Higher intracerebral concentration of tacrolimus after intermittent than continuous administration to rats.

Neurotoxicity associated with tacrolimus after liver transplantation is a serious problem. The optimal way to administer tacrolimus to reduce neurotoxicity remains to be clarified. Three groups of rats were administered tacrolimus for 2 weeks: group C, continuous intravenous infusion (0.25, 0.5, and 1.0 mg/kg/d); group I, intermittent intravenous bolus injection twice daily (0.25, 0.5, and 1.0 mg/kg/d); and group O, oral administration twice daily (5 mg/kg/d; n = 12 each). Rats were killed either day 7 or 14 to measure whole-blood and intracerebral trough concentrations of tacrolimus. The area under the whole-blood concentration-time curve (AUC) was determined day 7. The relative risk ratio of neurotoxicity was evaluated on the basis of the brain to blood concentration ratio (Kp) and intracerebral concentration to AUC ratio (R(AUC)). The whole-blood concentration of tacrolimus and AUC value were greater in group C than group I. Conversely, the intracerebral concentration and Kp and R(AUC) values were significantly greater in group I than group C. The difference in Kp values between groups C and I significantly increased with the dose and duration of administration. Whole-blood and intracerebral concentrations in group O were similar to those at the 0.25-mg/kg/d dose in group I. In conclusion, the intracerebral concentration of tacrolimus was greater after intermittent than continuous administration of the drug. Continuous administration of tacrolimus might be more advantageous than the intermittent method to reduce the intracerebral concentration and neurotoxicity.

Ventral dissection of replaced right hepatic artery during pancreatoduodenectomy.

A novel technique for dissecting a replaced right hepatic artery during pancreatoduodenectomy in patients with middle or lower bile duct carcinoma is presented. After skeletonizing the left, proper, common hepatic arteries and the portal vein, the replaced right hepatic artery is dissected from the ventro-medial side of the hepatoduodenal ligament by severing the thin connective tissue behind the portal vein. Thus the hepatic arteries and the portal vein are completely isolated without the Kocher maneuver, leaving the cancer and the bile duct untouched en bloc with the surrounding lymph nodes and the pancreas head. The periaortic lymph nodes can also be resected en bloc with the main lesion.

[Living-related liver transplantation and clinical pathology].

More than 1,100 cases of living-related liver transplantation have already been performed in Japan. It achieved good survival rates, 83.6% in children and 74.5% in adults. These good results depend on not only development of immunosuppressants and improvement of surgical techniques but also on progress of clinical examination and postoperative management. Many kinds of clinical examination were frequently performed after liver transplantation. Liver transplantation cannot be performed without the cooperation of staffs who are involved in clinical examination.

Reversible hepatofugal portal flow after liver transplantation using a small-for-size graft from a living donor.

We describe a case of reversible hepatofugal portal flow 1 week after transplantation of a small-for-size liver graft from a living donor. A transient increase in intrahepatic portal vascular resistance was the suspected cause. The portal venous flow normalized after residual collateral channels had been interrupted surgically. The patient was discharged on the 90th postoperative day. Liver transplant clinicians should be aware that hepatofugal flow can occur with small-for-size liver grafts, despite sufficient portal venous flow immediately after transplantation.

Randomized comparison of ultrasonic vs clamp transection of the liver.

HYPOTHESIS: Hepatic parenchymal transection is a technical priority in liver surgery. The use of an ultrasonic dissector for hepatectomy may result in less blood loss than conventional clamp crushing. DESIGN: Randomized controlled trial. SETTING: University teaching hospital. PATIENTS: The 132 patients scheduled to undergo partial hepatectomies were randomly assigned to receive hepatic transection by ultrasonic dissector or by clamp crushing (66 patients by each method). INTERVENTIONS: All resections were performed with inflow occlusion and were guided ultrasonographically. Hepatectomies were graded according to a predefined system based on 6 criteria (blood loss, transection time, technical error, surgical margin, landmark appearance, and postoperative morbidity), each with 3 scores (lower scores indicating higher quality). MAIN OUTCOME MEASURES: Blood loss and hepatectomy grade. RESULTS: No difference was found between the ultrasonic and clamp groups in median blood loss (515 mL [range, 15-2527 mL] vs 452 mL [range, 17-1912 mL]; P =.63), transection time (61 minutes [range, 16-177 minutes] vs 54 minutes [range, 7-205 minutes]; P =.58), or transection speed (1.1 cm(2)/min [range, 0.4-4.0 cm(2)/min] vs 1.0 cm(2)/min [range, 0.4-3.0 cm(2)/min]; P =.90). Ultrasonic dissection caused more frequent histologically proven tumor exposure at the surgical margin (9 vs 3 patients; P =.09), incomplete appearance of landmark hepatic veins on the cut surface after anatomical resection (12 vs 4 patients; P =.03), and postoperative morbidity (20 vs 14 patients; P =.32) than did clamp crushing. The hepatectomies with clamp crushing had significantly higher grades than those with ultrasonic dissection (P =.05), as indicated by the lower median sum score (4.0 [range, 0-12] vs 5.0 [range, 0-19]; 95% confidence interval for difference, -2.0 to 0; P =.03). The transection method independently influenced hepatectomy grade (adjusted odds ratio = 3.06; 95% confidence interval, 1.35-6.92; P =.01). CONCLUSIONS: Ultrasonic dissection offers no reduction in blood loss compared with clamp crushing for transection of the liver. Clamp crushing results in a higher quality of hepatectomy and is therefore the option of choice.

