Transcatheter arterial infusion chemotherapy combined with lipiodol chemoembolization for advanced gastric fundus and cardia cancer with obstruction

Transcatheter arterial infusion chemotherapy combined with lipiodol chemoembolization for advanced gastric fundus and cardia cancer with obstruction | 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 Transcatheter arterial infusion chemotherapy combined with lipiodol chemoembolization for advanced gastric fundus and cardia cancer with obstruction Gang Zhou, Yaozhen Ma, Yishu Ma, Xiaolong Ding, Tao Liu, Wei He, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5402538/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 Gastric fundus and cardia cancer are increasingly common, diagnosed at a late stage, often with severe obstruction, and have a poor prognosis. Transcatheter arterial lipiodol chemoembolization (TACE) is rarely used for gastric cancer. This single-center retrospective study aimed to analyze the efficacy and safety of transcatheter arterial infusion chemotherapy (TAI) combined with TACE in advanced gastric fundus and cardia cancer with obstruction and compare it to bland embolization (BE). Materials and Methods The clinical efficacy of TAI-TACE was evaluated through technical and clinical success rates, obstruction relief, tumor response, overall survival (OS), and postoperative adverse events. TAI-TACE and TAI-BE efficacies were compared. Results The study included 53 patients (age 70.0 ± 11.1 years, 38 males). Thirty-two patients underwent TAI-TACE, and 21 underwent TAI-BE. The cohort’s technical success rate was 100%. The pre- and post-intervention median Stooler grades were 4 and 2 in the TAI-TACE group and 3 and 3 in the TAI-BE group, respectively. Compared to the TAI-BE group, the TAI-TACE group had a higher clinical success rate (78.1%, 25/32 vs. 42.9%, 9/21; P = 0.009), a better objective response rate (53.1% vs. 38.1%; P = 0.016), and a longer median OS (13.0; 95% confidence interval (CI), 3.2–22.8 vs. 10.0; 95% CI, 8.5–11.5; P = 0.039) months. All adverse events were grade 1. Conclusion The TAI-TACE interventional therapy scheme was safe and effective, achieving rapid tumor shrinkage, obstructive symptom alleviation, improved quality of life, and a significantly better overall effect than TAI-BE. gastric cancer obstruction transcatheter infusion chemotherapy lipiodol chemoembolization Figures Figure 1 Figure 2 Figure 3 Introduction The overall incidence rate of gastric cancer has declined in recent years, but that of gastric fundus and cardia cancer has continuously increased. The global cancer data show that 952,000 new gastric cancer cases were diagnosed in 2012 worldwide, including 260,000 gastric cardia cancer cases, 52% of which occurred in China [ 1 – 3 ]. The prognosis of gastric fundus and cardia cancer is extremely poor, with a 5-year survival rate of just 16.7% [ 4 ]. Most patients are at an advanced stage when diagnosed, often presenting with obstruction as one of the first symptoms, followed by difficulty swallowing, nausea, and vomiting, which greatly affect the patients’ quality of life and survival. Obstruction relief and enteral nutrition restoration should be urgently addressed. Common clinical treatment methods include surgical resection and stent placement [ 5 – 7 ]. With the improvement of surgical techniques and instruments, various resection and reconstruction methods have been applied; however, postoperative complications such as gastroesophageal reflux, anastomotic fistula, and anastomotic stenosis greatly affect the patients’ quality of life [ 1 ]. Furthermore, patients with advanced gastric cancer often cannot undergo radical resection. Compared with surgical resection, stent placement is simpler and minimally invasive, making it the standard treatment for gastrointestinal obstruction and recanalization. However, major complications, including stent displacement, granulation tissue proliferation that leads to restenosis, and difficulty in stent removal, cannot be ignored [ 8 ]. Moreover, due to gastrointestinal tract peristalsis, the friction between the stent and the tumor surface might lead to bleeding. Transcatheter arterial chemoembolization (TACE) with lipiodol is being widely used to treat primary and metastatic liver cancers [ 9 , 10 ] and achieves very positive results; however, research on lipiodol chemoembolization for gastric cancer is limited. Bland embolization (BE), including particles of polyvinyl alcohol, gelatin sponge, and embolization microspheres, is commonly used to treat gastric cancer, especially in cases with bleeding [ 11 – 13 ]. The efficacy of BE in treating gastric cancer with obstruction is uncertain. This retrospective study aimed to assess the efficacy and safety of transcatheter arterial infusion chemotherapy (TAI) combined with TACE for advanced gastric fundus and cardia cancer with obstruction and compare it to TAI-BE. Materials and Methods Patients The study retrospectively analyzed patients diagnosed with advanced gastric fundus and cardia cancer with obstruction at our center between January 2014 and October 2024. Inclusion criteria: (1) diagnosed with advanced gastric fundus and cardia cancer with obstruction through upper gastrointestinal imaging, gastroscopy, and computed tomography (CT) examinations; (2) pathologically confirmed as gastric adenocarcinoma; (3) cannot undergo radical surgical resection based on a surgeon’s evaluation. Exclusion criteria: (1) with gastrointestinal obstruction caused by distal gastric, duodenal, pancreatic, or other lesions; (2) underwent gastrointestinal stent placement treatment. The Ethics Committee of Institutional Review Board approved this study (No. : 2021-KY-0910-002), and all patients signed an informed consent form before receiving treatment. Preoperative preparation Routine blood tests, electrolytes, coagulation function, tumor markers, liver and kidney functions, and electrocardiogram results were examined before the operation. Plain and enhanced upper abdomen CT confirmed the tumor location and size (Fig. 1 ). All patients were given nutritional support and symptomatic treatment. Procedure The Seldinger method was used to insert a vascular sheath through the right femoral artery. A 5F angiographic catheter (C2, RLG, or RH TYPE, Cook Corporation, Bloomington, IN, USA) was inserted into left gastric, short gastric, and esophageal proper arteries under fluoroscopy guidance, and the condition of each branch vessel was visualized by catheter angiography (Fig. 2 a). Then a 2.7F microcatheter was introduced into the artery that delivered blood supply to the tumor using the coaxial catheter technology. TAI and TACE or BE were performed based on the blood supply and staining degree of the tumor. TAI: 100 mg oxaliplatin was dissolved in 150 mL 5% glucose solution, and 4 mg raltitrexed was dissolved in 150 mL 0.9% sodium chloride solution. The solutions were injected through a catheter into the target artery at a constant rate of 10 mL/min. TACE: 