Surgical resection remains the most important curative treatment for liver tumors; however, it harbors the risk of developing posthepatectomy liver failure. The principal risk is associated with the ...quality and quantity of the future remnant liver. Therefore, preoperative assessment of the future remnant liver is essential in patients scheduled for major liver resection. Technetium-99m mebrofenin hepatobiliary scintigraphy (HBS) in combination with single-photon emission computed tomography/computed tomography is increasingly applied for the quantitative assessment of liver function before major liver surgery. This dynamic quantitative liver function test allows assessment of both total and regional liver function, represented by the hepatic mebrofenin uptake rate, thereby assisting in adequate patient selection. Since routine implementation, it has shown to reduce the risk of posthepatectomy liver failure and has proven to be more valuable than volumetric assessment. To ensure optimal and reproducible results that can be compared across different centers, it is crucial to standardize the methodology and ensure practical applicability of this technique, thereby facilitating external validation and multicenter trials. This article provides an overview of the HBS methodology used at some of the largest HBS centers and covers practical details in the application of HBS for the quantitative scintigraphic assessment of liver function.
Objective Reoperative aortic valve replacement (re-AVR) in octogenarians is considered high risk and therefore might be indicated for transcatheter AVR. The minimally invasive technique for re-AVR ...limits dissection and might benefit this patient population. We report the outcomes of re-AVR in high-risk octogenarians who might be considered candidates for transcatheter AVR to assess the safety of re-AVR and minimally invasive operative techniques. Methods We identified 105 patients, aged ≥80 years, who underwent open re-AVR at our institution from July 1997 to December 2011. Patients requiring concomitant coronary bypass surgery and/or other valve surgery were excluded. The outcomes of interest included operative mortality, postoperative complications, and midterm postoperative survival. Results Of the 105 patients, 51 underwent minimally re-AVR through upper hemisternotomy (Mre-AVR) and 54 standard full sternotomy (Fre-AVR). The mean patient age was 82.8 ± 3.8 years. No significant differences were found in the patient risk factors. Postoperatively, 6 patients (5.7%) underwent reoperation for bleeding, 4 (3.8%) experienced permanent stroke, 4 (3.8%) developed new renal failure, and 22 (21.0%) had new-onset atrial fibrillation. Overall, the operative mortality was 6.7%, and the 1- and 5-year survival was 87% and 53%, respectively. When Mre-AVR and Fre-AVR were compared, the operative mortality was 9.2% in the Fre-AVR group and 3.9% in the Mre-AVR group ( P = .438). Kaplan-Meier analysis showed a survival benefit at both 1 year (79% ± 11.7% vs 92% ± 7.8%) and 5 years (38% ± 17.6% vs 65% ± 15.7%, P = .028) favoring Mre-AVR. Cox regression analysis identified heparin-induced thrombocytopenia, reoperation for bleeding, older age, full sternotomy, and an infectious complication as predictors of mortality. Conclusions Octogenarians who undergo re-AVR are thought to be high-risk surgical candidates. The present single-center series revealed acceptable in-hospital outcomes and operative mortality. Mre-AVR was associated with better survival compared with Fre-AVR and might benefit this population.
Patients considered for liver resection with insufficient volume or function of the future remnant liver are candidates for portal vein embolization to allow safe resection. The aim of this study is ...to analyze the volumetric and functional responses after portal vein embolization and to evaluate predictors of the hypertrophy response.
All patients who underwent portal vein embolization before liver resection 2006-2017 were included. Patients who did not undergo computed tomography–volumetry and functional assessment with technetium-99m mebrofenin hepatobiliary scintigraphy before and after portal vein embolization were excluded. The functional and volumetric response rates were calculated. Multiple regression analysis was conducted to examine the relationship between the hypertrophy response and potential predictors.
A total of 90 patients underwent portal vein embolization of the right liver. After 3 weeks, there was a significant increase in both volumetric and functional share of the future remnant liver (both P < .01). The increase in functional share exceeded the increase in volumetric share (P < .01). The median functional contribution of segment 4 after portal vein embolization was 41.5% (31.7%–48.7%) of the nonembolized lobe. Preoperative chemotherapy was not a significant predictor of the increase in function or volume. Compared with benign lesions, malignant diseases were significant negative predictors of the functional response.
A total of 3 weeks after portal vein embolization, the functional response exceeded that of the volumetric response, meaning that the waiting time to resection potentially can be decreased. Segment 4 had a significant share of both volume and function, enabling surgical strategies only leaving segment 4 as a monosegment. Neoadjuvant chemotherapy had no negative influence on the hypertrophy response.
Nuclear receptor Nur77, also known as NR4A1, TR3, or NGFI-B, is expressed in human atherosclerotic lesions in macrophages, endothelial cells, T cells and smooth muscle cells. Macrophages play a ...critical role in atherosclerosis and the function of Nur77 in lesion macrophages has not yet been investigated.
