Impact of caudate lobe resection on overall survival and liver disease-free survival in colorectal liver metastases: A pilot study

Impact of caudate lobe resection on overall survival and liver disease-free survival in colorectal liver metastases: A pilot study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Impact of caudate lobe resection on overall survival and liver disease-free survival in colorectal liver metastases: A pilot study Melih Can Gul, Emin Demirel This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4454993/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract BACKGROUND This study aimed to evaluate the management of colorectal liver metastases (CRLM) and the role of anatomical resections, with particular reference to the caudate lobe. METHODS We obtained all patient data from the Preoperative CT and Survival Data for Patients Undergoing Resection of Colorectal Liver Metastases dataset. Patients who underwent total caudate lobe resection without radiological evidence of metastases were analyzed. To investigate the net effect of caudate lobe resection, propensity score matching (PSM) was applied to most other parameters. The Kaplan-Meier and log-rank tests were used to calculate overall survival (OS) and liver disease-free survival (liver-DFS) and to investigate differences between groups. RESULTS Patients who underwent total caudate resection had better results in terms of overall survival in the whole data set and after PSM (respectively, p < 0.001 HR: 0.43, 95%CI:0.26–0.72 p:0.024, HR: 0.65 95%CI:0.59–0.79).Patients who underwent total caudate resection had better results in terms of liver-DFS in the whole data set set and after PSM (respectively, p = 0.014, HR = 0.46, 95%CI: 0.24–0.85, p = 0.026 HR = 0.5, 95%CI: 0.37–0.79) CONCLUSİONS We believe that the addition of total caudate lobe resection to resection may contribute to both OS and liver DFS. Biological sciences/Cancer Health sciences/Anatomy Health sciences/Gastroenterology Colorektal carcinoma Liver Metastasis Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Colorectal cancer (CRC) is the second most common cancer in women and the third most common cancer in men, representing a significant health burden worldwide and accounting for 10% of all cancers and cancer-related deaths diagnosed annually worldwide. The liver is one of the most common sites of haematogenous metastasis among visceral tissues. The liver is the most common site of metastatic disease for patients with colorectal cancer and at least 25% develop colorectal liver metastases (CRLM) during the course of their disease. The management of CRLM has become a complex multidisciplinary field involving radiology (cross-sectional, nuclear medicine, and interventional), oncology, liver surgery, colorectal surgery, and pathology. Patient management is based on sophisticated clinical, radiological, and biomarker assessments. Despite the lack of evidence in this highly heterogeneous patient population, maximizing resection of CRLM using all available techniques remains a fundamental goal and offers the best chance of long-term survival and cure. Despite the addition of systemic chemotherapy, intrahepatic recurrence after curative surgery is common, occurring within 3 years in two-thirds of patients. . In an effort to preserve liver parenchyma, there has recently been an increased focus on parenchyma-sparing or non-anatomic resections (NAR) versus anatomic resections (AR) in patients with CRLM. As surgeons have recently accepted smaller margins for CRLM resection, this has favoured the preservation of liver parenchyma and thus the provision of larger remnant livers. Proponents of AR for CRLM suggest that individual tumour biology should be taken into account when planning surgery. Somatic tumour mutations in the RAS have been associated with worse long-term outcomes in patients with metastatic CRC, and indeed these mutations have been associated with surgical margins after hepatectomy. In fact, patients with RAS-mutant CRLM have been shown to have more positive surgical margins and narrower margins overall after hepatectomy. RAS-mutant tumours are known to have an increased risk of microscopic invasion into the intrahepatic vascular and biliary systems, which can lead to latent micrometastases along the portal triad. This has led researchers to propose the use of AR in RAS-mutant CRLM. The caudate lobe of the liver was first studied in the 13th century; it is located in the deep dorsal region between the inferior vena cava (IVC) and the portal triad. The identification of the caudate lobe has been controversial throughout history due to its unique anatomical location and complex venous return system, which originates from both the main portal veins and the biliary system. Meta-analyses have shown that the addition of total or partial caudate lobe resection in hilar colon cancer has a positive effect on overall and disease-free survival. Micrometastases in the biliary tract have been suggested to be the main contributing factor. In our study, we aimed to investigate the effect of caudate lobe resection on overall (OS) and liver-related disease-free survival (liver DFS) in CRLMs associated with both lobes due to its complex anatomy, which may be a potential bed of occult metastasis, using propensity score matching. Methods Patient Selection One hundred ninety-seven CRLM patients Preoperative CT and Survival Data for Patients Undergoing Resection of Colorectal Liver Metastases dataset ( 7 , 8 ), were retrieved from the Cancer Imaging Archive (TCIA) ( 9 ) Patient characteristics were obtained from TCIA, including age, sex, body mass index, Carcinoembryonic Antigen (CEA), maximum tumour size, synchronous CRLM, node-positive primary, multiple metastases, bilobar disease, extrahepatic disease and major comorbidity. Informed consent was not required as the TCIA data did not contain any personally identifiable information. Inclusion criteria were as follows: (a) patients with contrast-enhanced CT images in the preoperative portal venous phase. Exclusion criteria were defined as (a) patients with metastases closer than 1 cm to the caudate lobe and caudate lobe, (b) inadequate quality and images, (c) no survival data available. The definition of total caudate lobe resection was accepted as including the entire Spiegelian lobe and paracaval region in the resection. Patients were assessed independently by a general surgeon trained by a radiologist with 8 years' experience and another independent radiologist with 20 years' experience. Two patients for whom resection was controversial were re-evaluated, and a unanimous decision was reached. Data Availability Statement While the current study includes data from human clinical trials, the data analyzed were obtained from the cancer imaging archive (TCIA) https://doi.org/10.7937/QXK2-QG03 , which has been previously archived and made publicly available and does not impose privacy or ethical restrictions, and no changes were made to the existing dataset. Therefore, no