Mean Liver Volume Research Articles

Robotic Complete ALPPS (rALPPS)-First German Experiences.

ALPPS leads to fast and effective liver hypertrophy. This enables the resection of extended tumors. Conventional ALPPS is associated with high morbidity and mortality. MILS reduces morbidity and the robot adds technical features that make complex procedures safe. The MD-MILS was screened for patients who underwent rALPPS. Demographic and perioperative data were evaluated retrospectively. Ninety days postoperative morbidity was scored according to the CD classification. The findings were compared with the literature. Since November 2021, five patients have been identified. The mean age and BMI of the patients were 50.0 years and 22.7 kg/m2. In four cases, patients suffered from colorectal liver metastases and, in one case, intrahepatic cholangiocarcinoma. Prior to the first operation, the mean liver volume of the residual left liver was 380.9 mL with a FLR-BWR of 0.677%. Prior to the second operation, the mean volume of the residual liver was 529.8 mL with a FLR-BWR of 0.947%. This was an increase of 41.9% of the residual liver volume. The first and second operations were carried out within 17.8 days. The mean time of the first and second operations was 341.2 min and 440.6 min. The mean hospital stay was 27.2 days. Histopathology showed the largest tumor size of 39 mm in diameter with a mean amount of 4.7 tumors. The mean tumor-free margin was 12.3 mm. One complication CD > 3a occurred. No patient died during the 90-day follow up. In the first German series, we demonstrated that rALPPS can be carried out safely with reduced morbidity and mortality in selected patients.

Volumetric Remodeling of the Left Liver After Right Hepatectomy: Analysis of Factors Predicting Degree of Hypertrophy and Post-hepatectomy Liver Failure

BackgroundThis study investigated the volumetric remodeling of the left liver after right hepatectomy looking for factors predicting the degree of hypertrophy and severe post-hepatectomy liver failure (PHLF). MethodsIn a cohort of 121 right hepatectomies, we performed CT volumetrics study of the future left liver remnant (FLR) preoperatively and postoperatively. Factors influencing FLR degree of hypertrophy and severe PHLF were identified by multivariate analysis. ResultsAfter right hepatectomy, the mean degree of hypertrophy and kinetic growth rate of the left liver remnant were 25% and 3%/day respectively. The mean liver volume recovery rate was 77%. Liver remodeling volume was distributed for 79% on segments 2 and 3 and 21% on the segment 4 (p<0.001). Women showed a greater hypertrophy of segments 2 and 3 compared with men (p=0.002). The degree of hypertrophy of segment 4 was lower in case of middle hepatic vein resection (p=0.004). Left liver remnant kinetic growth rate was associated with the standardized future liver remnant (sFLR) (p<0.001) and a two-stage hepatectomy (p=0.023). Severe PHLF were predicted by intraoperative transfusion (p=0.009), biliary tumors (p=0.013), and male gender (p=0.022). ConclusionsVolumetric remodeling of the left liver after right hepatectomy is not uniform and is mainly influenced by gender and sacrifice of middle hepatic vein. Male gender, intraoperative transfusion, and biliary tumors increase the risk of postoperative liver failure after right hepatectomy.

Correlation of thermal burn hepatic dysfunction with outcomes

IntroductionOrgan dysfunction and failure increase the morbidity and mortality following major burn. Alteration of liver morphology and function is common following major burns; however, it has not received much attention. In this study we have assessed the impact of thermal burn on liver in relation with mortality. Material and methods55 patients (33 female and 22 males) with TBSA 10–90% and age ranged from 18 to 75 years were included. A bed side serial ultrasonography to assess the volume of liver and liver function tests was done on the 2nd, 9th and 16th day following burn. Baseline demographic and clinical information such as age, gender, burn size and outcome of patient were also collected. Results –8 patients died during 2nd week following burn and 47 survived. The mean TBSA for survivors was 37% and for non survivors 80%. Mean liver volume in survivors steadily decreased from 1693.70 cm3 to 1631.31 cm3 over 3 weeks. Mean liver volume in non- survivors steadily increased from 1855.88 cm3 to 2028.50 cm3 over 2 weeks. Liver function test in survivors steadily improved while in non survivors it deteriorated over 2 weeks. ConclusionThere is a correlation between altered liver morphology and function with mortality among severely burnt patients however liver volume did not show statistical significance. A decreasing trend of liver dysfunction parameters and hepatomegaly following burn is associated with good prognosis.

