{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:34:32Z","timestamp":1791819272605,"version":"4.3.4"},"reference-count":62,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The purpose of this study was to conduct a systematic review and meta-analysis of case reports presenting HCC spread to the diaphragm muscle and to determine possible risk factors for this condition. An extensive literature search was performed using the following electronic databases: MEDLINE, CINAHL, ScienceDirect, Google Scholar, and DOAJ. A total of 18 articles describing 27 hepatocellular carcinoma patients were included in this review. The presence of HCC cells in the superior liver segment is strongly associated with metastases to the diaphragm. Among the two types of diaphragm involvement by HCC cells, diaphragm infiltration occurs much more frequently than diaphragm adhesion. However, an HCC nodule in the 8th liver segment and a higher number of liver segments involved by HCC cells predispose patients to diaphragm adhesion. Hepatitis B is a risk factor for diaphragm metastases in recurrent HCC. The tumor diameter is not associated with HCC spread to the diaphragm muscle. We did not find specific symptoms reported by patients that could indicate HCC metastasis to the diaphragm muscle. The presence of hepatitis B and the localization of HCC cells in superior liver segments, especially in the 8th liver segment, should be take into consideration in the diagnostic process.<\/jats:p>","DOI":"10.3390\/cancers16173076","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T09:57:47Z","timestamp":1725443867000},"page":"3076","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Hepatocellular Carcinoma (HCC) Metastasis to the Diaphragm Muscle: A Systematic Review and Meta-Analysis of Case Reports"],"prefix":"10.3390","volume":"16","author":[{"given":"Janusz","family":"Kocjan","sequence":"first","affiliation":[{"name":"Diaphragm Concept Academy, Private Clinic Centre Specializing in Treating of Diaphragm Disorders, 32-300 Olkusz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Rydel","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Faculty of Medicine with Dentistry Division, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Adamek","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Faculty of Medicine with Dentistry Division, Medical University of Silesia, 40-055 Katowice, Poland"},{"name":"Faculty of Health Sciences with Institute of Maritime and Tropical Medicine, Department of Radiology, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S361","DOI":"10.21037\/jgo.2020.02.08","article-title":"Addressing the worldwide hepatocellular carcinoma: Epidemiology, prevention and management","volume":"12","author":"Samant","year":"2021","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kinsey, E., and Lee, H.M. (2024). Management of Hepatocellular Carcinoma in 2024: The Multidisciplinary Paradigm in an Evolving Treatment Landscape. Cancers, 16.","DOI":"10.3390\/cancers16030666"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.joim.2020.02.002","article-title":"Traditional Chinese medicine targeting cancer stem cells as an alternative treatment for hepatocellular carcinoma","volume":"18","author":"Tang","year":"2020","journal-title":"J. Integr. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.2147\/JHC.S420603","article-title":"Updates in Characteristics and Survival Rates of Hepatocellular Carcinoma in a Nationwide Cohort of Real-World US Patients, 2003\u20132021","volume":"10","author":"Tran","year":"2023","journal-title":"J. Hepatocell. Carcinoma."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"86","DOI":"10.4103\/jrms.JRMS_1017_18","article-title":"Predictors of 5 year survival rate in hepatocellular carcinoma patients","volume":"24","author":"Sarveazad","year":"2019","journal-title":"J. Res. Med. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.omtn.2022.05.031","article-title":"Upregulation of miR-520c-3p via hepatitis B virus drives hepatocellular migration and invasion by the PTEN\/AKT\/NF-\u03baB axis","volume":"29","author":"Liu","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s43657-023-00136-8","article-title":"A Noninvasive Approach to Evaluate Tumor Immune Microenvironment and Predict Outcomes in Hepatocellular Carcinoma","volume":"3","author":"Wu","year":"2023","journal-title":"Phenomics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1111\/j.1440-1746.2005.03919.x","article-title":"Clinical features of hepatocellular carcinoma with extrahepatic metastases","volume":"20","author":"Natsuizaka","year":"2005","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1148\/radiology.216.3.r00se24698","article-title":"Extrahepatic metastases of hepatocellular carcinoma","volume":"216","author":"Katyal","year":"2000","journal-title":"Radiology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1002\/1097-0142(19901115)66:10<2174::AID-CNCR2820661022>3.0.CO;2-A","article-title":"Growth and spread of hepatocellular carcinoma. A review of 240 consecutive autopsy cases","volume":"66","author":"Yuki","year":"1990","journal-title":"Cancer"},{"key":"ref_12","first-page":"441","article-title":"Tumors of the diaphragm","volume":"8","author":"Weksler","year":"1998","journal-title":"Chest Surg. Clin. N. Am."