Evaluation of pancreatic exocrine secretion using 13C-dipeptide (benzoyl-L-tyrosyl-[1-(13)C]alanine) breath test: focusing on pancreatoduodenectomy cases.

OBJECTIVES: We investigated whether a breath test using benzoyl-L-tyrosyl-[1-(13)C]alanine (Bz-Tyr-Ala) allows assessment of pancreatic exocrine function. METHODS: Benzoyl-L-tyrosyl-[1-(13)C]alanine was orally administered, and changes in (13)CO2 were expressed as delta per thousand. The breath test was performed in chronic pancreatitis patients and healthy subjects in a preliminary study and, subsequently, in 17 pancreatoduodenectomy patients, to examine the difference between the results obtained at the times of pancreatic tube insertion and removal, the relationship between breath test results after tube removal and the volume of pancreatic juice drained, and the difference in results between the presence versus the absence of histological changes of chronic pancreatitis. RESULTS: The delta per thousand was lower in the chronic pancreatitis patients than in healthy subjects. In the postoperative patients, the delta per thousand was higher at tube insertion than at tube removal. The correlations of the delta per thousand with the maximum volume of pancreatic juice, its mean volume, and pancreatic juice amylase levels were 0.865, 0.757, and 0.853, respectively. The delta per thousand was lower in 11 patients with that in 6 patients without histological changes of chronic pancreatitis. CONCLUSIONS: These results suggest that the Bz-Tyr-Ala breath test can measure pancreatic exocrine function.

Measurement of extra-pancreatic secretory function by 13C-dipeptide breath test.

A simple breath test was developed for assessment of exocrine pancreatic function employing 13C-dipeptide [ie, benzoyl-L-tyrosyl-[1-(13)C]alanine (Bz-Tyr-Ala)], and this test was examined to determine whether it can be used to diagnose exocrine pancreatic insufficiency in patients with chronic pancreatitis. The subjects, 24 patients with chronic pancreatitis and 16 healthy adult controls, underwent the Bz-Tyr-Ala breath test, in which breath samples were collected every 10 min up to 90 min after oral administration of an aqueous solution of 5-mg/kg Bz-Tyr-Ala (7 mM). They also underwent a breath test with [1-(13)C]alanine equimolar to that contained in Bz-Tyr-Ala and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) test. Delta13CO2 values at 10-60 min for the Bz-Tyr-Ala breath test were significantly lower in chronic pancreatitis patients than in normal controls. However, the [1-(13)C]alanine breath test results did not differ between patients and normal controls. The correlation coefficient between the Bz-Tyr-Ala breath test Delta13CO2 value at 20 min, and the results of the BT-PABA test were r=0.726 (r2=0.527, P<0.0001). The results suggest that this newly developed Bz-Tyr-Ala breath test can quickly and noninvasively diagnose the exocrine pancreatic dysfunction.

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

Compared to healthy subjects, patients with severe liver cirrhosis (LC) are reported to show lower values in the L-[1-(13)C] 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 (%(13)C dose h(-1)) and %(13)C 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 %(13)C dose h(-1) and %(13)C cumulative excretion decreased during his clinical course. We confirmed that PBT was useful for following the course of LC.

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.

L-[1-13C] 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.

Pheochromocytoma presenting as an abdominal emergency: association with perforation of the colon.

A pheochromocytoma is a rare tumor derived from the adrenal medulla (or from chromaffin cells of sympathetic ganglia). Its symptoms derive mostly from the excessive release of catecholamines (adrenaline and noradrenaline). Hypertension is the most recognized feature of this disease, but gastrointestinal manifestations can on rare occasions be just as serious and life threatening. This report describes a rare case of a 70-year-old woman with pheochromocytoma who developed an acute abdominal emergency with shock and panperitonitis as a result of perforation of the descending colon which was effectively treated by surgical removal of the tumor and the perforated colon. There have been 2 such cases in the English literature in whom a pheochromocytoma was associated with perforation of the colon. Successful surgical removal of such a pheochromocytoma has been not reported previously. Our case demonstrates the importance of recognizing that a pheochromocytoma presents with a wide spectrum of manifestations, and rapid treatment brings improvement to the patient.

l-[1-(13)C]Alanine is a useful substance for the evaluation of liver function.

BACKGROUND: Using a rat model of hepatectomy, we investigated whether the severity of hepatopathy could be quantitatively measured from changes in expiratory (13)CO(2) levels after intravenous administration of l-[1-(13)C]alanine. MATERIALS AND METHODS: Under nembutal anesthesia, 20 mg/kg l-[1-(13)C]alanine was administered to rats via the femoral vein, and expiratory (13)CO(2) levels were measured for 15 min. Then, 30, 70, or 90% hepatectomy was performed. In the control group, simple laparotomy was performed. A breath test was conducted 20 min after laparotomy. We examined the correlation of total (13)CO(2) output (S) or single point (13)CO(2) level (SP) every 1 min for 15 min with liver weight/body weight (LW/BW) (%). RESULTS: In the control group, the breath test graph showed a specific peak level about 3 min after administration, but in all groups undergoing hepatectomy, it did not show any peak level during measurement. The correlation coefficient between S(12--15) after l-[1-(13)C]alanine administration and LW/BW was 0.902 (P < 0.0001). The correlation coefficient between SP(7) after l-[1-(13)C]alanine administration and LW/BW was highest, 0.908 (P < 0.0001). The severity of hepatopathy could also be evaluated, with significant differences in S(12-14) compared to control when the volume of resected liver was 30% or greater, but there was no significant difference between the groups undergoing 70 and 90% hepatectomy. However, the severity of hepatopathy could be evaluated, with significant differences in S(15) and SP(7) in all comparisons between groups. CONCLUSION: In the breath test with intravenously administered l-[1-(13)C]alanine, the severity of hepatopathy could be quantitatively evaluated in a short period by measuring S(15) and SP(7).