additional permission was required from the local ethics committees where the authors work. Statistical Analysis Statistical analysis was performed using SPSS version 25 (IBM Corporation, Armonk, NY, USA). Continuous variables were given as mean (± standard deviation), and categorical variables were given as a number (ratio). Normality tests were made for continuous variables Kolmogorov-Smirnov and Shapiro-Wilk tests. Comparisons between groups were made using the following statistical tests: chi-square test for categorical variables, Student’s t-test for normal-distributed continuous variables and Mann-Whitney U test for non-normal-distributed continuous variables. We also used propensity score matching (PSM) with a 1:1 ratio to minimize selection bias and adjust the imbalance between groups. SPSS R plug-in (SPSS R Essentials) was applied for matching( 10 ). We used the SPSS ‘PS Matching’ feature to perform propensity score-matched analysis. Matching factors include age, gender, body mass index, CEA,maximum tumour size, synchronous CRLM,node positive primary,multiple metastasis,bilobar disease,extrahepatic disesase and majör comorbidity. Patients with caudat lobe resected/non resected were matched 1:1 in a multivariable logistic analysis using stepwise regression based on a greedy matching algorithm with a caliper of 0.05 times the standard deviation (SD) of the logit. After applying 1:1 propensity score matching (PSM), 23 eligible patients were matched to each group. The Kaplan–Meier curve was used to calculate the OS and liver DFS curve, and the log-rank test was applied to investigate differences in OS and liver DFS between caudat lobe resected non-resected groups p values < 0.05 were considered to indicate statistical significance. Age, gender, body mass index, CEA,maximum tumour size, synchronous CRLM,node positive primary,multiple metastasis,bilobar disease,extrahepatic disesase and majör comorbidity faktörlerine göre total kaudektominin Results Demographic data of the overall dataset is shared in (Table 1 ) . In the evaluation made according to all parameters, no significant difference was detected in the patient groups with and without caudate lobe resection. Table 1 Demographic data of whole datasets No caudate lobe resection added (n:169) Added caudate lobe resection (n:23) p Age mean(sd) 59,36( 12 , 23 ) 63,17 (11,62) ,373 Body_mass_index mean(sd) 27,27(4,92) 27,90(4,81) ,841 Clinic risk_score mean(sd) 2,05(0,95) 1,73(0,92) ,762 Carcinoembryonic_antigen mean(sd) 30,56(96,16) 21,77(34,48) ,730 Maximum tumor_size mean(sd) 3,51(2,63) 3,30( 2 , 21 ) ,491 Overall_survival(months) mean(sd) 62,99(33,14) 99(33,6) ,762 Sex (male n, %) 102 (%60,4) 12(%52,2) ,454 Major_comorbidity (n,%) 93(%55) 13(%56,5) ,893 Node_positive_primary (n,%) 58(%34,3) 9(%39,1) ,650 Synchronous_CRLM (n,%) 95(%56,2) 13(%56,5) ,978 Multiple_metastases (n,%) 99(%58,6) 13(%56,5) ,851 Bilobar_disease (n,%) 74(%43,8) 10(%43,5) ,978 Extrahepatic_disease (n,%) 12(%7,1) 4(%17,4) ,094 Local liver recurrence, lung metastasis as a distant organ, bone metastasis, and lymph node metastasis were examined in the data set. No statistical difference was found for lung metastasis, bone metastasis, and lymph node metastasis in patients with total caudate lobe resection. In terms of overall survival and recurrent liver metastases after resection, patients with total caudate resection had statistically superior OS and DFS compared to patients without caudate resection, both in the general patient group and after the PSM procedure. Patients who underwent total caudate resection had better results in terms of overall survival in the overall data set. ( Fig. 1 ) (p < 0.001), (HR: 0.43 95%CI:0.26–0.72), ( Fig. 2 ) (long rank, p: 0.024), (HR: 0.65 95%CI:0.59–0.79) Patients who underwent total caudate resection had better results in terms of liver recurrence-free survival in the whole data set ( Fig. 3 ) (long rank, p: 0.014), HR: 0.46 (0.24–0.85), and patients who underwent total caudate resection after PSM procedure had better liver disease-free survival ( Fig. 4 ) (long rank, p: 0.026), HR: 0.51 (0.37–0.79). Discussions Colorectal cancer (CRC) is the second most common cause of cancer-related deaths worldwide, especially when metastatic disease is considered ( 4 ). The most common site of metastasis of CRC is the liver, with a frequency of approximately 25% at the time of diagnosis. Currently, the most effective treatment method for colorectal metastases is hepatectomy if the metastasis location and liver volume are sufficient ( 11 ). However, there are few studies on whether the location of hepatic metastases affects prognosis. Kuo et al. suggest that liver metastases located in the central segments and caudate lobe may be a poor prognostic factor after hepatectomy and are associated with early recurrence in colorectal cancer. ( 12 ). The caudate lobe was first analysed in the 13th century and took its current form with the definition of modern coinaud segments. ( 13 ). The caudate lobe receives portal blood supply from the right and left branches of the portal vein separately and from the portal vein itself via three different routes. ( 14 ). The success rates of non-surgical treatments such as ablation and transcatheter arterial embolisation in treating caudate lobe tumours are lower than surgical treatment. Therefore, surgical resection is virtually the only way to treat caudate lobe tumours ( 15 ). The bile duct of the caudate lobe of the liver drains close to the common bile duct at the level of the liver hilus and is always considered to be tumour-retained in terms of perihilar cholangiocarcinomas, so caudate lobe resection is a natural part of its operation ( 16 ). In many studies investigating the metastasis distribution of colorectal cancers according to the coinaud segmental classification of the liver, the caudate lobe was excluded from the study because it was known to have isolated portal, biliary tract and v.cava drainage and inter-segmental homogenisation could not be achieved during the study ( 17 ). In patients with colorectal cancer, survival in patients with caudate lobe metastasis in isolation or with metastasis of another segment was found to be worse than in patients without caudate lobe metastasis ( 18 ). CRLMs involving the caudate lobe increase the complexity of curative hepatectomy due to the difficult anatomical location. The caudate lobe is closely associated with the inferior vena cava, the portal confluence and the junction of the left and middle hepatic veins ( 19 ). Although mobilisation of the caudate lobe from the superior vena cava by ligation of the short hepatic veins during resection is thought to increase the risk of intraoperative bleeding and associated morbidity due to lack of surgical experience, publications are showing that resection of the caudate lobe is increasingly performed with increasing surgical experience and that there is no difference in terms of postoperative complications, although there are patients who have undergone