Role of liver augmentation prior to hepatic resection – standards, procedures and indications in Germany, Switzerland, and Austria

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Torsello, Ali Seif Amir Hosseini, Anne-Christine Zygmunt, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3985193/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Jul, 2024 Read the published version in Langenbeck's Archives of Surgery → Version 1 posted 9 You are reading this latest preprint version Abstract Purpose For primary and secondary liver tumors oncological resection remains a chance of cure. Augmentation of functional liver tissue may be necessary to preserve sufficient future liver remnant (FLR). Clinical decision-making on liver augmentation techniques and indications may differ internationally. Thus, this study aims to identify standards of liver augmentation in high-volume centers in Germany, Switzerland, and Austria. Methods Using a web-based survey, 48 hospitals in Germany, Switzerland and Austria were invited to report their surgical indication, standard procedures, and results of liver augmentation. Results Forty (83.3%) of the hospitals invited participated. Most of the hospitals were certified liver centers (55%), performing complex surgeries such as liver transplantation (57.5%) and ALPPS (80%). The standard liver augmentation technique in all countries was portal vein embolization (PVE; 56%), followed by ALPPS (32.1%) in Germany or PVE with hepatic vein embolization (33.3%) in Switzerland and Austria. Standard procedure for liver augmentation did not correlate with certification as liver center, performance of liver transplantation or ALPPS. Surgical indication for PVE varied depending on tumor entity. Most hospitals rated the importance of PVE before resection of cholangiocarcinoma or colorectal metastases as high, while PVE for hepatocellular carcinoma was rated as low. Conclusion The survey gives an overview of the clinical routine in high-volume centers in Germany, Austria, and Switzerland. PVE seems to dominate as standard technique to increase the FLR. However, there is a variety in the main indication for liver augmentation. Further studies are necessary evaluating the differing PVE techniques for liver augmentation. liver augmentation future liver remnant portal vein embolization associating liver partition and portal vein occlusion for staged hepatectomy Figures Figure 1 Figure 2 Figure 3 Introduction Future liver remnant (FLR) limits the indication for oncological liver resection due to the risk of posthepatectomy liver failure. Adequately measuring FLR prior to resection is consequently necessary to avoid postoperative liver failure. However, to evaluate the risk of post-hepatectomy liver failure not only size but also function of the remaining tissue must be considered. Therefore, it might be necessary to assess the growth rate of the FLR or use liver function tests such as LiMON [ 1 , 2 ]. Primary liver tumors may develop in a cirrhotic liver, whereas patients with secondary liver metastases, i.e. colorectal liver metastases (CRLM)[ 3 , 4 ], undergo chemotherapy prior liver resection and suffer from chemotherapy-induced liver injury[ 5 ]. Severely deteriorated liver tissue due to chemotherapy or cirrhosis increases the risk for post-hepatectomy liver failure. While an oncological resection of malignant liver tumors allows a curative therapy option, the ‘too-small-for-size’ liver is therefore one of the leading reasons for high morbidity following major liver resection[ 6 – 9 ]. Several liver augmentation techniques have been discussed for optimal hypertrophy results in case of insufficient FLR. An interventional approach by embolization of the portal vein (PVE) induces hypertrophy of the FLR by approximately 30–50% within four to eight weeks, with a resectability rate of up to 75% and considerably low morbidity[ 10 – 12 ]. If necessary, additional segment IV embolization and/or hepatic vein embolization (HVE) further increases and accelerates growth[ 13 ]. Complications through non-target-embolization are usually qualitatively mild and rare[ 12 ]. A surgical approach through associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS) was demonstrated as a fast and strategically effective technique to increase liver tissue up to 74% in approximately ten days[ 14 ] with a 92% resectability rate but in comparison to PVE with a higher morbidity[ 15 – 17 ]. Furthermore, selective internal radiation therapy (SIRT), though not commonly used, is another technique to induce liver hypertrophy[ 18 , 19 ]. Although liver augmentation techniques sufficiently induce hypertrophy, two staged hepatectomies (TSH) still might be challenging harboring considerable morbidity rates[ 12 ]. Depending on the liver augmentation technique the existing tissue, hypertrophy rate in relation to complications and surgical outcome differ. In this context, in the literature it is not safely clear which technique should be use in the different indications for surgery. Also, a surgeons’ expertise and a hospitals’ setting influence the approach of oncological resections. Therefore, clinical decision-making concerning liver augmentation techniques may differ in high-volume hospitals, but ensuring good clinical practice management strategies are needed. Thus, this study aims to identify clinical routine strategies of liver augmentation in high-volume centers in Germany, Switzerland, and Austria. Material and Methods By sending a web-based survey, 48 high-volume hospitals in Germany, Switzerland and Austria were invited to participate. Chief surgeons or section leaders were contacted by email. Participation and consent to participate was carried out by answering the survey online via google forms ( www.docs.google.com ). The participation and the survey responses were anonymized. The survey contained 24 questions assessing clinical decision-making concerning surgical indication, used standard procedure, technical issues, and results of liver augmentation techniques. Questions were either ordinal or nominal minded. The listed questions are shown in Appendix 1. Results were summarized and analyzed in categories and for the different countries. All data were analyzed using Microsoft Excel (Microsoft Corporation, Redmond, VA, USA). Figures were generated using GraphPad Prism (version 8.0, GraphPad Software Inc., Boston, MA, USA). Results Forty of 48 (83.3%) hospitals invited participated. The attendance quota was 28/31 (90.3%) in Germany (G), 9/14 (64.2%) in Switzerland (S) and 3/3 (100%) in Austria (A). Most of the participating hospitals were certified liver centers (n = 22/40, 55%) and performed complex surgeries such as ALPPS (n = 32/40, 80%) or liver transplantation (n = 23/40, 57.5%). In Germany and Austria, most hospitals performed more than 100 liver resections per year (G n = 22/28, 78.5%; A n = 2/3, 66.7%) whereas in Switzerland all participating hospitals performed less than 100 liver resections. Since Switzerland has only a tenth of the population compared to Germany, these numbers are comparable. In Germany and Austria only university hospitals participated while in Switzerland 44.4% (4/9) were university hospitals (Table 1 ). Table 1 Characteristics of participating centers in Germany, Switzerland, and Austria. Values in parenthesis are percentages (DKG, Deutsche Krebsgesellschaft – German Cancer society; DGAV, Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie – German society for general and visceral surgery; ALPPS, associating liver partition and portal vein ligation for staged hepatectomy). Germany (n = 28) Switzerland (n = 9) Austria (n = 3) University hospital Yes 28 (100) 4 (44.4) 3 (100) No 0 5 (55.6) 0 Certified liver center (DKG, DGAV, etc.) Yes 19 (67.9) 3 (33.3) 0 (0) No 9 (32.1) 6 (66.7) 3 (100) Liver transplant program Yes 17 (60.7) 3 (33.3) 3 (100) No 11 (39.3) 6 (66.7) 0 ALPPS performed