Management of peritoneal carcinomatosis from appendiceal mucinous adenocarcinoma by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: Experience on 48 patients from a single center

Management of peritoneal carcinomatosis from appendiceal mucinous adenocarcinoma by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: Experience on 48 patients from a single center | 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 Research Article Management of peritoneal carcinomatosis from appendiceal mucinous adenocarcinoma by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: Experience on 48 patients from a single center Jie Jiao, Chengzhen Li, Guanying Yu, Zhenpeng Liu, Lei Zhang, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3014807/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 Purpose To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of patients with peritoneal carcinomatosis (PC) from appendiceal mucinous adenocarcinoma. Methods The clinical data of 48 cases of PC with mucinous appendiceal adenocarcinoma treated with CRS + HIPEC were retrospectively analyzed. The study indices included survival, perioperative safety, and adverse reactions. Results The peritoneal cancer index (PCI) score ranged from 1 to 39 in the 48 patients with peritoneal cancer of appendix adenocarcinoma, with a median score of 21. The degree of tumor reduction (CC) was 0 to 3, with a median score of 2. The follow-up period ranged from 16 to 44 months. Of the 48 patients, 18 patients (37.5%) died and 30 patients (62.5%) survived. The median survival time was 37 months (95% CI: 26.0-47.9 months). The 1-, 2-, and 3-year survival rates were 78.0%, 60.9%, and 51.4%. The 1-, 2-, and 3-year survival rates in patients with PCI ≥ 20 were 63.6%, 43.8%, and 32.8%, respectively, while the patients with PCI 1, and 95%, 88.2%, and 69.4% in patients with CC ≤ 1 (P = 0.004). The incidence of perioperative adverse events was 8.3%, including 3 cases of incision infection and 1 case of intestinal anastomotic fistula. Conclusion CRS + HIPEC is feasible and effective in the treatment of patients with peritoneal carcinoma from appendiceal mucinous adenocarcinoma. appendiceal mucinous adenocarcinoma cytoreductive surgery hyperthermic intraperitoneal chemotherapy Figures Figure 1 Figure 2 Figure 3 1. Introduction In the realm of digestive tract tumors, appendiceal tumors have a low incidence, representing less than 0.5% of all gastrointestinal tumors 1 . Besides, there are few patients with a definitive preoperative diagnosis, and the majority of cases are diagnosed through intraoperative or postoperative pathological examination. Tumors account for 0.7–1.4% of all post-appendectomy specimens 2 . Among them, the appendiceal mucinous tumor is a highly uncommon pathological type, categorized as a low-grade malignant epithelial tumor of the appendix, accounting for approximately 0.2–0.3% of all postoperative pathology cases following appendicitis surgery 3 . Since the 5th edition of the 2019 classification of digestive tumors, a distinction has been made between low-grade mucinous tumors of the appendix (LAMN) and high-grade mucinous carcinomas of the appendix (MA, mucinous adenocarcinoma of the appendix). This differentiation allows for a more precise classification of these types of tumors 4 . Among these tumors, the incidence of mucinous adenocarcinoma of the appendix (MA) is even lower, accounting for only 0.01–0.08% of the total number of appendiceal tumors. It is a relatively rare subtype of appendiceal tumors 5 . Adenocarcinoma of the appendix is known for its tendency to invade the serosal membrane of the appendix, penetrate the wall, and spread to the abdominal and pelvic peritoneum, resulting in peritoneal metastasis. This peritoneal dissemination is commonly referred to as peritoneal cancer, indicating the spread of cancer cells throughout the peritoneal cavity 6 . Currently, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in prolonging the survival of patients with gastric cancer, colorectal cancer, and ovarian cancer. This treatment approach has demonstrated significant clinical efficacy and has become an established treatment modality in the international medical community. Furthermore, clinical studies investigating the efficacy of CRS and HIPEC in the management of mucinous adenocarcinoma of the appendix and peritoneal cancer are increasingly being conducted, aiming to further validate its clinical effectiveness in these specific conditions 7 . The purpose of this article is to summarize the experience of treatment of 48 cases of peritoneal metastasis of mucinous adenocarcinoma of the appendix. 2. Materials and methods 2.1. General Information We conducted a retrospective analysis of forty-eight patients with peritoneal metastatic appendiceal mucinous adenocarcinoma who were treated at our hospital from June 2017 to July 2020. The study focused on various indicators, including symptoms, signs, laboratory examinations, medical imaging examinations, perioperative information, and specifically emphasized efficacy and safety data. 2.2. The main process of CRS + HIPEC Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is performed by a specialized peritoneal cancer team. The procedure begins with a median abdominal incision made under general anesthesia. A thorough exploration is conducted during laparotomy to assess the extent of tumor invasion, ranging from the diaphragm peritoneum to the pelvic peritoneum. The peritoneal cancer index (PCI) is determined using the Sugarbaker Assessment and Record System 8 , 9 . Additionally, detailed records of the nature and quantity of peritoneal effusion are documented. Following the surgical protocol formulated by Sugarbaker, tumor regions, involved organs or tissues, and lymph nodes are removed. Complete tumor reduction is pursued, and if achievable, radical