Effect of Sarcopenia on the Increase in Liver Volume and Function After Portal Vein Embolization

Purpose: Sarcopenia is associated with a decreased kinetic growth rate (KGR) of the future liver remnant (FLR) after portal vein embolization (PVE). However, little is known on the increase in FLR function (FLRF) after PVE. This study evaluated the effect of sarcopenia on the functional growth rate (FGR) after PVE measured with hepatobiliary scintigraphy (HBS). Methods: All patients who underwent PVE at the Amsterdam UMC between January 2005 and August 2017 were analyzed. Functional imaging by HBS was used to determine FGR. Liver volumetry was performed using multiphase contrast computed tomography (CT). Muscle area measurement to determine sarcopenia was taken at the third lumbar level (L3). Results: Out of the 95 included patients, 9 were excluded due to unavailable data. 70/86 (81%) patients were sarcopenic. In the multivariate logistic regression analysis, sarcopenia (p = 0.009) and FLR volume (FRLV) before PVE (p = 0.021) were the only factors correlated with KGR, while no correlation was found with FGR. 90-day mortality was similar across the sarcopenic and non-sarcopenic group (4/53 [8%] versus 1/11 [9%]; p = 1.000). The resection rates were also comparable (53/70 [75%] versus 11/16 [69%]; p = 0.542). Conclusion: FGR after PVE as measured by HBS appears to be preserved in sarcopenic patients. This is in contrast to KGR after PVE as measured by liver volumetry which is decreased in sarcopenic patients. Level of Evidence: Level 3b, cohort and case control studies.</p

Effect of Sarcopenia on the Increase in Liver Volume and Function After Portal Vein Embolization

Purpose: Sarcopenia is associated with a decreased kinetic growth rate (KGR) of the future liver remnant (FLR) after portal vein embolization (PVE). However, little is known on the increase in FLR function (FLRF) after PVE. This study evaluated the effect of sarcopenia on the functional growth rate (FGR) after PVE measured with hepatobiliary scintigraphy (HBS). Methods: All patients who underwent PVE at the Amsterdam UMC between January 2005 and August 2017 were analyzed. Functional imaging by HBS was used to determine FGR. Liver volumetry was performed using multiphase contrast computed tomography (CT). Muscle area measurement to determine sarcopenia was taken at the third lumbar level (L3). Results: Out of the 95 included patients, 9 were excluded due to unavailable data. 70/86 (81%) patients were sarcopenic. In the multivariate logistic regression analysis, sarcopenia (p = 0.009) and FLR volume (FRLV) before PVE (p = 0.021) were the only factors correlated with KGR, while no correlation was found with FGR. 90-day mortality was similar across the sarcopenic and non-sarcopenic group (4/53 [8%] versus 1/11 [9%]; p = 1.000). The resection rates were also comparable (53/70 [75%] versus 11/16 [69%]; p = 0.542). Conclusion: FGR after PVE as measured by HBS appears to be preserved in sarcopenic patients. This is in contrast to KGR after PVE as measured by liver volumetry which is decreased in sarcopenic patients. Level of Evidence: Level 3b, cohort and case control studies.</p

In-Vivo Biodistribution and Safety of 99mTc-LLP2A-HYNIC in Canine Non-Hodgkin Lymphoma

Theranostic agents are critical for improving the diagnosis and treatment of non-Hodgkin Lymphoma (NHL). The peptidomimetic LLP2A is a novel peptide receptor radiotherapy candidate for treating NHL that expresses the activated α4β1 integrin. Tumor-bearing dogs are an excellent model of human NHL with similar clinical characteristics, behavior, and compressed clinical course. Canine in vivo imaging studies will provide valuable biodistribution and affinity information that reflects a diverse clinical population of lymphoma. This may also help to determine potential dose-limiting radiotoxicity to organs in human clinical trials. To validate this construct in a naturally occurring model of NHL, we performed in-vivo molecular targeted imaging and biodistribution in 3 normal dogs and 5 NHL bearing dogs. 99mTc-LLP2A-HYNIC-PEG and 99mTc-LLP2A-HYNIC were successfully synthesized and had very good labeling efficiency and radiochemical purity. 99mTc-LLP2A-HYNIC and 99mTc-LLP2A-HYNIC-PEG had biodistribution in keeping with their molecular size, with 99mTc-LLP2A-HYNIC-PEG remaining longer in the circulation, having higher tissue uptake, and having more activity in the liver compared to 99mTc-LLP2A-HYNIC. 99mTc-LLP2A-HYNIC was mainly eliminated through the kidneys with some residual activity. Radioactivity was reduced to near-background levels at 6 hours after injection. In NHL dogs, tumor showed moderately increased activity over background, with tumor activity in B-cell lymphoma dogs decreasing after chemotherapy. This compound is promising in the development of targeted drug-delivery radiopharmaceuticals and may contribute to translational work in people affected by non-Hodgkin lymphoma

