Hirotaka Ishizu

Usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose for predicting outcome in patients with hepatocellular carcinoma

OBJECTIVES:The present study was designed to assess the usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) for predicting outcome in patients with hepatocellular carcinoma.METHODS:FDG-PET was performed in 48 patients with hepatocellular carcinoma. For quantitative evaluation, a region of interest (ROI) was placed over the area of maximum activity within the lesion. A background ROI was then placed over the nontumor region of the liver. The average activity within each ROI was subsequently corrected for radioactive decay, and the standardized uptake value (SUV) was calculated by dividing the tissue activity by the injected dose of radioactivity per unit body weight. SUV ratio was expressed as the tumor-to-nontumor ratio of the SUV.RESULTS:The tumor-volume doubling time, as index of the growth rate of hepatocellular carcinoma, correlated significantly with SUV ratio but did not correlate with SUV. On the basis of the SUV ratio, the patients were divided into two groups of similar size: group A, SUV ratio of ≤1.5; and group B, SUV ratio >1.5. The cumulative survival rate was significantly lower in group B than in group A. On the basis of the SUV, the patients were divided into two groups of roughly equal size: group C, ≤SUV 2.6; and group D, >SUV 2.6. The cumulative survival rate was similar in these groups. On regression analysis with the Cox proportional hazards model, the SUV ratio and tumor number were significantly related to survival.CONCLUSIONS:These results suggest that FDG-PET is useful not only for the evaluation of the malignancy of hepatocellular carcinoma but also for the prediction of outcome in patients with hepatocellular carcinoma.

Natural course of changes in hepatic functional reserve in patients with chronic liver diseases evaluated by scintigraphy with GSA

Hepatic functional reserve can be evaluated in a noninvasive way by scintigraphy with 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA). We monitored hepatic functional reserve in patients with chronic hepatitis and cirrhosis using scintigraphy with 99mTc-GSA to determine the natural course of changes in their hepatic functional reserve. Computer acquisition of gamma-camera data was started before the injection of 185 MBq of 99mTc-GSA and was stopped 20 min later. Time-activity curves were generated from ROI for the heart and liver. A receptor index and index of blood clearance were calculated from radioactivity in the heart and liver. Scintigraphy with 99mTc-GSA was performed in 12 healthy subjects, 86 patients with chronic hepatitis, and 226 patients with cirrhosis. Seventy-two patients (23 with chronic hepatitis, 32 with cirrhosis in Child-Pugh stage A, 15 in stage B, and 2 in stage C) were examined at least twice with 12-72 months intervening. The receptor index was lower for more severe disorders, decreasing in the order of chronic hepatitis and cirrhosis in stages A, B, and C. The index of blood clearance was higher for more severe disorders, increasing in the order of chronic hepatitis and cirrhosis in stages A, B, and C. The mean annual change in the receptor index with chronic hepatitis was -0.0007, that with cirrhosis in stage A was -0.0023, and that with cirrhosis in stage B or C was -0.0117. The difference between the median annual change with cirrhosis in stage B or C and that with chronic hepatitis or cirrhosis in stage A was not significant (P=0.064 and 0.251, respectively). The mean annual change in the index of blood clearance with chronic hepatitis was 0.0018, that with cirrhosis in stage A was 0.0060, and that with cirrhosis in stage B or C was 0.0330. The difference between the median annual change in the index of blood clearance with cirrhosis in stage B or C and that with chronic hepatitis or cirrhosis in stage A was significant (P=0.004 and 0.007, respectively). Hepatic receptor imaging with 99mTc-GSA could be used to noninvasively evaluate the hepatic reserve of various liver diseases. Changes in hepatic functional reserve were not steady; it decreased gradually as disease advanced from chronic hepatitis to cirrhosis in Child-Pugh stage A, and decrease rapidly after development of stage B cirrhosis.