Use of Ambroxol as Therapy for Gaucher Disease

Ambroxol was identified as an enhancer of stability and residual activity of several misfolded glucocerebrosidase variants in 2009. To assess hematologic and visceral outcomes, biomarker changes, and safety of ambroxol therapy for patients with Gaucher disease (GD) without disease-specific treatment. Patients with GD who could not afford enzyme replacement therapy were enrolled and received oral ambroxol from May 6, 2015, to November 9, 2022, at Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China. Thirty-two patients with GD (29 with GD type 1, 2 with GD type 3, and 1 with GD intermediate types 2-3) were enrolled. Of those, 28 patients were followed up for longer than 6 months; 4 were excluded due to loss of follow-up. Data analyses were performed from May 2015 to November 2022. An escalating dose of oral ambroxol (mean [SD] dose, 12.7 [3.9] mg/kg/d). Patients with GD receiving ambroxol were followed up in a genetic metabolism center. Biomarkers of chitotriosidase activity and glucosylsphingosine level, liver and spleen volumes, and hematologic parameters were measured at baseline and various time points throughout the ambroxol treatment. A total of 28 patients (mean [SD] age, 16.9 [15.3] years; 15 male patients [53.6%]) received ambroxol for a mean (SD) duration of 2.6 (1.7) years. Two patients with severe symptoms at baseline experienced deterioration of hematologic parameters and biomarkers and were deemed nonresponders; clinical response was observed in the other 26 patients. After 2.6 years of ambroxol treatment, the mean (SD) hemoglobin concentration improved from 10.4 (1.7) to 11.9 (1.7) g/dL (mean [SD], 1.6 [1.7] g/dL; 95% CI, 0.8-2.3 g/dL; P < .001), and the mean (SD) platelet count improved from 69 (25) to 78 (30) × 103/µL (mean [SD], 9 [22] × 103/µL; 95% CI, -2 to 19 × 103/µL; P = .09). The mean (SD) spleen volume decreased from 17.47 (7.18) to 12.31 (4.71) multiples of normal (MN) (mean [SD], -5.16 [5.44] MN; 95% CI, -10.19 to -0.13; P = .04), and the mean (SD) liver volume decreased from 1.90 (0.44) to 1.50 (0.53) MN (mean [SD], -0.39 [0.42] MN; 95% CI, -0.75 to -0.04; P = .03). Biomarker median percentage changes from baseline were -43.1% for chitotriosidase activity (from 14 598 [range, 3849-29 628] to 8312 [range, 1831-16 842] nmol/mL/h; z = -3.413; P = .001) and -34.1% for glucosylsphingosine level (from 251.3 [range, 73.6-944.2] to 165.7 [range, 21.3-764.8] ng/mL; z = -2.756; P = .006). Patients were divided into subgroups according to age when initiating treatment; those who received treatment at a younger age (mean [SD] age, 6.3 [2.7] years) experienced more rapid improvements: hemoglobin concentration increased by 16.5% (from 10.3 [1.5] to 12.0 [1.5] g/dL; mean [SD] change, 1.6 [1.6] g/dL; 95% CI, 0.7-2.5 g/dL; P = .002), and platelet count increased by 12.0% (from 75 [24] to 84 [33] × 103/µL; mean [SD] change, 9 [26] × 103/µL; 95% CI, -5 to 24 × 103/µL; P = .17); whereas chitotriosidase activity decreased by 64.0% (from 15 710 [range, 4092-28 422] to 5658 [range, 1146-16 843] nmol/mL/h; z = -2.803; P = .005), and glucosylsphingosine level decreased by 47.3% (from 248.5 [range, 122.8-674.9] to 131.0 [range, 41.1-448.5] ng/mL; z = -2.385; P = .02). Three of the 28 patients experienced mild and transient adverse events. In this case series of ambroxol repurposing among patients with GD, long-term treatment with ambroxol was safe and associated with patient improvement. Improvements in hematologic parameters, visceral volumes, and plasma biomarkers were larger among patients with relatively mild symptoms of GD and patients who received initial treatment at younger ages.

Changes and influencing factors of liver volume after transjugular intrahepatic portosystemic shunt: a retrospective cohort study.

Liver volume is an important measure of liver reserve and helps to determine the course of liver disease. This study aimed to observe the dynamic changes of liver volume after transjugular intrahepatic portosystemic shunt (TIPS) and analyze the related factors. Clinical data of 168 patients who underwent TIPS procedures between February 2016 and December 2021 were collected and analyzed retrospectively. The changes in liver volume after TIPS in the patients were observed, and the independent predictors affecting increases in liver volume were analyzed using a multivariable logistic regression model. The mean liver volume was decreased by 12.9% at 2±1 months post TIPS and rebounded at 9±3 months post TIPS, but did not recover to its pre-TIPS level completely. Most patients (78.6%) had decreased liver volume at 2±1 months post TIPS, and in multivariable logistic regression, a lower albumin (ALB) level, a lower subcutaneous fat area at L3 (L3-SFA), and a higher degree of ascites were identified as independent factors predicting increased liver volume. The risk score model for predicting increased liver volume was Logit(P)=1.683-0.078 (ALB) -0.01 (pre TIPS L3-SFA) +0.996 (grade 3 ascites =1; non-grade 3 ascites =0). The area under the curve of the receiver operating characteristic curve was 0.729, and the cut-off value was 0.375. The rate of liver volume change at 2±1 months post TIPS was significantly correlated with that of spleen volume change (R2=0.378, P<0.001). The rate of subcutaneous fat change at 9±3 months post TIPS was significantly correlated with that of liver volume change (R2=0.782, P<0.001). In patients with a liver volume increase, the mean computed tomography value (Hounsfield units) decreased significantly after TIPS placement (65.9±17.7 vs. 57.8±18.2, P=0.009). Liver volume was decreased at 2±1 months post TIPS and slightly increased at 9±3 months post TIPS; however, it did not recover to its pre-TIPS level completely. A lower ALB level, a lower L3-SFA, and a higher degree of ascites were all predictors for increased liver volume post TIPS.