This study aims to delineate the function of Nur77 in macrophages and to assess the effect of bone marrow-specific deficiency of Nur77 on atherosclerosis.
We investigated Nur77 in macrophage polarization using bone marrow-derived macrophages (BMM) from wild-type and Nur77-knockout (Nur77(-/-)) mice. Nur77(-/-) BMM exhibit changed expression of M2-specific markers and an inflammatory M1-phenotype with enhanced expression of interleukin-12, IFNγ, and SDF-1α and increased NO synthesis in (non)-stimulated Nur77(-/-) BMM cells. SDF-1α expression in nonstimulated Nur77(-/-) BMM is repressed by Nur77 and the chemoattractive activity of Nur77(-/-) BMM is abolished by SDF-1α inhibiting antibodies. Furthermore, Nur77(-/-) mice show enhanced thioglycollate-elicited migration of macrophages and B cells. The effect of bone marrow-specific deficiency of Nur77 on atherosclerosis was studied in low density lipoprotein receptor-deficient (Ldlr(-/-)) mice. Ldlr(-/-) mice with a Nur77(-/-)-deficient bone marrow transplant developed 2.1-fold larger atherosclerotic lesions than wild-type bone marrow-transplanted mice. These lesions contain more macrophages, T cells, smooth muscle cells and larger necrotic cores. SDF-1α expression is higher in lesions of Nur77(-/-)-transplanted mice, which may explain the observed aggravation of lesion formation.
In conclusion, in bone marrow-derived cells the nuclear receptor Nur77 has an anti-inflammatory function, represses SDF-1α expression and inhibits atherosclerosis.
While imaging studies such as computed tomography or magnetic resonance imaging allow the volumetric assessment of the liver segments, only indirect information is provided concerning the quality of ...the liver parenchyma and its actual functional capacity. Assessment of liver function is therefore crucial in the preoperative workup of patients who require extensive liver resection and in whom portal vein embolization is considered. This review deals with the modalities currently available for the measurement of liver function. Passive liver function tests include biochemical parameters and clinical grading systems such as the Child-Pugh and MELD scores. Dynamic quantitative tests of liver function can be based on clearance capacity tests such as the indocyanine green (ICG) clearance test. Although widely used, discrepancies have been reported for the ICG clearance test in relation with clinical outcome. Nuclear imaging studies have the advantage of providing simultaneous morphologic (visual) and physiologic (quantitative functional) information about the liver. In addition, regional (segmental) differentiation allows specific functional assessment of the future remnant liver. Technetium-99m (99mTc)-galactosyl human serum albumin scintigraphy and 99mTc-mebrofenin hepatobiliary scintigraphy potentially identify patients at risk for post-resectional liver failure who might benefit from liver-augmenting techniques. As there is no one test that can measure all the components of liver function, liver functional reserve is estimated based on a combination of clinical parameters and quantitative liver function tests.
Portal vein embolization (PVE) is performed to induce hypertrophy of an insufficient future remnant liver (FRL) before major liver resection. Associating liver partition and portal vein ligation for ...staged hepatectomy (ALPPS) aims to offer a more rapid and increased hypertrophy response. The first stage can be performed with complete or partial (laparoscopic) transection of the liver parenchyma. This study aimed to investigate the increase in FRL volume and function, as well as postoperative outcomes after PVE or complete- or partial-ALPPS1.
Patients with insufficient FRL undergoing either PVE or ALPPS underwent CT-volumetry and functional assessment using
Tc-mebrofenin hepatobiliary scintigraphy (HBS). Severe complications and 90-day mortality were evaluated after liver resection.
Seventy-two patients were included; 51 underwent PVE, 12 complete-ALPPS1 and 9 partial-ALPPS1 of which 7 laparoscopic. The median increase in FRL function was 1.5-, 1.7- and 1.3-fold higher, respectively, than the increase in volume; (P<0.01, P<0.01 and P=0.44). The target hypertrophy response did not differ between the groups, but was reached earlier in both ALPPS1 groups (8 and 10 days) compared to the PVE group (23 days). Of the resected patients, 18%, 30% and 17% had severe postoperative complications and the 90-day mortality was 2%, 25% and 0%, respectively.
Increase of FRL function exceeded increase of volume after both PVE and ALPPS1. The target hypertrophy response was reached earlier in ALPPS. Complete and partial-ALPPS1 showed comparable functional and volumetric hypertrophy responses. A (laparoscopic) partial-ALPPS1 is preferred considering lower morbidity and mortality rates after resection.
The microvascular effects occurring after unilateral preoperative portal vein embolization (PVE) are poorly understood. The aim of this study was to assess the microvascular changes in the embolized ...and the non-embolized lobes after right PVE.