excision is performed. In cases where complete tumor reduction cannot be achieved, maximum CRS is conducted, and the completeness of tumor reduction (CC) is scored. Open HIPEC is initiated after CRS is completed. During HIPEC, a liquid input tube is placed in the shallow abdominal pelvic area, while the output tube is placed in the deep area. A circular retractor is used to hold the abdominal incision open, and a disposable incision protective film is applied and closed. The poris Medical (Bright dominate, BRM) heat body cavity perfusion treatment system (BR-TRG-II from Guangzhou poris Medical Technology Co. Ltd.) is connected and started, with relevant parameters set. Each chemotherapeutic agent is added to 3 L of normal saline, heated to (43 ± 0.5) ℃, and infused continuously at a flow rate of 400 mL/min for 30 minutes. The HIPEC chemotherapy regimen consists of lobaplatin 50 mg or Tomudex 4 mg. After completing HIPEC, the chemotherapy solution is drained, and reconstruction of organs such as the digestive tract and urinary tract is performed. Bleeding is controlled, and the abdomen is closed after placing a drainage tube. The patient is safely returned to the ward for monitoring and further treatment. During the surgery, four HIPEC special tubes are placed. HIPEC is performed four times postoperatively, with intervals of ≥ 24 hours between each treatment. 2.3. Postoperative chemotherapy and follow-up After recovering from surgery and being discharged, all patients underwent 6–8 cycles of chemotherapy with FOLFOX or FOLFIRI. Regular follow-up was conducted through telephone or outpatient services, which included monitoring their survival status, recording any adverse events experienced, monitoring tumor markers, and performing imaging reassessment of the abdomen and pelvis. The administration of targeted drugs, such as bevacizumab or cetuximab, was determined based on the results of genetic testing. 2.4. Statistical analysis Statistical analysis was performed using SPSS 21.0 software. Measurement data were presented as mean ± standard deviation (x ± s), and a t-test was used to compare groups. Enumeration data were reported as frequencies, and the χ2 test was used for group comparisons. Survival analysis was conducted using the Kaplan-Meier method, and the log-rank test was utilized for univariate survival analysis. A significance level of P < 0.05 was considered statistically significant. 3. Results 3.1. Main clinical features Among the 48 patients with peritoneal metastasis from appendiceal mucinous adenocarcinoma, 25 cases were male (52.1%), while 23 cases were female (47.9%). The age of the patients ranged from 30 to 84, with a median age of 57 years. The PCI scores ranged from 1 to 39, with a median score of 21. The CC scores ranged from 0 to 3, with a median score of 2. Serious adverse events occurred in 4 cases (14.3%) 15 days after surgery. (Table 1 ) Table 1 The main clinicopathological Characteristics of 48 patients with peritoneal carcinoma of appendiceal adenocarcinoma Characteristics n (%) Gender Male 25(52.1%) Female 23(47.9%) Median age 57 PCI Median PCI 21 < 20 22(45.8%) ≥ 20 26(54.2%) CC(score) Median CC 2 0 4(8.3%) 1 18(37.5%) 2 18(37.5%) 3 8(16.7%) PCI: peritoneal cancer index; CC: completeness of cytoreduction. 3.2. Survival curve analysis The follow-up period for the 48 patients ranged from 16 to 44 months. Among them, 18 patients (37.5%) unfortunately passed away, while 30 patients (62.5%) survived. The median survival time was 37 months (95%CI: 26.0-47.9 months). The 1-year, 2-year, and 3-year survival rates were 78.0%, 60.9%, and 51.4% respectively. (Fig. 1 ) Correlation factor analysis revealed that PCI and CC were identified as risk factors influencing the survival of patients. In patients with PCI ≥ 20, the 1-year, 2-year, and 3-year survival rates were 63.6%, 43.8%, and 32.8% respectively, whereas in patients with PCI 1 demonstrated 1-year, 2-year, and 3-year survival rates of 64.4%, 40.9%, and 40.9%, while patients with CC ≤ 1 had rates of 95%, 88.2%, and 69.4% (P = 0.004). Please refer to Fig. 2 for graphical representation. (Fig. 3 ) 4. Discussion Peritoneal cancer can be classified as primary or secondary peritoneal cancer 10 . Primary peritoneal cancer includes primary peritoneal cancer and malignant peritoneal mesothelioma, while secondary peritoneal cancer refers to peritoneal implantation metastasis from gastrointestinal and gynecological tumors 11 , 12 , 13 , 14 . Clinical studies have demonstrated that cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the most effective treatment approach for peritoneal cancer arising from gastrointestinal and gynecological tumors. This treatment strategy has been shown to prolong survival and improve the quality of life of patients, and in some cases, it can even lead to clinical cure 15 , 16 , 17 , 18 . Appendiceal adenocarcinoma is a relatively rare form of cancer, accounting for approximately 0.2–0.5% of cases. However, its incidence has been increasing over the years 19 . Most patients with appendiceal adenocarcinoma are already diagnosed with peritoneal implantation metastasis. Studies have reported that CRS + HIPEC can achieve favorable clinical outcomes in patients with appendiceal adenocarcinoma and peritoneal metastasis 20 , 21 . Compared to traditional palliative surgery and chemotherapy, this treatment regimen offers obvious advantages: (1) CRS can remove visible tumor tissue through organ resection and peritoneal resection, minimizing the tumor burden; (2) HIPEC kills micro-metastases and free cancer cells, completely eliminating primary tumors and metastases in the abdominal cavity. 