Gastric emptying in patients with chronic liver diseases

There have been a number of reports of gastric emptying in cirrhosis, all with unconfirmed results. Moreover, the mechanism for delayed emptying in cirrhotic patients is unclear. We evaluated gastric emptying in patients with chronic hepatitis and cirrhosis by means of gastric emptying scintigraphy.Methods: The subjects were 18 normal controls and 75 patients with chronic viral hepatitis (50 patients had chronic hepatitis and 25 patients had cirrhosis). Tc-99m diethyltriamine pentaacetic acid labeled solid meals were used to evaluate gastric emptying; the half-time (T 1/2) of which was calculated. Digestive symptom scores were determined at the time of gastric emptying tests.Results: Fourteen (28%) of 50 patients with chronic hepatitis and 16 (64%) of 25 patients with cirrhosis had delayed gastric emptying. T 1/2 in patients with cirrhosis was significantly higher than that in normal controls and patients with chronic hepatitis (p=0.0001 and 0.0003, respectively). The difference between T 1/2 in patients with chronic hepatitis and that in normal controls was not significant. On regression analysis, two indices—the serum albumin level and platelet count—were found to be significantly related to delayed gastric emptying.Conclusions: Gastric emptying was more delayed in cirrhotic patients than in those with chronic hepatitis and normal controls. Delayed gastric emptying may be related to liver function and portal hypertension.

FDG uptake by tongue and muscles of mastication reflecting increased metabolic activity of muscles after chewing gum.

Glucose metabolic activity of the muscles increases during exercise. The authors report an example of intense F-18 fluorodeoxyglucose (FDG) uptake by the tongue and the muscles of mastication in a patient after 3 hours of chewing sugar-free gum before F-18 FDG administration.

Accessory spleen in the pelvis diagnosed by Tc-99m phytate scintigraphy.

We report a 58-year-old woman with an accessory spleen in the left side of the pelvis. She visited our outpatient clinic complaining of lower abdominal discomfort. Abdominal ultrasonography revealed a tumor 4 cm in diameter in the left side of the pelvis. Color Doppler ultrasonography demonstrated plentiful pulsating blood flow. Magnetic resonance angiography revealed that the blood supply for the tumor was from a branch of the splenic artery. Scintigraphy with Tc-99m phytate revealed accumulation of radioactivity concordant with a mass in the left side of the pelvis, and the spleen was normally visualized. These findings suggested that this tumor was an accessory spleen, and the patient underwent no further invasive procedures.

Factors Associated with Potassium-Competitive Acid Blocker Non-Response in Patients with Proton Pump Inhibitor-Refractory Gastroesophageal Reflux Disease

Background/Aims: Approximately 20-40% of patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI) treatment. The acid-inhibitory effect of vonoprazan, a novel potassium-competitive acid blocker (P-CAB), is significantly greater when compared to the effect of PPIs. We investigated the efficacy of vonoprazan treatment for PPI-refractory GERD and factors associated with P-CAB non-response. Methods: We enrolled 277 GERD patients receiving continuous PPI therapy. Subjects completed a self-report questionnaire including the frequency scale for the symptoms of GERD (FSSG). Patients with PPI-refractory GERD received 20 mg of vonoprazan once daily for 8 weeks. After that, subjects completed the same questionnaire, and the results were used to identify P-CAB responders and non-responders. Results: Twenty-eight patients were identified as P-CAB responders and 26 were non-responders. Vonoprazan treatment significantly decreased scores of FSSG, nighttime symptom, and Athens Insomnia Scale. Multivariate analysis demonstrated co-existing functional dyspepsia (FD; OR 4.94) and the presence of sleep disturbances (OR 4.34) was associated with P-CAB non-response, whereas alcohol consumption was inversely associated. Conclusions: Vonoprazan treatment might be appropriate as a promising new strategy for PPI-refractory GERD. Co-existing FD, sleep disturbances, and alcohol abstinence were significantly associated with P-CAB non-response. Other therapeutic options should be considered in patients with these factors.

A case of glucagonoma with high uptake on F-18 fluorodeoxyglucose positron emission tomography

Glucagonomas are relatively rare, and can be difficult to differentiate from other pancreatic tumors. A 62-year-old woman who had suffered from diabetes mellitus was hospitalized for further evaluation of a space-occupying lesion in the head of the pancreas and tumors in the liver. F-18 fluorodeoxyglucose positron emission tomography revealed accumulation of isotope corresponding to a tumor of the pancreas with a standardized uptake value of 4.3, and tumors in the liver with standardized uptake values of 2.4 and 2.8. The serum glucagon level was high (1,170 pg/ml) and the secretin tolerance test was negative. She was diagnosed with glucagonoma with a high serum glucagon level and clinical findings. It is suggested that glucagonoma may be one of the tumors which show high uptake of F-18 fluorodeoxyglucose.