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/BF00048966","article-title":"Tumor invasion and host extracellular matrix","volume":"2","author":"Pauli","year":"1983","journal-title":"Cancer Metastasis Rev."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Herring, C.L., Harrelson, J.M., and Scully, S.P. (1998). Metastatic carcinoma to skeletal muscle. A report of 15 patients. Clin. Orthop. Relat. Res., 272\u2013281.","DOI":"10.1097\/00003086-199810000-00029"},{"key":"ref_15","first-page":"112","article-title":"Metastatic carcinoma of skeletal muscles","volume":"35","author":"Mulsow","year":"1943","journal-title":"Arch. Pathol."},{"key":"ref_16","first-page":"224","article-title":"Network of Breathing","volume":"85","author":"Kocjan","year":"2017","journal-title":"Multifunct. Role Diaphragm Rev. Adv. Respir. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1148\/radiographics.14.3.8066267","article-title":"Direct dissemination of pathologic abdominal processes through perihepatic ligaments: Identification with CT","volume":"14","author":"Arenas","year":"1994","journal-title":"Radiographics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e220076","DOI":"10.1148\/rg.220076","article-title":"Hepatocellular Carcinoma Supplied by the Inferior Phrenic Artery or Cystic Artery: Anatomic and Technical Considerations","volume":"43","author":"Kim","year":"2023","journal-title":"Radiographics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/XEB.0000000000000064","article-title":"Conducting systematic reviews of association (etiology): The Joanna Briggs Institute\u2019s approach","volume":"13","author":"Moola","year":"2015","journal-title":"Int. J. Evid. Based Healthc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.2169\/internalmedicine.50.5499","article-title":"Ectopic Hepatocellular Carcinoma of the Left Sub-diaphragm with Metastasis","volume":"50","author":"Nishikawa","year":"2011","journal-title":"Intern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kaur, R., Abdullah, B., and Rajasingam, V. (2008). Hepatocellular carcinoma with extension to the diaphragm, falciform ligament, rectus abdominis and paraumbilical vein. Biomed. Imaging Interv. J., 4.","DOI":"10.2349\/biij.4.4.e37"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1272\/jnms.78.30","article-title":"Resection of hepatocellular carcinoma recurring in the diaphragm after right hepatic lobectomy","volume":"78","author":"Ueda","year":"2011","journal-title":"J. Nippon. Med. Sch."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1749-7922-7-30","article-title":"One stage resection of spontaneous rupture of hepatocellular carcinoma in the triangular ligament with diaphragm invasion: Case report and review of the literature","volume":"7","author":"Park","year":"2012","journal-title":"World J. Emerg. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1272\/jnms.79.147","article-title":"Surgical treatment of a patient with diaphragmatic invasion by a ruptured hepatocellular carcinoma with biliary and portal venous tumor thrombi","volume":"79","author":"Maruyama","year":"2012","journal-title":"J. Nippon. Med. Sch."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4583","DOI":"10.3748\/wjg.14.4583","article-title":"Direct invasion to the colon by hepatocellular carcinoma: Report of two cases","volume":"14","author":"Hirashita","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6231","DOI":"10.12998\/wjcc.v11.i26.6231","article-title":"Left epigastric isolated tumor fed by the inferior phrenic artery diagnosed as ectopic hepatocellular carcinoma: A case report","volume":"11","author":"Liu","year":"2023","journal-title":"World J. Clin. Cases"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"rjaa084","DOI":"10.1093\/jscr\/rjaa084","article-title":"En bloc transdiaphragmatic lung resection for locally advanced hepatocellular carcinoma: A case report","volume":"2020","author":"Lee","year":"2020","journal-title":"J. Surg. Case Rep."},{"key":"ref_29","first-page":"229","article-title":"Images in surgery","volume":"127","author":"Chen","year":"2000","journal-title":"Front. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1186\/s40792-020-01078-3","article-title":"Conversion hepatectomy for advanced hepatocellular carcinoma after right portal vein transection and lenvatinib therapy","volume":"6","author":"Ohya","year":"2020","journal-title":"Surg. Case Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1111\/j.1440-1746.2009.05962.x","article-title":"Hepatobiliary and pancreatic: Isolated diaphragmatic metastasis from hepatocellular carcinoma","volume":"24","author":"Sano","year":"2009","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1186\/s40792-022-01530-6","article-title":"Primary spindle cell tumor originating from the liver that was difficult to diagnose","volume":"8","author":"Ikehara","year":"2022","journal-title":"Surg. Case Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s00795-013-0041-0","article-title":"Collision tumors of hepatocellular carcinoma and malignant peritoneal mesothelioma","volume":"46","author":"Uemoto","year":"2013","journal-title":"Med. Mol. Morphol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s40792-016-0241-7","article-title":"Surgical resection of recurrent extrahepatic hepatocellular carcinoma with tumor thrombus extending into the right atrium under cardiopulmonary bypass: A case report and review of the literature","volume":"2","author":"Ohta","year":"2016","journal-title":"Surg. Case Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e256931","DOI":"10.1136\/bcr-2023-256931","article-title":"Large hepatocellular carcinoma treated with sequential SBRT and immunotherapy with anti-VEGF (Vascular Endothelial Growth Factor) therapy","volume":"16","author":"Bidarmaghz","year":"2023","journal-title":"BMJ Case Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1159\/000050137","article-title":"Successful Treatment of Dissemination of Hepatocellular Carcinoma to the Pleura and Diaphragm after Percutaneous Liver Biopsy","volume":"18","author":"Uenishi","year":"2001","journal-title":"Dig. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1600-0676.1998.tb00161.x","article-title":"Diaphragmatic and subcutaneous seeding of hepatocellular carcinoma following fine-needle aspiration biopsy","volume":"18","author":"Navarro","year":"1998","journal-title":"Liver"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s11701-018-0880-8","article-title":"Successful robotic extirpation of diaphragmatic seeding of hepatocellular carcinoma after previous rupture","volume":"13","author":"Lee","year":"2019","journal-title":"J. Robot. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s005950170082","article-title":"Hepatocellular Carcinoma with a Sarcomatous Appearance: Report of a Case","volume":"31","author":"Tsuji","year":"2001","journal-title":"Surg. Today"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"78","DOI":"10.23838\/pfm.2021.00086","article-title":"Infiltrative invasion of the diaphragm: An uncommon manifestation of recurrent hepatocellular carcinoma A retrospective cohort study","volume":"6","author":"Kim","year":"2022","journal-title":"Precis. Future Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1188\/08.CJON.759-766","article-title":"Symptom management in hepatocellular carcinoma","volume":"12","author":"Sun","year":"2008","journal-title":"Clin. J. Oncol. Nurs."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105728","DOI":"10.1016\/j.ijscr.2021.105728","article-title":"Laparoscopic repair of diaphragmatic hernia after radiofrequency ablation for hepatocellular carcinoma: Case report","volume":"81","author":"Ushijima","year":"2021","journal-title":"Int. J. Surg. Case Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S241","DOI":"10.2214\/AJR.04.0931","article-title":"Diaphragmatic hernia after radiofrequency ablation therapy for hepatocellular carcinoma","volume":"186","author":"Shibuya","year":"2006","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4300","DOI":"10.3748\/wjg.14.4300","article-title":"Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis","volume":"14","author":"Gomaa","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1159\/000480186","article-title":"Impact of Tumor Factors on Survival in Patients with Hepatocellular Carcinoma Classified Based on Kinki Criteria Stage B2","volume":"35","author":"Arizumi","year":"2017","journal-title":"Dig. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"257","DOI":"10.2957\/kanzo.54.257","article-title":"The significance of extrahepatic feeding arteries in patients with extrahepatically growing hepatocellular carcinoma infiltrating into other organs","volume":"54","author":"Miyagawa","year":"2013","journal-title":"Kanzo"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1102\/1470-7330.2013.0040","article-title":"Quantitative characterization of hepatocellular carcinoma and metastatic liver tumor by CT perfusion","volume":"13","author":"Hayano","year":"2013","journal-title":"Cancer Imaging"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/hpb.12157","article-title":"Three-dimensional volumetry in 107 normal livers reveals clinically relevant inter-segment variation in size","volume":"16","author":"Mise","year":"2014","journal-title":"HPB"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.clinimag.2023.03.002","article-title":"Multimodality imaging approach in identifying invasive hepatocellular carcinoma","volume":"97","author":"Shroff","year":"2023","journal-title":"Clin. Imaging"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Angeli-Pahim, I., Chambers, A., Duarte, S., and Zarrinpar, A. (2023). Current Trends in Surgical Management of Hepatocellular Carcinoma. Cancers, 15.","DOI":"10.3390\/cancers15225378"},{"key":"ref_51","unstructured":"Amin, M.B., Greene, F.L., Edge, S.B., Compton, C.C., Gershenwald, J.E., Brookland, R.K., Meyer, L., Gress, D.M., Byrd, D.R., and Winchester, D.P. (2017). AJCC Cancer Staging Manual, Springer. [8th ed.]."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ijsu.2018.03.033","article-title":"Hepatocellular carcinoma with en bloc diaphragmatic resection: A single-center experience over 14 years","volume":"53","author":"Liu","year":"2018","journal-title":"Int. J. Surg."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e12194","DOI":"10.1097\/MD.0000000000012194","article-title":"Outcomes of anterior approach major hepatectomy with diaphragmatic resection for single huge right lobe HCC with diaphragmatic invasion","volume":"97","author":"Zheng","year":"2018","journal-title":"Medicine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/bjs.1800820242","article-title":"Resection of hepatocellular carcinoma with diaphragmatic invasion","volume":"82","author":"Lau","year":"1995","journal-title":"Br. J. Surg."},{"key":"ref_55","first-page":"1497","article-title":"Surgical results of hepatic resection for hepatocellular carcinoma with gross diaphragmatic invasion","volume":"52","author":"Lin","year":"2005","journal-title":"Hepatogastroenterology"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Invenizzi, F., Iavarone, M., Donato, M.F., Mazzucco, A., Torre, M., Conforti, S., Rimessi, A., Zavaglia, C., Schiavon, M., and Comacchio, G. (2020). Pulmonary Resection for Metastasis of Hepatocellular Carcinoma Recurring After Liver Transplant: An Italian Multicenter Experience. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00381"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12957-021-02138-0","article-title":"Surgical outcomes of pulmonary metastasectomy in hepatocellular carcinoma patients according to approach method: Thoracoscopic versus open approach","volume":"19","author":"Lee","year":"2021","journal-title":"World J. Surg. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s12072-008-9052-7","article-title":"Prognostic analysis of pulmonary metastases from hepatocellular carcinoma","volume":"2","author":"Zhang","year":"2008","journal-title":"Hepatol. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e31399","DOI":"10.1097\/MD.0000000000031399","article-title":"Short-term prognosis for hepatocellular carcinoma patients with lung metastasis: A retrospective cohort study based on the SEER database","volume":"101","author":"Chen","year":"2022","journal-title":"Medicine"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.2147\/JHC.S417273","article-title":"Effects of Clinical and Tumor Characteristics on Survival in Patients with Hepatocellular Carcinoma with Bone Metastasis","volume":"10","author":"Ozer","year":"2023","journal-title":"J. Hepatocell. Carcinoma"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"207","DOI":"10.3857\/roj.2019.00136","article-title":"Prognostic factors in hepatocellular carcinoma patients with bone metastases","volume":"37","author":"Kim","year":"2019","journal-title":"Radiat. Oncol. J."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Yuan, X., Zhuang, M., Zhu, X., Cheng, D., Liu, J., Sun, D., Qiu, X., Lu, Y., and Sartorius, K. (2022). Emerging Perspectives of Bone Metastasis in Hepatocellular Carcinoma. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.943866"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/17\/3076\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:48:40Z","timestamp":1760111320000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/17\/3076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,4]]},"references-count":62,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["cancers16173076"],"URL":"https:\/\/doi.org\/10.3390\/cancers16173076","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,4]]}}}