Yes 26 (92.9) 4 (44.4) 2 (66.7) No 2 (7.1) 5 (55.6) 1 (33.3) Liver resections per year ≤100 6 (21.4) 9 (100) 1 (33.3) 101–150 10 (35.7) 0 1 (33.3) 151–200 6 (21.4) 0 1 (33.3) ≥201 6 (21.4) 0 0 Portal vein embolizations per year ≤10 14 (50) 8 (88.9) 1 (33.3) 11–20 7 (25) 1 (11.1) 1 (33.3) 21–30 7 (25) 0 1 (33.3) The most common augmentation technique was PVE (G n = 12/28, 42.9%; S n = 4/9, 44.4%; A n = 2/3, 66.7%) in all countries, followed by ALPPS in Germany (n = 9/28, 32.1%) and PVE/HVE in Switzerland and Austria (S n = 3/9, 33.3%; A n = 1/3, 33.3%) (Fig. 1 ). We asked for possible reasons influencing the different choices for augmentation techniques since the chosen liver augmentation technique may be influenced by the number of performed liver resections. Nonetheless, the respective chosen standard procedure for liver augmentation did not correlate with the number of liver resections performed per year in any country. A hospitals’ setting may also influence the chosen augmentation technique. Thus, we analyzed whether the chosen augmentation technique differed between certified or non-certified hospitals. Certified liver centers predominantly chose PVE (n = 8/22, 36.4%), then ALPPS (n = 7/22, 31.8%) and PVE/HVE (n = 6/22, 27.3%), and portal vein ligation (PVL, n = 1/22, 4.5%) respectively. Non-certified hospitals also preferred PVE (n = 10/18, 55.6%), then PVE/HVE (n = 4/18, 22.2%) and ALPPS (n = 3/18, 16.7%) for liver augmentation, showing that certification had no influence. The vast majority of hospitals perform ALPPS (n = 32/40, 80%), but ALPPS is not the standard technique to induce hypertrophy. Within the clinics preforming ALPPS, PVE dominated as a standard (n = 13/32, 40.6%), followed by ALPPS (n = 10/32, 31.3%), then by PVE/HVE (n = 7/32, 21.9%). Moreover, we also asked whether the underlying disease influences the indication for PVE (Fig. 2 ). A majority of 22 centers (55%) considered colorectal liver metastases (CRLM) and cholangiocarcinoma (CCC) to be a very good indication for PVE. In contrast, the majority of 21 centers (52.5%) considered hepatocellular carcinoma (HCC) to be a very poor indication for PVE. Nonetheless, still most participants through all countries saw an indication for hypertrophy in HCC with CHILD A cirrhosis (G n = 20/28, 71.4%; S n = 5/9, 55.6%; A n = 2/3, 66.7%). This study shows that the majority of participants experience SIRT neither as an adequate (G n = 18/28, 64.3%; S n = 5/9, 55.5%; A n = 2/3, 66.7%) nor a common technique (G n = 22/28, 78.6%; S n = 7/9, 77.8%; A n = 3/3, 100%) to induce hypertrophy. The majority of the hospitals used particles with coils/plugs to embolize the right branch of the portal vein (G n = 16/28, 57.1%; S n = 5/9, 55.6%; A n = 2/3, 66.7%). Complications due to non-target-embolization after PVE are rarely seen (all countries, n = 35/40, 87.5%), confirming PVE as safe. If FLR was considered insufficient after PVE, additional HVE might be performed[ 12 , 13 ]. However, in Germany and Switzerland 32.1% (n = 9/28) and 44.4% (n = 4/9), respectively, never combined PVE and HVE. However, if PVE/HVE was done, it was mostly performed simultaneously (G n = 11/28, 39.3%; S n = 5/9, 55.6%; A n = 2/3, 66.7%). Most respondents through all countries at least considered additionally embolizing segment IV (G n = 19/28, 67.9%; S n = 8/9, 88.9%; A n = 2/3, 66.7%). Commonly the centers waited for 3–6 weeks for resection after PVE (n = 28/40, 70%) and during this period 85% of the hospitals (n = 34/40) treated patients with bridging chemotherapy (Fig. 3 ). In Germany, 23 of 28 hospitals (82.1%) had a resection rate above 75% for embolized patients, while in Switzerland and Austria, all hospitals (n = 12/12; 100%) reported a resection rate above 75% of the embolized patients (Fig. 3 ). Progression of the hepatic tumor load was the main reason for no hepatic resection (G n = 16/28, 57.1%; S n = 3/9, 33.3%; A n = 1/3, 33%) followed by an insufficient hypertrophy of FLR (G n = 8/28, 28.6%; S n = 4/9, 44.4%; A n = 2/3, 66.7%). Assessment of liver function was not done on a regular basis. However, 42,9% (n = 12/28) in Germany, 33,3% (n = 3/9) in Switzerland and even 66,7% (n = 2/3) in Austria performed a liver function test if necessary. Discussion The survey emphasizes the daily clinical routine of liver augmentation techniques in high-volume centers in Germany, Switzerland, and Austria. The present study shows that PVE dominates as a technique to increase FLR. However, there is a wide variety in main indications for liver augmentation, particularly for PVE. With 40 contributing hospitals as centers for hepatobiliary surgery, the results of this overview are representative. FLR has been shown as a major predictor among blood transfusion, hepatic parenchyma quality and BMI of posthepatectomy liver failure[ 1 , 13 , 20 ]. To avoid post-hepatectomy liver failure because of an insufficient FLR, which is considered the main cause of mortality after major liver resection[ 21 ], at minimum a ratio of FLR to body weight of 0.5 is needed[ 8 , 9 ]. FLR values of > 20% of total liver volume with normal liver function[ 20 , 22 ] and FLR > 30% in steatosis/hepatitis or > 40% in cirrhosis were defined as sufficient, respectively[ 8 , 23 , 24 ]. However, not only size, but also degree of hypertrophy with a cut off value of < 5% correlated with posthepatectomy liver failure[ 22 , 25 ], implying that not only the absolute amount of liver tissue but also the function and its’ ability to regenerate were crucial. recent study showed that perioperative testing of liver function significantly reduced the complication rate[ 26 ]. However, preoperative assessment of liver function is not tested regularly. The present results also support this claim of rare testing, meanwhile showing that a low but considerable number of patients were not resected due to insufficient FLR after PVE. This births the question why testing was not frequently done beforehand, especially when functional liver measurement preoperatively may impact the decision making on augmentation. Additionally, our results confirm earlier studies highlighting the need for a standardized algorithm for liver augmentation techniques[ 27 , 28 ]. Induction of hypertrophy has a significant impact on the long-term survival for patients with malignant liver tumors. In this respect, the prognosis of CRLM improved after introduction of liver augmentation techniques due to higher resection rates[ 15 , 29 , 30 ]. Especially for large liver metastases, which by itself negatively impacts survival, surgery has better long-term results than other treatment options, such as chemotherapy alone or radiofrequency ablation[ 31 ]. Given that, one might expect that liver augmentation is needed. In clinical practice, the indication for PVE was ranked high for the surgical treatment of CRLM and was mostly chosen as a liver augmentation technique in hospitals in this study. Also, when PVE was performed, a high number of patients were resected thereafter, thus confirming earlier results of high resection rates[ 30 ]. On the one hand, PVE is a relatively simple intervention and has a comparatively low complication rate. Furthermore, it has only few contraindications, such as tumor invasion of the ipsilateral portal vein[ 32 ], making it a standard procedure to induce hypertrophy [ 13 ]. Additionally, to current recommendations for metastatic liver tumors, our study shows that PVE was also used for primary liver tumors, such as CCC or even HCC in CHILD A cirrhosis, making it a treatment option for a broad spectrum of diseases. On the other hand, kinetic growth rate is relatively low and may take inadequately long periods of time considering the underlying oncological disease that is for this period left untreated. Consequently, augmentation of PVE by embolization the hepatic vein and segment IV have been suggested to allow a faster increase for