Evaluation of ammonia metabolism in the skeletal muscles of patients with cirrhosis using N-13 ammonia PET

Objective: Skeletal muscle is said to compensate for the decreased ammonia metabolism in patients with cirrhosis. Branched-chain amino acids (BCAA) are being used as a treatment for hyperammonemia, and are believed to decrease blood ammonia by consumption of BCAA in skeletal muscles. We examined ammonia metabolism of the skeletal muscles in patients with liver cirrhosis after administration of BCAA using13N-ammonia positron emission tomography (PET).Methods: The subjects were patients with compensated or decompensated liver cirrhosis. PET studies were performed before and 2 hours after injection of BCAA. Serial dynamic PET scans (2 min × 10 frames) were started simultaneously with13N-ammonia injection. The standardized uptake value (SUV) of both thighs was calculated.Results: In the patient with compensated liver cirrhosis, there was little difference in the rate of increase in SUV before to after administration of BCAA. However, in the patient with decompensated liver cirrhosis, the rate of increase in SUV after administration was higher than that before administration of BCAA.Conclusion: Ammonia metabolism in the muscle of patients with liver cirrhosis could be examined noninvasively under physiological conditions using13N-ammonia PET. The muscles were found to metabolize ammonia partially, and the role of this contribution to metabolism of ammonia in patients with decompensated liver cirrhosis is particularly important.

Relationship between branched-chain amino acid to tyrosine ratio (BTR) and porto-systemic shunt in the Child-Pugh grade A cirrhosis determined by per-rectal portal scintigraphy

We examined the difference between early cirrhotic patients with lower branched-chain amino acids (BCAA) to tyrosine ratio (BTR) (<4) and higher BTR (>4) in portal circulation using per-rectal portal scintigraphy with technetium-99m pertechnetate. Forty patients with Child-Pugh grade A cirrhosis and serum albumin level between 3.5 and 3.9 g/dl were enrolled in this study. Sixteen patients were infected with HBV and 24 with HCV. Thirteen patients had BTR<4.0 and 27 had BTR>4.0. Shunt index (SI) obtained through per-rectal portal scintigraphy was significantly correlated with BTR (r=-0.558, P<0.0002). ICGR-15 was most strongly correlated with BTR among six parameters representing liver reserve capacity. The mean SI of patients with BTR less than 4 (38.4+/-28.0%) was significantly higher than that of patients with BTR greater than 4 (17.3+/-14.3%) (P=0.0388). The mean concentration of serum BCAA did not significantly differ between the two groups, but the mean concentration of serum tyrosine in the patients with BTR<4 was significantly higher than that in the patients with BTR>4 (P=0.0081). These results suggested that the increase in porto-systemic shunt caused tyrosine passing through liver and stagnating in the serum, as a result of which BTR fall in early cirrhosis. In conclusion, decrease of blood flow through liver and increase in porto-systemic shunt might be partly responsible for deterioration of BTR in early cirrhosis.

Associations among gastroesophageal reflux disease, psychological stress, and sleep disturbances in Japanese adults.

Abstract Background and aim: Gastroesophageal reflux disease (GERD) and psychological stress are associated with sleep disturbances. The aim of the present study was to examine the prevalence of sleep disturbances, anxiety, and depression by GERD subtypes and to identify factors associated with sleep disturbances in general population. Methods: A total of 2002 Japanese subjects, who underwent annual health checkups, were enrolled and asked to fill out a questionnaire, including the frequency scale for the symptoms of GERD (FSSG), Athens Insomnia Scale (AIS), Rome III questionnaire, and Hospital Anxiety and Depression Scale (HADS). GERD was divided into asymptomatic erosive reflux disease (a-ERD), symptomatic ERD (s-ERD), and non-erosive reflux disease (NERD), according to the presence or absence of esophageal mucosal injury on endoscopy, and the FSSG scores. Sleep disturbances were diagnosed in subjects with AIS score ≥6. Results: Prevalence of sleep disturbances was significantly higher in GERD subjects than in controls (35.9 and 14.7%, respectively), especially, in the NERD group (45.1%). Sleep duration was significantly shorter in the s-ERD group compared with other groups. Subjects in the NERD and s-ERD groups showed higher HADS scores, resulting in higher incidences of anxiety and depression than those in the control and a-ERD groups. Reflux symptoms, anxiety, depression, and coexisting functional dyspepsia, but not the presence of esophageal mucosal injury, were associated with an increased odds ratio for sleep disturbances. Conclusion: There were significant positive associations among reflux symptoms, psychological stress, and sleep disturbance in Japanese adults. Further studies investigating the efficacy of therapy are needed.