The effect of hepatic steatosis on liver volume determined by proton density fat fraction and deep learning-measured liver volume.

We aimed to evaluate the effect of hepatic steatosis (HS) on liver volume and to develop a formula to estimate lean liver volume correcting the HS effect. This retrospective study included healthy adult liver donors who underwent gadoxetic acid-enhanced MRI and proton density fat fraction (PDFF) measurement from 2015 to 2019. The degree of HS was graded at 5% PDFF intervals from grade 0 (no HS; PDFF < 5.5%). Liver volume was measured with hepatobiliary phase MRI using deep learning algorithm, and standard liver volume (SLV) was calculated as the reference lean liver volume. The association between liver volume and SLV ratio with PDFF grades was evaluated using Spearman's correlation (ρ). The effect of PDFF grades on liver volume was evaluated using the multivariable linear regression model. The study population included 1038 donors (mean age, 31 ± 9years; 689 men). Mean liver volume to SLV ratio increased according to PDFF grades (ρ = 0.234, p < 0.001). The multivariable analysis indicated that SLV (β = 1.004, p < 0.001) and PDFF grade*SLV (β = 0.044, p < 0.001) independently affected liver volume, suggesting a 4.4% increase in liver volume per one-point increment in the PDFF grade. PDFF-adjusted lean liver volume was estimated using the formula, liver volume/[1.004 + 0.044 × PDFF grade]. The mean estimated lean liver volume to SLV ratio approximated to one for all PDFF grades, with no significant association with PDFF grades (p = 0.851). HS increases liver volume. The formula to estimate lean liver volume may be useful to adjust for the effect of HS on liver volume. • Hepatic steatosis increases liver volume. • The presented formula to estimate lean liver volume using MRI-measured proton density fat fraction and liver volume may be useful to adjust for the effect of hepatic steatosis on measured liver volume.

Liver and spleen volume and stiffness in patients post-Fontan procedure and patients with ARPKD compared to normal controls

PurposeBoth congestive (patients post-Fontan hepatopathy) and congenital (patients with ARPKD) disease can lead to hepatic fibrosis and portal hypertension with eventual development of splenomegaly. We investigated liver and spleen stiffness as measured by MRE between post-Fontan, ARPKD patients and controls independent of organ volume. MethodsOur study included 122 subjects (70 Fontan patients, 14 ARPKD patients, and 38 controls). The mean MRE liver and spleen stiffness values of Fontan patients and patients with ARPKD were compared to controls. Similarly, the liver and spleen volumes of the Fontan patients and patients with ARPKD were then compared to the volumes of controls. ResultsPost-Fontan and ARPKD patients, mean liver stiffness, mean liver volume as well as mean spleen stiffness and mean spleen volume were higher than mean liver stiffness, mean liver volume, mean spleen stiffness, and mean spleen volume of controls. While liver stiffness correlated to liver volume in controls, we found no correlation between stiffness and volume in either Fontan or ARPKD patients, which indicates MRE's ability to act as an independent biomarker. However, these findings are not true in the spleen, where there is significant association between volume and stiffness in patients with ARPKD, but not in Fontan patients or controls. ConclusionLiver and spleen stiffness and volumes are significantly different among Fontan patients, ARPKD patients, and controls. Our findings suggest that beyond diagnosing fibrosis, MRE cut-off values could be disease-specific since not only the severity but the underlying pathology causing organ congestion or fibrosis influences MRE results.

Correlation between liver volume and liver weight in a cohort with chronic liver disease: a semiautomated CT-volumetry study.

To estimate the optimal density coefficient for conversion of liver volume into liver weight in patients with chronic liver disease based on semiautomated CT-liver volumetry data and the histologic Ishak score of explanted liver. A total of 114 patients (39 female; age, 46±20 years) with chronic liver diseases who underwent liver transplantation between January 2010 and September 2020 were identified over a patient chart search at our institution and subsequently analyzed in retrospect. All patients had contrast-enhanced CT-examinations (mean, 24 days) to liver transplantation. Liver volume was calculated by a semiautomated software and results compared with the liver weight registered by the pathologist. Each explanted liver was histologically scored into six classes according to the Ishak classification where the categories were subgrouped based on recommendation of the pathologists into the following categories 0-3, 4-5 and 6. Mean liver volume was 1,870±1,195, 1,162±679 and 1,278±510 mL for the categories 0-3, 4-5 and 6, respectively. Mean liver weight was 1,624±999, 1,082±669 and 1,346±559 g for the categories 0-3, 4-5 and 6, respectively. A coefficient of 0.92±0.22, 0.98±0.28 and 1.06±0.20 g/mL was found at best for conversion of liver volume into liver weight in these subgroups. Differences between Ishak-subgroups proved significant (0.002). In 4 patients with cystic liver disease, density coefficients varied significantly and were found generally lower compared to the other liver disorders. Our results yielded significant differences between the density coefficients calculated along with the Ishak score and also for the subgroup with cystic liver disease.

Dosimetric Comparison of Intraoperative Radiotherapy and SRS for Liver Metastases.

