Baranski, A.

Bennink, R.J.

Burgmans, M.C.

Geus-Oei, L.F. de

Hoek, B. van

Lam, H.D.

Pas, S.L. van der

NARCIS 

The role of proportionate kinetic growth rate fraction in future remnant liver function over volume determined by Tc-99m-Mebrofenin hepatobiliary scintigraphy including SPELT and computed tomography in the risk prediction of postoperative mortality in ALPPS

Leiden University Scholary Publications

Surgery 165 (2019) 1244e1249Contents lists available at ScienceDirectSurgeryjournal homepage: www.elsevier.com/locate/surgLetters to the EditorThe role of proportionate kinetic growth rate fractionin future remnant liver function over volumedetermined by 99mTc-Mebrofenin hepatobiliaryscintigraphy including SPECT and computedtomography in the risk prediction of postoperativemortality in ALPPSWe would like to propose a potential novel method for predict-ing posthepatectomy liver failure (PHLF) after associating liver par-titioning and portal vein ligation for staged hepatectomy (ALPPS).This technique uses the combined results of future remnant livervolume (fRLV)1,2 based on volumetric computed tomography (CT)measurements and future remnant liver function (fRLF) based ontechnetium-99m (99mTc)-Mebrofenin hepatobiliary scintigraphy(HBS) with a Single Photon Emission Computed Tomography(SPECT) camera.3e6 Individually, the standard analysis of these pre-operative assessments have shown shortcomings in predictingPHLF in the interstage of ALPPS.7e10 But, by using the results incombination, we suggest a new integrated parameter: the relativeproportion kinetic growth rate (KGR) fraction of functional overvolume increase that might prove to be better at predicting PHLFat the interstage of ALPPS.In 5 patients (48e57 years of age) who underwent the hybridALPPS procedure11,12 for hepaticmalignancy (2 intrahepatic cholan-giocarcinoma, 1 colorectal liver metastasis, 1 gallbladder cancer,and 1 hepatocellular carcinoma), fRLVmeasurements by volumetricCT and fRLF assessment by HBS scan5 were performed both preop-eratively and during the interstage ALPPS. The decision to proceedto completion hepatectomy was performed if the predefined crit-ical cutoff levels of both fRLV (>30%) and fRLF (>2.7%/min/m2)were met.All patients had an insufficient fRLV (mean 22%; 10%e28.9%)preoperatively. The preoperative mean fRLF was 2.6 %/min/m2(range: 0.9%e3.5 %/min/m2). At the interstage, the fRLV increasedin all patients, showing a mean 98% increase after a mean intervalof 10.4 days after completion of the first step (7e14 days). However,all, but 1 patient, had a fRLF growth with a mean 49% increasemeasured at a mean interval of 10.6 days (8e28 days; Table 1).The patient without fRLF growth did not proceed to completionTable 1Preoperative and interstage volumetric and HBS results with calculatedpostoperative outcome for all 5 patients.PatientnumberPreoperativefRLV (%)InterstagefRLV (%)PreoperativefRLF (%/min/m2)Patient 1 22.1 45.0 3.5Patient 2 9.9 31.6 2.7Patient 3 28.7 40.4 3.3Patient 4 24.5 52.0 2.8Patient 5 25.5 28.8 (42.1*) 0.9Mean 22.1 39.6 2.6* 28 days after PVE.hepatectomy. The remaining patients underwent completion hep-atectomy. In 1 of these 4 remaining