Yoshiro Taki

Significance of arterial ketone body ratio measurement in human liver transplantation

Arterial ketone body ratio (KBR), which reflects the NAD+/NADH ratio of hepatic mitochondria, was measured sequentially in 39 liver transplantations. In 22 cases, KBR was increased to above 0.7 within 6 hr after reperfusion (group A). In 11 cases, restoration of KBR was delayed until the first postoperative day (group B) and in 6 cases, KBR failed to recover (group C). The patients in group A survived liver transplantation without complications. By contrast, morbidity and mortality were significantly higher in groups B and C. In 2 cases in group C, the livers were clinically diagnosed as initially nonfunctioning grafts and the patients underwent retransplantation. Another two died of hepatic failure soon after the operation. It is suggested that delayed recovery of KBR is an early indicator of metabolic overload in the liver allograft, and that a delay exceeding 24 hr may imply the need for retransplantation.

Usefulness of FDG-positron emission tomography in diagnosing peritoneal recurrence of colorectal cancer

BACKGROUND Accurate detection of peritoneal recurrence in colorectal cancer remains a diagnostic challenge. We retrospectively examined sensitivity and accuracy of fluorine-18-2-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in the diagnosis of peritoneal recurrence. METHODS FDG-PET and computed tomography (CT) were performed on 23 patients with colorectal cancer suspected of having a recurrence based on clinical symptoms, a tumor marker (CEA), and so forth. The final diagnosis was compared with the results of FDG-PET and CT. RESULTS Peritoneal recurrence was suspected in 6 patients with FDG-PET, and 5 of them were finally diagnosed as recurrences. The sensitivity of FDG-PET was 88% and its diagnostic accuracy was 78%, whereas those of CT were 38% and 44%, respectively. A lesion as small as 15 mm in diameter was diagnosed by FDG-PET. CONCLUSIONS FDG-PET is an effective method for diagnosing peritoneal recurrence of colorectal cancer. FDG-PET is expected to become more important for detecting peritoneal recurrence at an early stage.

Adenylate energy charge and cytochrome a (+a3) in the cirrhotic rat liver

In the cirrhotic rat liver induced by phenobarbitone and carbon tetrachloride, adenylate energy charge, mitochondrial oxidative phosphorylation, and respiratory enzyme concentrations were studied along with serum albumin concentrations. Cytochrome a (+a3) concentrations of the liver increased with the severity of cirrhosis and were negatively correlated with the ATP-synthesizing ability per unit of cytochrome a (+a3). These changes were associated with the decrease in hepatic energy charge. Such decreased energy charge may be responsible for the decreased serum albumin level in the cirrhotic rat. It is suggested that such falls in hepatic energy charge may be one of the most important factors contributing to the decreased functional reserve of cirrhotic patients.

Short-term changes in blood ketone body ratio in the phase immediately after liver transplantation

Arterial blood ketone body ratio was measured after orthotopic liver transplantation in piglets. Ketone body ratio immediately decreased at the beginning of the anhepatic phase and was rapidly restored to the normal levels within 30 min after the revascularization of the allograft. Serum lactate and pyruvate levels increased in anhepatic phase and gradually decreased after revascularization. Changes in the lactate and pyruvate levels were always preceded by changes in ketone body ratio. In the case of transplantation after 12-hr-preservation of the allograft, ketone body ratio failed to maintain normal levels after transplantation, resulting in a high mortality. It is suggested that the elevation of decreased ketone body ratio is prerequisite for the normalization of the deranged metabolic state after liver transplantation, and that ketone body ratio provides an accurate means to assess the initial metabolic function of the allograft.

Evaluation of the liver graft before procurement : Significance of arterial ketone body ratio in brain-dead patients

Hepatic energy metabolism was assessed by measuring the blood ketone body ratio (KBR), that is, the ratio of acetoacetate to β-hydroxybutyrate in the arterial blood, in 31 brain-dead patients in an intensive care unit (ICU) in Japan and in 25 donors just before procurement of the liver for transplantation in Germany. In the study in Japan, 7 of the 12 brain-dead patients treated with highdose catecholamine showed significantly decreased KBRs, revealing the detrimental effect of catecholamine on livermmetabolism. In contrast, 8 of the 9 untreated patients with blood pressure below 80 mm Hg showed almost normal KBRs. In the 25 donors in Germany, KBR was maintained within the normal range. Based upon conventional criteria, 21 livers were selected for use and the other 4 were discarded. Nineteen of the grafts were able to normalize KBR within 24 h after reperfusion, while 2 failed to function and required a second transplantation. It was suggested that a KBR in the normal range in donors is a prerequisite to immediate recovery of metabolic function of the liver graft after transplantation, and that hypotensive donors as a potential source of liver grafts may warrant further study.