Videos of the hepatic microcirculation in patients undergoing right hemihepatectomy following PVE were recorded using a handheld vital microscope (Cytocam) based on incident dark field imaging. Hepatic microcirculation was measured in the embolized and the non-embolized lobes at laparotomy, 3–6 weeks after PVE. The following microcirculatory parameters were assessed: total vessel density (TVD), microcirculatory flow index (MFI), proportion of perfused vessel (PPV), perfused vessel density (PVD), sinusoidal diameter (SinD) and the absolute red blood cell velocity (RBCv).
16 patients after major liver resection were included, 8 with and 8 without preoperative PVE. Microvascular density parameters were higher in the non-embolized lobes when compared to the embolized lobes (TVD: 40.3 ± 8.9 vs. 26.8 ± 4.6 mm/mm2 (p < 0.003), PVD: 40.3 ± 8.8 vs. 26.7 ± 4.7 mm/mm2 (p < 0.002), SinD: 9.2 ± 1.7 vs. 6.3 ± 0.8 μm (p < 0.040)). RBCv, PPV and the MFI were not significantly different.
The non-embolized lobe has a significantly higher microvascular density, however without differences in microvascular flow. These findings indicate increased angiogenesis in the hypertrophic lobe.
Introduction: The microvascular events following portal vein embolization (PVE) are poorly understood despite the pivotal role of the microcirculation in liver regeneration and tumor progression. We ...aimed to assess the changes in hepatic microvascular perfusion and neo-angiogenesis after experimental PVE. Methods: PVE of the cranial liver lobes was performed in 12 New Zealand White rabbits divided into 2 groups of permanent (P-PVE) and reversible PVE (R-PVE), respectively. Hepatobiliary scintigraphy and CT were used to evaluate hepatic function and volume. Hepatic microcirculation was assessed using a handheld vital microscope (Cytocam) to measure microvascular density (total vessel density; TVD) before PVE, right after PVE, and 20 min after PVE, as well as at 14 days (D14 post-PVE) and 35 days (D35 post-PVE). Additionally, on D35, microvascular PO 2 and liver parenchymal VEGF were assessed. Results: Eleven rabbits were included after PVE (R-PVE, n = 5; P-PVE, n = 6). TVD in the nonembolized (hypertrophic) lobes was higher than in the embolized (atrophic) lobes of the P-PVE group at D35 post-PVE (36.7 ± 7.2 vs. 23.4 ± 4.9 mm/mm 2 ; p < 0.05). In the R-PVE group, TVD in the nonembolized lobes was not increased at D35. Function and volume were increased in the nonembolized lobes of the P-PVE group compared to the embolized lobes, but not in the R-PVE group. Likewise, the mmicrovascular PO 2 and VEGF staining rate were higher in the nonembolized lobes of the P-PVE group at D35 post-PVE. Discussion/Conclusion: Successful volumetric and functional hypertrophy of the nonembolized lobe was accompanied by microvascular alterations featuring increased neo-angiogenesis, microvascular density, and microvascular oxygen pressure following P-PVE.
•ALPPS is a two stage hepatectomy with rapid liver hypertrophy.•ALPPS had high morbidity and mortality rates compared to conventional procedures.•Interstage morbidity is especially predictive of ...mortality after ALPPS.•Topical hemostatic agents might reduce interstage morbidity.
ALPPS (Associating Liver Partition and Portal vein Ligation for Staged hepatectomy) is a new two-stage hepatectomy for patients in whom conventional treatment is not feasible due to insufficient future liver remnant (FLR). During stage one of ALPPS, accelerated growth of the FLR is induced by ligation of the portal vein and in situ split of the liver, which prevents interlobar collateral portal circulation and attributes to the accelerated hypertrophy response. This can present a risk for postoperative haemorrhage. Furthermore, adhesion of the adjacent resection surfaces might complicate the second stage of the procedure. Hemopatch® is a flexible, NHS-PEG coated, absorbable collagen-based sealant that provides haemostasis. This paper illustrates the use of Hemopatch during ALPPS for hemostasis and prevention of adhesions between the cut-surfaces of the liver.
An 81-year-old patient requiring right hemihepatectomy for synchronous liver metastases underwent ALPPS. During stage one, Hemopatch was applied according to the manufacturer’s instructions to the hepatic resection surfaces. Stage-2 was performed uneventfully, with no adhesions observed in the resection plane 18days after the first stage. The patient was discharged without any major complications.
Hemopatch is a useful tool in prevention of postoperative haemorrhage in patients undergoing ALPPS procedure as well as in the prevention of adhesions between the cut-surfaces after transection. This facilitates stage-2 of the procedure which potentially improves postoperative outcomes.
Topic haemostatic agents to cover the transection surface during stage one of ALPPS could help to prevent adverse interstage events.
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