patients, completion hepatec-tomy had been postponed to 28 days after liver partitioningowing to an initially insufficient fRLF, but this patient developed le-thal PHLF on postop day 4. The clinical course of this patient furtherdemonstrates the drawbacks of using absolute cutoff values of fRLVor fRLF as described elsewhere7,9,10, and the alleged importance ofusing KGR in clinical context as a better predictor for PHLF.13e16The “disproportionate” increase of the remnant liver volumecompared to fRLF might be the cause of the greater morbidityand mortality reported in ALPPS.7 In addition, recent pathologicstudies of the remnant liver showing a higher density but smallerhepatocytes in the remnant liver seem to support the dysfunctionalvolume theory. These hepatocytes also contain fewer organellesand are thus less metabolic active.17 This intangible relationshiphas led us to recommend the increase over time of function relativeto volume (proportionate KGR function over volume fraction [pKGRf/V]) as a predictor for PHLF.pKGR f=V ¼0@ðfRLF interstagefRLF preoperativeÞfRLF preoperativeIntervalðdaysÞ fRLF1A,0@ðfRLV interstagefRLV preoperativeÞfRLV preoperativeInterval ðdaysÞ fRLV1AWe encourage further research to validate the ideal cutoff valueof proportionate KGR function over volume fraction in larger series.Conflict of interestThe authors have indicated that they have no conflicts ofinterest regarding the content of this article.References1. Khan AS, Garcia-Aroz S, Ansari MA, Atiq SM, Senter-Zapata M, Fowler K, et al.Assessment and optimization of liver volume before major hepatic resection:current guidelines and a narrative review. Int J Surg (London, England).2018;52:74e81.fraction proportionate KGR function over volume fraction againstInterstagefRLF (%/min/m2)Fraction proportionateKGR function overvolume fractionPostoperativeoutcome4.4 0.2 Alive4.1 0.2 Alive4.1 0.6 Alive2.1 0.2 Aborted2.4 (3.9*) 5.1 Deceased3.4 2.7Letters to the Editor / Surgery 165 (2019) 1244e1249 12452. Bertens KA, Hawel J, Lung K, Buac S, Pineda-Solis K, Hernandez-Alejandro R.ALPPS: challenging the concept of unresectabilityda systematic review. Inter-national J Surg (London, England). 2015;13:280e287.3. Erdogan D, Heijnen BH, Bennink RJ, Kok M, Dinant S, Straatsburg IH, et al. Pre-operative assessment of liver function: a comparison of 99mTc-Mebrofeninscintigraphy with indocyanine green clearance test. Liver Int. 2004;24:117e123.4. de Graaf W, van Lienden KP, Dinant S, Roelofs JJ, Busch OR, Gouma DJ, et al.Assessment of future remnant liver function using hepatobiliary scintigraphy inpatients undergoing major liver resection. J Gastrointest Surg. 2010;14:369e378.5. de Graaf W, van Lienden KP, van Gulik TM, Bennink RJ. (99m)Tc-mebrofeninhepatobiliary scintigraphy with SPECT for the assessment of hepatic functionand liver functional volume before partial hepatectomy. JNucl Med. 2010;51:229e236.6. Cieslak KP, Runge JH, Heger M, Stoker J, Bennink RJ, van Gulik TM. New per-spectives in the assessment of future remnant liver. Dig Surg. 2014;31:255e268.7. Kang D, Schadde E. Hypertrophy and liver function in ALPPS: correlation withmorbidity and mortality. Visc Med. 2017;33:426e433.8. Schnitzbauer