Tuberculous Lymphadenitis as a Cause of Obstructive Jaundice : Report of a Case

Abstract.We report a rare case of obstructive jaundice caused by enlarged tuberculous lymph nodes compressing the common bile duct in the retropancreatic region, mimicking pancreatic cancer. A 32-year-old man was admitted to our hospital with a 1-month of history of jaundice. An abdominal computed tomography (CT) scan showed a tumor in the pancreatic head, but an endoscopic retrograde cholangiopancreatogram (ERCP) showed a normal pancreatic duct system. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG-PET) revealed a hot spot only in the pancreatic head. Under a presumptive diagnosis of malignancy, a laparotomy was performed and an intraoperative biopsy specimen revealed epithelioid granuloma with caseous necrosis, which led us to suspect tuberculous lymphadenitis. This diagnosis was confirmed by culture, and antituberculous therapy was commenced postoperatively. The patient has not suffered any further episodes of obstructive jaundice. This case report demonstrates that positive FDG-PET results should be interpreted carefully when diagnosing tumors of the pancreatic head.

Change in Mitochondrial Membrane Potential in Peripheral Blood Lymphocytes, Especially in Natural Killer Cells, Is a Possible Marker for Surgical Stress on the Immune System

There is accumulating evidence that surgical stresses cause impairment of systemic immune responses, which may promote susceptibility to infection as well as growth of remnant cancer cells in cancer patients. Although alterations in numbers, populations, and functions of lymphocytes have been extensively studied to assess modulation of the immune system, the precise mechanisms of immunosuppression caused by surgical stresses have not been identified, nor have methods been developed to estimate the magnitude of surgical stresses on the immune system. In the present study, to evaluate the effects of surgical procedures on the immune system, the mitochondrial membrane potential (ΔΨm) of peripheral blood lymphocytes (PBL) from 25 patients who underwent various types of operation was measured by flow cytometry using 3,3′-dihexiloxacarbocyanine iodide (DiOC6(3)) on the day before operation and on postoperative day (POD) 1, POD 3, and POD 7. The ΔΨm in PBL, especially in natural killer (NK) cell population, was reduced after major surgery. In particular, the reduction of ΨΔm in NK cells appeared to be proportional to the severity of the surgical procedures and reflected the impairment of cellular function. Interestingly, the ΔΨm in NK cells was also negatively correlated with the level of plasma noradrenaline after major surgery, suggesting that the reduction of ΔΨm in NK cells induced by surgical stresses may bemediated, at least in part, by the accompanying increase in plasma noradrenaline. Monitoring of ΔΨm in PBL after operation may be one of the useful markers for estimating the magnitude of surgical stresses on the immune system.

Changes in acetoacetate/β-hydroxybutyrate ratio in arterial blood following hepatic artery embolization in man

Acetoacetate/beta-hydroxybutyrate ratio in the hepatic venous blood was compared to the ratios in arterial blood and peripheral venous blood in hypoxic state following right hepatic artery embolization in 5 patients with liver cancer. Ketone body ratios in right hepatic venous blood were positively correlated with those in arterial blood (r = 0.960, p less than 0.001), but not with those in peripheral venous blood. The free NAD+/NADH ratio of the liver mitochondria, which is reflected by the ketone body ration in hepatic venous blood, can be evaluated by the ketone body ratio in the arterial blood.

Changes in Energy Metabolism of Allografts after Liver Transplantation

To evaluate the function of energy metabolism in allografts after liver transplantation, changes in hepatic energy charge levels, oxidative and phosphorylative activities of mitochondria and arterial blood ketone body ratio (acetoacetate/3-hydroxybutyrate; KBR) were studied in piglets. Hepatic energy charge levels decreased to 0.831 +/- 0.010 at 3 days and 0.836 +/- 0.009 at 3 weeks after operation compared to the preoperative value of 0.868 +/- 0.006 (p less than 0.01), and returned to 0.856 +/- 0.007 at 6 weeks. Mitochondrial oxidative and phosphorylative activities were moderately enhanced to 19.14 +/- 2.07 (10(-10) mol ATP/mg of mitochondrial protein/s) at 3 days and 20.89 +/- 1.72 at 3 weeks compared to the preoperative value of 16.74 +/- 2.36, and returned to 16.65 +/- 1.54 at 6 weeks. There was no significant difference in the concentrations of mitochondrial respiratory components, except in cytochrome c + c1. KBR decreased immediately at the beginning of the anhepatic phase and rapidly recovered to the preoperative level within 60 min after revascularization of allografts. There was no change in KBR during the postoperative course except in cases with clinical deterioration. From these results, it is suggested that the mitochondrial capacity for ATP synthesis was enhanced to compensate for the decreased energy charge level and that a decreased KBR is a sign of a critically deranged metabolic function in allografts.

The Influence of Hemodilution in Normal and Cirrhotic Rats in Relation to Hepatic Energy Metabolism

The effects of acute hemodilution on hepatic energy status were compared between carbon-tetrachloride-induced cirrhotic rats and normal rats, using arterial blood ketone body ratio and hepatic energy charge as indices. Arterial blood was withdrawn and replaced with rat plasma in hemodiluted rats and with whole blood in sham-diluted control rats. In normal rats, arterial blood ketone body ratio and energy charge level at 6 hours after hemodilution decreased when the hematocrit value was less than 15%. In contrast, the values decreased at an even higher hematocrit level in cirrhotic rats. It was suggested from these results that the hemodilution procedure exerts a more profound hypoxic effect at a milder hemodilution on a cirrhotic liver than on a normal liver.