Masashi Ishikawa

Perioperative immune responses in cancer patients undergoing digestive surgeries

BackgroundTh1/Th2 cell balance is thought to be shifted toward a Th2-type immune response not only by malignancy but also by surgical stress. The aim of this study was to estimate perioperative immune responses with respect to the Th1/Th2 balance in patients with gastrointestinal cancer.MethodsNinety-four patients who underwent abdominal surgeries were divided into three groups: gastric resection (n = 40), colorectal resection (n = 34) and hepatic resection (n = 20). Twelve patients undergoing laparoscopic cholecystectomy and 20 healthy subjects were served as control groups. Intracellular cytokine staining in CD4+ T lymphocytes was identified to characterize Th1/Th2 balance. Th1/Th2 balance was evaluated before operation and until postoperative days (POD) 14.ResultsThe preoperative Th1/Th2 ratio was significantly lower in patients with malignancy compared with control. The Th1/Th2 ratio of patients in all groups decreased significantly postoperatively. Th1/Th2 balance on POD 2 in patients with malignancy was significantly decreased compared to patients with laparoscopic cholecystectomy, but there were no significant differences among the four groups on POD 14.ConclusionPatients with malignancy showed an abnormal perioperative Th1/Th2 balance suggesting predominance of a type-2 immune response. Major abdominal surgeries induce a marked shift in Th1/Th2 balance toward Th2 in the early postoperative stage.

Changes in surgical strategies for peptic ulcers before and after the introduction of H2-receptor antagonists and endoscopic hemostasis.

A total of 902 surgical patients with peptic ulcer disease were evaluated to clarify the effects of H2-receptor antagonists and endoscopic hemostasis on surgical treatment. Following the introduction of these treatments to our institute in 1982, the number of operations performed annually decreased by 40%, or 36 cases per year. However, a remarkable increase in the frequency of surgical emergency intervention since 1982 was concurrently observed, with the ratio of emergency procedures to the total number of operated cases increasing to 72.5% in the last 5 years of the study. Moreover, intractability as an indication for surgery decreased to 34.1%, compared with an increase in the number of patients with bleeding and perforated ulcers requiring operation. There were 13 postoperative deaths recorded (1.4%). All of the deaths were in patients who had undergone emergency surgery in poor health. Of these 13 patients, 10 had bleeding ulcers. A study of bleeding ulcers for which endoscopic hemostasis had been unsuccessful revealed that shock on admission and a concomitant medical condition had been evident in all the patients who died, and in 52.2% and 30.4% of the survivors, respectively. The current study suggests that the frequency of high-risk patients requiring surgery is increasing since the introduction of H2-receptor antagonists and endoscopic hemostasis, and thus, prompt surgical treatment and intensive management for such patients is essential.

Spontaneous intramural duodenal hematoma complicating acute pancreatitis.

A 49-YEAR-OLD MAN WHO is also a heavy drinker was referred to our hospital with sudden back pain and drowsiness. He had no history of anticoagulant use or trauma. He reported 1-week history of recurrent abdominal pain and vomiting after every meal. Physical examination revealed localized resistance with tenderness in the right upper abdomen. Laboratory examination revealed potassium, 2.5 mEq/L; urea nitrogen, 42 mg/dL; creatinine, 1.9 mg/dL; total bilirubin, 2.8 mg/dL; gamma-glutamyltransferase, 952 U/L; and amylase, 1,374 U/L; these values indicated acute pancreatitis. The International Normalized Ratio was within normal range. Arterial blood gases on room air were as follows: pH, 7.541; PO2, 56.1 mmHg; PCO2, 64.4 mmHg; base excess, 28.5 mmol/L; and bicarbonate 55 mmol/L, suggesting metabolic alkalosis. Abdominal contrast-enhanced computed tomography (CT) in the early phase revealed an nonenhancing intramural hematoma with luminal narrowing in the descending part of the duodenum and peripancreatic fluid

Effect of donor-specific splenocytes via portal vein and FK506 in rat small bowel transplantation.

