expression levels of Oat3 and Mrp4 were significantly decreased. Our data suggest that Oat3- and Mrp4-mediated PGD2 elimination across the BBB is attenuated under inflammatory conditions.

Preoperative mechanical bowel preparation with oral antibiotics reduces surgical site infection after elective colorectal surgery for malignancies: results of a propensity matching analysis.

BACKGROUND: Surgical site infections (SSIs) are a major postoperative complication after colorectal surgery. Current study aims to evaluate prophylactic function of oral antibiotic (OA) intake in combination with mechanical bowel preparation (MBP) relative to MBP alone with respect to postoperative SSI incidence. METHODS: A retrospective analysis of eligible patients was conducted using the databases of the Gastrointestinal Surgery Centre, Third Affiliated Hospital of Sun Yat-sen University from 2011 to 2017. Data pertaining to postoperative hospital stay length, expenses, SSI incidence, anastomotic fistula incidence, and rates of other complications were extracted and compared. A propensity analysis was conducted to minimize bias associated with demographic characteristics. Subgroup analyses were performed to further explore protective effects of OA in different surgical sites. RESULTS: The combination of OAs and MBP was related to a significant decrease in the incidence of overall SSIs, superficial SSI, and hospitalization expenses. The MBP + OA modality was particularly beneficial for patients undergoing left-side colon or rectum resections, with clear prophylactic efficacy. The combination of MPB + OA did not exhibit significant prophylactic efficacy in patients undergoing right hemi-colon resection. Age, surgical duration, and application of OA were all independent factors associated with the occurrence of SSIs. CONCLUSION: These results suggest that the combination of OA + MBP should be recommended for patients undergoing elective colorectal surgery, particularly for operations on the left side of the colon or rectum. TRIAL REGISTRATION: NCT04258098. Retrospectively registered.

The use of broad-spectrum antibiotics reduces the incidence of surgical site infection after pancreatoduodenectomy.

PURPOSE: The development of surgical site infection (SSI) after biliary reconstruction is highly influenced by the presence of preoperative bacteria in the bile juice. We selected vancomycin and piperacillin/tazobactam (VCM + PIPC/TAZ) as perioperative prophylactic antibiotics for patients undergoing pancreaticoduodenectomy. This study aimed to retrospectively analyze the effectiveness of VCM + PIPC/TAZ compared to cefmetazole. METHODS: Seventy-two patients who underwent pancreaticoduodenectomy between April 2015 and March 2017 at our department were evaluated. Forty patients were administered cefmetazole as the perioperative prophylactic antibiotic, and 32 were administered VCM + PIPC/TAZ. The intraoperative VCM blood concentration (incision, biliary reconstruction, and wound closure) was measured during surgery to confirm the hemodynamics. RESULTS: The frequency of SSIs was significantly lower in the VCM + PIPC/TAZ group (8/32 patients) than in the cefmetazole group (20/40 patients, P = 0.031). Postoperatively, significantly fewer patients in the VCM + PIPC/TAZ group (4/32 patients) required ≥ 15 days of additional antibiotic administration compared to those in the cefmetazole group (14/40 patients, P = 0.033). Six of 32 patients in the VCM + PIPC/TAZ group showed redneck syndrome symptoms. There was no significant difference in the VCM blood concentration between patients with and without SSIs. CONCLUSIONS: The use of VCM + PIPC/TAZ can reduce the incidence of SSI after pancreaticoduodenectomy and also reduce the need for the additional administration of antibiotics for ≥ 15 days after surgery.

Predicting postoperative fever and bacterial colonization on packing material following endoscopic endonasal surgery.