Purpose/ObjectivesTo perform a dosimetric comparison between kilovoltage intraoperative radiotherapy (IORT) and stereotactic radiosurgery (SRS) simulating both deep-inspiration breath-hold (DIBH) and free-breathing (FB) modalities for patients with liver metastases.Methods/MaterialsDiagnostic computed tomographies (CT) of patients carrying one or two lesions <4 cm and who underwent surgery were retrospectively screened and randomly selected for the study. For DIBH-SRS, a gross target volume (GTV) plus planning target volume (PTV) were delineated. For FB-SRS, a GTV plus an internal target volume (ITV) and PTV were defined. Accounting for the maximal GTV diameters, a modified GTV (GTV-IORT) was expanded circumferentially to simulate a resection cavity. The best suitable round-applicator size was thereafter selected. All treatment plans were calculated homogeneously to deliver 40 Gy. Doses delivered to organs at risk (OAR) and target volumes were compared for IORT vs. both SRS modalities.ResultsEight patients encompassing 10 lesions were included in the study. The mean liver volume was 2,050.97 cm3 (SD, 650.82), and the mean GTV volume was 12.23 cm3 (SD, 12.62). As for target structures, GTV-IORT [19.44 cm3 (SD, 17.26)] were significantly smaller than both PTV DIBH-SRS [30.74 cm3 (SD, 24.64), p = 0.002] and PTV FB-SRS [75.82 cm3 (SD, 45.65), p = 0.002]. The median applicator size was 3 cm (1.5–4.5), and the mean IORT simulated delivery time was 45.45 min (SD, 19.88). All constraints were met in all modalities. Liver V9.1 showed significantly smaller volumes with IORT [63.39 cm3 (SD, 35.67)] when compared to DIBH-SRS [150.12 cm3 (SD, 81.43), p = 0.002] or FB-SRS [306.13 cm3 (SD, 128.75), p = 0.002]. No other statistical or dosimetrically relevant difference was observed for stomach, spinal cord, or biliary tract. Mean IORT D90 was 85.3% (SD, 6.05), whereas D95 for DIBH-SRS and FB-SRS were 99.03% (SD, 1.71; p = 0.042) and 98.04% (SD, 3.46; p = 0.036), respectively.ConclusionKilovoltage IORT bears the potential as novel add-on treatment for resectable liver metastases, significantly reducing healthy liver exposure to radiation in comparison to SRS. Prospective clinical evidence is required to confirm this hypothesis.

The effects of somatostatin analogues on liver volume and quality of life in polycystic liver disease: a meta-analysis of randomized controlled trials

A clear evidence on the benefits of somatostatin analogues (SA) on liver outcome in patients affected by polycystic liver disease is still lacking. We performed a meta-analysis of RCTs and a trial sequential analysis (TSA) evaluating the effects of SA in adult patients with polycystic liver disease on change in liver volume. As secondary outcome, we evaluated the effects on quality of life as measured by SF36-questionnaire. Six RCTs were selected with an overall sample size of 332 adult patients with polycystic liver disease (mean age: 46 years). Mean liver volume at baseline was 3289 ml in SA group and 3089 ml in placebo group. Overall, unstandardized mean difference in liver volume was − 176 ml (95%CI, − 406, 54; p < 0.133). Heterogeneity was low (I2:0%, p < 0.992). However, we performed a moderator analysis and we found that a higher eGFR significantly correlates to a more pronounced effect of SA on liver volume reduction (p = 0.036). Cumulative Z-curve in TSA did not reach either significance and futility boundaries or required information size. Three RCTs have evaluated Quality of life parameters measured by SF36-QOL questionnaire for a total of 124 patients; no significant difference was found on the effect of SA on QOL parameters when compared with placebo. The present meta-analysis revealed a potential effect of SA on reduction of liver volume and quality of life parameters, but results did not reach a statistical significance. These data could be explained by the need of further studies, as demonstrated through TSA, to reach an adequate sample size to confirm the beneficial outcomes of SAs treatment.

Clinical-genetic characteristics and treatment outcomes of Turkish children with Gaucher disease type 1 and type 3: A sixteen year single-center experience

Data from 38 children were retrospectively analyzed to determine the patient characteristics of Turkish children with Gaucher disease (GD) and evaluate the impact of enzyme replacement therapy (ERT) in a pediatric cohort consisting of two different sub-types of the disease, Gaucher disease type 1 (GD1) and type 3 (GD3). Both types were represented equally (GD1/GD3 = 20/18). L444P (35.5%) was the most common mutant allele while L444P/L444P (34.2%) was the most common genotype overall. Compound heterozygosity of N370S and L444P homozygosity were the dominant genotypes in Turkish children with GD1 and GD3, respectively. None of the patients had moderate to severe thrombocytopenia at last follow-up while the percent of patients with anemia decreased from 60% to 5.7% (p < 0.001). Significant improvements in mean liver (from 2.2 to 1.6 MN, p < 0.001) and spleen (from 15.5 to 7.6 MN, p < 0.001) volumes were observed in the first year of ERT. Linear growth was ameliorated as shown by the decrease in the percent of patients having short stature from 34.3% to 13.3% (p < 0.01) at year 5. Erlenmeyer flask deformity, osteopenia and scoliosis were common skeletal findings. Although none of the patients had lung disease at diagnosis, 20% developed radiological findings suggestive of pulmonary involvement. This single center experience is the first comprehensive study from Turkey not only reporting clinical and genetic characteristics of GD patients but also providing information on the outcomes of ERT in two different sub-types of GD. Genotypic background of Turkish children with GD is similar to western populations. Although visceral and hematological therapeutic goals are reached as early as one year of ERT in both sub-types, achieving normal growth takes several more years than suggested in significant number of children with GD.