BACKGROUND To investigate the role of the liver in immune responses after small bowel transplantation, donor-specific splenocytes were infused perioperatively, via the portal vein, in a rat heterotopic small bowel transplant model. METHODS Heterotopic small bowel transplantation between the fully allogenic Brown Norway (BN) (RT1n) and Lewis (RT1[1]) strain rats were performed. We prepared donor splenocytes from BN or third-party WKA (RT1k) rat spleens for Lewis hosts and injected the splenocytes perioperatively via the host portal vein or the systemic vein. The hosts were treated with a short course of the immunosuppressive agent, FK506 (0.5 mg/kg, 0-3 days postoperatively), following the experimental protocols. RESULTS Untreated Lewis hosts rejected BN small bowel grafts at 5.4+/-0.9 days (n=8). BN splenocytes given alone caused fatal graft-versus-host disease in six of eight animals, and two others died from graft rejection. FK506 alone did not significantly prolong graft survival (6.3+/-1.0 days, n=10). However, BN splenocytes injected via the portal vein, combined with FK506, prolonged graft survival to 12.7+/-2.1 days (n=12, P < 0.01) and 10 of 12 rats survived more than 70 days. This was donor antigen specific. BN splenocytes administered systemically caused fatal graft-versus-host disease in all recipients, and FK506 did not ameliorate this. Histologic findings of graft rejection were remarkably mild in the recipients of the combined therapy, compared with the recipients that were given FK506 alone. Down-regulation of one-way mixed lymphocyte reaction to BN splenocytes was observed in the splenocytes of the tolerant hosts. CONCLUSIONS Combined administration of donor splenocytes and FK506 reduced allograft rejection and prolonged survival in this rat model of small bowel transplantation.

Can three-dimensional helical CT cholangiography before laparoscopic cholecystectomy be a substitute study for endoscopic retrograde cholangiography?

The study investigated the usefulness of three-dimensional helical computed tomography (3D-CT) before laparoscopic cholecystectomy (LSC) when compared with that of endoscopic retrograde cholangiography (ERC). Forty-five patients referred for LSC, who had undergone 3D-CT cholangiography and ERC simultaneously, participated in the study. Endoscopic retrograde cholangiography and 3D-CT cholangiography were compared in each patient with regard to opacification of the biliary tree, stones, and anatomic variations. Three-dimensional helical CT cholangiography and ERC imaging for predicting operative difficulties in LSC also were compared. The common bile duct and cystic duct were shown in the patients by the images, but the gallbladder was shown in 43 patients (96%) with use of 3D-CT cholangiography and in 36 patients (80%) with use of ERC. A third or more peripheral branches were shown completely with use of 3D-CT cholangiography in 33 patients (73%) and in 32 patients (71%) with use of ERC. Cystic duct stones were found in two of three patients with use of 3D-CT cholangiography and ERC. Common bile duct stones in five of seven patients were detected with use of 3D-CT cholangiography, but all of the common bile duct stones were detected with use of ERC. Anatomic variations of the bile duct were shown in three of four patients by 3D-CT cholangiography and in all patients with use of ERC. No significant differences in findings of the angle of bifurcation and presence of Heister valves between operative easy and complex cases were shown by 3D-CT cholangiography and ERC, despite the more accurate assessment of the cystic duct anatomy with use of 3D-CT cholangiography than with use of ERC. Three-dimensional helical CT cholangiography is useful clinically in preoperative assessment of biliary anatomy, but it is not reliable in the detection of common bile duct stones, and it is not helpful in predicting technical difficulty during LSC.

Hepatobiliary cystadenoma exhibiting morphologic changes from simple hepatic cyst shown by 11-year follow up imagings.

BackgroundA long-term follow up case of hepatobiliary cystadenoma originating from simple hepatic cyst is rare.Case presentationWe report a case of progressive morphologic changes from simple hepatic cyst to hepatobiliary cystadenoma by 11 – year follow up imaging. A 25-year-old man visited our hospital in 1993 for a simple hepatic cyst. The cyst was located in the left lobe of the liver, was 6 cm in diameter, and did not exhibit calcification, septa or papillary projections. No surgical treatment was performed, although the cyst was observed to gradually enlarge upon subsequent examination. The patient was admitted to our hospital in 2004 due to epigastralgia. Re-examination of the simple hepatic cyst revealed mounting calcification and septa. Abdominal CT on admission revealed a hepatic cyst over 10 cm in diameter and a high-density area within the thickened wall. MRI revealed a mass of low intensity and partly high intensity on a T1-weighted image. Abdominal angiography revealed hypovascular tumor. The serum levels of AST and ALT were elevated slightly, but tumor markers were within normal ranges. Left lobectomy of the liver was performed with diagnosis of hepatobiliary cystadenoma or hepatobiliary cystadenocarcinoma. The resected specimen had a solid component with papillary projections and the cyst was filled with liquid-like muddy bile. Histologically, the inner layer of the cyst was lined with columnar epithelium showing mild grade dysplasia. On the basis of these findings, hepatobiliary cystadenoma was diagnosed.ConclusionWe believe this case provides evidence of a simple hepatic cyst gradually changing into hepatobiliary cystadenoma.

Clinical relevance of antibiotic-induced endotoxin release in patients undergoing hepatic resection.