two-staged hepatectomy[ 12 , 13 ]. To analyze whether PVE/HVE accelerates further growth, the recruiting DRAGON 2 trial compares PVE to PVE/HVE in a randomized controlled trial[ 33 ]. In this study, additional HVE and segment IV embolization was also carried out or at least considered in most cases. During the time of growth, most hospitals considered treating patients with chemotherapy addressing the oncological needs. The increase of the FLR depends on the embolisate used and a possible reflow in the embolized portal branch may decrease the hypertrophy effect[ 10 , 34 ]. In this study, favored materials were particles with coils and plugs, while acrylic glue or mono-particles were significantly less frequently chosen. In recent studies ALPPS was predominantly reserved for treating CRLM and has been shown to have a better long term survival in patients with CRLM compared to TSH after PVE[ 15 , 16 ]. However, in the present analysis ALPPS was the preferred liver augmentation technique in only 31.3% (n = 10/32), although most of the hospitals performed a high number of major liver resections annually, including liver transplantation. Another reason ALPPS may be less prevalent in clinical use might be the historically high morbidity and mortality rate after ALPPS as mentioned above. This however was due to a number of perioperative issues of the then newly introduced technique, unsuitable patient-selection, low surgical expertise, and postoperative care[ 27 ]. The ALPPS-registry was initiated to enable standardization by collecting data and identifying adequate indications for this procedure[ 27 ]. Although 80% of questioned hospitals performed ALPPS, our study shows that it was only the second choice for liver augmentation in Germany, third choice in Switzerland and no standard at all in Austria. Clinical standard for liver augmentation did not correlate with whether a hospital performed a high number of liver resections, was a certified liver center, or performed liver transplantation and ALPPS. In this study, the hospitals using ALPPS as a standard augmentation technique usually tested liver function prior to resection and mainly named insufficient FLR after PVE as reason to not resect – indicating that patient selection and anticipation of failure due to PVE might have led to the decision of operating firsthand. Earlier studies demonstrated that SIRT can induce hypertrophy. Although SIRT showed lower growth rates and significantly longer growth periods compared to PVE[ 21 , 35 ], it is an option when simultaneous treatment of the hepatic tumor burden is needed[ 19 , 34 ]. A major disadvantage of PVE is an increased arterial flow of the tumor bearing lobe after portal obstruction which might support tumor growth during time of hypertrophy[ 36 ]. A radioembolization might bypass this by simultaneously damaging the tumor beforehand[ 37 ]. A recent study by Addeo et al. has shown in five patients that sequential PVE and yttrium-90 ( 90 Y) liver radioembolization (TARE) can induce liver hypertrophy while downstaging liver tumors[ 33 , 38 ]. Nonetheless, most of the hospitals did not experience SIRT as an adequate or common technique to induce hypertrophy. With proven success to induce hypertrophy, the European SIR-Spheres Surgical Registry (ESSURE) was introduced to improve comprehensibility of cases and optimize the process by recruiting patients[ 39 ]. Despite being a novel technique with lower growth rates, SIRT may still play a small role in liver augmentation[ 36 , 37 ]. Our study has limitations. Methodically, the sent survey allowed mostly university hospitals to participate, possibly not representing the heterogeneity of hospitals treating primary and secondary liver tumors. However, with a considerable high number of participating hospitals of three different countries these results are representable. Also, a survey, phrasing general questions cannot predict a matter of consequence and answers given were surgeons opinions, which cannot exclude reporting bias. On the other hand, a survey is suitable to enable a general overview of the clinical routine. This study asked for the decision-making according to common choice, which naturally excludes generalization to all decision making and alter the results. Conclusion In conclusion, PVE dominates as the standard liver augmentation technique in Germany, Austria and Switzerland. Since postoperative complications after major hepatectomies and two-staged hepatectomies are associated with decreased long-term survival, this study underlines the need for further studies implementing indication algorithms for liver augmentation. Abbreviations A Austria ALPPS Associating liver partition and portal vein occlusion for staged hepatectomy CCC Cholangiocarcinoma CRLM Colorectal liver metastases DGAV Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie, German Society for General and Visceral Surgery DKG Deutsche Krebsgesellschaft, German Cancer Society ESSURE European SIR-Spheres Surgical Registry FLR Future liver remnant G Germany HCC Hepatocellular carcinoma HVE Hepatic vein embolization PVE/HVE Portal and hepatic vein embolization PVE Portal vein embolization PVL Portal vein ligation S Switzerland SIRT Selective internal radiation therapy TARE Transarterial radioembolization TSH Two staged hepatectomy Declarations The authors did not receive support from any organization for the submitted work. No funding was received to assist with the preparation of this manuscript. No funding was received for conducting this study. No funds, grants, or other support was received. The authors have no relevant financial or non-financial interests to disclose. The authors have no conflicts of interest to declare that are relevant to the content of this article. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. The authors have no financial or proprietary interests in any material discussed in this article. Authors’ Contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Elif Yilmaz, Giovanni F. Torsello, Ali Seif Amir Hosseini, Florian Bösch, Rupert Oberhuber, Otto Kollmar, and Björn Wellge. The first draft of the manuscript was written by Elif Yilmaz and Florian Bösch and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. 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HPB 18:684–690. https://doi.org/10.1016/j.hpb.2016.05.012 Addeo P, De Mathelin P, De Marini P, et al (2023) Sequential Y90 liver radioembolization and portal vein embolization: an additional strategy to downstage liver tumors and to enhance liver hypertrophy before major hepatectomies. Langenbecks Arch Surg 408:339. https://doi.org/10.1007/s00423-023-03083-0 Wahba R, Bunck AC, Schmidt M, et al (2022) Neoadjuvant Hemi-Liver Directed Selective Internal Radiation Therapy (SIRT) Followed by Portal Vein and Liver Vein Embolization Could Make Non-Operable Patients with Liver Cancer Eligible for Curative Intended Major Liver Resection. HPB 24:S230. https://doi.org/10.1016/j.hpb.2022.05.477 Additional Declarations No competing interests reported. Supplementary Files LAoSSupplementary.docx Cite Share Download PDF Status: Published Journal Publication published 27 Jul, 2024 Read the published version in Langenbeck's Archives of Surgery → Version 1 posted Editorial decision: Revision requested 12 May, 2024 Reviews received at journal 16 Apr, 2024 Reviewers agreed at journal 10 Apr, 2024 Reviews received at journal 17 Mar, 2024 Reviewers agreed at journal 04 Mar, 2024 Reviewers invited by journal 03 Mar, 2024 Editor assigned by journal 02 Mar, 2024 Submission checks completed at journal 27 Feb, 2024 First submitted to journal 24 Feb, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Torsello","email":"","orcid":"","institution":"University Medical Center Göttingen","correspondingAuthor":false,"prefix":"","firstName":"Giovanni","middleName":"F.","lastName":"Torsello","suffix":""},{"id":275141312,"identity":"d6cac258-f665-45f3-a1cc-1e1b8746008f","order_by":2,"name":"Ali