Functional elements associated with hepatic regeneration in living donors after right hepatic lobectomy.

We quantified the rates of hepatic regeneration and functional recovery for 6 months after right hepatic lobectomy in living donors for liver transplantation. Twelve donors were studied pre-donation (baseline); 8 were retested at a mean ± SD of 11±3 days after donation (T1), 10 were retested at a mean of 91±9 days after donation (T2), and 10 were retested at a mean of 185±17 days after donation (T3). Liver and spleen volumes were measured with computed tomography (CT) and single-photon emission computed tomography (SPECT). Hepatic metabolism was assessed with caffeine and erythromycin, and hepatic blood flow (HBF) was assessed with cholates, galactose, and the perfused hepatic mass (PHM) by SPECT. The regeneration rates (mL kg(-1) of body weight day(-1)) by CT were 0.60±0.22 mL from the baseline to T1, 0.05±0.02 mL from T1 to T2, and 0.01±0.01 from T2 to T3; by SPECT they were 0.54±0.20, 0.04±0.01, and 0.01±0.02, respectively. At T3, the liver volumes were 84%±7% of the baseline according to CT and 92%±13% of the baseline according to SPECT. Changes in the hepatic metabolism did not achieve statistical significance. At T1, the unadjusted clearance ratios with respect to the baseline were 0.75±0.07 for intravenous cholate (P<0.001), 0.88±0.15 for galactose (P=0.07), 0.84±0.08 for PHM (P=0.002), and 0.83±0.19 for the estimated HBF (P=0.06). At T1, these ratios adjusted per liter of liver were up to 50% greater than the baseline values, suggesting recruitment of HBF by the regenerating liver. Increased cholate shunt, increased spleen volume, and decreased platelet count, were consistent with an altered portal circulation. In conclusion, initial hepatic regeneration is rapid, accounts for nearly two-thirds of total regeneration, and is associated with increases in HBF and cholate uptake. Right lobe donation alters the portal circulation of living donors, but the long-term clinical consequences, if there are any, are unknown.

18F-Fallypride PET of pancreatic islets: in vitro and in vivo rodent studies.

UNLABELLED: Islet cell loss in the pancreas results in diabetes. A noninvasive method that measures islet cell loss and also tracks the fate of transplanted islets would facilitate the development of novel therapeutics and improve the management of diabetes. We describe a novel dopamine D(2)/D(3) receptor (D(2)/D(3)R)-based PET method to study islet cells in the rat pancreas and in islet cell transplantation. METHODS: (18)F-fallypride binding to isolated rat islets and pancreas was evaluated in the absence and presence of the D(2)/D(3)R inhibitor haloperidol. After intravenous (18)F-fallypride (28-37 MBq) administration, normal rats and rats pretreated with haloperidol were imaged in a PET/CT scanner and subsequently studied ex vivo for (18)F-fallypride localization in the pancreas. A streptozotocin-treated diabetic rat model was used to study localization of (18)F-fallypride in the pancreas, in vitro and ex vivo. Rat islet cells were transplanted into the spleen and visualized using (18)F-fallypride PET. RESULTS: (18)F-fallypride bound to isolated islet cells and pancreatic sections with an endocrine or exocrine selectivity of approximately 4; selectivity was reduced by haloperidol, suggesting that binding was D(2)/D(3)R-specific. Chemical destruction of islets by streptozotocin decreased (18)F-fallypride binding in pancreas by greater than 50%, paralleling the decrease in insulin immunostaining. Uptake of (18)F-fallypride in the pancreas was confirmed by radiochromatography and was 0.05% injected dose/cm(3) as measured by PET/CT. The ratio of (18)F-fallypride uptake in the pancreas to reference tissue (erector spinae muscle) was 5.5. Rat islets transplanted into the spleen were visualized in vivo by (18)F-fallypride and confirmed by immunostaining. The ratio of spleen-transplanted islets to erector spinae muscle was greater than 5, compared with a ratio of 2.8 in untransplanted rats. CONCLUSION: These studies demonstrate the potential utility of (18)F-fallypride as a PET agent for islet cells.

Poor correlation between left and right ventricular ejection fractions in patients with normal ventricular function.

BACKGROUND AND OBJECTIVE: Correlation between right and left ventricular ejection fraction (RVEF, LVEF) has been studied in only a small number of patients with a marked decrease in RVEF and LVEF. The goal of the present study was to compare LVEF and RVEF in a large population with low and normal ejection fractions (EFs) measured by blood pool scintigraphy. METHODS: A series of 152 patients who underwent LVEF measurement for a clinical indication also underwent simultaneous measurement of the RVEF. The correlation between RVEF and LVEF in patients with or without depressed EF was studied using Pearson's regression analysis. RESULTS: Although RVEF and LVEF were significantly correlated in an S curve mathematical function, the correlation was weak when the entire cohort was considered (r=0.32; P<0.001). However, when patients with lower EF (LVEF and RVEF less than 50%) were considered, the correlation was stronger (r=0.41; P<0.001), and in patients with normal biventricular EF (LVEF and RVEF 50% or greater), the correlation was completely absent (r=0.001; P=0.86). The strongest correlation between RVEF and LVEF occurred in patients with LVEF and RVEF less than 30% (r=0.75, P=0.03). CONCLUSION: Patients with decreased EF have highest correlation between LVEF and RVEF in comparison with no correlation in patients with normal EF. The cause of this discrepancy is not known.

Presence of biventricular dysfunction in patients with type II diabetes mellitus.