AA, Lang SA, Goessmann H, Nadalin S, Baumgart J, Farkas SA, et al.Right portal vein ligation combined with in situ splitting induces rapid leftlateral liver lobe hypertrophy enabling 2-staged extended right hepatic resec-tion in small-for-size settings. Ann Surg. 2012;255:405e414.9. Schadde E, Schnitzbauer AA, Tschuor C, Raptis DA, Bechstein WO, Clavien PA.Systematic review and meta-analysis of feasibility, safety, and efficacy of anovel procedure: associating liver partition and portal vein ligation for stagedhepatectomy. Ann Surg Oncol. 2015;22:3109e3120.10. Olthof PB, Tomassini F, Huespe PE, Truant S, Pruvot FR, Troisi RI, et al. Hepato-biliary scintigraphy to evaluate liver function in associating liver partition andportal vein ligation for staged hepatectomy: liver volume overestimates liverfunction. Surgery. 2017;162:775e783.11. Li J, Kantas A, Ittrich H, Koops A, Achilles EG, Fischer L, et al. Avoid “all-Touch”by hybrid ALPPS to achieve oncological efficacy. Ann Surg. 2016;263:e6ee7.12. Lai Q, Melandro F, Rossi M. Hybrid partial ALPPS: a feasible approach in case ofright trisegmentectomy and macrovascular invasion. Ann Surg. 2018;267:e80ee82.13. Kambakamba P, Stocker D, Reiner CS, Nguyen-Kim TD, Linecker M,Eshmuminov D, et al. Liver kinetic growth rate predicts postoperative liver fail-ure after ALPPS. HPB (Oxford). 2016;18:800e805.14. Shindoh J, Truty MJ, Aloia TA, Curley SA, Zimmitti G, Huang SY, et al. Kineticgrowth rate after portal vein embolization predicts posthepatectomy out-comes: toward zero liver-related mortality in patients with colorectal liver me-tastases and small future liver remnant. J Am Coll Surg. 2013;216:201e209.15. Sparrelid E, Jonas E, Tzortzakakis A, Dahlen U, Murquist G, Brismar T, et al. Dy-namic evaluation of liver volume and function in associating liver partition andportal vein ligation for staged hepatectomy. J Gastrointest Surg. 2017;21:967e974.16. Tani K, Shindoh J, Takamoto T, Shibahara J, Nishioka Y, Hashimoto T, et al. Ki-netic changes in liver parenchyma after preoperative chemotherapy for pa-tients with colorectal liver metastases. J Gastrointest Surg. 2017;21:813e821.17. Matsuo K, Murakami T, Kawaguchi D, Hiroshima Y, Koda K, Yamazaki K, et al.Histologic features after surgery associating liver partition and portal vein liga-tion for staged hepatectomy versus those after hepatectomy with portal veinembolization. Surgery. 2016;159:1289e1298.Hwai-Ding Lam, MD*Department of Surgery, Leiden University Medical Center, Leiden,the NetherlandsStephanie Louise van der Pas, PhDMedical Statistics, Department of Biomedical Data Sciences, LeidenUniversity Medical Center, Leiden, the NetherlandsMathematical Institute, Leiden University, Leiden, the NetherlandsAndrzej Baranski, MD, PhDDepartment of Surgery, Leiden University Medical Center, Leiden,the NetherlandsBart van Hoek, MD, PhDDepartment of Gastroenterology and Hepatology, Leiden UniversityMedical Center, Leiden, the NetherlandsMark Christiaan Burgmans, MD, PhDDepartment of Radiology, Leiden University Medical Center, Leiden,the NetherlandsRoelof Johannes Bennink, MD, PhDDepartment of Radiology and Nuclear Medicine, Academic MedicalCenter, Amsterdam, the NetherlandsLioe-Fee de Geus-Oei, MD, PhDDepartment of Radiology, Leiden University Medical Center, Leiden,the NetherlandsBiomedical Photonic Imaging Group, Faculty of Science andTechnology, University of Twente, the Netherlands* Corresponding author: Leiden University Medical Center,Department of Surgery, Albinusdreef 2, 2333 ZA, Leiden,the Netherlands.E-mail address: h.lam@lumc.nl (H.