20 mg pirarubicin was fully emulsified with 10 mL of 48% lipiodol and injected slowly into the target artery through the microcatheter (Fig. 2 b-c). BE: 350–560 µm polyvinyl alcohol particles were mixed with a 15 mL solution containing contrast medium and normal saline at a 1:1 ratio and injected slowly into the target artery. The embolization endpoint was blood stasis in the target artery and the disappearance of staining in the tumor. Nasojejunal nutrition tubes were inserted after the procedure for patients with difficulty or inability to ingest liquids. The guide wire, catheter, and nutrition tubes were passed through the nasal cavity and esophagus and across the narrow segment, gastric cavity, pylorus, and duodenum to the proximal jejunum under fluoroscopy. Postoperative management After the procedure, patients were given symptomatic treatment, including proton pump inhibitors, analgesics, antiemetics, and enteral and parenteral nutritional support. Usually, the patients’ obstruction was reevaluated one week after the procedure. The nutrition tube was removed if the obstruction was relieved and the nutritional status allowed it. Definitions The patients’ dysphagia degree was evaluated based on the Stooler classification [ 14 ] one week before and after the intervention: grade 0, can eat normal food; grade 1, obstruction in the consumption of soft food; grade 2, can consume a semiliquid diet; grade 3, can consume a liquid diet; grade 4, difficulty or inability in ingesting liquids. The Eastern Cooperative Oncology Group (ECOG) performance status assessed the general condition of the patients [ 15 ]. Technical success was defined as injecting the chemotherapy and embolic agents into the target artery and reaching the embolization endpoint without serious complications such as major bleeding, perforation, or death. Clinical success was defined as an improvement in the Stooler grade by more than one level after one week of treatment compared to before the intervention. According to the response evaluation criteria in solid tumours’ standard [ 16 ], the local lesion response was evaluated by abdominal CT and expressed as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). The objective response rate (ORR) was defined as the sum of CR and PR; disease control rate (DCR) was defined as the sum of CR, PR, and SD. Overall Survival (OS) was used as the outcome measure. Adverse events were classified according to the Common Terms Criteria for Adverse Events (V.5.0). Statistical analysis Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 26.0 (IBM Corp., Armonk, NY, USA). Categorical variables are presented as median with its interquartile range and continuous variables as means and standard deviations. An independent sample t -test or Chi-squared test was used to compare variables between groups as suitable. The Kaplan-Meier test analyzed the OS, and the groups were compared using the log-rank test. All hypothesis tests were considered significant when P < 0.05. Results Patient characteristics This study included 53 patients, 38 males and 15 females, aged 70.0 ± 11.1 (46–93) years, with clinical stages III and IV advanced gastric fundus and cardia cancer with obstruction. Among them, 32 were in the TAI-TACE group, and 21 were in the TAI-BE group. Preoperative chemotherapy failed in 20 patients in the TAI-TACE group. Nasojejunal nutrition tubes were placed in 25 patients in the TAI-TACE group and six in the TAI-BE group. The median pre-intervention Stooler grades of the two groups were 4 and 3 ( P = 0.016). Baseline variables, including sex, age, preoperative chemotherapy, clinical stages, albumin, hemoglobin, carcinoembryonic antigen, and ECOG, were similar in the two groups ( P > 0.05; Table 1 ). Table 1 Baseline patient information Characteristic TAI-TACE group n = 32 TAI-BE group n = 21 P -value Sex 0.200 Male 25 (78.1%) 13 (61.9%) Female 7 (21.9%) 8 (38.1%) Age (years) History of chemotherapy 70.5 ± 10.3 20 (62.5%) 68.7 ± 12.9 0 0.496 - Clinical stage 0.528 Ⅲ 15 (46.9%) 8 (38.1%) Ⅳ 17 (53.1%) 13 (40.6%) Albumin (g/L) 32.4 ± 9.4 33.7 ± 14.2 0.077 Hemoglobin (g/L) 109.4 ± 36.2 121.3 ± 37.6 0.254 CEA (ng/mL) 5.4 ± 2.3 12.5 ± 4.3 0.722 ECOG 0.727 0–1 23 (71.9%) 16 (76.2%) 2 9 (28.1%) 5 (23.8%) Baseline Stooler grade 0.016 3 12(37.5%) 15(71.4%) 4 20 (62.5%) 6 (28.6%) Note: Variables are expressed as mean ± standard deviation or n (%). CEA, carcinoembryonic antigen; ECOG, the eastern cooperative oncology group; TAI-TACE, transcatheter arterial infusion chemotherapy combined with transcatheter arterial lipiodol chemoembolization; TAI-BE, transcatheter arterial infusion chemotherapy combined with bland embolization. Interventional treatment and efficacy The 53 patients underwent 94 interventional treatments; 22 patients (41.5%) received one treatment, 21 (39.6%) received two treatments, and 10 (18.9%) received three treatments. All cases underwent angiography to stain the tumors and detect the arteries delivering blood supply to them, which included 53 left gastric arteries and six proper esophageal arteries. The average lipiodol emulsion volume used in the TAI-TACE group was 3.1 ± 0.9 (1.5–6.0) mL. The technical success rate in both groups was 100%. The patients’ median Stooler grades after the intervention are shown in Table 2 . The Stooler grades in the TAI-TACE and TAI-BE groups were 2 and 3, respectively. The clinical success rate in the TAI-TACE group (78.1%, 25/32) was higher than in the TAI-BE group (42.9%, 9/21; P = 0.009). In the TAI-TACE group, clinical success was observed in 13 cases (65.0%) who failed preoperative chemotherapy and 16 (64.0%) who met the criteria for removing the nasojejunal nutrition tube. However, all six patients with nasojejunal nutrition tubes in the TAI-BE group did not meet the criteria. Table 2 Interventional treatment efficacy and outcomes Parameter TAI-TACE group n = 32 TAI-BE group n = 21 P -value Treatment number (n) 2.3 ± 1.3 1.1 ± 2.1 0.083 Procedure duration (min) 60.0 ± 15.4 54.5 ± 11.2 0.426 Technical success rate 100% 100% Clinical success rate, ( n ) Stooler grade 78.1% (25) 42.9% (9) 0.009 - 1/2/3/4 7/12/5/8 1/8/9/3 Tumor response, % ( n ) ORR 62.5% (20) 28.6% (6) 0.016 DCR 87.5% (28) 76.2% (16) 0.485 Median OS (months) 95% CI 13.0 3.2–22.8 10.0 8.5–11.5 0.039 Note: Variables are expressed as the mean ± standard deviation or n (%). ORR, objective response rate; DCR, disease control rate; OS, overall survival; CI, confidence interval; TAI-TACE, transcatheter arterial infusion chemotherapy combined with transcatheter arterial lipiodol chemoembolization; TAI-BE, transcatheter arterial infusion chemotherapy combined with bland embolization. The tumor curative effect, assessed after treatment, was CR in 5 (15.6%), PR in 15 (46.9%), SD in 8 (25.0%), PD in 4 (12.5%) in the TAI-TACE group, and CR in 1 (4.8%), PR in 5 (23.8%), SD in 10 (47.6%), PD in 5 (23.8%) in the TAI-BE group. The ORR in the TAI-TACE group (62.5%) was significantly higher than in the TAI-BE group (28.6%; P = 