Toshio Kanai

A novel approach to the prevention of postoperative delirium in the elderly after gastrointestinal surgery

AbstractPurpose. Postoperative delirium (POD) is known to be one of the most critical complications of major operative procedures in elderly patients. Since disorders of the sleep-wake cycle have been reported to be one of the key factors in POD, we attempted to clarify the effectiveness of improving sleep-wake cycle disorders with medication after surgery to prevent POD, by conducting a prospective randomized study of 42 elderly patients who underwent resection of either gastric or colon cancer through an open laparotomy. Methods. The delirium-free protocol (DFP) group was given an intramuscular injection of diazepam at 20:00 h each night, as well as a continuous intravenous infusion of flunitrazepam and pethidine administered over 8 h, for the first three nights postoperatively. Two patients were excluded because of failure to complete the DFP. Results. The incidence of POD was 7/20 (35.0%) in the non-DFP group and 1/20 (5.0%) in the DFP group, this difference being significant (P = 0.023). Morning lethargy produced by the DFP was observed in 40% of the DFP group; however, no other side effects were seen. Conclusions. These findings indicate that DFP treatment is effective for controlling POD in elderly patients after general surgery and does not appear to be associated with severe complications or side effects. To our knowledge, this is the first report proposing artificial control of the sleep-awake rhythm by medication as a means of preventing POD in elderly patients.

Relationship between pathologic prognostic factors and abnormal levels of des-γ-carboxy prothrombin and α-fetoprotein in hepatocellular carcinoma

Abstract The relationship between pathologic prognostic factors and abnormal levels of des-γ-carboxy prothrombin and α-fetoprotein was investigated in 42 patients with resectable hepatocellular carcinoma. The frequencies of macroscopic massive type, intrahepatic metastasis, and portal vein tumor thrombus were significantly higher in patients with positive des-γ-carboxy prothrombin (p

Plasma hepatocyte growth factor levels are increased in systemic inflammatory response syndrome

Interleukin-1 (IL-1), a cytokine released from macrophages by endotoxin stimulation, has been shown to upregulate the genetic expression of the hepatocyte growth factor (HGF). The present study was conducted to determine whether plasma HGF is increased in patients with systemic inflammatory response syndrome (SIRS). The plasma levels of HGF, endotoxin, and beta-glucan were measured in 41 surgical patients without hepatic diseases, 18 of whom had been diagnosed with sepsis, and 33, with nonseptic SIRS. The plasma HGF was found to be significantly increased in the 18 patients with sepsis, at 0.69±0.47 ng/ml (mean ± SD), and in the 23 patients with nonseptic SIRS, at 0.49±0.37 ng/ml, compared to values in 40 normal controls, at 0.10±0.03 ng/ml (P<0.001). No significant correlations were observed between the plasma levels of HGF and endotoxin (r=0.02) or beta-glucan (r=−0.05) in any of the patients; however, plasma HGF was significantly correlated with the WBC count (r=0.34, P<0.05) and with total bilirubin (r=0.45, P<0.01). Plasma HGF was also strongly correlated with alanine transaminase (ALT) in 8 patients with ALT levels higher than 50 U/I (r=0.70), but there was no such correlation in 33 patients with ALT levels of 50 U/I or less (r=0.30). Thus, although the clinicopathologic significance of HGF is not well understood, the present findings indicate that plasma HGF increases in response to infection or inflammation.

CILIATED FOREGUT CYST IN CIRRHOTIC LIVER

We encountered a patient with a ciliated hepatic foregut cyst with accompanying liver cirrhosis, which was hard to distinguish from well-differentiated hepatocellular carcinoma. A lesion 2 cm in diameter was found in the subcapsular region of the medial segment of the liver. It was slightly hypoechoic on ultrasononraphy, of high attenuation on nonenhanced computed tomography (CT), of high intensity on T1-weighted spin echo images of magnetic resonance imaging (MRI), and of isointensity on T2-weighted spin echo images. It was not enhanced in the arterial phase images of MRI, and was shown as a complete perfusion defect on CT arterial portography. The cyst was enucleated and found to be filled with bloody mucinous fluid.

Determination of the presence of interleukin-6 in bile after orthotopic liver transplantation. Its role in the diagnosis of acute rejection.