Postoperative fever following endoscopic endonasal surgery is a rare occurrence of concern to surgeons. To elucidate preoperative and operative predictors of postoperative fever, we analyzed the characteristics of patients and their perioperative background in association with postoperative fever. A retrospective review of 371 patients who had undergone endoscopic endonasal surgery was conducted. Predictors, including intake of antibiotics, steroids, history of asthma, preoperative nasal bacterial culture, duration of operation, duration of packing and intraoperative intravenous antibiotics on the occurrence of postoperative fever, and bacterial colonization on the packing material, were analyzed retrospectively. Fever (≥38 °C) occurred in 63 (17 %) patients. Most incidences of fever occurred on postoperative day one. In majority of these cases, the fever subsided after removal of the packing material without further antibiotic administration. However, one patient who experienced persistent fever after the removal of packing material developed meningitis. History of asthma, prolonged operation time (≥108 min), and intravenous cefazolin administration instead of cefmetazole were associated with postoperative fever. Odds ratios (ORs) for each were 2.3, 4.6, and 2.0, respectively. Positive preoperative bacterial colonization was associated with postoperative bacterial colonization on the packing material (OR 2.3). Postoperative fever subsided in most patients after removal of the packing material. When this postoperative fever persists, its underlying cause should be examined.

Oral and Parenteral Versus Parenteral Antibiotic Prophylaxis in Elective Laparoscopic Colorectal Surgery (JMTO PREV 07-01): A Phase 3, Multicenter, Open-label, Randomized Trial.

OBJECTIVE: To confirm the efficacy of oral and parenteral antibiotic prophylaxis (ABX) in the elective laparoscopic colorectal surgery. BACKGROUND: There is no evidence for the establishment of an optimal ABX regimen for laparoscopic colorectal surgery, which has become an important choice for the colorectal cancer patients. METHODS: The colorectal cancer patients scheduled to undergo laparoscopic surgery were eligible for this multicenter, open-label, randomized trial. They were randomized to receive either oral and parenteral prophylaxis (1 g cefmetazole before and every 3 h during the surgery plus 1 g oral kanamycin and 750 mg metronidazole twice on the day before the surgery; Oral-IV group) or parenteral prophylaxis alone (the same IV regimen; IV group). The primary endpoint was the incidence of surgical site infections (SSIs). Secondary endpoints were the incidence rates of Clostridium difficile colitis, other infections, and postoperative noninfectious complications, as well as the frequency of isolating specific organisms. RESULTS: Between November 2007 and December 2012, 579 patients (289 in the Oral-IV group and 290 in IV group) were evaluated for this study. The incidence of SSIs was 7.26% (21/289) in the Oral-IV group and 12.8% (37/290) in the IV group with an odds ratio of 0.536 (95% CI, 0.305-0.940; P = 0.028). The 2 groups had similar incidence rates of C difficile colitis (1/289 vs 3/290), other infections (6/289 vs 5/290), and postoperative noninfectious complications (11/289 vs 12/290). CONCLUSIONS: Our oral-parenteral ABX regimen significantly reduced the risk of SSIs following elective laparoscopic colorectal surgery.

Randomized clinical trial of oral and intravenous versus intravenous antibiotic prophylaxis for laparoscopic colorectal resection.

BACKGROUND: The use of oral prophylactic antibiotics for the prevention of surgical-site infection (SSI) in patients undergoing laparoscopic surgery for colorectal cancer is controversial. The aim of this RCT was to evaluate whether intravenous perioperative antibiotics are inferior to combined preoperative oral and perioperative intravenous antibiotics in this setting. METHODS: Patients undergoing elective laparoscopic colorectal resection in a single cancer centre were assigned randomly to combined preoperative oral antibiotics (metronidazole and kanamycin) and perioperative intravenous antibiotics (cefmetazole) (oral/IV group) or to perioperative intravenous antibiotics (cefmetazole) alone (IV-only group). Patients were stratified for the analyses based on type of operation (colonic surgery, anterior resection or abdominoperineal resection), preoperative use of mechanical bowel preparation, preoperative chemoradiotherapy and the presence of diabetes mellitus. The primary endpoint was the overall rate of SSI. Secondary endpoints were the rates of incisional site infection, organ/space infection, anastomotic leakage, intra-abdominal abscess, adverse events and postoperative complications. RESULTS: Of 540 patients offered participation in the trial in 2013-2014, 515 agreed to take part and were randomized. Some 256 patients in the IV-only group and 255 in the oral/IV group completed the treatment per protocol. The overall rate of SSI was 7·8 per cent (20 of 256) in the IV-only group and 7·8 per cent (20 of 255) in the oral/IV group, confirming that perioperative administration of intravenous antibiotics alone was not inferior to the combined regimen (P = 0·017). There were no differences in rates of incisional site infection (5·5 versus 5·9 per cent respectively), organ/space infection (2·3 versus 2·0 per cent) or other secondary endpoints between the two groups. CONCLUSION: Intravenous perioperative antimicrobial prophylaxis alone is not inferior to combined preoperative oral and intravenous perioperative prophylaxis with regard to SSI in patients with colorectal cancer undergoing elective laparoscopic resection. Registration number: UMIN000019339 ( http://www.umin.ac.jp/ctr/).