0.016), but the groups showed similar DCR, treatment number, and procedure duration ( P > 0.05; Table 2 ). Six (18.8%) patients were lost to follow-up in the TAI-TACE group and three (14.3%) in the TAI-BE group. The median follow-up in the entire cohort was 32 (3–65) months. The median OS in the TAI-TACE group (13.0 months; 95% confidence interval [CI], 3.2–22.8) was longer than in the TAI-BE group (10.0 months; 95% CI, 8.5–11.5; P = 0.039; Fig. 3 ). Adverse events None of the patients experienced severe complications such as bleeding, perforation, or death during or after the procedure. Postoperative adverse events in both groups included nausea, vomiting, fever, abdominal pain, decreased platelet and white blood cell counts, and increased ALT and AST levels, all defined as grade 1 adverse events. The incidence of nausea and vomiting (84.4% vs. 57.1%) and fever (59.4% vs. 23.8%) was higher in the TAI-TACE group than in the TAI-BE group ( P < 0.05), while the other symptoms appeared in similar rates in both groups (Table 3 ). The above adverse events disappeared within three days of the procedure after delivering symptomatic antiemetic, antipyretic, pain relieving, platelet raising, white blood cell raising, and liver-protecting treatments. Table 3 Adverse events Symptom TAI-TACE group n = 32 TAI-BE group n = 21 P -value Nausea/vomiting 27 (84.4%) 12 (57.1%) 0.028 Fever 19 (59.4%) 5 (23.8%) 0.011 Abdominal pain 19 (59.4%) 8 (38.1%) 0.130 Decreased platelet count 13 (40.6%) 8 (38.1%) 0.854 Decreased WBC count 14 (43.8%) 5 (23.8%) 0.139 Increased ALT/AST 15 (46.9%) 7 (33.3%) 0.328 Note: Variables are expressed as n (%). WBC, white blood cell count; ALT, alanine transaminase; AST, aspartate transaminase; TAI-TACE, transcatheter arterial infusion chemotherapy combined with transcatheter arterial lipiodol chemoembolization; TAI-BE, transcatheter arterial infusion chemotherapy combined with bland embolization. Discussion It is usually impossible to perform radical resection in advanced gastric fundus and cardia cancer with obstruction, so palliative treatment is usually selected to alleviate the obstruction symptoms and improve the patients’ quality of life. The treatment options are mainly stent placement or active and effective tumor contraction to alleviate the obstruction symptoms. Restoring enteral nutrition mainly involves placing a nasal enteral nutrition tube or stent. Although past research indicated that stent placement was highly successful in quickly alleviating gastric obstruction symptoms in the short-term [ 17 ], the displacement rate of stents in the lower esophagus and gastric cardia is high (10–30%) because their distal end is in the gastric cavity, and they could lead to esophageal injury and bleeding [ 7 , 18 ]. In this study, patients with severe swallowing difficulties were treated with a nasal nasojejunal nutrition tube to restore their enteral nutrition. The insertion was simple and convenient, with few related complications. The nasojejunal nutrition tube could be removed once the patient's tumor has shrunk. The main methods for reducing tumor size are palliative radiotherapy, palliative chemotherapy, and intravascular intervention therapy. Related studies have shown that palliative radiotherapy has a good therapeutic effect on gastric cancer. Kim et al. showed that palliative radiotherapy had an effective rate of 81% in alleviating obstruction [ 19 ]. Still, its efficacy depends on the degree of cell differentiation and might lead to severe radiation gastritis [ 20 , 21 ]. In recent years, chemotherapy has become an important method for advanced cancer management, as it can prolong the OS rate and provide patients with better quality of life. Chemotherapy has been shown to improve the survival rate of patients with gastric cancer [ 22 , 23 ], but it is often accompanied by serious adverse effects, poor tolerance, and drug resistance, and the treatment success rate was only 36.2% [ 24 ]. More importantly, in clinical practice, radiotherapy and chemotherapy usually require multiple treatments, with longer cycles and time for tumor shrinkage. Endovascular intervention therapy includes TAI and TACE. TAI involves direct injection of chemotherapy drugs into the artery that delivers blood supply to the tumor, while TACE slows the blood flow, increases local blood drug concentration, enhances the killing effect of chemotherapy drugs on tumor cells, reduces systemic toxicity, and reduces the treatment side effects [ 25 ]. Unlike systemic chemotherapy, local treatment can quickly narrow the scope on alleviating obstruction symptoms. The ORRs in the two groups in our study were 62.5% and 28.6%, respectively, and the clinical success rates were 78.1% and 42.9%. This approach is also applicable to patients who have failed chemotherapy. In this study, 13 patients received TAI-TACE after systemic chemotherapy failure, yet their lesions were still sensitive to the treatment. The complications of interventional therapy are relatively mild, and patients can usually tolerate them. Most patients had only mild bone marrow suppression and common embolism syndrome after the procedure. The patients' treatment-related symptoms were relieved within 1–3 days of the procedure with symptomatic treatment. Many clinical scholars are concerned that TACE might cause gastric perforation. However, previous study found that TACE with lipiodol was a safe and reliable treatment for gastric cancer [ 26 ]. Earlier studies by Nagamitsu and Ikoma et al. applied lipiodol to the colon of rabbit VX2 colorectal cancer and pig models, respectively, and demonstrated the safety of this embolic agent [ 27 , 28 ]. Studies have shown that edema and necrosis caused by lipiodol embolization usually repair independently within about four weeks [ 13 ]. Moreover, the blood supply to the stomach has extensive collateral circulation, so when some blood vessels are ischemic, nearby blood vessels branch out to prevent gastric wall necrosis and perforation. In this study, the 37 patients in the TAI-TACE group experienced no severe complications such as major bleeding, perforation, or death, reconfirming the safety of iodized oil as an embolic agent. The data from this study showed that TAI-TACE was superior to TAI-BE. TAI-TACE demonstrated its superiority to TAI-BE in alleviating patient obstruction (clinical success rate, 78.1 vs. 42.9%, P = 0.009), controlling local lesions (ORR, 62.5 vs. 28.6%, P = 0.016), and ensuring longer OS (median, 13.0 vs. 10.0 months, P = 0.039). This might be because lipiodol emulsion is a liquid embolic agent, which forms small oil droplets at a diameter that can embolize the capillary bed of the tumor, causing complete tumor necrosis. Conversely, reaching the tumor capillary bed with particle embolic agents is difficult, and the tumor can recover the agents’ invasiveness by developing collateral branches. Furthermore, lipiodol can carry chemotherapeutic drugs, so in addition to playing an excellent role in embolizing tumor blood