A Novel Formula for Estimating Liver Volume in Elderly Subjects: A Cadaveric study

Introduction In general, the size of a human liver is believed to increase with age, reaching a maximum weight between 41 and 60 years of age. Afterwards, its size gradually decreases. Knowledge of how liver diameter measurements and calculated volume indices correlate with actual liver volume in elderly patients might improve volume assessments before liver transplantation and hepatic resection; and aid in the diagnosis of parenchymal diseases affecting liver size. Objectives The goals of this study were to establish reference values for liver volume in elderly subjects, and to derive a simple formula for estimating liver volume in these individuals. Methods Morphometric analyses were conducted on livers from 34 embalmed cadavers used in a medical school gross anatomy course. The actual liver volume was determined by dividing liver weight by the mean liver density. The three major diameters of the liver, craniocaudal (CC), anteroposterior (AP), and transverse (TRANS), were obtained using both manual measurements on actual specimens, as well as ImageJ metrics on photographs of these same livers. Each diameter was measured at its maximum dimension (Fig.1). The product of these diameters yielded the hepatic volume index (HVI). Based on measured diameters and HVI, estimated liver volumes were calculated and correlated with actual liver volume, and demographic factors such as age and gender. Using regression analyses, formulas correlating measured diameters as independent variables or HVI to the actual liver volume were established. Results Mean liver volume (± SD) was 982 ± 295 cm3 with a range of 613 to 1,904 cm3. The mean age was 84.1 ± 10.8 years, with no significant difference in age between female and male subjects (86.9 ± 11.6 years vs 80.5 ± 8.8 years, respectively, P = .08). Measured diameters showed strong correlation with actual liver volume for CC, AP and TRANS diameters (rs = .605, .744, and .478, respectively). Correlation with actual liver volume was stronger for calculated HVI compared to simple diameters analyzed as independent variables. Liver diameters measured with ImageJ produced an HVI showing the strongest correlation with actual liver volume (rs = .86; P < .001). A simple linear regression formula for estimating liver volume in elderly subjects, based on HVI, was obtained: LV (cm3) = (HVI*0.17) + 294.5 (R2 = .67; P < .001). No significant differences were found in assessing both intra-/inter-observer reproducibility of liver diameter measurements (P > 0.05). The accuracy of the new formula was compared with previously reported formulas (Fig.2) Conclusion These results suggested that both measured diameters and calculated HVI demonstrated excellent reproducibility and correlated strongly with liver size. This new formula, derived from these correlations, improved the accuracy of liver volume estimations in an elderly population. Implications To our knowledge, this is the first study to publish reference values of liver volume in subjects with a mean age > 70 years. Previously reported reference values and formulas resulted from data obtained from younger subjects (means of 48-57 years) and reported formulas which overestimated liver size in older subjects. This new formula might be better at predicting liver volume in elderly subjects.

Variability of Standard Liver Volume by 2D Ultrasound: A Cross-sectional Study from Eastern India

Introduction: Liver volume estimation is an essential component prior to major hepatic surgery and liver transplantation. Liver volume is evaluated with different formulae, gold standard Computed Tomography (CT) volumetry and Magnetic Resonance Imaging (MRI). As per literature review, studies comparing ultrasonography with formula based liver volume estimation are very few. Ultrasonography is non-invasive in nature and inexpensive. It is gaining popularity among clinicians as it helps in rapid evaluation of liver volumes. Aim: To compare variability of liver volume using 2D ultrasound with a standard well-established method based on formula derived by Johnson et al. Materials and Methods: This was a cross-sectional study done between August-October 2020 and patients were selected by the physician from general Outpatient Department (OPD) pool and clinically screened for further biochemical studies. Participants aged 20-60 years with normal liver function test were recruited in the study. Images were taken on a Siemens Ultrasound System. Study variables included were liver volumes estimated by two methods, age, weight, height and Body Surface Area (BSA). F test was used to compare variability between liver volumes estimated by two different methods. Bivariate correlation between ultrasonography-based liver volume and different body indices was also tested. Results: Variability comparison using F test shows no significant difference (F=1.095, df1=149, df2=149, p=0.29). Liver volumes estimated by two methods showed good correlation with each other and is significant at the 0.01 level, r=0.574. The mean difference (125 cc) in volumes between two methods were statistically significant (t=10.92, degree of freedom=149, p&lt;0.001) and were not in agreement with each other. Body parameters were correlated with liver volume estimated by 2D ultrasound. Conclusion: Ultrasonography is a useful tool in estimating liver volume prior to major hepatic resection. Formula based calculation of Standard Liver Volume (SLV) does not agree with USG based volume and underestimates the mean liver volume obtained by USG method.