Multicenter prospective randomized phase II study of antimicrobial prophylaxis in low-risk patients undergoing colon surgery.

PURPOSE: Postoperative antimicrobial therapy is generally administered as standard prophylaxis against postoperative infection, despite a lack of sufficient evidence for its usefulness. This study was a phase II study to evaluate the necessity of postoperative antibiotic prophylaxis in patients undergoing a colectomy. METHODS: Patients received 1 g cefmetazole or flomoxef immediately after anesthetic induction, every 3 h during surgery, and then later once again on the next day. They were randomly assigned to receive either cefmetazole or flomoxef. RESULTS: Ninety-one patients were enrolled in the study. A surgical site infection (SSI) occurred in 7.7% (7/91) of patients. All cases were superficial incisional infections. When comparing the two drugs, SSI occurred in 8.3% (4/48) of patients treated with cefmetazole and in 7.0% (3/43) treated with flomoxef, showing no significant difference (P > 0.99). CONCLUSION: Antimicrobial prophylaxis was well tolerated when used on the day of a colectomy and once again on the next day.

Implementing a standard protocol to decrease the incidence of surgical site infections in rectal cancer surgery.

PURPOSE: To evaluate the effectiveness of our surgical site infection (SSI) preventive strategies for rectal cancer patients. METHODS: We compared the incidences and risk factors for SSI before (1990-1999) and after the implementation of our SSI prevention policies (2002-2006). A total of 250 patients who underwent surgery for rectal cancer were enrolled in this study. Peripheral venous blood samples were obtained perioperatively to measure the circulating pro- and anti-inflammatory cytokines. RESULTS: The incidence of SSI was significantly lower after the introduction of SSI prevention policies [SPP(+)] than before [SPP(-)], at 13.1% vs 32.0%, respectively (P = 0.0004). Even with the infection control programs, abdominoperineal resection (APR) was an independent factor predictor of SSI after rectal cancer surgery. The consumption of postoperative interleukin (IL)-6 soluble receptor was much higher in the APR patients than in the non-APR patients. The exaggeration of postoperative IL-6 response was more pronounced in the APR patients in the SPP(+) group than in those in the SPP(-) group, although preoperative chemotherapy and/or radiotherapy might have influenced the inflammatory response. CONCLUSIONS: These findings suggest that the introduction of SPP helped reduce the incidence of SSI, especially in the non-APR patients.

One-day versus four-day antibiotic treatment for acute right colonic uncomplicated diverticulitis: A randomized clinical trial.

BACKGROUND/AIMS: Currently, right colonic uncomplicated diverticulitis is typically treated with antibiotic therapy. However, the optimal duration of treatment is unknown. The aim of the present study was to compare the treatment failure rates between 1- and 4-day antibiotic treatment protocols. MATERIALS AND METHODS: A prospective randomized study in adults presenting with uncomplicated diverticulitis at the first episode from July 2011 to June 2014 was performed. Patients were randomized to receive intravenous antibiotics for 1 day (1-day group) or intravenous and oral antibiotics for 4 days (4-day group). All patients received cefmetazole and metronidazole. Treatment failure was defined as readmission within 30 days and disease recurrence during the follow-up period. RESULTS: Overall, 87 and 89 patients were randomized to the 1-day and 4-day groups, respectively. All patients were successfully treated initially. The hospital length of stay was shorter in the 1-day group than in the 4-day group (3.1 vs. 3.8 days, respectively; p<0.001). After discharge, there were no significant differences between the groups in treatment failure (15/87, 17.2% vs. 19/89, 21.3%; p=0.493). In each group, there were readmission within 30 days (9.2% vs. 12.4%; p=0.502) and recurrence over a median follow-up period of 32 months (10.3% vs. 9.0%; p=0.762). In 34 patients who experienced treatment failure, 6 required surgery. CONCLUSION: Single-day antibiotic treatment is as effective as 4-day therapy for the prevention of readmission and recurrence in patients with right colonic uncomplicated diverticulitis.