vessels, it can continuously exert anti-tumor effects locally. The incidence of postoperative nausea, vomiting, and fever in the TAI-TACE group was higher than in the TAI-BE group, which might be related to faster and more extensive tumor necrosis after TACE. However, overall, the adverse events were mild and controllable. Locating all tumor blood supply arteries is a prerequisite for a successful treatment. The left gastric arteries and some from lower esophageal branches should be the main arteries of concern for tumors near the gastric fundus and cardia. Patients with advanced tumors are generally older, and the blood vessels are often tortuous, narrow, or even deviated from the normal anatomical position. Choosing appropriate catheters and adopting the coaxial catheter technology to introduce microcatheters can ensure better access and reduced damage to the target blood vessels. This study is limited by its single-center retrospective, uncontrolled observational design, the results of which are easily affected by selection and recall bias. In the future, we hope to further illustrate the clinical value of this procedure through more rigorous prospective research. In summary, TAI combined with TACE is a safe and effective treatment for patients with advanced gastric fundus and cardia cancer with obstruction, suitable also for patients who had failed chemotherapy. This treatment can quickly shrink the tumor, alleviate the obstruction symptoms, and improve the patients’ quality of life. TAI-TACE showed a more significant overall effect than TAI-BE. Declarations Ethics approval and consent to participate This study was approved by The First Affiliated Hospital of Zhengzhou University Ethics Review Committee (Ethics ID: 2021-KY-0910-002). This study was performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients enrolled in this study. Consent for publication Not applicable Availability of data and materials The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request. Competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Funding No financial grants or other funding have been received in support of this study. Authors' contributions Gang Zhou participated in the design of the study, data collection and paper writing. Yaozhen Ma and Chunxia Li participated in the design of the study and manuscript editing. Yishu Ma and Wei He participated in the design of the study. Xiaolong Ding and Shuiling Jin participated in the design of the study and data collection. Meipan Yin and Tao Liu participated in the data collection. Gang Wu participated in the design of the study and helped to revise the manuscript. All authors read and approved the final manuscript. Acknowledgements Not applicable. References Zhao L, Ling R, Chen J, et al. Clinical Outcomes of Proximal Gastrectomy versus Total Gastrectomy for Proximal Gastric Cancer: A Systematic Review and Meta-Analysis. Dig Surg. 2021; 38: 1-13. Colquhoun A, Arnold M, Ferlay J, et al. Global patterns of cardia and non-cardia gastric cancer incidence in 2012. Gut. 2015; 64: 1881-1888. Blot WJ, Devesa SS, Kneller RW, et al. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. Jama. 1991; 265: 1287-1289. Wang Y, Huang CM, Wang JB, et al. 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Regional Arterial Infusion Chemotherapy improves the Pathological Response rate for advanced gastric cancer with Short-term Neoadjuvant Chemotherapy. Sci Rep. 2015; 5: 17516. Wang S, Yin M, Ma Y, et al. Transcatheter arterial chemoembolization with lipiodol for advanced gastric fundus and cardia cancer. Eur J Cancer Prev. 2023; 32: 305-306. Nagamitsu A, Konno T, Oda T, et al. Targeted cancer chemotherapy for VX2 tumour implanted in the colon with lipiodol as a carrier. Eur J Cancer. 1998; 34: 1764-1769. Ikoma A, Kawai N, Sato M, et al. Ischemic effects of transcatheter arterial embolization with N-butyl cyanoacrylate-lipiodol on the colon in a Swine model. Cardiovasc Intervent Radiol. 2010; 33: 1009-1015. Additional Declarations No competing interests reported. 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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-5402538","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":380738642,"identity":"5d10bbf9-1589-4ee0-9fae-ad897ed6cf18","order_by":0,"name":"Gang Zhou","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Gang","middleName":"","lastName":"Zhou","suffix":""},{"id":380738643,"identity":"0faac9a3-1e0d-4f61-9949-ec6d86f95b3f","order_by":1,"name":"Yaozhen Ma","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Yaozhen","middleName":"","lastName":"Ma","suffix":""},{"id":380738644,"identity":"3a065552-55b3-48bd-94d4-6331d35e0ace","order_by":2,"name":"Yishu Ma","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Yishu","middleName":"","lastName":"Ma","suffix":""},{"id":380738645,"identity":"d5b10aa3-9383-432e-9187-66e169c75e4f","order_by":3,"name":"Xiaolong Ding","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Xiaolong","middleName":"","lastName":"Ding","suffix":""},{"id":380738646,"identity":"969225be-4f11-4890-b50a-0d24144e72d7","order_by":4,"name":"Tao Liu","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Tao","middleName":"","lastName":"Liu","suffix":""},{"id":380738647,"identity":"e44223ad-37b7-40f0-b328-184893f59a9a","order_by":5,"name":"Wei He","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"He","suffix":""},{"id":380738648,"identity":"3850ddbb-b355-45dc-955d-e5019795c85a","order_by":6,"name":"Shuiling Jin","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Shuiling","middleName":"","lastName":"Jin","suffix":""},{"id":380738649,"identity":"0b187364-184a-44f8-aa8a-09008e225e02","order_by":7,"name":"Chunxia Li","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Chunxia","middleName":"","lastName":"Li","suffix":""},{"id":380738650,"identity":"ddef0c73-b62c-43ed-8230-dc2d066a4e81","order_by":8,"name":"Meipan Yin","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Meipan","middleName":"","lastName":"Yin","suffix":""},{"id":380738651,"identity":"fe8ce3c2-2a8f-45ae-9ef4-11e0b6f97ed4","order_by":9,"name":"Gang Wu","email":"data:image/png;base64,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","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":true,"prefix":"","firstName":"Gang","middleName":"","lastName":"Wu","suffix":""}],"badges":[],"createdAt":"2024-11-06 11:53:40","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5402538/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5402538/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":71757146,"identity":"032e595c-825f-462b-8404-00c29d96609c","added_by":"auto","created_at":"2024-12-18 10:18:00","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3748973,"visible":true,"origin":"","legend":"\u003cp\u003eA 69-year-old female with difficulty swallowing as the initial symptom was diagnosed with Stooler grade 3 gastric cancer. (a-c) Upper abdominal computed tomography (CT) images show thickened gastric cardia and fundus and distinct masses protruding into the gastric cavity and affecting the entire gastric wall layer (white arrows), with tumor metastases in the omentum. And she was evaluated as clinical stage IV. (d-f) CT performed one month after the interventional treatment showed partial lipiodol deposition in the lesion, markedly less than before the procedure.