vascular resection in the patient groups ( 20 ). A careful analysis of the content of the studies on caudate lobe resection in the surgical treatment of liver metastases from colorectal cancer reveals that all of them included patients with either multiple metastases including the caudate lobe or isolated caudate lobe metastases. ( 21 ). In this context, our study is the first to look at overall survival, disease-free survival, and distant organ metastases between patients who underwent total caudate resection during liver resection without metastases in the caudate lobe, which is the segment closest to the portal vein and the first segment to drain into the portal vein, and patients who did not undergo caudate resection. In a study involving extended left hepatectomy and caudate resection for metastases involving the left lobe and caudate lobe in colorectal cancer patients, 17 patients underwent left hemicolectomy with caudate lobectomy. In 14 patients, only extended left hepatectomy was performed, and morbidity and postoperative recurrence rates in the liver were similar between the groups. However, postoperative distant organ metastasis was more common in the group that underwent caudate lobectomy due to metastasis in the caudate lobe, and this was associated with the prominent caval drainage of the caudate lobe ( 22 ). In our data series, there was no difference between the groups with and without caudate resection in terms of distant organ metastasis, but postoperative liver recurrence was more common in the parenchymal-sparing group without caudate resection, and a statistically significant difference was found. The extent of hepatectomy in the surgical treatment of liver metastases from colorectal cancer is still a controversial issue ( 23 ). In recent meta-analyses comparing parenchyma-sparing surgery with anatomical resections, no significant difference was found between the groups in terms of 1,3,5-year OS, while parenchyma-sparing surgery was found to be less successful in terms of positive resection margins, intrahepatic recurrence and the need for repeat hepatectomy ( 4 , 24 ). As a matter of fact, in our study, the patient group in which caudate lobe was included in the resection was found to be superior in terms of OS and liver DFS. We do not have a definite idea as to why patients with caudate lobe resection had a superior DFS and OS. However, we think that the genotype structure of the primary tumour may be a factor in this. In many retrospective cohorts, it has been reported that parenchyma-sparing surgery is more disadvantageous in terms of OS and DFS in the liver in patient groups with RAS mutation. ( 25 ). It has been reported that the presence of undetectable micrometastases in the liver in patients with KRAS mutation predisposes to R1 resection with parenchymal preservation and to reduced overall survival in patients with tumour recurrence in the residual liver( 26 ). In our study, we think that caudate lobe may be a micrometastasis bed. Although OS and liver DFS were found to be more favourable in caudate lobectomy groups with higher parenchymal resection in our study, the presence of mutations in the parenchymal sparing group is not known due to the lack of genome data in the data set. There are very important limitations in our study. Due to the retrospective planning of the study, the necessary optimizations could not be made. The effect of isolated caudate lobe resection on patients could not be investigated. In fact, the group examined included extended right and left lobe resections. Due to the small number of patients, the disease in both lobes could not be examined separately. For this reason, no recommendation has been made to add caudectomy to a specific group. The genomic profile of the primary tumor is unknown. Therefore, the groups compared are quite heterogeneous. For a very common disease like CRLM, the sample group is relatively small. For all these reasons, our study is actually a pilot study. In conclusion, we hypothesised that the caudate lobe is more susceptible to micrometastases because it is an isolated specific lobe with high vascular and biliary drainage located at the hilar junction. Although superior oncological outcomes in terms of OS and DFS were found in the surgery group in which resection was added, the effect of these on the disease is not known since the genomic status of the patients, tumour biology and tumour differentiation were not revealed due to the insufficiency of the current data set. Nevertheless, our findings are promising. Declarations DISCLOSURE OF INTEREST The authors declare that they have no competing interest. FUNDING This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author Contribution Protocol/project development: MCG, ED . Data acquisition and interpretation of data: MCG,ED.Statistics analysis of data: ED. Manuscript drafing: MCG,ED . Manuscript Revision and accountablefor all aspects of the work: MCG, ED . All authors read and approved the fnal manuscript. Data Availability The datasets generated and analysed during the current study are available in the [Colorectal-Liver-Metastases | Preoperative CT and Survival Data for Patients Undergoing Resection of Colorectal Liver Metastases] repository, [Simpson, A. L., Peoples, J., Creasy, J. M., Fichtinger, G., Gangai, N., Lasso, A., Keshava Murthy, K. N., Shia, J., D’Angelica, M. I., & Do, R. K. G. (2023). Preoperative CT and Survival Data for Patients Undergoing Resection of Colorectal Liver Metastases (Colorectal-Liver-Metastases) (Version 2) [Data set]. The Cancer Imaging Archive. https://doi.org/10.7937/QXK2-QG03 INFORMED CONSENT AND PATIENT DETAİLS The authors declare that this report does not contain any personal information that could lead to the identification of the patients. References Klimeck L, Heisser T, Hoffmeister M, et al. Colorectal cancer: A health and economic problem. Best Pract Res Clin Gastroenterol 2023;66:101839. Martin J, Petrillo A, Smyth EC, et al. Colorectal liver metastases: Current management and future perspectives. http://www.wjgnet.com/ 2020;11:761–808. Chow FCL, Chok KSH. Colorectal liver metastases: An update on multidisciplinary approach. http://www.wjgnet.com/ 2019;11:150–172. Wang K, Liu Y, Hao M, et al. Clinical outcomes of parenchymal-sparing versus anatomic resection for colorectal liver metastases: a systematic review and meta-analysis. 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Preoperative CT and Survival Data for Patients Undergoing Resection of Colorectal Liver Metastases (Colorectal-Liver-Metastases) (Version 2) [Data set]. The Cancer Imaging Archive. Cancer Imaging Arch. Clark K, Vendt B, Smith K, et al. The Cancer Imaging Archive (TCIA): Maintaining and Operating a Public Information Repository. J Digit Imaging 2013;26:1045–1057. Thoemmes F, Thoemmes F. Propensity score matching in SPSS Available from: https://arxiv.org/abs/1201.6385v1 . 