Diabetes mellitus (DM) has been found to be associated with depressed left ventricular (LV) function. Right ventricular (RV) function in DM patients, however, has not been well studied. The goal of this study was to evaluate the occurrence of LV and RV dysfunction in patients with DM. A series of 157 patients underwent simultaneous measurement of LV ejection fraction (LVEF) and RV ejection fraction (RVEF). Four of 26 DM patients had RVEF <30% (15.4%) vs 4 of 126 controls (3.2%) (P=.01). Eleven of 27 (40.7%) patients with DM had LVEF <30% vs 9 of 128 controls (7%) (P<.0001). Using multivariate analysis, DM remained independently associated with severely decreased biventricular function (RVEF <30%; odds ratio, 5.7; confidence interval, 1.3-25.4 [P=.02] and LVEF <30%; odds ratio, 12.9; confidence interval, 3.8-43.7 [P<.0001]). These results suggest that diabetic cardiomyopathy involves both ventricles as an independent pathologic process.

Flattening of the interventricular septum (D-shaped left ventricle) in addition to high right ventricular tracer uptake and increased right ventricular volume found on gated SPECT studies strongly correlates with right ventricular overload.

BACKGROUND: Flattening of the interventricular septum (D-shaped left ventricle) detected during echocardiographic examination is correlated with significant right ventricular (RV) overload. There are no reports of this finding with cardiac gated single photon emission computed tomography (SPECT) imaging. We report an observational study correlating this finding with the presence of RV overload. METHODS AND RESULTS: Retrospectively, we compared 8 cases with flattening of the interventricular septum on cardiac gated SPECT imaging for which echocardiographic correlations and clinical data were available regarding the presence of RV overload. All patients but 1 had pulmonary hypertension ranging from 42 to 52 mm Hg measured by echocardiographic Doppler studies. All patients but 1 had reasons for RV overload (chronic obstructive pulmonary disease in 3, history of atrial septal defect in 3, pulmonary embolism in 1, and obstructive sleep apnea in 1). Septal flattening present on gated SPECT images was seen in 50% of the cases by echocardiography. Other signs of RV overload (RV enlargement, RV hypertrophy) were observed by echocardiography in 5 patients and by the gated SPECT in 7 patients. CONCLUSION: The presence of interventricular septal flattening on gated SPECT studies correlates with RV overload and should be routinely assessed during interpretation of gated SPECT studies.

Factors affecting the quantitative liver-spleen scan in normal individuals.

The quantitative liver-spleen scan (QLSS) can estimate the functional hepatic mass and the organ volumes by precise measurement of sulfur colloid (SC) distribution. The normal range determined in prior studies was estimated from patients with absence of chronic liver disease in which intense fasting appeared to produce slightly abnormal values. This study was to determine the effect of fasting or fed status and colloid particle size on quantitative measurements from the QLSS in a small cohort of normal individuals. Twelve persons without any medical problems had QLSS taken twice, 2 weeks apart, one fasting and one postprandial. Patients were scanned after injection of 5-6 mCi of SC; six patients were given solution A (5- to 12-microm particle size) and six patients solution B (2- to 12-microm particle size). SPECT and planar analysis were performed. SC distribution of total counts between the liver and the spleen {[L/(L + S)]t ratio}, liver-spleen index (LSI), and liver-bone marrow index (LBI) were calculated. The perfused hepatic mass (PHM) is the average of the LSI and LBI. Spleen and liver volumes are expressed as milliliters per pound ideal body weight (IBW). Results showed that the liver and spleen volumes (solution B postprandial, 9.27 +/- 2.48 and 1.47 +/- 0.57 ml/lb IBW, respectively) and LBI were not affected by the type of SC solution or by ingestion status. L/(L + S) total and pixel count ratios were significantly higher for solution B and postprandial studies. [L/(L + S)]t, LSI, and PHM increased significantly (P < 0.05) from fasting to postprandial for solution A (0.71 +/- 0.13 vs 0.79 +/- 0.08, 80 +/- 14 vs 91 +/- 8, and 102 +/- 10 vs 106 +/- 8, respectively) and for solution B (0.81 +/- 0.05 vs 0.90 +/- 0.02, 86 +/- 4 vs 95 +/- 3, and 101 +/- 5 vs 110 +/- 3). Neither fasting nor postprandial LSI and PHM were significantly different between solution A and solution B. We conclude the following. (1) The QLSS functional indices in "true" normal patients fall within the previously reported normal range. (2) Calculated liver and spleen volumes are not altered by fasting or sulfur colloid particle size. (3) Fasting significantly decreased the [L/(L + S)]t, LSI, and PHM. (4) A postprandial scan may be preferable since the normal values for [L/(L + S)]t, LSI, and PHM are greater, with a narrower range, than fasting values.

Use of Yttrium-90 TheraSphere for the treatment of unresectable hepatocellular carcinoma.

This is a retrospective analysis of a new treatment modality, intra-arterial administration of Yttrium-90 TheraSphere, for unresectable hepatocellular carcinoma (HCC). Patients with HCC not amenable to surgical treatment who had satisfactory physiological function without comorbid disease or significant pulmonary shunting were eligible for treatment. Patients were categorized into complete, partial, or no response based on serum alpha-fetoprotein (AFP) levels and CT or MRI imaging. Fourteen patients were considered candidates for treatment. Three patients were excluded due to significant hepatopulmonary shunting. Eleven patients were treated with TheraSphere. One patient (9%) had a complete response, eight patients (78%) had a partial response, and two patients (18%) showed no response. Partial and complete responders with AFP-associated HCC demonstrated a median decrease in AFP levels of 79 per cent at 73 days. No patients developed liver toxicity nor died due to treatment. Five patients (45%) died of progressive disease at a median of 7 months post-treatment. Six patients (54%) were alive at a median of 11 months (range, 9 to 20 months). Okuda stage 2 and 3 patients showed a median survival of 11 months and 7 months, respectively. Yttrium-90 TheraSphere treatment for unresectable hepatocellular carcinoma is well tolerated and appears to extend survival.