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5402538/v1/ebbee5e8b99fb6cf55fee3cd.png"},{"id":71758394,"identity":"2b7a599c-ca37-4553-a068-a831ce4d0e25","added_by":"auto","created_at":"2024-12-18 10:26:00","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1641914,"visible":true,"origin":"","legend":"\u003cp\u003eThe interventional treatment process. (a) The transcatheter angiography showed thickening and tortuosity of the left gastric artery, increased branching, and apparent tumor-like staining in the gastric cardia region. (b) Lipiodol emulsion was injected slowly through a microcatheter. (c) Lipiodol deposition in the tumor area after embolization.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5402538/v1/163a6b7321c5366280e7073b.png"},{"id":71757144,"identity":"591b84f0-cd14-4400-97b5-6cf9661bc5e1","added_by":"auto","created_at":"2024-12-18 10:18:00","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":84226,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival analysis curves for two groups. Group 1 was treated by transcatheter arterial infusion chemotherapy combined with transcatheter arterial lipiodol chemoembolization (TAI-TACE), and Group 2 by transcatheter arterial infusion chemotherapy combined with bland embolization (TAI-BE).\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5402538/v1/6fb193d6135239689d4b629b.png"},{"id":74953589,"identity":"fc75a595-a91f-45be-9b7f-53f05da16151","added_by":"auto","created_at":"2025-01-28 16:46:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5850544,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5402538/v1/8770949e-9a89-4e6a-82e5-d3db702ab196.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Transcatheter arterial infusion chemotherapy combined with lipiodol chemoembolization for advanced gastric fundus and cardia cancer with obstruction","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe overall incidence rate of gastric cancer has declined in recent years, but that of gastric fundus and cardia cancer has continuously increased. The global cancer data show that 952,000 new gastric cancer cases were diagnosed in 2012 worldwide, including 260,000 gastric cardia cancer cases, 52% of which occurred in China [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The prognosis of gastric fundus and cardia cancer is extremely poor, with a 5-year survival rate of just 16.7% [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Most patients are at an advanced stage when diagnosed, often presenting with obstruction as one of the first symptoms, followed by difficulty swallowing, nausea, and vomiting, which greatly affect the patients\u0026rsquo; quality of life and survival.\u003c/p\u003e \u003cp\u003eObstruction relief and enteral nutrition restoration should be urgently addressed. Common clinical treatment methods include surgical resection and stent placement [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. With the improvement of surgical techniques and instruments, various resection and reconstruction methods have been applied; however, postoperative complications such as gastroesophageal reflux, anastomotic fistula, and anastomotic stenosis greatly affect the patients\u0026rsquo; quality of life [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Furthermore, patients with advanced gastric cancer often cannot undergo radical resection. Compared with surgical resection, stent placement is simpler and minimally invasive, making it the standard treatment for gastrointestinal obstruction and recanalization. However, major complications, including stent displacement, granulation tissue proliferation that leads to restenosis, and difficulty in stent removal, cannot be ignored [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Moreover, due to gastrointestinal tract peristalsis, the friction between the stent and the tumor surface might lead to bleeding.\u003c/p\u003e \u003cp\u003eTranscatheter arterial chemoembolization (TACE) with lipiodol is being widely used to treat primary and metastatic liver cancers [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and achieves very positive results; however, research on lipiodol chemoembolization for gastric cancer is limited. Bland embolization (BE), including particles of polyvinyl alcohol, gelatin sponge, and embolization microspheres, is commonly used to treat gastric cancer, especially in cases with bleeding [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The efficacy of BE in treating gastric cancer with obstruction is uncertain. This retrospective study aimed to assess the efficacy and safety of transcatheter arterial infusion chemotherapy (TAI) combined with TACE for advanced gastric fundus and cardia cancer with obstruction and compare it to TAI-BE.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eThe study retrospectively analyzed patients diagnosed with advanced gastric fundus and cardia cancer with obstruction at our center between January 2014 and October 2024. Inclusion criteria: (1) diagnosed with advanced gastric fundus and cardia cancer with obstruction through upper gastrointestinal imaging, gastroscopy, and computed tomography (CT) examinations; (2) pathologically confirmed as gastric adenocarcinoma; (3) cannot undergo radical surgical resection based on a surgeon\u0026rsquo;s evaluation. Exclusion criteria: (1) with gastrointestinal obstruction caused by distal gastric, duodenal, pancreatic, or other lesions; (2) underwent gastrointestinal stent placement treatment.\u003c/p\u003e \u003cp\u003eThe Ethics Committee of Institutional Review Board approved this study (No. : 2021-KY-0910-002), and all patients signed an informed consent form before receiving treatment.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePreoperative preparation\u003c/h3\u003e\n\u003cp\u003eRoutine blood tests, electrolytes, coagulation function, tumor markers, liver and kidney functions, and electrocardiogram results were examined before the operation. Plain and enhanced upper abdomen CT confirmed the tumor location and size (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). All patients were given nutritional support and symptomatic treatment.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eProcedure\u003c/h3\u003e\n\u003cp\u003eThe Seldinger method was used to insert a vascular sheath through the right femoral artery. A 5F angiographic catheter (C2, RLG, or RH TYPE, Cook Corporation, Bloomington, IN, USA) was inserted into left gastric, short gastric, and esophageal proper arteries under fluoroscopy guidance, and the condition of each branch vessel was visualized by catheter angiography (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). Then a 2.7F microcatheter was introduced into the artery that delivered blood supply to the tumor using the coaxial catheter technology. TAI and TACE or BE were performed based on the blood supply and staining degree of the tumor.