2012. Accessed November 6, 2023. Hackl C, Neumann P, Gerken M, et al. Treatment of colorectal liver metastases in Germany: A ten-year population-based analysis of 5772 cases of primary colorectal adenocarcinoma. BMC Cancer 2014;14:1–10. Kuo IM, Huang SF, Chiang JM, et al. Clinical features and prognosis in hepatectomy for colorectal cancer with centrally located liver metastasis. World J Surg Oncol 2015;13:1–12. Kumon M, Kumon T, Sakamoto Y. Demonstration of the right-side boundary of the caudate lobe in a liver cast. 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Isolated caudate lobe resection: technical challenges. Ann Gastroenterol Q Publ Hell Soc Gastroenterol 2013;26:150. Khan AZ, Wong VK, Malik HZ, et al. The impact of caudate lobe involvement after hepatic resection for colorectal metastases. Eur J Surg Oncol 2009;35:510–514. Thomas RL, Lordan JT, Devalia K, et al. Liver resection for colorectal cancer metastases involving the caudate lobe. Br J Surg 2011;98:1476–1482. Wicherts DA, De Haas RJ, Andreani P, et al. Short- and long-term results of extended left hepatectomy for colorectal metastases. HPB 2011;13:536–543. Viganò L, Capussotti L, Lapointe R, et al. Early recurrence after liver resection for colorectal metastases: Risk factors, prognosis, and treatment. A LiverMetSurvey-based study of 6,025 patients. Ann Surg Oncol 2014;21:1276–1286. Rengers T, Warner S. Surgery for colorectal liver metastases: Anatomic and non-anatomic approach. Surg (United States) 2023;174:119–122. Papaconstantinou D, Pararas N, Pikouli A, et al. Precision Surgery of Colorectal Liver Metastases in the Current Era: A Systematic Review. Cancers 2023, Vol 15, Page 2083 2023;15:2083. Zhang Q, Peng J, Ye M, et al. KRAS Mutation Predicted More Mirometastases and Closer Resection Margins in Patients with Colorectal Cancer Liver Metastases. Ann Surg Oncol 2020;27:1164–1173. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4454993","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":312210167,"identity":"0f4fa3d6-11db-46a7-83eb-e808bec66012","order_by":0,"name":"Melih Can 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set\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4454993/v1/e0177246c27df58a5ecb861b.png"},{"id":58223837,"identity":"92c6a28a-bb9e-488a-8739-62a72068f4b1","added_by":"auto","created_at":"2024-06-12 17:26:26","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":27349,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan Meier liver disease-free survival in case set after PSM\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4454993/v1/77bb73016e15dc5dca9dd14a.png"},{"id":64651138,"identity":"a4ad06d5-9d6f-4709-9831-80a7be48657a","added_by":"auto","created_at":"2024-09-17 05:32:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":542654,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4454993/v1/fd15f2fc-4e73-42d4-8710-e911370d6ede.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":" Impact of caudate lobe resection on overall survival and liver disease-free survival in colorectal liver metastases: A pilot study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eColorectal cancer (CRC) is the second most common cancer in women and the third most common cancer in men, representing a significant health burden worldwide and accounting for 10% of all cancers and cancer-related deaths diagnosed annually worldwide.\u003c/p\u003e \u003cp\u003eThe liver is one of the most common sites of haematogenous metastasis among visceral tissues. The liver is the most common site of metastatic disease for patients with colorectal cancer and at least 25% develop colorectal liver metastases (CRLM) during the course of their disease. The management of CRLM has become a complex multidisciplinary field involving radiology (cross-sectional, nuclear medicine, and interventional), oncology, liver surgery, colorectal surgery, and pathology. Patient management is based on sophisticated clinical, radiological, and biomarker assessments. Despite the lack of evidence in this highly heterogeneous patient population, maximizing resection of CRLM using all available techniques remains a fundamental goal and offers the best chance of long-term survival and cure. Despite the addition of systemic chemotherapy, intrahepatic recurrence after curative surgery is common, occurring within 3 years in two-thirds of patients. .\u003c/p\u003e \u003cp\u003eIn an effort to preserve liver parenchyma, there has recently been an increased focus on parenchyma-sparing or non-anatomic resections (NAR) versus anatomic resections (AR) in patients with CRLM. As surgeons have recently accepted smaller margins for CRLM resection, this has favoured the preservation of liver parenchyma and thus the provision of larger remnant livers.\u003c/p\u003e \u003cp\u003eProponents of AR for CRLM suggest that individual tumour biology should be taken into account when planning surgery. Somatic tumour mutations in the RAS have been associated with worse long-term outcomes in patients with metastatic CRC, and indeed these mutations have been associated with surgical margins after hepatectomy. In fact, patients with RAS-mutant CRLM have been shown to have more positive surgical margins and narrower margins overall after hepatectomy. RAS-mutant tumours are known to have an increased risk of microscopic invasion into the intrahepatic vascular and biliary systems, which can lead to latent micrometastases along the portal triad. This has led researchers to propose the use of AR in RAS-mutant CRLM.\u003c/p\u003e \u003cp\u003eThe caudate lobe of the liver was first studied in the 13th century; it is located in the deep dorsal region between the inferior vena cava (IVC) and the portal triad. The identification of the caudate lobe has been controversial throughout history due to its unique anatomical location and complex venous return system, which originates from both the main portal veins and the biliary system. Meta-analyses have shown that the addition of total or partial caudate lobe resection in hilar colon cancer has a positive effect on overall and disease-free survival. Micrometastases in the biliary tract have been suggested to be the main contributing factor.\u003c/p\u003e \u003cp\u003eIn our study, we aimed to investigate the effect of caudate lobe resection on overall (OS) and liver-related disease-free survival (liver DFS) in CRLMs associated with both lobes due to its complex anatomy, which may be a potential bed of occult metastasis, using propensity score matching.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient Selection\u003c/h2\u003e \u003cp\u003eOne hundred ninety-seven CRLM patients Preoperative CT and Survival Data for Patients Undergoing Resection of Colorectal Liver Metastases dataset (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), were retrieved from the Cancer Imaging Archive (TCIA) (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) Patient characteristics were obtained from TCIA, including age, sex, body mass index, Carcinoembryonic Antigen (CEA), maximum tumour size, synchronous CRLM, node-positive primary, multiple metastases, bilobar disease, extrahepatic disease and major comorbidity. Informed consent was not required as the TCIA data did not contain any personally identifiable information.