Masaru Aoki

L-[1-13C] phenylalanine breath test reflects histological changes in the liver

OBJECTIVE Compared with healthy individuals, patients with chronic liver disease reportedly have lower L-[1-13C] phenylalanine breath test (PBT) values. However, there is no report detailing the relationship between the results of PBT and pathological data in liver disease patients. This study was designed to investigate the degree of histological changes in the liver that induce PBT changes and the time of measurement that reflects the histological change. MATERIALS AND METHODS PBT was performed in 47 patients (10 with a normal liver, and 37 with chronic hepatitis C). After administering 10 mg/kg L-[1-13C] phenylalanine, 300 mL of expired air was collected over 90 min at 15-min intervals. The rate of hepatic phenylalanine oxidation (%13C dose h(-1)) at each time point was calculated from the amount of 13CO(2) in the exhaled air, assuming a CO(2) production rate of 300 mmol m(-2) body surface area per hour. Subsequently, we examined the relationship between the results of PBT and METAVIR pathological scoring. RESULTS The highest correlation coefficients between the fibrosis score and %13C dose h(-1) and between the fibrosis score and %13C cumulative excretion were obtained at 45 min (r = -0.779, R(2) = 0.607; P < 0.0001) and 75 min (r = -0.768, R(2) = 0.590; P < 0.0001), respectively. CONCLUSION PBT is a useful adjunct for detecting histological changes in the liver. The %13C dose h(-1) value at 45 min and the %13C cumulative excretion value at 75 min of PBT are useful for detecting hepatic histological change.

Characteristics of printing company workers newly diagnosed with occupational cholangiocarcinoma

Cholangiocarcinoma has been reported in workers exposed to chlorinated organic solvents and has consequently been classified as an occupational disease (occupational cholangiocarcinoma) by the Japanese Ministry of Health, Labour and Welfare. This study aimed to identify the characteristics of nine workers newly diagnosed with occupational cholangiocarcinoma.

L-[1-13C] phenylalanine breath test reflects phenylalanine hydroxylase activity of the whole liver.

Abstract Object The purpose of this study was to perform L-[1- 13 C] phenylalanine breath test (PBT), measure phenylalanine hydroxylase (PAH) activity in liver tissue biopsies from patients, analyze the relationship between PBT results and PAH activity, and determine the time point at which measurements best reflect PAH activity in liver tissue. Methods PBT was performed in 25 patients (10 with normal liver and 15 with liver cirrhosis). After administering 10 mg/kg L-[1- 13 C] phenylalanine, 300 ml of expired air was collected over 90 min at 15-min intervals. The rate of hepatic phenylalanine oxidation (% 13 C dose h −1 ) at each time point was calculated from the amount of 13 CO 2 in the breath, assuming a CO 2 production rate of 300 mmol m −2 body surface area per hour. Subsequently, we examined the relationship between the results of PBT and PAH activity. Results PAH activity of the whole liver was significantly decreased in hepatic cirrhosis patients ( P 13 C dose h −1 correlated with the PAH activity/liver, with correlation coefficients at 30, 45, and 60 min of more than 0.7, and the maximum correlation was at 30 min ( r = 0.821, P 13 C cumulative excretion correlated with the PAH activity/liver with correlation coefficients of more than 0.7 after 45 min. The maximum correlation was at 90 min ( r = 0.770, P = 0.001). Conclusion PBT values reflect PAH activity in the whole liver and, in particular, the % dose h −1 at 30 min after oral administration highly correlates with PAH activity, providing an important indicator for monitoring changes in whole liver PAH activity.

Patients with severe liver cirrhosis followed up by L-[1-13C] phenylalanine breath test

Compared to healthy subjects, patients with severe liver cirrhosis (LC) are reported to show lower values in the L-[1-13C] phenylalanine breath test (PBT). We performed this test several times during the clinical course in two patients with severe liver cirrhosis (LC). Patient 1 was a 67-year-old woman with non-B, non-C LC and hepatocellular carcinoma (HCC) in the lateral hepatic segment. Because the patient wanted to receive nonsurgical treatment for HCC, intraarterial administration of zinostatin stimalamer was performed. The patient was hospitalized four times before her death from liver failure on December 20, 2000. During her clinical course, PBT was performed four times. Values for both the rate of hepatic phenylalanine oxidation (%13C dose h−1) and %13C cumulative excretion gradually decreased during her clinical course. Patient 2 was a 57-year-old man with hepatitis C virus (HCV)-positive LC. He was hospitalized seven times between December 1998 and his death on May 24, 2001. During his clinical course, PBT was performed four times. Values for both %13C dose h−1 and %13C cumulative excretion decreased during his clinical course. We confirmed that PBT was useful for following the course of LC.