Multilaboratory Comparison of Pneumococcal Multiplex Immunoassays Used in lmmunosurveillance of Streptococcus pneumoniae across Europe

Surveillance studies are required to estimate the impact of pneumococcal vaccination in both children and the elderly across Europe. The World Health Organization (WHO) recommends use of enzyme immunoassays (EIAs) as standard methods for immune surveillance of pneumococcal antibodies. However, as levels of antibodies to multiple serotypes are monitored in thousands of samples, a need for a less laborious and more flexible method has evolved. Fluorescent-bead-based multiplex immunoassays (MIAs) are suitable for this purpose. An increasing number of public health and diagnostic laboratories use MIAs, although the method is not standardized and no international quality assessment scheme exists. The EU Pneumo Multiplex Assay Consortium was initiated in 2013 to advance harmonization of MIAs and to create an international quality assessment scheme. In a multilaboratory comparison organized by the consortium, agreement among nine laboratories that used their own optimized MIA was assessed on a panel of 15 reference sera for 13 pneumococcal serotypes with the new WHO standard 007sp. Agreement was assessed in terms of assay accuracy, reproducibility, repeatability, precision, and bias. The results indicate that the evaluated MIAs are robust and reproducible for measurement of vaccine-induced antibody responses. However, some serotype-specific variability in the results was observed in comparisons of polysaccharides from different sources and of different conjugation methods, especially for serotype 4. On the basis of the results, the consortium has contributed to the harmonization of MIA protocols to improve reliability of immune surveillance of Streptococcus pneumoniae

Improving the Safety of Major Resection for Hepatobiliary Malignancy: Portal Vein Embolization and Recent Innovations in Liver Regeneration Strategies

Purpose of review: For three decades, portal vein embolization (PVE) has been the “gold-standard” strategy to hypertrophy the anticipated future liver remnant (FLR) in advance of major hepatectomy. During this time, CT volumetry was the most common method to preoperatively assess FLR quality and function and used to determine which patients are appropriate surgical candidates. This review provides the most up-to-date methods for preoperatively assessing the anticipated FLR and summarizes data from the currently available strategies used to induce FLR hypertrophy before surgery for hepatobiliary malignancy. Recent findings: Functional and physiological imaging is increasingly replacing standard CT volumetry as the method of choice for preoperative FLR assessment. PVE, associating liver partition and portal vein ligation, radiation lobectomy, and liver venous deprivation are all currently available techniques to hypertrophy the FLR. Each strategy has pros and cons based on tumor type, extent of resection, presence or absence of underlying liver disease, age, performance status, complication rates, and other factors. Summary: Numerous strategies can lead to FLR hypertrophy and improve the safety of major hepatectomy. Which is best has yet to be determined

Hepatic parenchymal transection increases liver volume but not function after portal vein embolization in rabbits

Associating liver partition with portal vein ligation for staged hepatectomy induces more extensive liver hypertrophy than ligation alone; however, the mechanisms underlying the accelerated liver regrowth and the functional quality of the hypertrophic liver are presently elusive. This study, therefore, investigated the effect of parenchymal transection on liver volume and function after portal vein embolization in a standardized rabbit model. Twelve rabbits were subjected to portal vein embolization of the cranial liver lobes and randomized between parenchymal transection of the left lateral liver lobe versus no transection (portal vein embolization only). Liver volume of the nonembolized liver lobe was assessed using computed tomography-volumetry, and liver uptake function was determined by (99m)Tc-mebrofenin hepatobiliary scintigraphy before and 3 and 7 days after portal vein embolization. The increase in nonembolized liver volume 3 days after portal vein embolization was 2.7-fold greater in the transected group compared with the portal vein embolization only group (56 ± 16% vs 21 ± 12%, respectively, P < .01) and 1.7-fold greater 7 days after portal vein embolization (113 ± 34% vs 68 ± 24%, P < .01). Liver uptake function did not differ between groups before portal vein embolization (8.4 ± 3.7%/min in the transection group vs 8.9 ± 1.6%/min) on day 3 (33.2 ± 4.7% after transection vs 30.3 ± 4.6%/min, respectively) and day 7 after portal vein embolization (42.6 ± 8.4% vs 39.1 ± 5.3%/min, respectively). Parenchymal transection after portal vein embolization increases liver growth in terms of volume but not function. These results indicate that the rapid volume increase observed after associating liver partition with portal vein ligation for staged hepatectomy does not coincide with the clinically more relevant functional increase. Quantitative liver function tests might be essential in associating liver partition with portal vein ligation for staged hepatectomy to better assess the hypertrophy response and improve clinical decision-makin