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTAI: 100 mg oxaliplatin was dissolved in 150 mL 5% glucose solution, and 4 mg raltitrexed was dissolved in 150 mL 0.9% sodium chloride solution. The solutions were injected through a catheter into the target artery at a constant rate of 10 mL/min. TACE: 20 mg pirarubicin was fully emulsified with 10 mL of 48% lipiodol and injected slowly into the target artery through the microcatheter (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb-c). BE: 350\u0026ndash;560 \u0026micro;m polyvinyl alcohol particles were mixed with a 15 mL solution containing contrast medium and normal saline at a 1:1 ratio and injected slowly into the target artery. The embolization endpoint was blood stasis in the target artery and the disappearance of staining in the tumor.\u003c/p\u003e \u003cp\u003eNasojejunal nutrition tubes were inserted after the procedure for patients with difficulty or inability to ingest liquids. The guide wire, catheter, and nutrition tubes were passed through the nasal cavity and esophagus and across the narrow segment, gastric cavity, pylorus, and duodenum to the proximal jejunum under fluoroscopy.\u003c/p\u003e\n\u003ch3\u003ePostoperative management\u003c/h3\u003e\n\u003cp\u003eAfter the procedure, patients were given symptomatic treatment, including proton pump inhibitors, analgesics, antiemetics, and enteral and parenteral nutritional support. Usually, the patients\u0026rsquo; obstruction was reevaluated one week after the procedure. The nutrition tube was removed if the obstruction was relieved and the nutritional status allowed it.\u003c/p\u003e\n\u003ch3\u003eDefinitions\u003c/h3\u003e\n\u003cp\u003eThe patients\u0026rsquo; dysphagia degree was evaluated based on the Stooler classification [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] one week before and after the intervention: grade 0, can eat normal food; grade 1, obstruction in the consumption of soft food; grade 2, can consume a semiliquid diet; grade 3, can consume a liquid diet; grade 4, difficulty or inability in ingesting liquids. The Eastern Cooperative Oncology Group (ECOG) performance status assessed the general condition of the patients [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTechnical success was defined as injecting the chemotherapy and embolic agents into the target artery and reaching the embolization endpoint without serious complications such as major bleeding, perforation, or death. Clinical success was defined as an improvement in the Stooler grade by more than one level after one week of treatment compared to before the intervention.\u003c/p\u003e \u003cp\u003eAccording to the response evaluation criteria in solid tumours\u0026rsquo; standard [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], the local lesion response was evaluated by abdominal CT and expressed as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). The objective response rate (ORR) was defined as the sum of CR and PR; disease control rate (DCR) was defined as the sum of CR, PR, and SD. Overall Survival (OS) was used as the outcome measure. Adverse events were classified according to the Common Terms Criteria for Adverse Events (V.5.0).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using IBM SPSS Statistics for Windows, Version 26.0 (IBM Corp., Armonk, NY, USA). Categorical variables are presented as median with its interquartile range and continuous variables as means and standard deviations. An independent sample \u003cem\u003et\u003c/em\u003e-test or Chi-squared test was used to compare variables between groups as suitable. The Kaplan-Meier test analyzed the OS, and the groups were compared using the log-rank test. All hypothesis tests were considered significant when \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eThis study included 53 patients, 38 males and 15 females, aged 70.0\u0026thinsp;\u0026plusmn;\u0026thinsp;11.1 (46\u0026ndash;93) years, with clinical stages III and IV advanced gastric fundus and cardia cancer with obstruction. Among them, 32 were in the TAI-TACE group, and 21 were in the TAI-BE group. Preoperative chemotherapy failed in 20 patients in the TAI-TACE group. Nasojejunal nutrition tubes were placed in 25 patients in the TAI-TACE group and six in the TAI-BE group. The median pre-intervention Stooler grades of the two groups were 4 and 3 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016). Baseline variables, including sex, age, preoperative chemotherapy, clinical stages, albumin, hemoglobin, carcinoembryonic antigen, and ECOG, were similar in the two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\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\u003eBaseline patient information\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=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTAI-TACE group\u003c/p\u003e \u003cp\u003e\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;32\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTAI-BE group\u003c/p\u003e \u003cp\u003e\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;21\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25 (78.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (61.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (21.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (38.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003cp\u003eHistory of chemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e70.5\u0026thinsp;\u0026plusmn;\u0026thinsp;10.3\u003c/p\u003e \u003cp\u003e20 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e68.7\u0026thinsp;\u0026plusmn;\u0026thinsp;12.9\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.496\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.528\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eⅢ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (46.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (38.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eⅣ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17 (53.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (40.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin (g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33.7\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.077\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin (g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e109.4\u0026thinsp;\u0026plusmn;\u0026thinsp;36.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e121.3\u0026thinsp;\u0026plusmn;\u0026thinsp;37.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.254\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCEA (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.722\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.727\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23 (71.