Screening and surveillance for occupational cholangiocarcinoma in workers exposed to organic solvents

PurposeThis study aimed to establish an efficient strategy for screening and surveillance for occupational cholangiocarcinoma.MethodsWe evaluated the consecutive changes in laboratory findings during regular health examinations and in abdominal ultrasonography findings before the diagnosis of occupational cholangiocarcinoma in nine patients. The results of laboratory tests and abdominal ultrasonography at the time of diagnosis were also examined.ResultsIn all patients, the serum γ-glutamyl transpeptidase (γ-GTP) activity increased several years before the diagnosis of cholangiocarcinoma. The serum alanine aminotransferase (ALT) activity also increased several years before the diagnosis, following an increase in the serum aspartate aminotransferase (AST) activity in most patients. Abdominal ultrasonography before the diagnosis revealed regional dilatation of the bile ducts, which continued to enlarge. At the time of diagnosis, the γ-GTP, AST, and ALT activities were increased in nine, seven, and seven patients, respectively. The regional dilatation of bile ducts without tumor-induced stenosis, dilated bile ducts due to tumor-induced stenosis, space-occupying lesions, and/or lymph node swelling were observed. The serum concentrations of carbohydrate antigen 19-9 (CA 19-9) and/or carcinoembryonic antigen (CEA) were increased in all patients.ConclusionsRegular health examinations with a combination of ultrasonography and laboratory tests including the γ-GTP, AST, ALT, CA 19-9, and CEA levels are useful for screening and surveillance for occupational cholangiocarcinoma.

A Case of Solid Adenocarcinoma Arising from the Cystic Duct with Tumor Thrombus in the Common Bile Duct

A 74-year-old man with general fatigue and obstructive jaundice was referred to our hospital. Percutaneous transhepatic cholangiography showed a complete obstruction of the middle and distal bile duct. Dynamic computed tomography demonstrated a low-attenuated mass, occupying both the cystic duct and the common bile duct (Fig. 1, arrowheads). On the preoperative diagnosis of a cystic duct and/or bile duct cancer, the patient underwent pylorus-preserving pancreaticoduodenectomy. The resected specimen contained a brownish fragile tumor in the common bile duct, 8 2 cm in size (Fig. 2; a color version of this figure is available as supplementary data at http://www.jjco.oxfordjournals.org). Histologically, the tumor was diagnosed as solid adenocarcinoma originating from the epithelium of the cystic duct (Fig. 3; a color version of this figure is available as supplementary data at http://www.jjco.oxfordjournals.org). The main tumor involved the subserosal space of the gall bladder, and the tumor thrombus extended to the middle and distal bile duct. The epithelium of the upper bile duct was free from the tumor. The patient is doing well without recurrence 2 years after the operation.

Neither ischemic parenchymal volume nor severe grade complication correlate transient high transaminase elevation after liver resection

To clarify whether high transient elevation of serum transaminase predicts severe complications and is related to the ischemic area on CT. Postoperative laboratory data and ischemia area on CT were analyzed on the basis of the presence of high transaminase elevation (aspartate aminotransferase (AST) > 1,000 IU/L within postoperative day (POD) 2 after liver resection. In the high elevation group, volume of ischemic areas was assessed by CT on POD2. The 538 patients were divided into a high transaminase group (n = 51) and a control group (n = 487). Median operation time (527 min vs. 360 min, p < 0.01) and liver ischemia time (121 min vs. 70 min, p < 0.01) were significantly longer, and intraoperative blood loss (478 mL [85-1572 mL] vs. 269 mL [5-4491 mL], p < 0.01) was significantly greater in the high transaminase group. No significant differences observed in frequency of severe complications (Clavien-Dindo classification Grade III or more) or postoperative hospitalization. Operation time (> 500 min; odds ratio (OR), 4.86; 95% confidence interval (CI), 2.40-9.89; p < 0.01) and liver ischemia time (> 120 min; OR, 3.47; 95%CI, 1.67-7.17; p < 0.01) were independent predictors of high transaminase elevation. No relationship was observed between degree of transaminase elevation and ischemic area (correlation coefficients: AST, R2 < 0.001; alanine aminotransferase, R2 = 0.005) CT volumetry on POD2. In conclusions, high transaminase elevations do not predict severe complications or reflect remnant ischemic area.

L-l-13C phenylalanine breath test reflects phenylalanine hydroxylase activity of the whole liver

OBJECT The purpose of this study was to perform L-[1-13C] phenylalanine breath test (PBT), measure phenylalanine hydroxylase (PAH) activity in liver tissue biopsies from patients, analyze the relationship between PBT results and PAH activity, and determine the time point at which measurements best reflect PAH activity in liver tissue. METHODS PBT was performed in 25 patients (10 with normal liver and 15 with liver cirrhosis). After administering 10 mg/kg L-[1-13C] phenylalanine, 300 ml of expired air was collected over 90 min at 15-min intervals. The rate of hepatic phenylalanine oxidation (%13C dose h(-1)) at each time point was calculated from the amount of 13CO(2) in the breath, assuming a CO(2) production rate of 300 mmol m(-2) body surface area per hour. Subsequently, we examined the relationship between the results of PBT and PAH activity. RESULTS PAH activity of the whole liver was significantly decreased in hepatic cirrhosis patients (P < 0.05). The results of PBT %13C dose h(-1) correlated with the PAH activity/liver, with correlation coefficients at 30, 45, and 60 min of more than 0.7, and the maximum correlation was at 30 min (r = 0.821, P < 0.0001). %13C cumulative excretion correlated with the PAH activity/liver with correlation coefficients of more than 0.7 after 45 min. The maximum correlation was at 90 min (r = 0.770, P = 0.001). CONCLUSION PBT values reflect PAH activity in the whole liver and, in particular, the % dose h(-1) at 30 min after oral administration highly correlates with PAH activity, providing an important indicator for monitoring changes in whole liver PAH activity.