Seif Amir Hosseini","email":"","orcid":"","institution":"University Medical Center Göttingen","correspondingAuthor":false,"prefix":"","firstName":"Ali","middleName":"Seif Amir","lastName":"Hosseini","suffix":""},{"id":275141313,"identity":"45cebec2-df6a-41e3-8cef-6d965c619e08","order_by":3,"name":"Anne-Christine Zygmunt","email":"","orcid":"","institution":"University Medical Center Göttingen","correspondingAuthor":false,"prefix":"","firstName":"Anne-Christine","middleName":"","lastName":"Zygmunt","suffix":""},{"id":275141314,"identity":"5f442bc9-fc43-4deb-ac80-d9ef867d3ff2","order_by":4,"name":"Thomas Lorf","email":"","orcid":"","institution":"University Medical Center 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Göttingen","correspondingAuthor":true,"prefix":"","firstName":"Florian","middleName":"","lastName":"Bösch","suffix":""}],"badges":[],"createdAt":"2024-02-24 14:16:52","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3985193/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3985193/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00423-024-03418-5","type":"published","date":"2024-07-27T16:15:59+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":51826142,"identity":"e29c5135-36cd-41b8-b5fd-d0eaab3eb459","added_by":"auto","created_at":"2024-02-29 17:04:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":575527,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"LAoSFig1Countries.png","url":"https://assets-eu.researchsquare.com/files/rs-3985193/v1/7207cc0730c51df60c0fd506.png"},{"id":51826146,"identity":"b478b084-f210-4b59-90c9-4a3fcf466e1d","added_by":"auto","created_at":"2024-02-29 17:04:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":355678,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"LAoSFig2Diseases.png","url":"https://assets-eu.researchsquare.com/files/rs-3985193/v1/c1c2df3c81b1f82caae1eda7.png"},{"id":51826144,"identity":"3cdf97c6-8296-416b-84f3-c306bf559f1f","added_by":"auto","created_at":"2024-02-29 17:04:12","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":616963,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"LAoSFig3Timeframe.png","url":"https://assets-eu.researchsquare.com/files/rs-3985193/v1/824158621b666a44a60ff704.png"},{"id":61596350,"identity":"625af5ba-2c33-45a3-929b-6b652a4d7c5c","added_by":"auto","created_at":"2024-08-01 17:26:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1865233,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3985193/v1/e6cee39a-8581-452b-834a-a4f43e381827.pdf"},{"id":51827371,"identity":"5a37c527-c889-4df0-bc6c-d0761f10a675","added_by":"auto","created_at":"2024-02-29 17:12:12","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":32345,"visible":true,"origin":"","legend":"","description":"","filename":"LAoSSupplementary.docx","url":"https://assets-eu.researchsquare.com/files/rs-3985193/v1/7bfd1e4426282954c28cc00e.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Role of liver augmentation prior to hepatic resection – standards, procedures and indications in Germany, Switzerland, and Austria","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFuture liver remnant (FLR) limits the indication for oncological liver resection due to the risk of posthepatectomy liver failure. Adequately measuring FLR prior to resection is consequently necessary to avoid postoperative liver failure. However, to evaluate the risk of post-hepatectomy liver failure not only size but also function of the remaining tissue must be considered. Therefore, it might be necessary to assess the growth rate of the FLR or use liver function tests such as LiMON [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Primary liver tumors may develop in a cirrhotic liver, whereas patients with secondary liver metastases, i.e. colorectal liver metastases (CRLM)[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], undergo chemotherapy prior liver resection and suffer from chemotherapy-induced liver injury[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Severely deteriorated liver tissue due to chemotherapy or cirrhosis increases the risk for post-hepatectomy liver failure. While an oncological resection of malignant liver tumors allows a curative therapy option, the \u0026lsquo;too-small-for-size\u0026rsquo; liver is therefore one of the leading reasons for high morbidity following major liver resection[\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeveral liver augmentation techniques have been discussed for optimal hypertrophy results in case of insufficient FLR. An interventional approach by embolization of the portal vein (PVE) induces hypertrophy of the FLR by approximately 30\u0026ndash;50% within four to eight weeks, with a resectability rate of up to 75% and considerably low morbidity[\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. If necessary, additional segment IV embolization and/or hepatic vein embolization (HVE) further increases and accelerates growth[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Complications through non-target-embolization are usually qualitatively mild and rare[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. A surgical approach through associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS) was demonstrated as a fast and strategically effective technique to increase liver tissue up to 74% in approximately ten days[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] with a 92% resectability rate but in comparison to PVE with a higher morbidity[\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Furthermore, selective internal radiation therapy (SIRT), though not commonly used, is another technique to induce liver hypertrophy[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough liver augmentation techniques sufficiently induce hypertrophy, two staged hepatectomies (TSH) still might be challenging harboring considerable morbidity rates[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Depending on the liver augmentation technique the existing tissue, hypertrophy rate in relation to complications and surgical outcome differ. In this context, in the literature it is not safely clear which technique should be use in the different indications for surgery. Also, a surgeons\u0026rsquo; expertise and a hospitals\u0026rsquo; setting influence the approach of oncological resections. Therefore, clinical decision-making concerning liver augmentation techniques may differ in high-volume hospitals, but ensuring good clinical practice management strategies are needed. Thus, this study aims to identify clinical routine strategies of liver augmentation in high-volume centers in Germany, Switzerland, and Austria.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cp\u003eBy sending a web-based survey, 48 high-volume hospitals in Germany, Switzerland and Austria were invited to participate. Chief surgeons or section leaders were contacted by email. Participation and consent to participate was carried out by answering the survey online via google forms (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ewww.docs.google.com\u003c/span\u003e\u003c/span\u003e). The participation and the survey responses were anonymized.