Real‐world effectiveness of eliglustat in treatment‐naïve and switch patients enrolled in the International Collaborative Gaucher Group Gaucher Registry

Eliglustat is a first‐line oral therapy for adults with Gaucher disease type 1 (GD1) with extensive, intermediate, or poor CYP2D6‐metabolizer phenotypes (90% of patients). We report real‐world outcomes after 2 years of eliglustat therapy in the International Collaborative Gaucher Group Gaucher Registry (NCT00358943). As of January 2019, baseline and 2‐year data (±1 year) were available for 231 eliglustat‐treated GD1 patients: 19 treatment‐naïve (zero splenectomized) and 212 ERT patients who switched to eliglustat (36 splenectomized). Most patients (89%) were from the United States, where eliglustat was first approved. In treatment‐naïve patients, mean hemoglobin increased from 12.4 to 13.4 g/dL (P = .004, n = 18), mean platelet count increased from 113 to 156 × 109/L (P < .001, n = 17); mean spleen volume decreased from 7.4 to 3.5 multiples of normal (MN) (P = .02, n = 7); mean liver volume remained normal (n = 7), and median spine Z‐score was unchanged (−1.3 to −1.2, n = 6). In non‐splenectomized switch patients, mean hemoglobin remained stable/non‐anemic (n = 167); mean platelet count remained stable/normal (n = 165); mean spleen volume decreased from 3.3 to 2.8 MN (P < .001, n = 64); mean liver volume remained normal (n = 63), and median lumbar spine Z‐score improved from −0.7 to −0.4 (P = .014, n = 68). In splenectomized switch patients, mean hemoglobin remained stable/non‐anemic (n = 31); mean platelet count increased from 297 to 324 × 109/L (non‐significant, n = 29); mean liver volume remained normal (n = 13); median spine Z‐score improved from −0.8 to −0.6 (non‐significant, n = 11). Median chitotriosidase decreased in all groups (P < .01 for all). These real‐world results are consistent with eliglustat clinical trial results demonstrating long‐term benefit in treatment‐naïve patients and stability in ERT switch patients.

Natural history of untreated patients with type 1 Gaucher disease

Data from 38 children were retrospectively analyzed to determine the patient characteristics of Turkish children with Gaucher disease (GD) and evaluate the impact of enzyme replacement therapy (ERT) in a pediatric cohort consisting of two different sub-types of the disease, Gaucher disease type 1 (GD1) and type 3 (GD3). Both types were represented equally (GD1/GD3 = 20/18). L444P (35.5%) was the most common mutant allele while L444P/L444P (34.2%) was the most common genotype overall. Compound heterozygosity of N370S and L444P homozygosity were the dominant genotypes in Turkish children with GD1 and GD3, respectively. None of the patients had moderate to severe thrombocytopenia at last follow-up while the percent of patients with anemia decreased from 60% to 5.7% (p < 0.001). Significant improvements in mean liver (from 2.2 to 1.6 MN, p < 0.001) and spleen (from 15.5 to 7.6 MN, p < 0.001) volumes were observed in the first year of ERT. Linear growth was ameliorated as shown by the decrease in the percent of patients having short stature from 34.3% to 13.3% (p < 0.01) at year 5. Erlenmeyer flask deformity, osteopenia and scoliosis were common skeletal findings. Although none of the patients had lung disease at diagnosis, 20% developed radiological findings suggestive of pulmonary involvement. This single center experience is the first comprehensive study from Turkey not only reporting clinical and genetic characteristics of GD patients but also providing information on the outcomes of ERT in two different sub-types of GD. Genotypic background of Turkish children with GD is similar to western populations. Although visceral and hematological therapeutic goals are reached as early as one year of ERT in both sub-types, achieving normal growth takes several more years than suggested in significant number of children with GD.

A Framework for Automatic Morphological Feature Extraction and Analysis of Abdominal Organs in MRI Volumes

The accurate 3D reconstruction of organs from radiological scans is an essential tool in computer-aided diagnosis (CADx) and plays a critical role in clinical, biomedical and forensic science research. The structure and shape of the organ, combined with morphological measurements such as volume and curvature, can provide significant guidance towards establishing progression or severity of a condition, and thus support improved diagnosis and therapy planning. Furthermore, the classification and stratification of organ abnormalities aim to explore and investigate organ deformations following injury, trauma and illness. This paper presents a framework for automatic morphological feature extraction in computer-aided 3D organ reconstructions following organ segmentation in 3D radiological scans. Two different magnetic resonance imaging (MRI) datasets are evaluated. Using the MRI scans of 85 adult volunteers, the overall mean volume for the pancreas organ is 69.30 ± 32.50cm3, and the 3D global curvature is (35.23 ± 6.83) × 10−3. Another experiment evaluates the MRI scans of 30 volunteers, and achieves mean liver volume of 1547.48 ± 204.19cm3 and 3D global curvature (19.87 ± 3.62) × 10− 3. Both experiments highlight a negative correlation between 3D curvature and volume with a statistical difference (p < 0.0001). Such a tool can support the investigation into organ related conditions such as obesity, type 2 diabetes mellitus and liver disease.

Real-time Magnetic Resonance-guided Liver Stereotactic Body Radiation Therapy: An Institutional Report Using a Magnetic Resonance-Linac System.