OBJECTIVE The authors evaluated the significance of interleukin-6 (IL-6) in bile in the diagnosis of acute rejection after liver transplantation. SUMMARY BACKGROUND DATA Interleukin-6 in blood has not been shown to be useful as a marker of acute rejection in clinical liver transplantation. In a rat liver transplantation model, the authors have found that bile IL-6 levels correlated well with the severity of rejection as determined histologically, whereas kinetics of serum IL-6 differed among rats without any definite feature related to graft rejection. METHODS Fifty-one patients who underwent orthotopic liver transplantation between May 1990 and February 1991 at the University of California, Los Angeles, were included in the study. After liver transplantation, bile and blood were collected daily, and IL-6 levels were measured by the enzyme-linked immunosorbent assay. RESULTS Bile IL-6 increased to 1228 +/- 317 pg/mL on the day of transplantation and decreased to 50 pg/mL or less within 48 hours. Patients who had uneventful postoperative courses had low levels of bile IL-6 throughout their hospitalization. In patients with acute rejection, bile IL-6 significantly increased (1090 +/- 990 pg/mL; p<0.05), but decreased in response to antirejection therapy. In patients who had liver dysfunction due to ischemic change or sepsis, bile IL-6 did not increase. Patients with cholangitis had significantly increased levels of bile IL-6 (146 +/- 47; p<0.05). Interleukin-6 in blood increased with many kinds of complications other than rejection and seemed to be less specific than that in bile. CONCLUSIONS Measurement of IL-6 in bile may be a useful, noninvasive tool for diagnosing acute rejection.

Obstructive jaundice caused by a huge liver cyst riding on the hilum: report of a case.

A 71-year-old man presented to our hospital with obstructive jaundice, found to be caused by a huge liver cyst which was centrally located and riding on the hilum. Percutaneous transhepatic cyst drainage was performed, following which obstruction of the bile duct was relieved and the jaundice subsided. As jaundice recurred after removal of the drainage tube, the patient underwent deroofing, since when he has remained well. Only 13 cases of liver cysts producing obstructive jaundice have been reported in the English literature, most of which were characteristically enormous, located centrally, and riding on the hilum. Liver cysts possessing such features are likely to cause obstructive jaundice by compressing the hepatic hilum. Cyst drainage is helpful for ameliorating the jaundice and making an accurate diagnosis; however, subsequent deroofing or injection therapy is necessary to prevent recurrence.

Multiple donor allotransplantation: a new approach to pancreatic islet transplantation

Currently it is not feasible to isolate sufficient numbers of islets from a single pancreas for clinical transplantation. We examined whether small numbers of islets obtained from multiple donors could be used for transplantation. Islets were isolated from four inbred strains of mice (DBA/2, DBA/1, C3H, and A.SW) by a stationary collagenase digestion and Ficoll separation and transplanted into the renal subcapsular space of spreptozotocin-induced diabetic B6AF1 mice. At least 200 handpicked islets were required to produce nor-moglycemia in syngeneic and allogeneic diabetic recipient mice. None of the mice given 50 islets became normoglycemic within 2 weeks postgrafting. When various numbers of purified islets from a single donor were transplanted, the survival was significantly better for 200-islet allografts than for 800-islet and 400-islet allografts. When a 200-islet composite graft was prepared from four donors (50 fresh handpicked islets from each donor), the survival of the composite graft as measured by sustained normoglycemia in nonimmunosuppressed recipients was dramatic, with 17 of 18 recipients maintaining normoglycemia indefinitely (>200 days). Similarly, when islets isolated from four donors and cultured for various periods were mixed and transplanted (200 islets/recipient) all recipient mice (n=8) enjoyed indefinite graft survival. Use of higher numbers of purified islets or crude islets in a composite multiple-donor islet allograft was less effective in achieving indefinite graft survival. Thus, transplantation of a composite graft made up with subtherapeutic numbers of islets from multiple histoincompatible donors to provide adequate therapeutic numbers is a practical solution to the lack of islet availability. In addition, composite islet grafts appear to possess immunological advantages, with significantly prolonged survival over that produced by single-donor islet grafts.