22 , 23 . The main mechanisms of HIPEC in the treatment of peritoneal cancer are as follows: (1) The peritoneal-plasma barrier limits the absorption of macromolecular drugs in the peritoneal membrane, delaying the metabolism of chemotherapeutic drugs and maintaining a high intraperitoneal drug concentration, which is 10 − 1,000 times higher than the concentration in the blood. This increases the lethality of intraperitoneal tumors. (2) At the tissue level, the thermal effect induces microvascular embolization in tumor tissues, leading to degeneration and necrosis of tumor cells. It disrupts the self-stabilization mechanism of tumor cells, interferes with tumor cell metabolism, activates lysosomes, and disrupts protein, DNA, and RNA synthesis in tumor cells at the molecular level. (3) The thermal effect exhibits a synergistic effect with chemotherapeutic drugs and is significantly enhanced at 42°C. (4) During the perfusion process, the shear force of fluid flow directly induces tumor cell death, and tissue erosion leads to tumor cell apoptosis. 18 , 24 , 25 . 5. Conclusions In conclusion, this study demonstrates the effectiveness and feasibility of the CRS + HIPEC comprehensive diagnosis and treatment technique for mucinous adenocarcinoma of the appendix combined with peritoneal metastasis. However, this study has some limitations, including the small number of cases included and the lack of a prospective randomized controlled design. Further confirmation of the efficacy and safety of CRS + HIPEC is needed to benefit a larger number of patients with peritoneal carcinoma of mucinous adenocarcinoma of the appendix. Declarations Acknowledgements Not applicable. Authors’ contributions Peiming Guo conceived the study. Jie Jiao, Chengzhen Li, Guanying Yu, Zhenpeng Liu, Lei Zhan, Xiaoyan Shi, Jingdu Yan, Houjun Zhang and Jingbo Shi collected the study materials and patient data. Jie Jiao drafted the manuscript. Jie Jiao analyzed data. All authors confrm the authenticity of all the raw data. All authors wrote the manuscript, and read and approved the final manuscript. Funding This work was supported by the Science and Technology Plan Project of Jinan Municipal Health and Family Planning Commission (grant no. 2019-2- 06). Availability of data and materials The datasets used and/or analyzed in the present study are available from the corresponding author upon reasonable request. Ethics approval and consent to participate The study was done after an agreement from the local ethics committee (Jinan Central Hospital ethics committee) and with the patients’ informed consent. (Ref.: 2019-107-01). Date of approval: August 1, 2019. Consent for publication Not applicable. Competing interests The authors declare no competing interests. References Shaib W L , Assi R , Shamseddine A, et al., Appendiceal Mucinous Neoplasms: Diagnosis and Management. Oncologist, 2017. 22(9): p. 1107-1116. Valasek, M.A. and R.K. Pai, An Update on the Diagnosis, Grading, and Staging of Appendiceal Mucinous Neoplasms. Adv Anat Pathol, 2018. 25(1): p. 38-60. Nutu O A , Quinto A M , Municio A M, et al., Mucinous appendiceal neoplasms: Incidence, diagnosis and surgical treatment. Cir Esp, 2017. 95(6): p. 321-327. Ahadi M , Sokolova A , Brown I, et al., The 2019 World Health Organization Classification of appendiceal, colorectal and anal canal tumours: an update and critical assessment. Pathology, 2021. 53(4): p. 454-461. Erickson, L.A. and M. Rivera, Mucinous Neoplasm of the Appendix and Pseudomyxoma Peritonei. Mayo Clin Proc, 2018. 93(2): p. 267-268. Carr NJ, Bibeau F, Bradley RF, et al., The histopathological classification, diagnosis and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinomas and pseudomyxoma peritonei. Histopathology, 2017. 71(6): p. 847-858. Seshadri, R.A. and O. Glehen, Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer. World J Gastroenterol, 2016. 22(3): p. 1114-30. Jacquet, P. and P.H. Sugarbaker, Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res, 1996. 82: p. 359-74. Bartoška P, Antoš F, Vítek P, et al., Pseudomyxoma Peritonei. Klin Onkol, 2019. 32(5): p. 329-332. Dong D, Tang L, Li ZY, et al., Development and validation of an individualized nomogram to identify occult peritoneal metastasis in patients with advanced gastric cancer. Ann Oncol, 2019. 30(3): p. 431-438. Clement, P.B., R.H. Young, and R.E. Scully, Malignant mesotheliomas presenting as ovarian masses. A report of nine cases, including two primary ovarian mesotheliomas. Am J Surg Pathol, 1996. 20(9): p. 1067-80. Schwartz, P.B. and D.E. Abbott, ASO Author Reflections: Predictors of Fiscal Outcomes in CRS-HIPEC and Opportunities for Improvement. Ann Surg Oncol, 2020. 27(13): p. 4929-4930. Sánchez-Hidalgo JM, Rodríguez-Ortiz L, Arjona-Sánchez Á, et al., Colorectal peritoneal metastases: Optimal management review. World J Gastroenterol, 2019. 25(27): p. 3484-3502. Ji ZH, An SL, Li XB, et al., Long-term progression-free survival of hepatocellular carcinoma with synchronous diffuse peritoneal metastasis treated by CRS+HIPEC: A case report and literature review. Medicine (Baltimore), 2019. 98(8): p. e14628. Bonnot PE, Piessen G, Kepenekian V, et al., Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer With Peritoneal Metastases (CYTO-CHIP study): A Propensity Score Analysis. J Clin Oncol, 2019. 37(23): p. 2028-2040. Ba, M., et al., Cytoreductive surgery and HIPEC for malignant ascites from colorectal cancer - a randomized study. Medicine (Baltimore), 2020. 99(33): p. e21546. Ba M, Chen C, Long H, et al., Colorectal Peritoneal Metastases Treated by Perioperative Systemic Chemotherapy and Cytoreductive Surgery With or Without Mitomycin C-Based HIPEC: A Comparative Study Using the Peritoneal Surface Disease Severity Score (PSDSS). Ann Surg Oncol, 2020. 27(1): p. 98-106. Leebmann, H. and P. Piso, [Hyperthermic intraperitoneal chemotherapy]. Chirurg, 2019. 90(7): p. 593-604. Ang CS, Shen JP, Hardy-Abeloos CJ, et al., Genomic Landscape of Appendiceal Neoplasms. JCO Precis Oncol, 2018. 