-D. Lam).Accepted 9 October 2018https://doi.org/10.1016/j.surg.2018.10.0200039-6060/© 2018 Elsevier Inc. All rights reserved.Familial nonmedullary thyroid cancer: When the dataand conclusions do not matchTo the Editors:When reading the paper by El Lakis et al.1 on familial nonmedul-lary thyroid cancer (FNMTC), it seems their conclusions contradicttheir data.The greater number of lymphnodemetastases (LNMs) in FNMTCpatients reported by El Lakis et al.1 were foundmostly in the centralcompartment; however, it is well recognized how common andclinically irrelevant these types of nodal metastases prove to be.Moreover, because total thyroidectomy was performed in FNMTCmore frequently than in the Surveillance, Epidemiology, and EndResults (SEER) patients (98.2% vs 84%, respectively), and becausemore extensive surgery could prompt more neck exploration andsubsequentlymore central neck dissections, a greater rate of centralLNMs in FNMTC patients could, in fact, represent a bias of the study.Similarly, the difference in the female-to-male ratios among groups,with more males included in the FNMTC group, could be anotherpossible bias. Of note, the SEER group patients presented with amore aggressive histopathology, with almost twice as many tallcell and follicular thyroid cancer (TC/FTC) variants.Separating the patients presenting with clinical disease fromthosediscoveredbyscreening isquite arbitrary.Most thyroidnodulestoday fall within the category of incidental findings, and it is unclearwhat definition of clinical disease the authors applied. Of interest, the20patientsdetectedbyscreeningpatientswithFNMTCshowedmorefavorable features and had fewer total thyroidectomies performedthan the SEER patients (84.2% vs 98.2%). However, after excludingthe screening group, there was little difference regarding age, TC/FTC types, extrathyroidal extension, and number of patients withT1 stage and lateral LNMs between FNMTC and the SEER patients.Moreover, the FNMTC patients with > 2 affected relatives had asimilar number of lateral LNMs and 3 times less TC/FTC variants.Considering that recurrence-risk stratificationwas not applied, arecurrence rate of 12.8% in the FNMTC group falls within the widelyaccepted lower range for sporadic NMTC. Although patients in theSEER group were registered from 1998 to 2007, we do not know theperiod for the FNMTC patients. Nevertheless, the mean follow-upfor the FNMTC patients was 220 ± 416 months (18 ± 35 years)compared with 70 ± 58 months (5.8 ± 4.8 years) in the SEER group.In such a timespan, the field of thyroid cancer has changed so much(American Thyroid Association risk stratification; response to initialtreatment assessment; Tumor, Node, and Metastasis 8th edition,etc) that assessment and definition of recurrent disease would bevery different today.