Clinicopathological and Immunohistochemical Features of Extragastrointestinal Stromal Tumors: Report of Two Cases

CD117 (c-kit proto-oncogene protein product) is expressed in most gastrointestinal stromal tumors (GISTs) and plays a crucial role in the pathogenesis and treatment of this disease. However, the clinicopathological and immunohistochemical features of CD117-positive mesenchymal tumors without connection to the gastrointestinal tract, known as extragastrointestinal stromal tumors (EGISTs), are not well documented because these tumors are rare. We describe the clinicopathological and immunohistochemical features of two cases of EGIST and compare them with those of GIST. Of the 1855 abdominal or esophageal tumors resected during the past 10 years at our hospital, 23 were GISTs and 2 were EGISTs. The clinicopathological or immunohistochemical characteristics do not seem to differ remarkably between EGISTs and GISTs. Although rare, CD117 positivity should be tested in abdominal mesenchymal tumors that have no connection to the gastrointestinal tract. The clinicopathological features of CD117-positive abdominal mesenchymal tumors may not depend on whether the tumor is connected to the gastrointestinal tract.

Low temperature collagenase digestion for islet isolation from 48-hour cold-preserved rat pancreas

We examined the efficacy of relatively low temperature collagenase digestion at 20 degrees C on the yield and viability of islets after long-term cold preservation. Wistar rat pancreases were distended with University of Wisconsin solution via a pancreatic duct at the time of harvesting to which collagenase and 2.5 mM calcium chloride were added. The pancreases were cold-preserved at 4 degrees C for 24 or 48 hr. After storage, they were incubated for collagenase digestion at 37 degrees C or 20 degrees C for various incubation periods to obtain the peak yield. At 20 degrees C, in vitro collagenase activity measured by the FALGPA method was one fourth of that at 37 degrees C, and pancreases were well digested with a prolonged digestion period (60-90 min vs. 15-20 min for the 37 degrees C group). In vitro insulin secretion of islets isolated from freshly removed pancreases was maintained at 20 degrees C for 120 min in University of Wisconsin solution as compared with 30 min at 37 degrees C. Therefore, the preserved pancreases used in this study were incubated either at 37 degrees C or 20 degrees C at various times in order to obtain peak islet yields. The islet yields from 24-hr cold-preserved pancreases at 37 degrees C and 20 degrees C digestion were 573 +/- 59/rat (n = 6) and 497 +/- 84/rat (n = 11), respectively, and those from 48-hr cold-preserved pancreases were 395 +/- 113/rat (n = 6) and 414 +/- 75/rat (n = 6), respectively. The yields from 24- and 48-hr cold-preserved pancreases were significantly low compared with 635 +/- 52/rat for fresh pancreases (n = 15), but there was no significant difference between the 2 methods. The viability of the isolated islets, which was examined by transplantation to streptozotocin-induced diabetic C57BL/6 mice, showed a significant difference in the capacity to ameliorate diabetes. The functional success rate of islet transplantation after 24-hr cold preservation was equally good (8/8 for 37 degrees C group vs. 9/10 for 20 degrees C group), but the rate for those from 48-hr cold-preserved pancreases was significantly better with digestion at 20 degrees C than at 37 degrees C (1/8 for 37 degrees C group vs. 7/8 for 20 degrees C group, P < 0.05). We concluded that viable islets can be isolated from 48-hr cold-preserved pancreases with the low temperature collagenase digestion method, which shows promise as a modality for successful clinical islet transplantation.

Effect of gamma-irradiation on mouse pancreatic islet-allograft survival.

Elimination or inactivation of lymphoid tissue in the pancreatic islet preparation achieves prolongation of islet-allograft survival. In this study we examined the effect of γ-irradiation on mouse islet-allograft survival. In a B6AF1 isograft model, irradiation up to 2400 rad did not induce deterioration of islet function over 200 days, but greater doses caused cessation of graft function between 83 and 186 days. When DBA/2 crude islets were transplanted into B6AF1 recipients, all nonirradiated allografts were acutely rejected. Marked prolongation of allograft survival was achieved by islet irradiation with doses between 800 and 12,000 rad. With higher doses, significant numbers of allografts survived beyond the controls, but many lost function between 78 and 180 days, with none surviving >200 days. Irradiation with 16,000 rad caused acute radiation damage. Because most secondary islet allografts in recipient mice that lost primary islet-graft function between 84 and 195 days survived >100 days, late functional loss was probably due to the radiation injury. Combined use of recipient treatment with cyclosporin A and graft irradiation (2400 rad) achieved prolongation of DBA/2 islets in B6AF1 mice.