\u003c/p\u003e \u003cp\u003eInclusion criteria were as follows: (a) patients with contrast-enhanced CT images in the preoperative portal venous phase. Exclusion criteria were defined as (a) patients with metastases closer than 1 cm to the caudate lobe and caudate lobe, (b) inadequate quality and images, (c) no survival data available.\u003c/p\u003e \u003cp\u003eThe definition of total caudate lobe resection was accepted as including the entire Spiegelian lobe and paracaval region in the resection. Patients were assessed independently by a general surgeon trained by a radiologist with 8 years' experience and another independent radiologist with 20 years' experience. Two patients for whom resection was controversial were re-evaluated, and a unanimous decision was reached.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData Availability Statement\u003c/h2\u003e \u003cp\u003eWhile the current study includes data from human clinical trials, the data analyzed were obtained from the cancer imaging archive (TCIA) \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.7937/QXK2-QG03\u003c/span\u003e\u003cspan address=\"10.7937/QXK2-QG03\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e, which has been previously archived and made publicly available and does not impose privacy or ethical restrictions, and no changes were made to the existing dataset. Therefore, no additional permission was required from the local ethics committees where the authors work.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using SPSS version 25 (IBM Corporation, Armonk, NY, USA). Continuous variables were given as mean (\u0026plusmn;\u0026thinsp;standard deviation), and categorical variables were given as a number (ratio). Normality tests were made for continuous variables Kolmogorov-Smirnov and Shapiro-Wilk tests. Comparisons between groups were made using the following statistical tests: chi-square test for categorical variables, Student\u0026rsquo;s t-test for normal-distributed continuous variables and Mann-Whitney U test for non-normal-distributed continuous variables.\u003c/p\u003e \u003cp\u003eWe also used propensity score matching (PSM) with a 1:1 ratio to minimize selection bias and adjust the imbalance between groups. SPSS R plug-in (SPSS R Essentials) was applied for matching(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). We used the SPSS \u0026lsquo;PS Matching\u0026rsquo; feature to perform propensity score-matched analysis. Matching factors include age, gender, body mass index, CEA,maximum tumour size, synchronous CRLM,node positive primary,multiple metastasis,bilobar disease,extrahepatic disesase and maj\u0026ouml;r comorbidity. Patients with caudat lobe resected/non resected were matched 1:1 in a multivariable logistic analysis using stepwise regression based on a greedy matching algorithm with a caliper of 0.05 times the standard deviation (SD) of the logit. After applying 1:1 propensity score matching (PSM), 23 eligible patients were matched to each group.\u003c/p\u003e \u003cp\u003eThe Kaplan\u0026ndash;Meier curve was used to calculate the OS and liver DFS curve, and the log-rank test was applied to investigate differences in OS and liver DFS between caudat lobe resected non-resected groups p values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered to indicate statistical significance. Age, gender, body mass index, CEA,maximum tumour size, synchronous CRLM,node positive primary,multiple metastasis,bilobar disease,extrahepatic disesase and maj\u0026ouml;r comorbidity fakt\u0026ouml;rlerine g\u0026ouml;re total kaudektominin\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eDemographic data of the overall dataset is shared in (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. In the evaluation made according to all parameters, no significant difference was detected in the patient groups with and without caudate lobe resection.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic data of whole datasets\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo caudate lobe resection added \u003c/p\u003e \u003cp\u003e(n:169)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAdded caudate lobe resection (n:23)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003cp\u003emean(sd)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59,36(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63,17 (11,62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e,373\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBody_mass_index\u003c/b\u003e\u003c/p\u003e \u003cp\u003emean(sd)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27,27(4,92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27,90(4,81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e,841\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinic risk_score\u003c/b\u003e\u003c/p\u003e \u003cp\u003emean(sd)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,05(0,95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,73(0,92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e,762\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCarcinoembryonic_antigen\u003c/b\u003e\u003c/p\u003e \u003cp\u003emean(sd)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30,56(96,16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21,77(34,48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e,730\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMaximum tumor_size\u003c/b\u003e\u003c/p\u003e \u003cp\u003emean(sd)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,51(2,63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3,30(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e,491\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOverall_survival(months)\u003c/b\u003e\u003c/p\u003e \u003cp\u003emean(sd)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62,99(33,14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99(33,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e,762\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(male n, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e102 (%60,4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(%52,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e,454\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMajor_comorbidity\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93(%55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(%56,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e,893\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNode_positive_primary\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58(%34,3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(%39,1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e,650\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSynchronous_CRLM\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95(%56,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(%56,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e,978\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMultiple_metastases\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99(%58,6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(%56,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e,851\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBilobar_disease\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74(%43,8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(%43,5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e,978\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExtrahepatic_disease\u003c/b\u003e\u003c/p\u003e \u003cp\u003e(n,%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(%7,1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(%17,4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e,094\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eLocal liver recurrence, lung metastasis as a distant organ, bone metastasis, and lymph node metastasis were examined in the data set. No statistical difference was found for lung metastasis, bone metastasis, and lymph node metastasis in patients with total caudate lobe resection.\u003c/p\u003e \u003cp\u003eIn terms of overall survival and recurrent liver metastases after resection, patients with total caudate resection had statistically superior OS and DFS compared to patients without caudate resection, both in the general patient group and after the PSM procedure.\u003c/p\u003e \u003cp\u003ePatients who underwent total caudate resection had better results in terms of overall survival in the overall data set. \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), (HR: 0.43 95%CI:0.26\u0026ndash;0.72), \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e (long rank, p: 0.024), (HR: 0.65 95%CI:0.59\u0026ndash;0.79)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePatients who underwent total caudate resection had better results in terms of liver recurrence-free survival in the whole data set \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e (long rank, p: 0.014), HR: 0.46 (0.24\u0026ndash;0.85), and patients who underwent total caudate resection after PSM procedure had better liver disease-free survival \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e (long rank, p: 0.026), HR: 0.51 (0.37\u0026ndash;0.79).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussions","content":"\u003cp\u003eColorectal cancer (CRC) is the second most common cause of cancer-related deaths worldwide, especially when metastatic disease is considered (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The most common site of metastasis of CRC is the liver, with a frequency of approximately 25% at the time of diagnosis. Currently, the most effective treatment method for colorectal metastases is hepatectomy if the metastasis location and liver volume are sufficient (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, there are few studies on whether the location of hepatic metastases affects prognosis. Kuo et al. suggest that liver metastases located in the central segments and caudate lobe may be a poor prognostic factor after hepatectomy and are associated with early recurrence in colorectal cancer. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe caudate lobe was first analysed in the 13th century and took its current form with the definition of modern coinaud segments. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The caudate lobe receives portal blood supply from the right and left branches of the portal vein separately and from the portal vein itself via three different routes. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). The success rates of non-surgical treatments such as ablation and transcatheter arterial embolisation in treating caudate lobe tumours are lower than surgical treatment. Therefore, surgical resection is virtually the only way to treat caudate lobe tumours (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The bile duct of the caudate lobe of the liver drains close to the common bile duct at the level of the liver hilus and is always considered to be tumour-retained in terms of perihilar cholangiocarcinomas, so caudate lobe resection is a natural part of its operation (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn many studies investigating the metastasis distribution of colorectal cancers according to the coinaud segmental classification of the liver, the caudate lobe was excluded from the study because it was known to have isolated portal, biliary tract and v.cava drainage and inter-segmental homogenisation could not be achieved during the study (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn patients with colorectal cancer, survival in patients with caudate lobe metastasis in isolation or with metastasis of another segment was found to be worse than in patients without caudate lobe metastasis (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCRLMs involving the caudate lobe increase the complexity of curative hepatectomy due to the difficult anatomical location. The caudate lobe is closely associated with the inferior vena cava, the portal confluence and the junction of the left and middle hepatic veins (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough mobilisation of the caudate lobe from the superior vena cava by ligation of the short hepatic veins during resection is thought to increase the risk of intraoperative bleeding and associated morbidity due to lack of surgical experience, publications are showing that resection of the caudate lobe is increasingly performed with increasing surgical experience and that there is no difference in terms of postoperative complications, although there are patients who have undergone vascular resection in the patient groups (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA careful analysis of the content of the studies on caudate lobe resection in the surgical treatment of liver metastases from colorectal cancer reveals that all of them included patients with either multiple metastases including the caudate lobe or isolated caudate lobe metastases. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this context, our study is the first to look at overall survival, disease-free survival, and distant organ metastases between patients who underwent total caudate resection during liver resection without metastases in the caudate lobe, which is the segment closest to the portal vein and the first segment to drain into the portal vein, and patients who did not undergo caudate resection.