It has been proved that antibiotics binding to penicillin-binding protein 3 (PBP3) are associated with the greater release of endotoxin than those that bind to PBP2 in both in vitro and animal models. The aim of this study is to evaluate the potential clinical implications of antibiotic-induced endotoxin release after hepatic resection. Forty-five patients who underwent hepatic resection in our clinic were enrolled. The patients were divided into two groups. Group A (n = 26): antibiotics that bind primarily to PBP3, including cefmetazole (CMZ), latamoxef (LMOX), flomoxef (FMOX), were used. Group B (n = 19); antibiotics that bind to both PBP2 and PBP3, including cefazolin (CEZ), cefoperazone (CPZ), cefotiam (CTM). Postoperative complications, liver functional tests, and chemical mediators [endotoxin, interleukins (IL-6, IL-8), tumor necrosis factor alpha (TNFalpha), granulocyte colony-stimulating factor (G-CSF), hepatotrophic growth factor (HGF) were examined after hepatic resection. There were no significant differences in the backgrounds of the two groups. Eight patients in each group developed postoperative complications; in particular, 9 of 13 patients with biliary tract carcinoma developed postoperative complications. No significant elevation of peripheral blood endotoxin was noted by the endospecy method, in any of the patients, although six died following sepsis. Pre- and postoperative levels of cytokines showed no significant difference between the two groups. Our data suggest that clinical antibiotic-induced endotoxin release would not occur after hepatic resection regardless of the antibiotic, probably owing to continuous scavenging of endotoxin from peripheral blood.

Limitations of endoscopic haemostasis by ethanol injection and surgical management for bleeding peptic ulcer.

Abstract Two hundred and fifty‐three patients with bleeding peptic ulcer underwent therapeutic endoscopy using local ethanol injection and were evaluated to determine the need for surgery and outcome. Permanent endoscopic haemostasis was achieved in 178 (70.4%) cases. Pulsatile arterial bleeding in ulcers and shock on admission (respectively, P < 0.01, P < 0.05) were significantly more frequent in patients with unsuccessful endoscopic treatment. Postoperative stay was significantly longer (P < 0.05) for patients with bleeding peptic ulcer than for patients requiring surgery for intractable ulcer without bleeding. Surgery was recommended if three attempts at endoscopic treatment did not achieve permanent haemostasis. The need for more than three such treatment sessions and the presence of a large excavated ulcer with an exposed vessel in an elderly patient were considered to indicate the necessity for surgery. Surgical procedures to which the operator is accustomed and intensive management were recommended for emergency cases to optimize the likelihood of survival.

Torsional modulus and internal friction of polyacrylonitrile- and pitch-based carbon fibers

In the present work, the torsional modulus and internal friction of different types of polyacrylonitrile (PAN)- and pitch-based carbon fibers were measured with the torsional pendulum method to evaluate the relationship between these properties and the microstructure of carbon fibers. For easier and more accurate measurement, an aluminum disk-type pendulum was used. The measured torsional moduli were comparable to the previously reported values, which indicates the validity of the proposed method. The experimental results and discussion based on Eshelby’s solution and Mori–Tanaka’s mean stress method revealed that the torsional modulus should have a significant relation to the volume fraction of the crystalline region in the fibers and amorphous modulus. The results imply that fibers with a smaller crystalline region and higher amorphous modulus should show a higher torsional modulus. The internal friction of the fibers increased with the torsional modulus. This suggests that the internal friction may also be related to the size of the crystalline region and that the amorphous region has greater internal friction than the crystalline region.

Lymphoepithelial cyst of the pancreas that was difficult to distinguish from branch duct-type intraductal papillary mucinous neoplasm: Report of a case

A 58-year-old woman was admitted to our hospital to optimize the management of her diabetes mellitus. A computed tomography (CT) scan showed a 30-mmdiameter, multilocular cyst in the head of the pancreas. The tumor markers, including DUPAN 2, SPAN-1, and carbohydrate antigen 19-9, were within the normal ranges. A contrast-enhanced CT scan showed a nonenhanced, multilocular cyst. Abdominal magnetic resonance imaging showed a multilocular cyst. Endoscopic retrograde cholangiopancreatography showed that the main pancreatic duct was normal. Based on these findings, we suspected a branch duct type intraductal papillary mucinous neoplasm. A distal pancreatectomy with a splenectomy was performed, since more of the mass was located on the dorsolateral side, inconsistent with the preoperative imaging results. On the resected specimen, a 4-cm-diameter, multilocular cyst containing serous fluid was found. Pathologically, the cyst wall was lined with squamous epithelium surrounded by abundant lymphoid tissue with follicles, consistent with a lymphoepithelial cyst of the pancreas, which is an unusual benign cyst.