\u003c/p\u003e\n\u003cp\u003eThe survey contained 24 questions assessing clinical decision-making concerning surgical indication, used standard procedure, technical issues, and results of liver augmentation techniques. Questions were either ordinal or nominal minded. The listed questions are shown in Appendix 1. Results were summarized and analyzed in categories and for the different countries. All data were analyzed using Microsoft Excel (Microsoft Corporation, Redmond, VA, USA). Figures were generated using GraphPad Prism (version 8.0, GraphPad Software Inc., Boston, MA, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eForty of 48 (83.3%) hospitals invited participated. The attendance quota was 28/31 (90.3%) in Germany (G), 9/14 (64.2%) in Switzerland (S) and 3/3 (100%) in Austria (A). Most of the participating hospitals were certified liver centers (n\u0026thinsp;=\u0026thinsp;22/40, 55%) and performed complex surgeries such as ALPPS (n\u0026thinsp;=\u0026thinsp;32/40, 80%) or liver transplantation (n\u0026thinsp;=\u0026thinsp;23/40, 57.5%). In Germany and Austria, most hospitals performed more than 100 liver resections per year (G n\u0026thinsp;=\u0026thinsp;22/28, 78.5%; A n\u0026thinsp;=\u0026thinsp;2/3, 66.7%) whereas in Switzerland all participating hospitals performed less than 100 liver resections. Since Switzerland has only a tenth of the population compared to Germany, these numbers are comparable. In Germany and Austria only university hospitals participated while in Switzerland 44.4% (4/9) were university hospitals (Table\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eCharacteristics of participating centers in Germany, Switzerland, and Austria. Values in parenthesis are percentages (DKG, Deutsche Krebsgesellschaft \u0026ndash; German Cancer society; DGAV, Deutsche Gesellschaft f\u0026uuml;r Allgemein- und Viszeralchirurgie \u0026ndash; German society for general and visceral surgery; ALPPS, associating liver partition and portal vein ligation for staged hepatectomy).\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGermany (n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSwitzerland (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAustria (n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eUniversity hospital\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (55.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eCertified liver center (DKG, DGAV, etc.)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 (67.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (32.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eLiver transplant program\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (60.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (39.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eALPPS performed\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26 (92.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (55.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eLiver resections per year\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e101\u0026ndash;150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e151\u0026ndash;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;201\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003ePortal vein embolizations per year\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (88.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u0026ndash;20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21\u0026ndash;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv\u003e\n\u003c/div\u003e\n\u003cp\u003eThe most common augmentation technique was PVE (G n\u0026thinsp;=\u0026thinsp;12/28, 42.9%; S n\u0026thinsp;=\u0026thinsp;4/9, 44.4%; A n\u0026thinsp;=\u0026thinsp;2/3, 66.7%) in all countries, followed by ALPPS in Germany (n\u0026thinsp;=\u0026thinsp;9/28, 32.1%) and PVE/HVE in Switzerland and Austria (S n\u0026thinsp;=\u0026thinsp;3/9, 33.3%; A n\u0026thinsp;=\u0026thinsp;1/3, 33.3%) (Fig.\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e). We asked for possible reasons influencing the different choices for augmentation techniques since the chosen liver augmentation technique may be influenced by the number of performed liver resections. Nonetheless, the respective chosen standard procedure for liver augmentation did not correlate with the number of liver resections performed per year in any country.\u003c/p\u003e\n\u003cp\u003eA hospitals\u0026rsquo; setting may also influence the chosen augmentation technique. Thus, we analyzed whether the chosen augmentation technique differed between certified or non-certified hospitals. Certified liver centers predominantly chose PVE (n\u0026thinsp;=\u0026thinsp;8/22, 36.4%), then ALPPS (n\u0026thinsp;=\u0026thinsp;7/22, 31.8%) and PVE/HVE (n\u0026thinsp;=\u0026thinsp;6/22, 27.3%), and portal vein ligation (PVL, n\u0026thinsp;=\u0026thinsp;1/22, 4.5%) respectively. Non-certified hospitals also preferred PVE (n\u0026thinsp;=\u0026thinsp;10/18, 55.6%), then PVE/HVE (n\u0026thinsp;=\u0026thinsp;4/18, 22.2%) and ALPPS (n\u0026thinsp;=\u0026thinsp;3/18, 16.7%) for liver augmentation, showing that certification had no influence. The vast majority of hospitals perform ALPPS (n\u0026thinsp;=\u0026thinsp;32/40, 80%), but ALPPS is not the standard technique to induce hypertrophy. Within the clinics preforming ALPPS, PVE dominated as a standard (n\u0026thinsp;=\u0026thinsp;13/32, 40.6%), followed by ALPPS (n\u0026thinsp;=\u0026thinsp;10/32, 31.3%), then by PVE/HVE (n\u0026thinsp;=\u0026thinsp;7/32, 21.9%).\u003c/p\u003e\n\u003cp\u003eMoreover, we also asked whether the underlying disease influences the indication for PVE (Fig.\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e). A majority of 22 centers (55%) considered colorectal liver metastases (CRLM) and cholangiocarcinoma (CCC) to be a very good indication for PVE. In contrast, the majority of 21 centers (52.5%) considered hepatocellular carcinoma (HCC) to be a very poor indication for PVE. Nonetheless, still most participants through all countries saw an indication for hypertrophy in HCC with CHILD A cirrhosis (G n\u0026thinsp;=\u0026thinsp;20/28, 71.4%; S n\u0026thinsp;=\u0026thinsp;5/9, 55.6%; A n\u0026thinsp;=\u0026thinsp;2/3, 66.7%). This study shows that the majority of participants experience SIRT neither as an adequate (G n\u0026thinsp;=\u0026thinsp;18/28, 64.3%; S n\u0026thinsp;=\u0026thinsp;5/9, 55.5%; A n\u0026thinsp;=\u0026thinsp;2/3, 66.7%) nor a common technique (G n\u0026thinsp;=\u0026thinsp;22/28, 78.6%; S n\u0026thinsp;=\u0026thinsp;7/9, 77.8%; A n\u0026thinsp;=\u0026thinsp;3/3, 100%) to induce hypertrophy.\u003c/p\u003e\n\u003cp\u003eThe majority of the hospitals used particles with coils/plugs to embolize the right branch of the portal vein (G n\u0026thinsp;=\u0026thinsp;16/28, 57.1%; S n\u0026thinsp;=\u0026thinsp;5/9, 55.6%; A n\u0026thinsp;=\u0026thinsp;2/3, 66.7%). Complications due to non-target-embolization after PVE are rarely seen (all countries, n\u0026thinsp;=\u0026thinsp;35/40, 87.5%), confirming PVE as safe. If FLR was considered insufficient after PVE, additional HVE might be performed[\u003cspan\u003e12\u003c/span\u003e, \u003cspan\u003e13\u003c/span\u003e]. However, in Germany and Switzerland 32.1% (n\u0026thinsp;=\u0026thinsp;9/28) and 44.4% (n\u0026thinsp;=\u0026thinsp;4/9), respectively, never combined PVE and HVE. However, if PVE/HVE was done, it was mostly performed simultaneously (G n\u0026thinsp;=\u0026thinsp;11/28, 39.3%; S n\u0026thinsp;=\u0026thinsp;5/9, 55.6%; A n\u0026thinsp;=\u0026thinsp;2/3, 66.7%). Most respondents through all countries at least considered additionally embolizing segment IV (G n\u0026thinsp;=\u0026thinsp;19/28, 67.9%; S n\u0026thinsp;=\u0026thinsp;8/9, 88.9%; A n\u0026thinsp;=\u0026thinsp;2/3, 66.7%). Commonly the centers waited for 3\u0026ndash;6 weeks for resection after PVE (n\u0026thinsp;=\u0026thinsp;28/40, 70%) and during this period 85% of the hospitals (n\u0026thinsp;=\u0026thinsp;34/40) treated patients with bridging chemotherapy (Fig.\u0026nbsp;\u003cspan\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eIn Germany, 23 of 28 hospitals (82.1%) had a resection rate above 75% for embolized patients, while in Switzerland and Austria, all hospitals (n\u0026thinsp;=\u0026thinsp;12/12; 100%) reported a resection rate above 75% of the embolized patients (Fig.