2. Raspé C, Flöther L, Schneider R, et al., Best practice for perioperative management of patients with cytoreductive surgery and HIPEC. Eur J Surg Oncol, 2017. 43(6): p. 1013-1027. Rizvi, S.A., W. Syed, and R. Shergill, Approach to pseudomyxoma peritonei. World J Gastrointest Surg, 2018. 10(5): p. 49-56. Huo YR, Richards A, Liauw W, et al., Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) in ovarian cancer: A systematic review and meta-analysis. Eur J Surg Oncol, 2015. 41(12): p. 1578-89. Mittal, R., A. Chandramohan, and B. Moran, Pseudomyxoma peritonei: natural history and treatment. Int J Hyperthermia, 2017. 33(5): p. 511-519. Hübner M, Kusamura S, Villeneuve L, et al., Guidelines for Perioperative Care in Cytoreductive Surgery (CRS) with or without hyperthermic IntraPEritoneal chemotherapy (HIPEC): Enhanced recovery after surgery (ERAS®) Society Recommendations - Part I: Preoperative and intraoperative management. Eur J Surg Oncol, 2020. 46(12): p. 2292-2310. Souadka, A. and A. Benkabbou, CRS and HIPEC: The need for an adaptable learning curve model. 2020. 122(6): p. 1187-1188. 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-3014807","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":207933718,"identity":"4e226409-846e-4d4a-803a-5068b324f9e7","order_by":0,"name":"Jie Jiao","email":"","orcid":"","institution":"Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Jiao","suffix":""},{"id":207933719,"identity":"ed886832-13bf-47da-ba6e-acd551ca0a10","order_by":1,"name":"Chengzhen Li","email":"","orcid":"","institution":"Central Hospital Affiliated to Shandong First Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chengzhen","middleName":"","lastName":"Li","suffix":""},{"id":207933720,"identity":"2d849742-3fcf-49e4-a681-dd17237c3959","order_by":2,"name":"Guanying Yu","email":"","orcid":"","institution":"Central Hospital Affiliated to Shandong First Medical University","correspondingAuthor":false,"prefix":"","firstName":"Guanying","middleName":"","lastName":"Yu","suffix":""},{"id":207933721,"identity":"c7805465-3ce6-49eb-af32-87899e5e1078","order_by":3,"name":"Zhenpeng Liu","email":"","orcid":"","institution":"Haifushan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhenpeng","middleName":"","lastName":"Liu","suffix":""},{"id":207933722,"identity":"776607c9-a28f-42b1-906f-7d0b259248ea","order_by":4,"name":"Lei Zhang","email":"","orcid":"","institution":"Central Hospital Affiliated to Shandong First Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Zhang","suffix":""},{"id":207933723,"identity":"3f4f7ef4-c318-4aba-8d68-6df91446b9ad","order_by":5,"name":"Xiaoyan Shi","email":"","orcid":"","institution":"Central Hospital Affiliated to Shandong First Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoyan","middleName":"","lastName":"Shi","suffix":""},{"id":207933724,"identity":"9fa3dba1-7ebe-45dd-af05-07b91a0bb4c7","order_by":6,"name":"Jingdu Yan","email":"","orcid":"","institution":"Central Hospital Affiliated to Shandong First Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jingdu","middleName":"","lastName":"Yan","suffix":""},{"id":207933725,"identity":"c543f70a-4147-4d8f-bfd9-3f139e88c3ae","order_by":7,"name":"Houjun Zhang","email":"","orcid":"","institution":"Central Hospital Affiliated to Shandong First Medical University","correspondingAuthor":false,"prefix":"","firstName":"Houjun","middleName":"","lastName":"Zhang","suffix":""},{"id":207933726,"identity":"436b53be-0332-4ba1-9ef5-b21437c2734a","order_by":8,"name":"Jingbo Shi","email":"","orcid":"","institution":"Central Hospital Affiliated to Shandong First Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jingbo","middleName":"","lastName":"Shi","suffix":""},{"id":207933727,"identity":"3565d255-932a-41b5-8dfc-c137fd6ae4dd","order_by":9,"name":"Peiming Guo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYNACAwYeECXBUyEhJ0+iljMWxoYNpFgmwdtWkchwgIAq+YjkYw8+FGyTMedfwHjj7TyJBMYG5oePbuDRYngjLd1whsFtHssZD5gt526TyGNnYDM2zsGnZUaOmTQPUIvBjQNs0rzbJIoZG3jYpAlq+QPXMkciseEAAS3yEkAtDCAt5xuAWhqI0GLA8yzdsAdsCwOz5ZxjEsaGzQT8It8ODLEff27bG5w/wHjjTU2dnDx788PHeG05wMAGYUnkf4AwmPEoB9vSANPCf4CA0lEwCkbBKBixAAAm10iZidBa6wAAAABJRU5ErkJggg==","orcid":"","institution":"Central Hospital Affiliated to Shandong First Medical University","correspondingAuthor":true,"prefix":"","firstName":"Peiming","middleName":"","lastName":"Guo","suffix":""}],"badges":[],"createdAt":"2023-06-02 13:14:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3014807/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3014807/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":38306388,"identity":"485549ba-4075-4450-bd45-288726ca77ba","added_by":"auto","created_at":"2023-06-09 18:04:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":60168,"visible":true,"origin":"","legend":"\u003cp\u003eAnalysis of survival curve in patients with peritoneal carcinoma of appendiceal mucinous adenocarcinoma\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3014807/v1/b3c3c2267c0c2026ad1ca0d3.png"},{"id":38306389,"identity":"4520c728-1358-445d-ba9b-ab5a240662e2","added_by":"auto","created_at":"2023-06-09 18:04:49","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":66867,"visible":true,"origin":"","legend":"\u003cp\u003eAnalysis of survival curves of patients with different PCI of peritoneal carcinoma of appendiceal mucinous adenocarcinoma\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-3014807/v1/d55ebcec0fdf8b40dc0c0cef.png"},{"id":38306688,"identity":"0e4c087c-9b9d-4328-9c68-08c3156b324d","added_by":"auto","created_at":"2023-06-09 18:12:49","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":74210,"visible":true,"origin":"","legend":"\u003cp\u003eAnalysis of survival curves of patients with different CC of peritoneal carcinoma of appendiceal mucinous adenocarcinoma\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-3014807/v1/150c569488311fe7753764eb.png"},{"id":39273329,"identity":"f49c1481-1304-4fa6-b693-81ea6439f1e9","added_by":"auto","created_at":"2023-06-29 05:14:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":446199,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3014807/v1/6ff768d5-c282-4802-8bcb-fb3b2c2c3634.