Randomized, multicenter trial of antibiotic prophylaxis in elective colorectal surgery: single dose vs 3 doses of a second-generation cephalosporin without metronidazole and oral antibiotics.

HYPOTHESIS: Use of prophylactic antibiotics in elective colorectal surgery is essential. Although single-dose prophylactic antibiotics are recommended, the efficacy of single-dose cephalosporin without metronidazole and oral antibiotics is not fully proven. We conducted a multicenter, randomized trial of a single dose vs 3 doses of the second-generation cephalosporin cefmetazole. DESIGN: A prospective, randomized, multicenter trial in patients undergoing elective colorectal surgery. SETTING: Seven major hospitals in Japan that offer cancer treatment. PATIENTS: Patients with colorectal cancer treated from May 6, 2004, to April 25, 2005. INTERVENTIONS: Patients were randomized to 1 of 2 groups: a single-dose group given a single dose of cefmetazole just before skin incision and a 3-dose group given 2 additional doses of cefmetazole every 8 hours after the first dose just before skin incision. MAIN OUTCOME MEASURES: Incidences of incisional surgical site infection (SSI), organ or space SSI, and all other infectious complications within 30 days after surgery. RESULTS: A total of 384 patients were enrolled. Seven patients were excluded because of additional surgery or the inability to tolerate mechanical preparation. The incidence of incisional SSI was higher in the single-dose group (27/190 or 14.2%) than in the 3-dose group (8/187 or 4.3%) (P = .009). Incidences of organ or space SSI and other postoperative infectious diseases did not differ significantly between the 2 groups. In multivariate analysis, antibiotic dose was the only significant factor related to the incidence of incisional SSI. CONCLUSION: Three-dose cefmetazole administration is significantly more effective for prevention of incisional SSI than single-dose antibiotic administration. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00292708.

Total bilirubin amount in drainage fluid can be an early predictor for severe biliary fistula after hepatobiliary surgery.

The ratio of the bilirubin concentration in abdominal drainage fluid to the serum bilirubin concentration (d-Bil/s-Bil) has been used as a predictor of biliary fistula (BF) formation after hepatobiliary surgery. The d-Bil/s-Bil ratio is highly influenced by the amount of drainage and is not always reliable, especially when the amount of drainage is large. In this study, the usefulness of the d-Bil/s-Bil ratio and total bilirubin amount in the drainage fluid (TBA) (bilirubin concentration in the drainage fluid x the amount of drainage) as predictors of severe BF (sBF) formation was evaluated retrospectively from the data of 306 patients who had undergone hepatobiliary surgery. Of the 306 patients, 201 patients were included in the training set and the remaining 105 in the validation set, to determine the best parameter to predict sBF formation after hepatobiliary surgery. Receiver-operating characteristic curve analysis revealed that the predictive power of TBA was superior to that of the d-Bil/s-Bil ratio throughout the postoperative period, and that the TBA on postoperative day (POD) 1 showed the highest discriminatory power in the training set (area under the curve, 0.789; cutoff value, 470 mg/day). The TBA on POD 1 also showed the highest predictive power for sBF formation in the validation set, with a sensitivity of 100%, specificity of 97.1%, and accuracy of 97.1%. In conclusion, TBA may be a more reliable predictor of sBF than the conventionally used d-Bil/s-Bil ratio. Early prediction of sBF may be useful for early removal of unnecessary prophylactic drainage tubes after hepatobiliary surgery.

[Prophylactic effect of fosfomycin on postoperative infection in gastroenterological surgery].