\u0026nbsp;\u003cspan\u003e3\u003c/span\u003e). Progression of the hepatic tumor load was the main reason for no hepatic resection (G n\u0026thinsp;=\u0026thinsp;16/28, 57.1%; S n\u0026thinsp;=\u0026thinsp;3/9, 33.3%; A n\u0026thinsp;=\u0026thinsp;1/3, 33%) followed by an insufficient hypertrophy of FLR (G n\u0026thinsp;=\u0026thinsp;8/28, 28.6%; S n\u0026thinsp;=\u0026thinsp;4/9, 44.4%; A n\u0026thinsp;=\u0026thinsp;2/3, 66.7%). Assessment of liver function was not done on a regular basis. However, 42,9% (n\u0026thinsp;=\u0026thinsp;12/28) in Germany, 33,3% (n\u0026thinsp;=\u0026thinsp;3/9) in Switzerland and even 66,7% (n\u0026thinsp;=\u0026thinsp;2/3) in Austria performed a liver function test if necessary.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe survey emphasizes the daily clinical routine of liver augmentation techniques in high-volume centers in Germany, Switzerland, and Austria. The present study shows that PVE dominates as a technique to increase FLR. However, there is a wide variety in main indications for liver augmentation, particularly for PVE. With 40 contributing hospitals as centers for hepatobiliary surgery, the results of this overview are representative.\u003c/p\u003e \u003cp\u003eFLR has been shown as a major predictor among blood transfusion, hepatic parenchyma quality and BMI of posthepatectomy liver failure[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. To avoid post-hepatectomy liver failure because of an insufficient FLR, which is considered the main cause of mortality after major liver resection[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], at minimum a ratio of FLR to body weight of 0.5 is needed[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. FLR values of \u0026gt;\u0026thinsp;20% of total liver volume with normal liver function[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] and FLR\u0026thinsp;\u0026gt;\u0026thinsp;30% in steatosis/hepatitis or \u0026gt;\u0026thinsp;40% in cirrhosis were defined as sufficient, respectively[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. However, not only size, but also degree of hypertrophy with a cut off value of \u0026lt;\u0026thinsp;5% correlated with posthepatectomy liver failure[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], implying that not only the absolute amount of liver tissue but also the function and its\u0026rsquo; ability to regenerate were crucial. recent study showed that perioperative testing of liver function significantly reduced the complication rate[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. However, preoperative assessment of liver function is not tested regularly. The present results also support this claim of rare testing, meanwhile showing that a low but considerable number of patients were not resected due to insufficient FLR after PVE. This births the question why testing was not frequently done beforehand, especially when functional liver measurement preoperatively may impact the decision making on augmentation. Additionally, our results confirm earlier studies highlighting the need for a standardized algorithm for liver augmentation techniques[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eInduction of hypertrophy has a significant impact on the long-term survival for patients with malignant liver tumors. In this respect, the prognosis of CRLM improved after introduction of liver augmentation techniques due to higher resection rates[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Especially for large liver metastases, which by itself negatively impacts survival, surgery has better long-term results than other treatment options, such as chemotherapy alone or radiofrequency ablation[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Given that, one might expect that liver augmentation is needed. In clinical practice, the indication for PVE was ranked high for the surgical treatment of CRLM and was mostly chosen as a liver augmentation technique in hospitals in this study. Also, when PVE was performed, a high number of patients were resected thereafter, thus confirming earlier results of high resection rates[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOn the one hand, PVE is a relatively simple intervention and has a comparatively low complication rate. Furthermore, it has only few contraindications, such as tumor invasion of the ipsilateral portal vein[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], making it a standard procedure to induce hypertrophy [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Additionally, to current recommendations for metastatic liver tumors, our study shows that PVE was also used for primary liver tumors, such as CCC or even HCC in CHILD A cirrhosis, making it a treatment option for a broad spectrum of diseases.\u003c/p\u003e \u003cp\u003eOn the other hand, kinetic growth rate is relatively low and may take inadequately long periods of time considering the underlying oncological disease that is for this period left untreated. Consequently, augmentation of PVE by embolization the hepatic vein and segment IV have been suggested to allow a faster increase for two-staged hepatectomy[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. To analyze whether PVE/HVE accelerates further growth, the recruiting DRAGON 2 trial compares PVE to PVE/HVE in a randomized controlled trial[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. In this study, additional HVE and segment IV embolization was also carried out or at least considered in most cases. During the time of growth, most hospitals considered treating patients with chemotherapy addressing the oncological needs.\u003c/p\u003e \u003cp\u003eThe increase of the FLR depends on the embolisate used and a possible reflow in the embolized portal branch may decrease the hypertrophy effect[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. In this study, favored materials were particles with coils and plugs, while acrylic glue or mono-particles were significantly less frequently chosen.\u003c/p\u003e \u003cp\u003eIn recent studies ALPPS was predominantly reserved for treating CRLM and has been shown to have a better long term survival in patients with CRLM compared to TSH after PVE[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, in the present analysis ALPPS was the preferred liver augmentation technique in only 31.3% (n\u0026thinsp;=\u0026thinsp;10/32), although most of the hospitals performed a high number of major liver resections annually, including liver transplantation. Another reason ALPPS may be less prevalent in clinical use might be the historically high morbidity and mortality rate after ALPPS as mentioned above. This however was due to a number of perioperative issues of the then newly introduced technique, unsuitable patient-selection, low surgical expertise, and postoperative care[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The ALPPS-registry was initiated to enable standardization by collecting data and identifying adequate indications for this procedure[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Although 80% of questioned hospitals performed ALPPS, our study shows that it was only the second choice for liver augmentation in Germany, third choice in Switzerland and no standard at all in Austria. Clinical standard for liver augmentation did not correlate with whether a hospital performed a high number of liver resections, was a certified liver center, or performed liver transplantation and ALPPS. In this study, the hospitals using ALPPS as a standard augmentation technique usually tested liver function prior to resection and mainly named insufficient FLR after PVE as reason to not resect \u0026ndash; indicating that patient selection and anticipation of failure due to PVE might have led to the decision of operating firsthand.