\u003c/p\u003e \u003cp\u003eIn a study involving extended left hepatectomy and caudate resection for metastases involving the left lobe and caudate lobe in colorectal cancer patients, 17 patients underwent left hemicolectomy with caudate lobectomy. In 14 patients, only extended left hepatectomy was performed, and morbidity and postoperative recurrence rates in the liver were similar between the groups. However, postoperative distant organ metastasis was more common in the group that underwent caudate lobectomy due to metastasis in the caudate lobe, and this was associated with the prominent caval drainage of the caudate lobe (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our data series, there was no difference between the groups with and without caudate resection in terms of distant organ metastasis, but postoperative liver recurrence was more common in the parenchymal-sparing group without caudate resection, and a statistically significant difference was found.\u003c/p\u003e \u003cp\u003eThe extent of hepatectomy in the surgical treatment of liver metastases from colorectal cancer is still a controversial issue (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). In recent meta-analyses comparing parenchyma-sparing surgery with anatomical resections, no significant difference was found between the groups in terms of 1,3,5-year OS, while parenchyma-sparing surgery was found to be less successful in terms of positive resection margins, intrahepatic recurrence and the need for repeat hepatectomy (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAs a matter of fact, in our study, the patient group in which caudate lobe was included in the resection was found to be superior in terms of OS and liver DFS. We do not have a definite idea as to why patients with caudate lobe resection had a superior DFS and OS. However, we think that the genotype structure of the primary tumour may be a factor in this. In many retrospective cohorts, it has been reported that parenchyma-sparing surgery is more disadvantageous in terms of OS and DFS in the liver in patient groups with RAS mutation. (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). It has been reported that the presence of undetectable micrometastases in the liver in patients with KRAS mutation predisposes to R1 resection with parenchymal preservation and to reduced overall survival in patients with tumour recurrence in the residual liver(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our study, we think that caudate lobe may be a micrometastasis bed. Although OS and liver DFS were found to be more favourable in caudate lobectomy groups with higher parenchymal resection in our study, the presence of mutations in the parenchymal sparing group is not known due to the lack of genome data in the data set.\u003c/p\u003e \u003cp\u003eThere are very important limitations in our study. Due to the retrospective planning of the study, the necessary optimizations could not be made. The effect of isolated caudate lobe resection on patients could not be investigated. In fact, the group examined included extended right and left lobe resections. Due to the small number of patients, the disease in both lobes could not be examined separately. For this reason, no recommendation has been made to add caudectomy to a specific group. The genomic profile of the primary tumor is unknown. Therefore, the groups compared are quite heterogeneous. For a very common disease like CRLM, the sample group is relatively small. For all these reasons, our study is actually a pilot study.\u003c/p\u003e \u003cp\u003eIn conclusion, we hypothesised that the caudate lobe is more susceptible to micrometastases because it is an isolated specific lobe with high vascular and biliary drainage located at the hilar junction. Although superior oncological outcomes in terms of OS and DFS were found in the surgery group in which resection was added, the effect of these on the disease is not known since the genomic status of the patients, tumour biology and tumour differentiation were not revealed due to the insufficiency of the current data set. Nevertheless, our findings are promising.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eDISCLOSURE OF INTEREST\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFUNDING\u003c/h2\u003e \u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eProtocol/project development: MCG, ED . Data acquisition and interpretation of data: MCG,ED.Statistics analysis of data: ED. Manuscript drafing: MCG,ED . Manuscript Revision and accountablefor all aspects of the work: MCG, ED . All authors read and approved the fnal manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated and analysed during the current study are available in the [Colorectal-Liver-Metastases | Preoperative CT and Survival Data for Patients Undergoing Resection of Colorectal Liver Metastases] repository, [Simpson, A. L., Peoples, J., Creasy, J. M., Fichtinger, G., Gangai, N., Lasso, A., Keshava Murthy, K. N., Shia, J., D\u0026rsquo;Angelica, M. I., \u0026amp; Do, R. K. G. (2023). Preoperative CT and Survival Data for Patients Undergoing Resection of Colorectal Liver Metastases (Colorectal-Liver-Metastases) (Version 2) [Data set]. The Cancer Imaging Archive. https://doi.org/10.7937/QXK2-QG03\u003c/p\u003e\u003ch2\u003eINFORMED CONSENT AND PATIENT DETAİLS\u003c/b\u003e \u003cp\u003eThe authors declare that this report does not contain any personal information that could lead to the identification of the patients.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKlimeck L, Heisser T, Hoffmeister M, et al. Colorectal cancer: A health and economic problem. Best Pract Res Clin Gastroenterol 2023;66:101839.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartin J, Petrillo A, Smyth EC, et al. 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World J Surg Oncol 2023;21:1\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMargonis GA, Kreis ME, Wang JJ, et al. Impact and clinical usefulness of genetic data in the surgical management of colorectal cancer liver metastasis: a narrative review. Hepatobiliary Surg Nutr 2020;9:70516\u0026ndash;70716.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRhaiem R, Rached L, Tashkandi A, et al. Implications of RAS Mutations on Oncological Outcomes of Surgical Resection and Thermal Ablation Techniques in the Treatment of Colorectal Liver Metastases. Cancers (Basel);14. Epub ahead of print February 1, 2022. DOI: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/CANCERS14030816\u003c/span\u003e\u003cspan address=\"10.3390/CANCERS14030816\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimpson AL, Doussot A, Creasy JM, et al. Computed Tomography Image Texture: A Noninvasive Prognostic Marker of Hepatic Recurrence After Hepatectomy for Metastatic Colorectal Cancer. Ann Surg Oncol 2017;24:2482\u0026ndash;2490.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimpson, A. L., Peoples, J., Creasy, J. M., Fichtinger, G., Gangai, N., Lasso, A., Keshava Murthy, K. N., Shia, J., D\u0026rsquo;Angelica, M. I., \u0026amp; Do RKG. Preoperative CT and Survival Data for Patients Undergoing Resection of Colorectal Liver Metastases (Colorectal-Liver-Metastases) (Version 2) [Data set]. The Cancer Imaging Archive. Cancer Imaging Arch.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClark K, Vendt B, Smith K, et al. The Cancer Imaging Archive (TCIA): Maintaining and Operating a Public Information Repository. J Digit Imaging 2013;26:1045\u0026ndash;1057.