Fosfomycin (FOM), a drug with unique mechanism of action against bacteria, was prospectively compared with cefmetazole (CMZ) and flomoxef (FMOX) to assess its effectiveness in preventing postoperative infections after upper gastroenterological and hepatobiliary surgery. FOM (2g/dose), CMZ (1 g/dose), or FMOX (lg/dose) was infused intravenously 2-3 times daily for basically 4 days including the day of surgery in order to examine whether or not infections would develop after surgery. According to the analysis results of 162 cases, efficacy in preventing infection was 86.8% for FOM, 73.1% for CMZ and 83.3% for FMOX, showing no significant differences among the 3 groups. Thus FOM was considered as efficacious as CMZ or FMOX in prophylaxis against postoperative infections. There were no adverse reactions in the FOM or CMZ group, but 3 cases of adverse reactions occurred in the FMOX group. Based on the above results, the usefulness of FOM for prophylaxis against postoperative infections has been confirmed. At present, the first- and second-generation cephems are most frequently used for prophylaxis against postoperative infections. In order to prevent an increase of resistant strains due to inappropriate use of these drugs, FOM, having no cross resistance with currently used drugs, is a promising candidate for prophylaxis against postoperative infections.

Cefmetazole sodium: pharmacology, pharmacokinetics, and clinical trials.

Cefmetazole sodium is a semisynthetic cephamycin antibiotic. It has a broad spectrum of activity comparable to that of the second-generation cephalosporins, covering gram-positive, gram-negative, and anaerobic bacteria. Unlike the second-generation cephalosporins, cephamycins such as cefmetazole are usually active against Bacteroides fragilis. Cefmetazole is also active against beta-lactamase-producing organisms that are resistant to first-generation cephalosporins or penicillins. The pharmacokinetics of cefmetazole allow parenteral administration (intravenous or intramuscular) 2-3 times daily for treatment of infection. The drug has been studied in gynecologic, intraabdominal, urinary tract, respiratory tract, and skin and soft tissue infections. Administered preoperatively, it may reduce the frequency of infection in certain clean-contaminated or potentially contaminated procedures, including cesarean section, abdominal or vaginal hysterectomy, cholecystectomy (high-risk patients), and colorectal surgery. On the basis of in vitro spectrum, pharmacokinetics, and data from a relatively small number of clinical trials, this agent may be considered when a second-generation cephalosporin is indicated.

Influence of timing of antibiotic administration on tissue concentrations during surgery.

BACKGROUND: Prophylactic antibiotics must be administered so as to achieve adequate tissue levels before the initial surgical incision. We characterized antimicrobial tissue concentrations following intravenous administration at various times prior to surgical incision. PATIENTS AND METHODS: Twelve patients scheduled for elective colorectal surgery were randomized to receive cefmetazole 2 g by intravenous push either immediately prior to incision or 15 to 60 minutes prior. Blood and wound-muscle samples were obtained at predetermined intervals and assayed by high-performance liquid chromatography. RESULTS: Tissue distribution of the study drug was extremely rapid. All patients had theoretically adequate tissue levels at the time of incision. Levels above MIC90 of the common pathogens were sustained throughout the surgical procedure regardless of the timing of administration. CONCLUSIONS: Administration of cefmetazole immediately prior to surgical incision should be effective prophylaxis for surgical wound infections.

Adjunctive antimicrobials in surgery of soft tissue infections: evaluation of cephalosporins and carbapenems.

The authors report three trials of B-lactams and carbapenems for soft tissue infections treated on a surgical service: 1) cefmetazole versus cefoperazone, n = 44; 2) cefotetan versus cefoxitin, n = 24; and 3) meropenem versus imipenem, n = 44. A total of 138 hospitalized patients were enrolled with 112 meeting evaluability criteria. Four hundred twenty-three isolates were cultured (mean, three/patient) of which 67 per cent were aerobes and 33 per cent anaerobes. Cure rates for each trial were: 1) 93 per cent; 2) 92 per cent; 3) 100 per cent. Failures were caused by resistant organisms (Streptococcus group D, Bacteroides fragilis and Pseudomonas) appearing in incompletely drained infection sites. Three patients receiving meropenem had adverse effects (headache, nausea) and one receiving cefoxitin (truncal rash). Operative drainage and debridement remain the critical elements in therapy. Agents with longer half lives allowing twice daily dosing (cefmetazole and cefotetan) were as effective and less expensive than multiple doses of short-acting agents. The extended spectrum carbapenems are most useful for severe infections or resistant organisms.

Compatibility of cefmetazole sodium with commonly used drugs during Y-site delivery.