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Management of peritoneal carcinomatosis from appendiceal mucinous adenocarcinoma by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: Experience on 48 patients from a single center","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eIn the realm of digestive tract tumors, appendiceal tumors have a low incidence, representing less than 0.5% of all gastrointestinal tumors\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Besides, there are few patients with a definitive preoperative diagnosis, and the majority of cases are diagnosed through intraoperative or postoperative pathological examination. Tumors account for 0.7\u0026ndash;1.4% of all post-appendectomy specimens\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAmong them, the appendiceal mucinous tumor is a highly uncommon pathological type, categorized as a low-grade malignant epithelial tumor of the appendix, accounting for approximately 0.2\u0026ndash;0.3% of all postoperative pathology cases following appendicitis surgery\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Since the 5th edition of the 2019 classification of digestive tumors, a distinction has been made between low-grade mucinous tumors of the appendix (LAMN) and high-grade mucinous carcinomas of the appendix (MA, mucinous adenocarcinoma of the appendix). This differentiation allows for a more precise classification of these types of tumors\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Among these tumors, the incidence of mucinous adenocarcinoma of the appendix (MA) is even lower, accounting for only 0.01\u0026ndash;0.08% of the total number of appendiceal tumors. It is a relatively rare subtype of appendiceal tumors\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Adenocarcinoma of the appendix is known for its tendency to invade the serosal membrane of the appendix, penetrate the wall, and spread to the abdominal and pelvic peritoneum, resulting in peritoneal metastasis. This peritoneal dissemination is commonly referred to as peritoneal cancer, indicating the spread of cancer cells throughout the peritoneal cavity\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Currently, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in prolonging the survival of patients with gastric cancer, colorectal cancer, and ovarian cancer. This treatment approach has demonstrated significant clinical efficacy and has become an established treatment modality in the international medical community. Furthermore, clinical studies investigating the efficacy of CRS and HIPEC in the management of mucinous adenocarcinoma of the appendix and peritoneal cancer are increasingly being conducted, aiming to further validate its clinical effectiveness in these specific conditions\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. The purpose of this article is to summarize the experience of treatment of 48 cases of peritoneal metastasis of mucinous adenocarcinoma of the appendix.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. General Information\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective analysis of forty-eight patients with peritoneal metastatic appendiceal mucinous adenocarcinoma who were treated at our hospital from June 2017 to July 2020. The study focused on various indicators, including symptoms, signs, laboratory examinations, medical imaging examinations, perioperative information, and specifically emphasized efficacy and safety data.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. The main process of CRS\u0026thinsp;+\u0026thinsp;HIPEC\u003c/h2\u003e \u003cp\u003eCytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is performed by a specialized peritoneal cancer team. The procedure begins with a median abdominal incision made under general anesthesia. A thorough exploration is conducted during laparotomy to assess the extent of tumor invasion, ranging from the diaphragm peritoneum to the pelvic peritoneum. The peritoneal cancer index (PCI) is determined using the Sugarbaker Assessment and Record System\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Additionally, detailed records of the nature and quantity of peritoneal effusion are documented.\u003c/p\u003e \u003cp\u003eFollowing the surgical protocol formulated by Sugarbaker, tumor regions, involved organs or tissues, and lymph nodes are removed. Complete tumor reduction is pursued, and if achievable, radical excision is performed. In cases where complete tumor reduction cannot be achieved, maximum CRS is conducted, and the completeness of tumor reduction (CC) is scored. Open HIPEC is initiated after CRS is completed.\u003c/p\u003e \u003cp\u003eDuring HIPEC, a liquid input tube is placed in the shallow abdominal pelvic area, while the output tube is placed in the deep area. A circular retractor is used to hold the abdominal incision open, and a disposable incision protective film is applied and closed. The poris Medical (Bright dominate, BRM) heat body cavity perfusion treatment system (BR-TRG-II from Guangzhou poris Medical Technology Co. Ltd.) is connected and started, with relevant parameters set. Each chemotherapeutic agent is added to 3 L of normal saline, heated to (43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5) ℃, and infused continuously at a flow rate of 400 mL/min for 30 minutes. The HIPEC chemotherapy regimen consists of lobaplatin 50 mg or Tomudex 4 mg. After completing HIPEC, the chemotherapy solution is drained, and reconstruction of organs such as the digestive tract and urinary tract is performed. Bleeding is controlled, and the abdomen is closed after placing a drainage tube. The patient is safely returned to the ward for monitoring and further treatment.