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThoemmes F, Thoemmes F. Propensity score matching in SPSS Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://arxiv.org/abs/1201.6385v1\u003c/span\u003e\u003cspan address=\"https://arxiv.org/abs/1201.6385v1\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 2012. Accessed November 6, 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHackl C, Neumann P, Gerken M, et al. Treatment of colorectal liver metastases in Germany: A ten-year population-based analysis of 5772 cases of primary colorectal adenocarcinoma. BMC Cancer 2014;14:1\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuo IM, Huang SF, Chiang JM, et al. Clinical features and prognosis in hepatectomy for colorectal cancer with centrally located liver metastasis. World J Surg Oncol 2015;13:1\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKumon M, Kumon T, Sakamoto Y. Demonstration of the right-side boundary of the caudate lobe in a liver cast. Glob Heal Med 2022;4:52\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbdalla EK, Vauthey JN, Couinaud C. The caudate lobe of the liver implications of embryology and anatomy for surgery. Surg Oncol Clin N Am 2002;11:835\u0026ndash;848.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang J, Sun DL, Xu D, et al. A comprehensive study and extensive review of the Caudate lobe: The last piece of \u0026ldquo;Jigsaw\u0026rdquo; puzzle. Asian J Surg. Epub ahead of print June 16, 2023. DOI: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/J.ASJSUR.2023.06.003\u003c/span\u003e\u003cspan address=\"10.1016/J.ASJSUR.2023.06.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHosokawa I, Shimizu H, Yoshidome H, et al. Surgical strategy for hilar cholangiocarcinoma of the left-side predominance: Current role of left trisectionectomy. Ann Surg 2014;259:1178\u0026ndash;1185.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKadiyoran C, Cizmecioglu HA, Cure E, et al. Liver metastasis in colorectal cancer: evaluation of segmental distribution. Gastroenterol Rev Gastroenterol 2019;14:188\u0026ndash;192.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbdalla EK, Ribero D, Pawlik TM, et al. Resection of hepatic colorectal metastases involving the caudate lobe: Perioperative outcome and survival. J Gastrointest Surg 2007;11:66\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePillai SA, Sathyanesan J, Perumal S, et al. Isolated caudate lobe resection: technical challenges. Ann Gastroenterol Q Publ Hell Soc Gastroenterol 2013;26:150.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhan AZ, Wong VK, Malik HZ, et al. The impact of caudate lobe involvement after hepatic resection for colorectal metastases. Eur J Surg Oncol 2009;35:510\u0026ndash;514.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThomas RL, Lordan JT, Devalia K, et al. Liver resection for colorectal cancer metastases involving the caudate lobe. Br J Surg 2011;98:1476\u0026ndash;1482.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWicherts DA, De Haas RJ, Andreani P, et al. Short- and long-term results of extended left hepatectomy for colorectal metastases. HPB 2011;13:536\u0026ndash;543.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVigan\u0026ograve; L, Capussotti L, Lapointe R, et al. Early recurrence after liver resection for colorectal metastases: Risk factors, prognosis, and treatment. A LiverMetSurvey-based study of 6,025 patients. Ann Surg Oncol 2014;21:1276\u0026ndash;1286.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRengers T, Warner S. Surgery for colorectal liver metastases: Anatomic and non-anatomic approach. Surg (United States) 2023;174:119\u0026ndash;122.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePapaconstantinou D, Pararas N, Pikouli A, et al. Precision Surgery of Colorectal Liver Metastases in the Current Era: A Systematic Review. Cancers 2023, Vol 15, Page 2083 2023;15:2083.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Q, Peng J, Ye M, et al. KRAS Mutation Predicted More Mirometastases and Closer Resection Margins in Patients with Colorectal Cancer Liver Metastases. Ann Surg Oncol 2020;27:1164\u0026ndash;1173.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Colorektal carcinoma, Liver, Metastasis","lastPublishedDoi":"10.21203/rs.3.rs-4454993/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4454993/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBACKGROUND\u003c/h2\u003e \u003cp\u003eThis study aimed to evaluate the management of colorectal liver metastases (CRLM) and the role of anatomical resections, with particular reference to the caudate lobe.\u003c/p\u003e\u003ch2\u003eMETHODS\u003c/h2\u003e \u003cp\u003eWe obtained all patient data from the Preoperative CT and Survival Data for Patients Undergoing Resection of Colorectal Liver Metastases dataset. Patients who underwent total caudate lobe resection without radiological evidence of metastases were analyzed. To investigate the net effect of caudate lobe resection, propensity score matching (PSM) was applied to most other parameters. The Kaplan-Meier and log-rank tests were used to calculate overall survival (OS) and liver disease-free survival (liver-DFS) and to investigate differences between groups.\u003c/p\u003e\u003ch2\u003eRESULTS\u003c/h2\u003e \u003cp\u003ePatients who underwent total caudate resection had better results in terms of overall survival in the whole data set and after PSM (respectively, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 HR: 0.43, 95%CI:0.26\u0026ndash;0.72 p:0.024, HR: 0.65 95%CI:0.59\u0026ndash;0.79).Patients who underwent total caudate resection had better results in terms of liver-DFS in the whole data set set and after PSM (respectively, p\u0026thinsp;=\u0026thinsp;0.014, HR\u0026thinsp;=\u0026thinsp;0.46, 95%CI: 0.24\u0026ndash;0.85, p\u0026thinsp;=\u0026thinsp;0.026 HR\u0026thinsp;=\u0026thinsp;0.5, 95%CI: 0.37\u0026ndash;0.79)\u003c/p\u003e\u003ch2\u003eCONCLUSİONS\u003c/h2\u003e \u003cp\u003eWe believe that the addition of total caudate lobe resection to resection may contribute to both OS and liver DFS.\u003c/p\u003e","manuscriptTitle":" Impact of caudate lobe resection on overall survival and liver disease-free survival in colorectal liver metastases: A pilot study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-12 17:26:21","doi":"10.21203/rs.3.rs-4454993/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f411a0b0-ad8a-41bb-9bb6-8ee61586f7e3","owner":[],"postedDate":"June 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":32999870,"name":"Biological sciences/Cancer"},{"id":32999871,"name":"Health sciences/Anatomy"},{"id":32999872,"name":"Health sciences/Gastroenterology"}],"tags":[],"updatedAt":"2024-09-17T05:24:14+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-12 17:26:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4454993","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4454993","identity":"rs-4454993","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}