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16 (76.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (28.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (23.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline Stooler grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12(37.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15(71.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: Variables are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or \u003cem\u003en\u003c/em\u003e (%).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eCEA, carcinoembryonic antigen; ECOG, the eastern cooperative oncology group; TAI-TACE, transcatheter arterial infusion chemotherapy combined with transcatheter arterial lipiodol chemoembolization; TAI-BE, transcatheter arterial infusion chemotherapy combined with bland embolization.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eInterventional treatment and efficacy\u003c/h2\u003e \u003cp\u003eThe 53 patients underwent 94 interventional treatments; 22 patients (41.5%) received one treatment, 21 (39.6%) received two treatments, and 10 (18.9%) received three treatments. All cases underwent angiography to stain the tumors and detect the arteries delivering blood supply to them, which included 53 left gastric arteries and six proper esophageal arteries. The average lipiodol emulsion volume used in the TAI-TACE group was 3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9 (1.5\u0026ndash;6.0) mL.\u003c/p\u003e \u003cp\u003eThe technical success rate in both groups was 100%. The patients\u0026rsquo; median Stooler grades after the intervention are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The Stooler grades in the TAI-TACE and TAI-BE groups were 2 and 3, respectively. The clinical success rate in the TAI-TACE group (78.1%, 25/32) was higher than in the TAI-BE group (42.9%, 9/21; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009). In the TAI-TACE group, clinical success was observed in 13 cases (65.0%) who failed preoperative chemotherapy and 16 (64.0%) who met the criteria for removing the nasojejunal nutrition tube. However, all six patients with nasojejunal nutrition tubes in the TAI-BE group did not meet the criteria.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eInterventional treatment efficacy and outcomes\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTAI-TACE group\u003c/p\u003e \u003cp\u003e\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;32\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTAI-BE group\u003c/p\u003e \u003cp\u003e\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;21\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment number (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.083\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProcedure duration (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.0\u0026thinsp;\u0026plusmn;\u0026thinsp;15.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.426\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTechnical success rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical success rate, (\u003cem\u003en\u003c/em\u003e)\u003c/p\u003e \u003cp\u003eStooler grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78.1% (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.9% (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1/2/3/4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7/12/5/8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1/8/9/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor response, % (\u003cem\u003en\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eORR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62.5% (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.6% (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e87.5% (28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.2% (16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.485\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian OS (months)\u003c/p\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.0\u003c/p\u003e \u003cp\u003e3.2\u0026ndash;22.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.0\u003c/p\u003e \u003cp\u003e8.5\u0026ndash;11.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: Variables are expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or \u003cem\u003en\u003c/em\u003e (%).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eORR, objective response rate; DCR, disease control rate; OS, overall survival; CI, confidence interval; TAI-TACE, transcatheter arterial infusion chemotherapy combined with transcatheter arterial lipiodol chemoembolization; TAI-BE, transcatheter arterial infusion chemotherapy combined with bland embolization.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe tumor curative effect, assessed after treatment, was CR in 5 (15.6%), PR in 15 (46.9%), SD in 8 (25.0%), PD in 4 (12.5%) in the TAI-TACE group, and CR in 1 (4.8%), PR in 5 (23.8%), SD in 10 (47.6%), PD in 5 (23.8%) in the TAI-BE group. The ORR in the TAI-TACE group (62.5%) was significantly higher than in the TAI-BE group (28.6%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016), but the groups showed similar DCR, treatment number, and procedure duration (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSix (18.8%) patients were lost to follow-up in the TAI-TACE group and three (14.3%) in the TAI-BE group. The median follow-up in the entire cohort was 32 (3\u0026ndash;65) months. The median OS in the TAI-TACE group (13.0 months; 95% confidence interval [CI], 3.2\u0026ndash;22.8) was longer than in the TAI-BE group (10.0 months; 95% CI, 8.5\u0026ndash;11.5; P\u0026thinsp;=\u0026thinsp;0.039; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eAdverse events\u003c/h2\u003e \u003cp\u003eNone of the patients experienced severe complications such as bleeding, perforation, or death during or after the procedure. Postoperative adverse events in both groups included nausea, vomiting, fever, abdominal pain, decreased platelet and white blood cell counts, and increased ALT and AST levels, all defined as grade 1 adverse events. The incidence of nausea and vomiting (84.4% vs. 57.1%) and fever (59.4% vs. 23.8%) was higher in the TAI-TACE group than in the TAI-BE group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), while the other symptoms appeared in similar rates in both groups (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The above adverse events disappeared within three days of the procedure after delivering symptomatic antiemetic, antipyretic, pain relieving, platelet raising, white blood cell raising, and liver-protecting treatments.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAdverse events\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=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSymptom\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTAI-TACE group\u003c/p\u003e \u003cp\u003e\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;32\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTAI-BE group\u003c/p\u003e \u003cp\u003e\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;21\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea/vomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27 (84.