\u003c/p\u003e \u003cp\u003eDuring the surgery, four HIPEC special tubes are placed. HIPEC is performed four times postoperatively, with intervals of \u0026ge;\u0026thinsp;24 hours between each treatment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Postoperative chemotherapy and follow-up\u003c/h2\u003e \u003cp\u003eAfter recovering from surgery and being discharged, all patients underwent 6\u0026ndash;8 cycles of chemotherapy with FOLFOX or FOLFIRI. Regular follow-up was conducted through telephone or outpatient services, which included monitoring their survival status, recording any adverse events experienced, monitoring tumor markers, and performing imaging reassessment of the abdomen and pelvis. The administration of targeted drugs, such as bevacizumab or cetuximab, was determined based on the results of genetic testing.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Statistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using SPSS 21.0 software. Measurement data were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (x\u0026thinsp;\u0026plusmn;\u0026thinsp;s), and a t-test was used to compare groups. Enumeration data were reported as frequencies, and the χ2 test was used for group comparisons. Survival analysis was conducted using the Kaplan-Meier method, and the log-rank test was utilized for univariate survival analysis. A significance level of P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n\u003ch3\u003e3.1. Main clinical features\u003c/h3\u003e\n\u003cp\u003eAmong the 48 patients with peritoneal metastasis from appendiceal mucinous adenocarcinoma, 25 cases were male (52.1%), while 23 cases were female (47.9%). The age of the patients ranged from 30 to 84, with a median age of 57 years. The PCI scores ranged from 1 to 39, with a median score of 21. The CC scores ranged from 0 to 3, with a median score of 2. Serious adverse events occurred in 4 cases (14.3%) 15 days after surgery. (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eThe main clinicopathological Characteristics of 48 patients with peritoneal carcinoma of appendiceal adenocarcinoma\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003en\u003c/em\u003e(%)\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\"\u003e\n\u003cp\u003eGender\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25(52.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23(47.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedian age\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e57\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePCI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedian PCI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22(45.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26(54.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCC(score)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedian CC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4(8.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18(37.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18(37.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8(16.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\"\u003ePCI: peritoneal cancer index; CC: completeness of cytoreduction.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003ch3\u003e3.2. Survival curve analysis\u003c/h3\u003e\n\u003cp\u003eThe follow-up period for the 48 patients ranged from 16 to 44 months. Among them, 18 patients (37.5%) unfortunately passed away, while 30 patients (62.5%) survived. The median survival time was 37 months (95%CI: 26.0-47.9 months). The 1-year, 2-year, and 3-year survival rates were 78.0%, 60.9%, and 51.4% respectively. (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003eCorrelation factor analysis revealed that PCI and CC were identified as risk factors influencing the survival of patients. In patients with PCI\u0026thinsp;\u0026ge;\u0026thinsp;20, the 1-year, 2-year, and 3-year survival rates were 63.6%, 43.8%, and 32.8% respectively, whereas in patients with PCI\u0026thinsp;\u0026lt;\u0026thinsp;20, the corresponding rates were 95%, 81.8%, and 72.7% (P\u0026thinsp;=\u0026thinsp;0.0139). Similarly, patients with CC\u0026thinsp;\u0026gt;\u0026thinsp;1 demonstrated 1-year, 2-year, and 3-year survival rates of 64.4%, 40.9%, and 40.9%, while patients with CC\u0026thinsp;\u0026le;\u0026thinsp;1 had rates of 95%, 88.2%, and 69.4% (P\u0026thinsp;=\u0026thinsp;0.004). Please refer to Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e for graphical representation. (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003ePeritoneal cancer can be classified as primary or secondary peritoneal cancer\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Primary peritoneal cancer includes primary peritoneal cancer and malignant peritoneal mesothelioma, while secondary peritoneal cancer refers to peritoneal implantation metastasis from gastrointestinal and gynecological tumors\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Clinical studies have demonstrated that cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the most effective treatment approach for peritoneal cancer arising from gastrointestinal and gynecological tumors. This treatment strategy has been shown to prolong survival and improve the quality of life of patients, and in some cases, it can even lead to clinical cure\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Appendiceal adenocarcinoma is a relatively rare form of cancer, accounting for approximately 0.2\u0026ndash;0.5% of cases. However, its incidence has been increasing over the years\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Most patients with appendiceal adenocarcinoma are already diagnosed with peritoneal implantation metastasis. Studies have reported that CRS\u0026thinsp;+\u0026thinsp;HIPEC can achieve favorable clinical outcomes in patients with appendiceal adenocarcinoma and peritoneal metastasis\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCompared to traditional palliative surgery and chemotherapy, this treatment regimen offers obvious advantages: (1) CRS can remove visible tumor tissue through organ resection and peritoneal resection, minimizing the tumor burden; (2) HIPEC kills micro-metastases and free cancer cells, completely eliminating primary tumors and metastases in the abdominal cavity.