    https://openaccess.leidenuniv.nl  License: Article 25fa pilot End User Agreement This publication is distributed under the terms of Article 25fa of the Dutch Copyright Act (Auteurswet) with explicit consent by the author. Dutch law entitles the maker of a short scientific work funded either wholly or partially by Dutch public funds to make that work publicly available for no consideration following a reasonable period of time after the work was first published, provided that clear reference is made to the source of the first publication of the work.  This publication is distributed under The Association of Universities in the Netherlands (VSNU) ‘Article 25fa implementation’ pilot project. In this pilot research outputs of researchers employed by Dutch Universities that comply with the legal requirements of Article 25fa of the Dutch Copyright Act are distributed online and free of cost or other barriers in institutional repositories. Research outputs are distributed six months after their first online publication in the original published version and with proper attribution to the source of the original publication.  You are permitted to download and use the publication for personal purposes. All rights remain with the author(s) and/or copyrights owner(s) of this work. Any use of the publication other than authorised under this licence or copyright law is prohibited. If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please contact the Library through email: OpenAccess@library.leidenuniv.nl    Article details Lam H.D., Pas S.L. van der, Baranski A., Hoek B. van, Burgmans M.C., Bennink R.J. & Geus-Oei L.F. de (2018), The role of proportionate kinetic growth rate fraction in future remnant liver function over volume determined by 99m Tc-Mebrofenin hepatobiliary scintigraphy including SPECT and computed tomography in the risk prediction of postoperative mortality in ALPPS, Surgery . Doi: 10.1016/j.surg.2018.10.020   ARTICLE IN PRESS JID: YMSY [m5G; November 19, 2018;14:57 ] Surgery xxx (xxxx) xxx Contents lists available at ScienceDirect Surgery journal homepage: www.elsevier.com/locate/surg The role of proportionate kinetic growth rate fraction in future remnant liver function over volume determined by 99m Tc-Mebrofenin hepatobiliary scintigraphy including SPECT and computed tomography in the risk prediction of postoperative mortality in ALPPS  i  t  T  v  m  o  p  p  p  P  c  p  v  a b  c  c  v  b  s  p  ( p(  i  o  a  m  T  h  a  t  t  P  d  o  u c  m  o  c  u  a  u  u  ap o  R                     1    1   1   1    h0We would like to propose a potential novel method for predict-ng posthepatectomy liver failure (PHLF) after associating liver par-itioning and portal vein ligation for staged hepatectomy (ALPPS).his technique uses the combined results of future remnant liverolume (fRLV) 1,2 based on volumetric computed tomography (CT)easurements and future remnant liver function (fRLF) basedn technetium-99m ( 99m Tc)-Mebrofenin hepatobiliary scintigra-hy (HBS) with a Single Photon Emission Computed Tomogra-hy (SPECT) camera. 3–6 Individually, the standard analysis of thesereoperative assessments have shown shortcomings in predictingHLF in the interstage of ALPPS. 7–10 But, by using the results inombination, we suggest a new integrated parameter: the relativeroportion kinetic growth rate (KGR) fraction of functional overolume increase that might prove to be better at predicting PHLFt the interstage of ALPPS. In 5 patients (48–57 years of age) who underwent the hy-rid ALPPS procedure 11,12 for hepatic malignancy (2 intrahepaticholangiocarcinoma, 1 colorectal liver metastasis, 1 gallbladderancer, and 1 hepatocellular carcinoma), fRLV measurements byolumetric CT and fRLF assessment by HBS scan 5 were performedoth preoperatively and during the interstage ALPPS. The deci-ion to proceed to completion hepatectomy was performed if theredefined critical cutoff levels of both fRLV ( > 30%) and fRLF > 2.7%/min/m2) were met. All patients had an insufficient fRLV (mean 22%; 10%–28.9%)reoperatively. The preoperative mean fRLF was 2.6 %/min/m 2 range: 0.9%–3.5 %/min/m 2 ). At the interstage, the fRLV increasedn all patients, showing a mean 98% increase after a mean intervalf 