BackgroundStereotactic body radiation therapy (SBRT) is a proven and effective modality for treatment of hepatic primary and metastatic tumors. However, these lesions are challenging for planning and treatment execution due to natural anatomic changes associated with respiration. Magnetic resonance imaging (MRI) offers superior soft tissue contrast resolution and the ability for real-time image-guided treatment delivery and lesion tracking.ObjectiveTo evaluate the plan quality, treatment delivery, and tumor response of a set of liver SBRT cancer treatments delivered with magnetic resonance (MR)-guided radiotherapy on a MR-linear accelerator (MR-linac).MethodsTreatment data from 29 consecutive patients treated with SBRT were reviewed. All treatments were performed using a step and shoot technique to one or more liver lesions on an MR-linac platform. Patients received 45 to 50 Gy prescribed to at least 95% of the planning target volume (PTV) in five fractions except for two patients who received 27-30 Gy in three fractions. Computed tomography and MRI simulation were performed in the supine position prior to treatment in the free-breathing, end exhalation, and end inhalation breath-hold positions to determine patient tolerability and potential dosimetric advantages of each technique. Immobilization consisted of using anterior and posterior torso MRI receive coils embedded in a medium-sized vacuum cushion. Gating was performed using sagittal cine images acquired at 4 frames/second. Gating boundaries were defined in the three major axes to be 0.3 to 0.5 cm. An overlapping region of interest, defined as the percentage volume allowed outside the boundary for beam-on to occur, was set between 1 and 10%. The contoured target was assigned a 5-mm PTV expansion. Organs at risk constraints adopted by the American Association of Physicists in Medicine Task Group 101 were used during optimization.ResultsTwenty-nine patients, with a total of 34 lesions, successfully completed the prescribed treatment with minimal treatment breaks or delays. Twenty-one patients were treated at end-exhale, and six were treated at end-inhale. Two patients were treated using a free-breathing technique due to poor compliance with breath-hold instructions. The reported mean liver dose was 5.56 Gy (1.39 - 10.43; STD 2.85) and the reported mean liver volume receiving the prescribed threshold dose was 103.1 cm3 (2.9 - 236.6; STD 75.2). Follow-up imaging at one to 12 months post treatment confirmed either stable or decreased size of treated lesions in all but one patient. Toxicities were mild and included nausea/vomiting, abdominal pain and one case of bloody diarrhea. Four patients died due to complications from liver cirrhosis unrelated to radiation effect.ConclusionSBRT treatment using a gated technique on an MR-linac has been successfully demonstrated. Potential benefits of this modality include decreased liver dose leading to decreased toxicities. Further studies to identify the benefits and risks associated with MR-guided SBRT are necessary.

Evaluating Safety and Dosimetry of SBRT following 90Y for Hepatocellular Carcinoma

Liver directed therapy is fundamental in the treatment of HCC. SBRT is the only non-invasive local therapy characterized by precise target delineation and accurate, quantifiable dosimetry. Often, SBRT is utilized following interventional therapy; however, there is a lack of data reporting safety and outcomes of patients receiving liver SBRT after yttrium-90 (90Y). We performed a safety and dosimetric evaluation in our series of HCC patients who received SBRT after 90Y by compiling post 90Y PET imaging fusions with SBRT treatment plans for accurate quantification of liver exposed to both SBRT and 90Y. An institutional review board-approved liver SBRT registry of 197 patients was used for data collection. All patients had post-90Y PET (measuring Bremsstrahlung component of 90Y) fused to SBRT treatment planning CT creating composite plans for dosimetric analysis. Volume of ablated liver was estimated using the sharp gradient edge of post-90Y PET, and the 30 Gy isodose line for SBRT (V30). Clinical and laboratory follow up 3 months post SBRT were used to evaluate safety. Changes in chemistry and hematology related to hepatic function, using CTCAE v4.0, were analyzed. Sixteen patients with non-metastatic HCC and prior 90Y were treated with SBRT to 18 intrahepatic sites. Patients received 23 prior 90Y administrations; six patients were treated twice and one patient treated three times. Child-Pugh (CP) category at SBRT was A in 12, and two each of B and C. SBRT dose was 35-50 Gy in 3-5 fractions (median 50 Gy/5). Median time between 90Y and SBRT was 4.6 months (range 1.3-34.8). Mean follow up was 14 months, and 11 patients were alive at analysis. Treatment intent was definitive for 13 patients and downstaging in 3. Mean total liver volume was 2,000 cc (range 986-3304), SBRT PTV 209 cc (range 26-494), and individual 90Y treatment volume 308 cc (range 36-1477). Liver ablative results summarized in Table 1.Abstract SU_13_2123; Table 1Mean valueMean %RangeV30 liver (SBRT)273 cc13.7%36-739 cc (3-34.8%)90Y volume (sum)436 cc22.6%95-1512 cc (3.5-52.6%)V30 volume within prior 90Y93 cc33.2%0-306 cc (0-75%) Open table in a new tab Laboratory data was available for 75% of patients. At 3 months post SBRT there were no new grade ≥2 changes from baseline in bilirubin, hemoglobin, INR, AST, ALT, and albumin in CP-A/B patients. The two CP-C patients, who had higher 90Y volumes and more overlap of 90Y with V30, demonstrated clinically significant hepatic decompensation. Although toxicity was noted, both patients were successfully down-staged within Milan then rescued with transplant 10 and 15 weeks post SBRT. This is the first series to incorporate PET delineation of 90Y ablation distribution in a composite plan with SBRT. Our experience of CP-A /B patients demonstrates minimal toxicity, but notable decompensation in CP-C patients. SBRT can be an effective tool to downstage within Milan but extra caution is warranted in this group, such that risk matches treatment intent, especially in patients that may not be rescued with transplant.