\u003c/p\u003e \u003cp\u003eEarlier studies demonstrated that SIRT can induce hypertrophy. Although SIRT showed lower growth rates and significantly longer growth periods compared to PVE[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], it is an option when simultaneous treatment of the hepatic tumor burden is needed[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. A major disadvantage of PVE is an increased arterial flow of the tumor bearing lobe after portal obstruction which might support tumor growth during time of hypertrophy[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. A radioembolization might bypass this by simultaneously damaging the tumor beforehand[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. A recent study by Addeo et al. has shown in five patients that sequential PVE and yttrium-90 (\u003csup\u003e90\u003c/sup\u003eY) liver radioembolization (TARE) can induce liver hypertrophy while downstaging liver tumors[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Nonetheless, most of the hospitals did not experience SIRT as an adequate or common technique to induce hypertrophy. With proven success to induce hypertrophy, the European SIR-Spheres Surgical Registry (ESSURE) was introduced to improve comprehensibility of cases and optimize the process by recruiting patients[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Despite being a novel technique with lower growth rates, SIRT may still play a small role in liver augmentation[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study has limitations. Methodically, the sent survey allowed mostly university hospitals to participate, possibly not representing the heterogeneity of hospitals treating primary and secondary liver tumors. However, with a considerable high number of participating hospitals of three different countries these results are representable. Also, a survey, phrasing general questions cannot predict a matter of consequence and answers given were surgeons opinions, which cannot exclude reporting bias. On the other hand, a survey is suitable to enable a general overview of the clinical routine. This study asked for the decision-making according to common choice, which naturally excludes generalization to all decision making and alter the results.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, PVE dominates as the standard liver augmentation technique in Germany, Austria and Switzerland. Since postoperative complications after major hepatectomies and two-staged hepatectomies are associated with decreased long-term survival, this study underlines the need for further studies implementing indication algorithms for liver augmentation.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eA\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Austria\u003c/p\u003e\n\u003cp\u003eALPPS\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Associating liver partition and portal vein occlusion for staged hepatectomy\u003c/p\u003e\n\u003cp\u003eCCC\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Cholangiocarcinoma\u003c/p\u003e\n\u003cp\u003eCRLM\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Colorectal liver metastases\u003c/p\u003e\n\u003cp\u003eDGAV\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Deutsche Gesellschaft f\u0026uuml;r Allgemein- und Viszeralchirurgie,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGerman Society for General and Visceral Surgery\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDKG \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Deutsche Krebsgesellschaft, German Cancer Society\u003c/p\u003e\n\u003cp\u003eESSURE\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;European SIR-Spheres Surgical Registry\u003c/p\u003e\n\u003cp\u003eFLR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Future liver remnant\u003c/p\u003e\n\u003cp\u003eG\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Germany\u003c/p\u003e\n\u003cp\u003eHCC\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Hepatocellular carcinoma\u003c/p\u003e\n\u003cp\u003eHVE\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Hepatic vein embolization\u003c/p\u003e\n\u003cp\u003ePVE/HVE\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Portal and hepatic vein embolization\u003c/p\u003e\n\u003cp\u003ePVE\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Portal vein embolization\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePVL\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Portal vein ligation\u003c/p\u003e\n\u003cp\u003eS\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Switzerland\u003c/p\u003e\n\u003cp\u003eSIRT\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Selective internal radiation therapy\u003c/p\u003e\n\u003cp\u003eTARE\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Transarterial radioembolization\u003c/p\u003e\n\u003cp\u003eTSH\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Two staged hepatectomy\u0026nbsp;\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003eThe authors did not receive support from any organization for the submitted work.\u003c/p\u003e\n\u003cp\u003eNo funding was received to assist with the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003eNo funding was received for conducting this study.\u003c/p\u003e\n\u003cp\u003eNo funds, grants, or other support was received.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare that are relevant to the content of this article.\u003c/p\u003e\n\u003cp\u003eAll authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.\u003c/p\u003e\n\u003cp\u003eThe authors have no financial or proprietary interests in any material discussed in this article.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Elif Yilmaz, Giovanni F. Torsello, Ali Seif Amir Hosseini, Florian B\u0026ouml;sch, Rupert Oberhuber, Otto Kollmar, and Bj\u0026ouml;rn Wellge. The first draft of the manuscript was written by Elif Yilmaz and Florian B\u0026ouml;sch and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKong F-H, Miao X-Y, Zou H, et al (2019) End-stage liver disease score and future liver remnant volume predict post-hepatectomy liver failure in hepatocellular carcinoma. WJCC 7:3734\u0026ndash;3741. https://doi.org/10.12998/wjcc.v7.i22.3734\u003c/li\u003e\n\u003cli\u003eThomas MN, Weninger E, Angele M, et al (2015) Intraoperative simulation of remnant liver function during anatomic liver resection with indocyanine green clearance (LiMON) measurements. HPB 17:471\u0026ndash;476. https://doi.org/10.1111/hpb.12380\u003c/li\u003e\n\u003cli\u003eBozzetti F, Doci R, Bignami P, et al (1987) Patterns of Failure Following Surgical Resection of Colorectal Cancer Liver Metastases: Rationale for a Multimodal Approach. Annals of Surgery 205:264\u0026ndash;270. https://doi.org/10.1097/00000658-198703000-00008\u003c/li\u003e\n\u003cli\u003eGoodman ZD (2007) Neoplasms of the liver. Modern Pathology 20:S49\u0026ndash;S60. https://doi.org/10.1038/modpathol.3800682\u003c/li\u003e\n\u003cli\u003eVauthey J-N, Pawlik TM, Ribero D, et al (2006) Chemotherapy Regimen Predicts Steatohepatitis and an Increase in 90-Day Mortality After Surgery for Hepatic Colorectal Metastases. JCO 24:2065\u0026ndash;2072. https://doi.org/10.1200/JCO.2005.05.3074\u003c/li\u003e\n\u003cli\u003eRahbari NN, Garden OJ, Padbury R, et al (2011) Posthepatectomy liver failure: A definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery 149:713\u0026ndash;724. https://doi.org/10.1016/j.surg.2010.10.001\u003c/li\u003e\n\u003cli\u003eSchreckenbach T, Liese J, Bechstein WO, Moench C (2012) Posthepatectomy Liver Failure. Dig Surg 29:79\u0026ndash;85. https://doi.org/10.1159/000335741\u003c/li\u003e\n\u003cli\u003eLafaro K, Buettner S, Maqsood H, et al (2015) Defining Post Hepatectomy Liver Insufficiency: Where do We stand? J Gastrointest Surg 19:2079\u0026ndash;2092. https://doi.org/10.1007/s11605-015-2872-6\u003c/li\u003e\n\u003cli\u003eTruant S, Oberlin O, Sergent G, et al (2007) Remnant Liver Volume to Body Weight Ratio \u0026ge; 0.5%: A New Cut-Off to Estimate Postoperative Risks after Extended Resection in Noncirrhotic Liver. 