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. The main mechanisms of HIPEC in the treatment of peritoneal cancer are as follows: (1) The peritoneal-plasma barrier limits the absorption of macromolecular drugs in the peritoneal membrane, delaying the metabolism of chemotherapeutic drugs and maintaining a high intraperitoneal drug concentration, which is 10\u0026thinsp;\u0026minus;\u0026thinsp;1,000 times higher than the concentration in the blood. This increases the lethality of intraperitoneal tumors. (2) At the tissue level, the thermal effect induces microvascular embolization in tumor tissues, leading to degeneration and necrosis of tumor cells. It disrupts the self-stabilization mechanism of tumor cells, interferes with tumor cell metabolism, activates lysosomes, and disrupts protein, DNA, and RNA synthesis in tumor cells at the molecular level. (3) The thermal effect exhibits a synergistic effect with chemotherapeutic drugs and is significantly enhanced at 42\u0026deg;C. (4) During the perfusion process, the shear force of fluid flow directly induces tumor cell death, and tissue erosion leads to tumor cell apoptosis.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eIn conclusion, this study demonstrates the effectiveness and feasibility of the CRS\u0026thinsp;+\u0026thinsp;HIPEC comprehensive diagnosis and treatment technique for mucinous adenocarcinoma of the appendix combined with peritoneal metastasis. However, this study has some limitations, including the small number of cases included and the lack of a prospective randomized controlled design. Further confirmation of the efficacy and safety of CRS\u0026thinsp;+\u0026thinsp;HIPEC is needed to benefit a larger number of patients with peritoneal carcinoma of mucinous adenocarcinoma of the appendix.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contributions\u003c/p\u003e\n\u003cp\u003ePeiming Guo conceived the study. Jie Jiao, Chengzhen Li, Guanying Yu, Zhenpeng Liu, Lei Zhan, Xiaoyan Shi, Jingdu Yan, Houjun Zhang and Jingbo Shi collected the study materials and patient data. Jie Jiao drafted the manuscript. Jie Jiao analyzed data. All authors confrm the authenticity of all the raw data. All authors wrote the manuscript, and read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Science and Technology Plan Project of Jinan Municipal Health and Family Planning Commission (grant no. 2019-2- 06).\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed in the present study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThe study was done after an agreement from the local ethics committee (Jinan Central Hospital ethics committee) and with the patients\u0026rsquo; informed consent. (Ref.: 2019-107-01). Date of approval: August 1, 2019.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eShaib W L , Assi R , Shamseddine A, et al., Appendiceal Mucinous Neoplasms: Diagnosis and Management. Oncologist, 2017. 22(9): p. 1107-1116.\u003c/li\u003e\n\u003cli\u003eValasek, M.A. and R.K. Pai, An Update on the Diagnosis, Grading, and Staging of Appendiceal Mucinous Neoplasms. Adv Anat Pathol, 2018. 25(1): p. 38-60.\u003c/li\u003e\n\u003cli\u003eNutu O A , Quinto A M , Municio A M, et al., Mucinous appendiceal neoplasms: Incidence, diagnosis and surgical treatment. Cir Esp, 2017. 95(6): p. 321-327.\u003c/li\u003e\n\u003cli\u003eAhadi M , Sokolova A , Brown I, et al., The 2019 World Health Organization Classification of appendiceal, colorectal and anal canal tumours: an update and critical assessment. Pathology, 2021. 53(4): p. 454-461.\u003c/li\u003e\n\u003cli\u003eErickson, L.A. and M. Rivera, Mucinous Neoplasm of the Appendix and Pseudomyxoma Peritonei. Mayo Clin Proc, 2018. 93(2): p. 267-268.\u003c/li\u003e\n\u003cli\u003eCarr NJ, Bibeau F, Bradley RF, et al., The histopathological classification, diagnosis and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinomas and pseudomyxoma peritonei. Histopathology, 2017. 71(6): p. 847-858.\u003c/li\u003e\n\u003cli\u003eSeshadri, R.A. and O. Glehen, Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer. World J Gastroenterol, 2016. 22(3): p. 1114-30.\u003c/li\u003e\n\u003cli\u003eJacquet, P. and P.H. Sugarbaker, Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res, 1996. 82: p. 359-74.\u003c/li\u003e\n\u003cli\u003eBarto\u0026scaron;ka P, Anto\u0026scaron; F, V\u0026iacute;tek P, et al., Pseudomyxoma Peritonei. Klin Onkol, 2019. 32(5): p. 329-332.\u003c/li\u003e\n\u003cli\u003eDong D, Tang L, Li ZY, et al., Development and validation of an individualized nomogram to identify occult peritoneal metastasis in patients with advanced gastric cancer. Ann Oncol, 2019. 30(3): p. 431-438.\u003c/li\u003e\n\u003cli\u003eClement, P.B., R.H. Young, and R.E. Scully, Malignant mesotheliomas presenting as ovarian masses. A report of nine cases, including two primary ovarian mesotheliomas. Am J Surg Pathol, 1996. 20(9): p. 1067-80.\u003c/li\u003e\n\u003cli\u003eSchwartz, P.B. and D.E. Abbott, ASO Author Reflections: Predictors of Fiscal Outcomes in CRS-HIPEC and Opportunities for Improvement. Ann Surg Oncol, 2020. 27(13): p. 4929-4930.\u003c/li\u003e\n\u003cli\u003eS\u0026aacute;nchez-Hidalgo JM, Rodr\u0026iacute;guez-Ortiz L, Arjona-S\u0026aacute;nchez \u0026Aacute;, et al., Colorectal peritoneal metastases: Optimal management review. World J Gastroenterol, 2019. 