10.4 days after completion of the first step (7–14 days). However,ll, but 1 patient, had a fRLF growth with a mean 49% increaseeasured at a mean interval of 10.6 days (8–28 days; Table 1 ).he patient without fRLF growth did not proceed to completionepatectomy. The remaining patients underwent completion hep-tectomy. In 1 of these 4 remaining patients, completion hepatec-omy had been postponed to 28 days after liver partitioning owingo an initially insufficient fRLF, but this patient developed lethalHLF on postop day 4. The clinical course of this patient furtheremonstrates the drawbacks of using absolute cutoff values of fRLVr fRLF as described elsewhere 7,9 , 10 , and the alleged importance ofsing KGR in clinical context as a better predictor for PHLF. 13–16 The “disproportionate” increase of the remnant liver volumeompared to fRLF might be the cause of the greater morbidity andortality reported in ALPPS. 7 In addition, recent pathologic studiesf the remnant liver showing a higher density but smaller hepato-ytes in the remnant liver seem to support the dysfunctional vol-ttps://doi.org/10.1016/j.surg.2018.10.020 039-6060/© 2018 Elsevier Inc. All rights reserved. me theory. These hepatocytes also contain fewer organelles andre thus less metabolic active. 17 This intangible relationship has leds to recommend the increase over time of function relative to vol-me (proportionate KGR function over volume fraction [pKGR f/V])s a predictor for PHLF. KGR f / V = ( ( fRLF inte rsta ge −fRLF preo pera tive ) fRLF preo pera tive Interval ( days ) fRLF ) / ( ( fRLV inte rsta ge −fRLV preo pera tive ) fRLV preo pera tive Inte rval ( days ) fRLV ) We encourage further research to validate the ideal cutoff valuef proportionate KGR function over volume fraction in larger series.eferences 1. Khan AS , Garcia-Aroz S , Ansari MA , Atiq SM , Senter-Zapata M , Fowler K ,et al. Assessment and optimization of liver volume before major hepatic re-section: current guidelines and a narrative review. Int J Surg (London, England) .2018;52:74–81 . 2. Bertens KA , Hawel J , Lung K , Buac S , Pineda-Solis K , Hernandez-Alejandro R .ALPPS: challenging the concept of unresectability—a systematic review. Interna-tional J Surg (London, England) . 2015;13:280–287 . 3. Erdogan D , Heijnen BH , Bennink RJ , Kok M , Dinant S , Straatsburg IH , et al.Preoperative assessment of liver function: a comparison of 99mTc-Mebrofeninscintigraphy with indocyanine green clearance test. Liver Int . 2004;24:117–123 . 4. de Graaf W , van Lienden KP , Dinant S , Roelofs JJ , Busch OR , Gouma DJ , et al. As-sessment of future remnant liver function using hepatobiliary scintigraphy inpatients undergoing major liver resection. J Gastrointest Surg . 2010;14:369–378 . 5. de Graaf W , van Lienden KP , van Gulik TM , Bennink RJ . (99m)Tc-mebrofeninhepatobiliary scintigraphy with SPECT for the assessment of hepatic func-tion and liver functional volume before partial hepatectomy. JNucl Med .2010;51:229–236 . 6. Cieslak KP , Runge JH , Heger M , Stoker J , Bennink RJ , van Gulik TM . New per-spectives in the assessment of future remnant liver. Dig Surg . 2014;31:255–268 .7. Kang D , Schadde E . Hypertrophy and liver function in ALPPS: correlation withmorbidity and mortality. Visc Med . 2017;33:426–433 . 8. Schnitzbauer AA , Lang SA , Goessmann H , Nadalin S , Baumgart J , Farkas SA ,et al. Right portal vein ligation combined with in situ splitting induces rapidleft lateral liver lobe hypertrophy enabling 2-staged extended right hepatic re-section in small-for-size settings. Ann Surg . 2012;255:405–414 . 9. Schadde E , Schnitzbauer AA , Tschuor C , Raptis DA , Bechstein WO , Clavien PA .Systematic review and meta-analysis of feasibility, safety, and efficacy of a novelprocedure: associating liver partition and portal vein ligation for staged hepa-tectomy. Ann Surg Oncol . 2015;22:3109–3120 . 0. Olthof PB , Tomassini F , Huespe PE , Truant S , Pruvot FR , Troisi RI , et al. Hepato-biliary scintigraphy to evaluate liver function in associating liver partition andportal vein ligation for staged hepatectomy: liver volume overestimates liverfunction. Surgery . 2017;162:775–783 . 