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Annals of Surgery 267:833\u0026ndash;840. https://doi.org/10.1097/SLA.0000000000002511\u003c/li\u003e\n\u003cli\u003eHasselgren K, R\u0026oslash;sok BI, Larsen PN, et al (2021) ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM: Survival Analysis From the Randomized Controlled Trial LIGRO. Annals of Surgery 273:442\u0026ndash;448. https://doi.org/10.1097/SLA.0000000000003701\u003c/li\u003e\n\u003cli\u003eWanis KN, Linecker M, Madenci AL, et al (2021) Variation in complications and mortality following ALPPS at early-adopting centers. HPB 23:46\u0026ndash;55. https://doi.org/10.1016/j.hpb.2020.04.009\u003c/li\u003e\n\u003cli\u003eTeo J-Y, Allen JC, Ng DC, et al (2016) A systematic review of contralateral liver lobe hypertrophy after unilobar selective internal radiation therapy with Y90. HPB 18:7\u0026ndash;12. https://doi.org/10.1016/j.hpb.2015.07.002\u003c/li\u003e\n\u003cli\u003eSalem R, Lewandowski RJ, Kulik L, et al (2011) Radioembolization Results in Longer Time-to-Progression and Reduced Toxicity Compared With Chemoembolization in Patients With Hepatocellular Carcinoma. Gastroenterology 140:497-507.e2. https://doi.org/10.1053/j.gastro.2010.10.049\u003c/li\u003e\n\u003cli\u003eKishi Y, Abdalla EK, Chun YS, et al (2009) Three Hundred and One Consecutive Extended Right Hepatectomies: Evaluation of Outcome Based on Systematic Liver Volumetry. Annals of Surgery 250:540\u0026ndash;548. https://doi.org/10.1097/SLA.0b013e3181b674df\u003c/li\u003e\n\u003cli\u003eGarlipp B, De Baere T, Damm R, et al (2014) Left-liver hypertrophy after therapeutic right-liver radioembolization is substantial but less than after portal vein embolization: Garlipp et al. 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Hepatobiliary Surg Nutr 9:312\u0026ndash;321. https://doi.org/10.21037/hbsn.2019.07.11\u003c/li\u003e\n\u003cli\u003eElias D, De Baere T, Roche A, et al (2002) During liver regeneration following right portal embolization the growth rate of liver metastases is more rapid than that of the liver parenchyma. British Journal of Surgery 86:784\u0026ndash;788. https://doi.org/10.1046/j.1365-2168.1999.01154.x\u003c/li\u003e\n\u003cli\u003eRonot M, Cauchy F, Gregoli B, et al (2016) Sequential transarterial chemoembolization and portal vein embolization before resection is a valid oncological strategy for unilobar hepatocellular carcinoma regardless of the tumor burden. HPB 18:684\u0026ndash;690. https://doi.org/10.1016/j.hpb.2016.05.012\u003c/li\u003e\n\u003cli\u003eAddeo P, De Mathelin P, De Marini P, et al (2023) Sequential Y90 liver radioembolization and portal vein embolization: an additional strategy to downstage liver tumors and to enhance liver hypertrophy before major hepatectomies. Langenbecks Arch Surg 408:339. https://doi.org/10.1007/s00423-023-03083-0\u003c/li\u003e\n\u003cli\u003eWahba R, Bunck AC, Schmidt M, et al (2022) Neoadjuvant Hemi-Liver Directed Selective Internal Radiation Therapy (SIRT) Followed by Portal Vein and Liver Vein Embolization Could Make Non-Operable Patients with Liver Cancer Eligible for Curative Intended Major Liver Resection. HPB 24:S230. https://doi.org/10.1016/j.hpb.2022.05.477\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"langenbecks-archives-of-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"laos","sideBox":"Learn more about [Langenbeck's Archives of Surgery](http://link.springer.com/journal/423)","snPcode":"423","submissionUrl":"https://submission.nature.com/new-submission/423/3","title":"Langenbeck's Archives of Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"liver augmentation, future liver remnant, portal vein embolization, associating liver partition and portal vein occlusion for staged hepatectomy","lastPublishedDoi":"10.21203/rs.3.rs-3985193/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3985193/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eFor primary and secondary liver tumors oncological resection remains a chance of cure. Augmentation of functional liver tissue may be necessary to preserve sufficient future liver remnant (FLR). Clinical decision-making on liver augmentation techniques and indications may differ internationally. Thus, this study aims to identify standards of liver augmentation in high-volume centers in Germany, Switzerland, and Austria.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eUsing a web-based survey, 48 hospitals in Germany, Switzerland and Austria were invited to report their surgical indication, standard procedures, and results of liver augmentation.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eForty (83.3%) of the hospitals invited participated. Most of the hospitals were certified liver centers (55%), performing complex surgeries such as liver transplantation (57.5%) and ALPPS (80%). The standard liver augmentation technique in all countries was portal vein embolization (PVE; 56%), followed by ALPPS (32.1%) in Germany or PVE with hepatic vein embolization (33.3%) in Switzerland and Austria. Standard procedure for liver augmentation did not correlate with certification as liver center, performance of liver transplantation or ALPPS. Surgical indication for PVE varied depending on tumor entity. Most hospitals rated the importance of PVE before resection of cholangiocarcinoma or colorectal metastases as high, while PVE for hepatocellular carcinoma was rated as low.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe survey gives an overview of the clinical routine in high-volume centers in Germany, Austria, and Switzerland. PVE seems to dominate as standard technique to increase the FLR. However, there is a variety in the main indication for liver augmentation. Further studies are necessary evaluating the differing PVE techniques for liver augmentation.\u003c/p\u003e","manuscriptTitle":"Role of liver augmentation prior to hepatic resection – standards, procedures and indications in Germany, Switzerland, and Austria","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-29 17:04:08","doi":"10.21203/rs.3.rs-3985193/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-12T09:21:59+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-04-16T14:28:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"7fe472da-6f8d-4586-9707-f9b3aa24ddd4","date":"2024-04-10T14:30:44+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-03-17T12:38:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"29ffbf1c-fc19-4109-88d6-e82eed2b3ef1","date":"2024-03-04T08:11:06+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-03T22:06:17+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-03-02T10:15:56+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-02-27T09:25:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"Langenbeck's Archives of Surgery","date":"2024-02-24T14:13:16+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"langenbecks-archives-of-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"laos","sideBox":"Learn more about [Langenbeck's Archives of Surgery](http://link.springer.com/journal/423)","snPcode":"423","submissionUrl":"https://submission.nature.com/new-submission/423/3","title":"Langenbeck's Archives of Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"dd3d3f2a-ed42-493b-b2ed-0d1a157eb6c5","owner":[],"postedDate":"February 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-01T17:10:18+00:00","versionOfRecord":{"articleIdentity":"rs-3985193","link":"https://doi.org/10.1007/s00423-024-03418-5","journal":{"identity":"langenbecks-archives-of-surgery","isVorOnly":false,"title":"Langenbeck's Archives of Surgery"},"publishedOn":"2024-07-27 16:15:59","publishedOnDateReadable":"July 27th, 2024"},"versionCreatedAt":"2024-02-29 17:04:08","video":"","vorDoi":"10.1007/s00423-024-03418-5","vorDoiUrl":"https://doi.org/10.1007/s00423-024-03418-5","workflowStages":[]},"version":"v1","identity":"rs-3985193","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3985193","identity":"rs-3985193","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}