25(27): p. 3484-3502.\u003c/li\u003e\n\u003cli\u003eJi ZH, An SL, Li XB, et al., Long-term progression-free survival of hepatocellular carcinoma with synchronous diffuse peritoneal metastasis treated by CRS+HIPEC: A case report and literature review. Medicine (Baltimore), 2019. 98(8): p. e14628.\u003c/li\u003e\n\u003cli\u003eBonnot PE, Piessen G, Kepenekian V, et al., Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer With Peritoneal Metastases (CYTO-CHIP study): A Propensity Score Analysis. J Clin Oncol, 2019. 37(23): p. 2028-2040.\u003c/li\u003e\n\u003cli\u003eBa, M., et al., Cytoreductive surgery and HIPEC for malignant ascites from colorectal cancer - a randomized study. Medicine (Baltimore), 2020. 99(33): p. e21546.\u003c/li\u003e\n\u003cli\u003eBa M, Chen C, Long H, et al., Colorectal Peritoneal Metastases Treated by Perioperative Systemic Chemotherapy and Cytoreductive Surgery With or Without Mitomycin C-Based HIPEC: A Comparative Study Using the Peritoneal Surface Disease Severity Score (PSDSS). Ann Surg Oncol, 2020. 27(1): p. 98-106.\u003c/li\u003e\n\u003cli\u003eLeebmann, H. and P. Piso, [Hyperthermic intraperitoneal chemotherapy]. Chirurg, 2019. 90(7): p. 593-604.\u003c/li\u003e\n\u003cli\u003eAng CS, Shen JP, Hardy-Abeloos CJ, et al., Genomic Landscape of Appendiceal Neoplasms. JCO Precis Oncol, 2018. 2.\u003c/li\u003e\n\u003cli\u003eRasp\u0026eacute; C, Fl\u0026ouml;ther L, Schneider R, et al., Best practice for perioperative management of patients with cytoreductive surgery and HIPEC. Eur J Surg Oncol, 2017. 43(6): p. 1013-1027.\u003c/li\u003e\n\u003cli\u003eRizvi, S.A., W. Syed, and R. Shergill, Approach to pseudomyxoma peritonei. World J Gastrointest Surg, 2018. 10(5): p. 49-56.\u003c/li\u003e\n\u003cli\u003eHuo YR, Richards A, Liauw W, et al., Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) in ovarian cancer: A systematic review and meta-analysis. Eur J Surg Oncol, 2015. 41(12): p. 1578-89.\u003c/li\u003e\n\u003cli\u003eMittal, R., A. Chandramohan, and B. Moran, Pseudomyxoma peritonei: natural history and treatment. Int J Hyperthermia, 2017. 33(5): p. 511-519.\u003c/li\u003e\n\u003cli\u003eH\u0026uuml;bner M, Kusamura S, Villeneuve L, et al., Guidelines for Perioperative Care in Cytoreductive Surgery (CRS) with or without hyperthermic IntraPEritoneal chemotherapy (HIPEC): Enhanced recovery after surgery (ERAS\u0026reg;) Society Recommendations - Part I: Preoperative and intraoperative management. Eur J Surg Oncol, 2020. 46(12): p. 2292-2310.\u003c/li\u003e\n\u003cli\u003eSouadka, A. and A. Benkabbou, CRS and HIPEC: The need for an adaptable learning curve model. 2020. 122(6): p. 1187-1188.\u003c/li\u003e\n\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":false,"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":"appendiceal mucinous adenocarcinoma, cytoreductive surgery, hyperthermic intraperitoneal chemotherapy","lastPublishedDoi":"10.21203/rs.3.rs-3014807/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3014807/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003ePurpose\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTo evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of patients with peritoneal carcinomatosis (PC) from appendiceal mucinous adenocarcinoma.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe clinical data of 48 cases of PC with mucinous appendiceal adenocarcinoma treated with CRS\u0026thinsp;+\u0026thinsp;HIPEC were retrospectively analyzed. The study indices included survival, perioperative safety, and adverse reactions.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe peritoneal cancer index (PCI) score ranged from 1 to 39 in the 48 patients with peritoneal cancer of appendix adenocarcinoma, with a median score of 21. The degree of tumor reduction (CC) was 0 to 3, with a median score of 2. The follow-up period ranged from 16 to 44 months. Of the 48 patients, 18 patients (37.5%) died and 30 patients (62.5%) survived. The median survival time was 37 months (95% CI: 26.0-47.9 months). The 1-, 2-, and 3-year survival rates were 78.0%, 60.9%, and 51.4%. The 1-, 2-, and 3-year survival rates in patients with PCI\u0026thinsp;\u0026ge;\u0026thinsp;20 were 63.6%, 43.8%, and 32.8%, respectively, while the patients with PCI\u0026thinsp;\u0026lt;\u0026thinsp;20 had rates of 95%, 81.8%, and 72.7% (P\u0026thinsp;=\u0026thinsp;0.0139). The 1-, 2-, and 3-year survival rates were 64.4%, 40.9%, and 40.9% in patients with CC\u0026thinsp;\u0026gt;\u0026thinsp;1, and 95%, 88.2%, and 69.4% in patients with CC\u0026thinsp;\u0026le;\u0026thinsp;1 (P\u0026thinsp;=\u0026thinsp;0.004). The incidence of perioperative adverse events was 8.3%, including 3 cases of incision infection and 1 case of intestinal anastomotic fistula.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eCRS\u0026thinsp;+\u0026thinsp;HIPEC is feasible and effective in the treatment of patients with peritoneal carcinoma from appendiceal mucinous adenocarcinoma.\u003c/p\u003e","manuscriptTitle":"Management of peritoneal carcinomatosis from appendiceal mucinous adenocarcinoma by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: Experience on 48 patients from a single center","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-06-09 18:04:44","doi":"10.21203/rs.3.rs-3014807/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":"6b0a9bfa-8fe9-42bb-a642-1df4dc26da38","owner":[],"postedDate":"June 9th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-06-29T05:14:31+00:00","versionOfRecord":[],"versionCreatedAt":"2023-06-09 18:04:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3014807","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3014807","identity":"rs-3014807","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}