11. Li J , Kantas A , Ittrich H , Koops A , Achilles EG , Fischer L , et al. Avoid “all-Touch”by hybrid ALPPS to achieve oncological efficacy. Ann Surg . 2016;263:e6–e7 . 2. Lai Q , Melandro F , Rossi M . Hybrid partial ALPPS: a feasible approachin case of right trisegmentectomy and macrovascular invasion. Ann Surg .2018;267:e80–e82 . 3. Kambakamba P , Stocker D , Reiner CS , Nguyen-Kim TD , Linecker M , Eshmumi-nov D , et al. Liver kinetic growth rate predicts postoperative liver failure afterALPPS. HPB (Oxford) . 2016;18:800–805 . 4. Shindoh J , Truty MJ , Aloia TA , Curley SA , Zimmitti G , Huang SY , et al. Kineticgrowth rate after portal vein embolization predicts posthepatectomy outcomes:toward zero liver-related mortality in patients with colorectal liver metastasesand small future liver remnant. J Am Coll Surg . 2013;216:201–209 . 2 Hwai-Ding Lam, Stéphanie Louise van der Pas and Andrzej Baranski, et al. / Surgery xxx (xxxx) xxx ARTICLE IN PRESS JID: YMSY [m5G; November 19, 2018;14:57 ] Table 1 Preoperative and interstage volumetric and HBS results with calculated fraction proportionate KGR function over volume fraction against postoperative outcome for all 5 patients. Patient number Preoperative fRLV (%) Interstage fRLV (%) Preoperative fRLF (%/min/m 2 ) Interstage fRLF (%/min/m 2 ) Fraction proportionate KGR function over volume fraction Postoperative outcome Patient 1 22.1 45.0 3.5 4.4 0.2 Alive Patient 2 9.9 31.6 2.7 4.1 0.2 Alive Patient 3 28.7 40.4 3.3 4.1 0.6 Alive Patient 4 24.5 52.0 2.8 2.1 −0.2 Aborted Patient 5 25.5 28.8 (42.1 ∗) 0.9 2.4 (3.9 ∗) 5.1 Deceased Mean 22.1 39.6 2.6 3.4 2.7 ∗ 28 days after PVE.                                     15. Sparrelid E , Jonas E , Tzortzakakis A , Dahlen U , Murquist G , Brismar T , et al. Dy-namic evaluation of liver volume and function in associating liver parti-tion and portal vein ligation for staged hepatectomy. J Gastrointest Surg .2017;21:967–974 . 16. Tani K , Shindoh J , Takamoto T , Shibahara J , Nishioka Y , Hashimoto T , et al. Ki-netic changes in liver parenchyma after preoperative chemotherapy for patientswith colorectal liver metastases. J Gastrointest Surg . 2017;21:813–821 . 17. Matsuo K , Murakami T , Kawaguchi D , Hiroshima Y , Koda K , Yamazaki K ,et al. Histologic features after surgery associating liver partition and portal veinligation for staged hepatectomy versus those after hepatectomy with portal veinembolization. Surgery . 2016;159:1289–1298 . Hwai-Ding Lam, MD ∗Department of Surgery, Leiden University Medical Center, Leiden,the NetherlandsStéphanie Louise van der Pas, PhDMedical Statistics, Department of Biomedical Data Sciences, LeidenUniversity Medical Center, Leiden, the NetherlandsMathematical Institute, Leiden University, Leiden, the NetherlandsAndrzej Baranski, MD, PhDDepartment of Surgery, Leiden University Medical Center, Leiden,the NetherlandsBart van Hoek, MD, PhDDepartment of Gastroenterology and Hepatology, Leiden UniversityMedical Center, Leiden, the NetherlandsMark Christiaan Burgmans, MD, PhDDepartment of Radiology, Leiden University Medical Center, Leiden,the NetherlandsRoelof Johannes Bennink, MD, PhDDepartment of Radiology and Nuclear Medicine, Academic MedicalCenter, Amsterdam, the NetherlandsLioe-Fee de Geus-Oei, MD, PhDDepartment of Radiology, Leiden University Medical Center, Leiden,the NetherlandsBiomedical Photonic Imaging Group, Faculty of Science andTechnology, University of Twente, the Netherlands∗Corresponding author: Leiden University Medical Center,Department of Surgery, Albinusdreef 2, 2333 ZA, Leiden,the Netherlands.E-mail address: h.lam@lumc.nl (H.-D. Lam)Accepted 9 October 2018

The role of proportionate kinetic growth rate fraction in future remnant liver function over volume determined by 99m Tc-Mebrofenin hepatobiliary scintigraphy including SPECT and computed tomography in the risk prediction of postoperative mortality in ALPPS

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The role of proportionate kinetic growth rate fraction in future remnant liver function over volume determined by Tc-99m-Mebrofenin hepatobiliary scintigraphy including SPELT and computed tomography in the risk prediction of postoperative mortality in ALPPS

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