The compatibility of cefmetazole sodium and selected other drugs during Y-site delivery was evaluated. Cefmetazole 100 mg/mL (as the sodium salt) in sterile water for injection and each of 34 drugs or solutions commonly used with it were mixed together by Y-site injection. Secondary drugs were administered at selected concentrations and rates and delivered by the method (i.v. push, i.v. infusion, or syringe pump) commonly used for the drug at the institution where the study was done. Each injection set included a filter system with a 0.8-micron filter disk. Tests were done in triplicate. After each test, the Y injection site and the tubing after it were visually inspected for precipitate and color change. If no particles or color change was detected, the filter disk was observed under a microscope. Drugs were deemed compatible with cefmetazole if unaided observation detected no color change or particles and the number of particles detected by microscopic examination was below that specified in USP guidelines. A precipitate formed when cefmetazole sodium mixed with diphenhydramine hydrochloride, droperidol, erythromycin (50 mg/mL, as the lactobionate), haloperidol lactate, prochlorperazine edisylate, promethazine hydrochloride, or vancomycin (50 mg/mL, as the hydrochloride salt). No particles or color change was detected by unaided observation of mixtures containing dobutamine or erythromycin 10 mg/mL, but the number of particles detected by microscopic examination exceeded USP limits. All other drugs tested were compatible with cefmetazole. Cefmetazole 100 mg/mL (as the sodium salt) in sterile water for injection was shown to be compatible with 25 of 34 tested drug solutions during Y-site delivery.

Myoclonic activity associated with cefmetazole, with a review of neurotoxicity of cephalosporins.

We reported a case of a 66-year-old female with uremia who developed myoclonic activity after administration of cefmetazole (4g/2 days). Curiously, the level of the antibiotics (236 micrograms/ml) in the cerebrospinal fluid (CSF) was higher than that in the blood (103 micrograms/ml). Myoclonic activity faded away after cessation of the antibiotics. This is the first case reported developing neurotoxicity associated with intravenous administration of cefmetazole. In addition, the curious pharmacokinetic dynamics of cephalosporin in uremia is discussed.

Treatment of osteomyelitis with antibiotic-soaked porous glass ceramic.

We have developed a new drug delivery system using porous apatite-wollastonite glass ceramic (A-W GC) to treat osteomyelitis. A-W GC (porosity, 70% and 20% to 30%), or porous hydroxyapatite (HA) blocks (porosity 35% to 48%) used as controls, were soaked in mixtures of two antibiotics, isepamicin sulphate (ISP) and cefmetazole (CMZ) under high vacuum. We evaluated the release concentrations of the antibiotics from the blocks. The bactericidal concentration of ISP from A-W GC was maintained for more than 42 days, but that from HA decreased to below the detection limit after 28 days. The concentrations of CMZ from both materials were lower than those of ISP. An in vivo study using rabbit femora showed that an osseous concentration of ISP was maintained at eight weeks after implantation. Osteoconduction of the A-W GC block was good. Four patients with infected hip arthroplasties and one with osteomyelitis of the tibia have been treated with the new delivery system with excellent results.

Successful conservative treatment for esophageal perforation by a fish bone associated with mediastinitis.

A 74 year-old man presenting with esophageal perforation associated with mediastinitis due to the swallowing of a fish bone is reported herein. Conservative treatment, including starvation therapy and the injection of antibiotic drugs, proved to be successful for this patient. Although the optimal treatment for esophageal perforation remains controversial, it is important to choose the appropriate strategies when treating cases of esophageal perforation with mediastinitis.

Eosinophilic gastroenteritis with ileus and ascites.

We report a case of eosinophilic gastroenteritis, which has features of the predominant subserosal type presented as an ileus and ascites. A 48-year-old Japanese woman was admitted to our hospital because of epigastralgia, lower abdominal pain and vomiting. She had a past history of allergic disorders. The computed tomographic scan revealed ascites, and marked wall thickening and dilatation of the intestine. This patient showed eosinophilic ascites without marked peripheral eosinophilia. Histologic examination demonstrated eosinophilic infiltrates did not predominate in the gastrointestinal tract. Conservative treatment of intravenous infusion of antibiotics and Ringer's solution was effective in this case.