A comparison of gene expression in murine cardiac allografts and isografts by means DNA microarray analysis.

BACKGROUND: Acute rejection of allografts remains a significant problem in clinical transplantation, and the fundamental mechanism underlying this rejection are as yet only poorly elucidated. Recently, DNA microarrays have come into use for the study of gene expression profiles, and we have taken advantage of this new technology to investigate acute rejection. We compared mRNA profiles in murine cardiac allografts with isografts using DNA microarrays with probe sets corresponding to more than 11,000 mice genes. METHODS: We screened for gene expression changes in murine cardiac allografts between fully incompatible mice strains (BALB/c H2d to C3H/He H2k) using a DNA microarray. The heart was heterotopically transplanted. Allografts (BALB/c to C3H/He) were removed on days 1, 3, and 5. As a control, isografts (C3H/He to C3H/He) harvested on days 1, 3, and 5 and native hearts of both strain mice (C3H/He and BALB/c) were obtained. RESULTS: On day 5, interferon-gamma (IFN-gamma) and many IFN-gamma-inducible genes were profoundly induced in the allograft relative to isograft. Monokine induced by IFN-gamma was most profoundly induced followed by inducibly expressed GTPase and Lmp-2. IFN-gamma was also profoundly induced. The induction was detectable from day 3. In contrast, genes regulated by other cytokines exhibited only modest changes. CONCLUSION: IFN-gamma-inducible genes are specifically up-regulated in murine cardiac allografts, suggesting that signaling mediated by IFN-gamma may play an important role in the late phase of acute rejection in vivo.

Kinetics of urinary trypsin inhibitor in patients undergoing partial hepatectomy.

BACKGROUND: The kinetics and role of urinary trypsin inhibitor (UTI) in liver surgery are unclear. We investigated the effects of preoperative liver function and the extent of liver resection on postoperative UTI synthesis in the liver after partial hepatectomy. METHODS: Sixty-one consecutive patients who underwent liver resection were the subjects of the study. Plasma and urine UTI, plasma C reactive protein (CRP) and plasma and urine creatinine were measured perioperatively. RESULTS: Although the average plasma UTI level did not change significantly, the average urine UTI level per day showed a change similar to that of the average plasma CRP level, reaching a maximum of approximately eight times the preoperative level on the second postoperative day (86,610 +/- 53,109 U/day). The maximum postoperative increase in urine UTI excretion per day (delta-uUTImax) correlated significantly with the maximum increase in CRP and the increase in creatinine clearance. Multiple regression analysis revealed that delta-uUTImax was significantly and positively correlated with the indocyanine green plasma disappearance rate and operation duration, and negatively correlated with the resection rate. CONCLUSIONS: The postoperative urine UTI level may reflect preoperative liver function and the extent of liver resection after partial hepatectomy.

[Risk management and clinical path].

In the risk management of medical practice, developing an efficient system to prevent medical accidents and trouble is required. For this purpose it is important to promote a cooperative team practice, to clarify each staff member's role, for each staff member to accurately carry out that role, for each staff member to always try to understand the patient's condition, and for staff members to ask each other whenever in doubt as to a patient's condition or the medical practice itself. These points for risk management share the same goal as the clinical path. The introduction of a clinical path is useful from the viewpoint of risk management. Electronic medical records and computer ordering systems in the medical practice should be developed as tools to decrease medical accidents.