Reference values of liver volume in Caucasian population and factors influencing liver size

PurposeTo investigate factors influencing liver size and to determine reference values of liver volume (LV) for healthy subjects. Methods2773 volunteers underwent magnetic resonance imaging (MRI) of the liver in the setting of the population based Study of Health in Pomerania. Based on measurement of maximum diameters in three orientations, LVs were calculated and correlated with demographic factors such as age, gender, and body mass index. In addition, LVs of healthy volunteers and participants with parenchymal liver diseases such as fatty liver disease, iron overload, fibrosis/cirrhosis were compared. Adjusted reference values of liver volumes were defined for the group of healthy participants. ResultsIn general, mean LV (mean ± standard deviation) was 1505 ± 385 cm3. Age, gender and body mass index correlated significantly with the liver volume (p ≤ 0.001). Parenchymal liver diseases significantly influence LV (with: 1624 ± 420 cm3, n = 1525 and without parenchymal liver diseases: 1360 ± 273 cm3; n = 1.248, p ≤ 0.001). Compared to LV of participants without liver diseases, LV was increased in volunteers with hepatic steatosis (1717 ± 419 cm3; n = 1111), liver iron overload (1558 ± 367 cm3; n = 553; p ≤ 0.001) as well as in participants with fibrosis/cirrhosis (1494 ± 459 cm3; n = 383). ConclusionsLV is influenced by age, body mass index and parenchymal liver diseases. Reference values were established to aid in the diagnosis of parenchymal liver diseases.

Abstract B144: LY3039478, a novel Notch inhibitor, potentiates the antitumor effects of sorafenib in hepatocellular carcinoma (HCC)

Abstract Introduction: Notch pathway has been involved in cell fate determination, cell differentiation, proliferation, and death. Notch promotes cell survival, angiogenesis, and treatment resistance in numerous cancers, making it a promising target for cancer therapy. The role of the Notch pathways in HCC tumorigenesis has shown some controversies over time and across studies, being endowed with both oncogenic and tumor-suppressive properties. Besides sorafenib, new therapies are needed to improve outcomes in patients with advanced HCC. Our study aimed at investigating the antitumoral effects of combining LY3039478, a novel Notch inhibitor, with sorafenib in an in vivo transgenic model of HCC. Materials and Methods: Transgenic mice developing stage-defined HCC were treated for 8 consecutive weeks (W) from W8 to W16 with either vehicle, LY3039478 (8mg/kg, thrice weekly, oral gavage), sorafenib (30mg/kg, daily, oral gavage), or LY3039478 plus sorafenib. Tumor growth was evaluated by ultrasound (liver size), by the number of macronodules, and the number of micronodules on hematoxylin phloxine saffron (HPS) sections at sacrifice. Angiogenesis was evaluated by Doppler (blood flow in the coeliac trunk) and by CD31 staining. Results: First, we confirmed the mode of action of LY3039478 by assessing Notch 1 expression before and after treatment. An 85% decrease in Notch 1 expression was observed in liver tumors treated by LY3039478 compared to placebo or sorafenib. Liver size and the number of liver tumor macronodules were significantly lower in all treatment arms compared to control placebo at both the W12 intermediate sacrifice and W16 final sacrifice; the combination of LY3039478 and sorafenib showed increased tumor control in the combination arm at W16 (4.39mm3 ±0,82 in mean liver volumes) vs sorafenib, LY3039478, and placebo arms (5.41±1,0, 5.84±0,47, 7.09±1,5 respectively). Tumor growth inhibition was confirmed in both the sorafenib and LY3039478 arms at W16 by a 22% and 32% decrease in the number of macronodules compared to placebo, respectively. This inhibition reached 52% in the combination arm compared to placebo. On Hematoxylin Phloxine Saffron (HPS) section, while the number of micronodules was similar between groups, their size was dramatically reduced, especially in the combination arm with a 65% decrease compared to placebo. Angiogenesis assessed by measuring the mean blood flow in the coeliac trunk (TCm) decreased in all treatment arms, compared to placebo. At W16, LY3039478 potentiated the effect of sorafenib, with a TCm decrease of 36% compared to 23% and 18% for the sorafenib and LY3039478 arms, respectively. CD31 confirmed the antiangiogenic effects of LY3039478 alone or in combination, with a 70% and 81% decrease in vessel number, compared to placebo. Conclusion: The combination of LY3039478 and sorafenib showed promising antitumor activity that was associated with decreased angiogenesis in a murine model of stage-defined HCC. Citation Format: Annemilai Tijeras-Raballand, Christian Hobeika, Matthieu Martinet, Elise Paven, Philippe Bonin, Clarisse Eveno, Marc Pocard, Mohamed Bouattour, Sandrine Faivre, Eric Raymond, Armand de Gramont. LY3039478, a novel Notch inhibitor, potentiates the antitumor effects of sorafenib in hepatocellular carcinoma (HCC) [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B144.