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (57.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.028\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19 (59.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (23.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19 (59.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (38.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.130\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDecreased platelet count\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (40.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (38.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.854\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDecreased WBC count\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (43.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (23.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.139\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncreased ALT/AST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (46.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.328\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: Variables are expressed as \u003cem\u003en\u003c/em\u003e (%).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eWBC, white blood cell count; ALT, alanine transaminase; AST, aspartate transaminase; TAI-TACE, transcatheter arterial infusion chemotherapy combined with transcatheter arterial lipiodol chemoembolization; TAI-BE, transcatheter arterial infusion chemotherapy combined with bland embolization.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIt is usually impossible to perform radical resection in advanced gastric fundus and cardia cancer with obstruction, so palliative treatment is usually selected to alleviate the obstruction symptoms and improve the patients\u0026rsquo; quality of life. The treatment options are mainly stent placement or active and effective tumor contraction to alleviate the obstruction symptoms.\u003c/p\u003e \u003cp\u003eRestoring enteral nutrition mainly involves placing a nasal enteral nutrition tube or stent. Although past research indicated that stent placement was highly successful in quickly alleviating gastric obstruction symptoms in the short-term [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], the displacement rate of stents in the lower esophagus and gastric cardia is high (10\u0026ndash;30%) because their distal end is in the gastric cavity, and they could lead to esophageal injury and bleeding [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In this study, patients with severe swallowing difficulties were treated with a nasal nasojejunal nutrition tube to restore their enteral nutrition. The insertion was simple and convenient, with few related complications. The nasojejunal nutrition tube could be removed once the patient's tumor has shrunk.\u003c/p\u003e \u003cp\u003eThe main methods for reducing tumor size are palliative radiotherapy, palliative chemotherapy, and intravascular intervention therapy. Related studies have shown that palliative radiotherapy has a good therapeutic effect on gastric cancer. Kim et al. showed that palliative radiotherapy had an effective rate of 81% in alleviating obstruction [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Still, its efficacy depends on the degree of cell differentiation and might lead to severe radiation gastritis [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In recent years, chemotherapy has become an important method for advanced cancer management, as it can prolong the OS rate and provide patients with better quality of life. Chemotherapy has been shown to improve the survival rate of patients with gastric cancer [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], but it is often accompanied by serious adverse effects, poor tolerance, and drug resistance, and the treatment success rate was only 36.2% [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. More importantly, in clinical practice, radiotherapy and chemotherapy usually require multiple treatments, with longer cycles and time for tumor shrinkage.\u003c/p\u003e \u003cp\u003eEndovascular intervention therapy includes TAI and TACE. TAI involves direct injection of chemotherapy drugs into the artery that delivers blood supply to the tumor, while TACE slows the blood flow, increases local blood drug concentration, enhances the killing effect of chemotherapy drugs on tumor cells, reduces systemic toxicity, and reduces the treatment side effects [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Unlike systemic chemotherapy, local treatment can quickly narrow the scope on alleviating obstruction symptoms. The ORRs in the two groups in our study were 62.5% and 28.6%, respectively, and the clinical success rates were 78.1% and 42.9%. This approach is also applicable to patients who have failed chemotherapy. In this study, 13 patients received TAI-TACE after systemic chemotherapy failure, yet their lesions were still sensitive to the treatment. The complications of interventional therapy are relatively mild, and patients can usually tolerate them. Most patients had only mild bone marrow suppression and common embolism syndrome after the procedure. The patients' treatment-related symptoms were relieved within 1\u0026ndash;3 days of the procedure with symptomatic treatment.\u003c/p\u003e \u003cp\u003eMany clinical scholars are concerned that TACE might cause gastric perforation. However, previous study found that TACE with lipiodol was a safe and reliable treatment for gastric cancer [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Earlier studies by Nagamitsu and Ikoma et al. applied lipiodol to the colon of rabbit VX2 colorectal cancer and pig models, respectively, and demonstrated the safety of this embolic agent [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Studies have shown that edema and necrosis caused by lipiodol embolization usually repair independently within about four weeks [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Moreover, the blood supply to the stomach has extensive collateral circulation, so when some blood vessels are ischemic, nearby blood vessels branch out to prevent gastric wall necrosis and perforation. In this study, the 37 patients in the TAI-TACE group experienced no severe complications such as major bleeding, perforation, or death, reconfirming the safety of iodized oil as an embolic agent.\u003c/p\u003e \u003cp\u003eThe data from this study showed that TAI-TACE was superior to TAI-BE. TAI-TACE demonstrated its superiority to TAI-BE in alleviating patient obstruction (clinical success rate, 78.1 vs. 42.9%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009), controlling local lesions (ORR, 62.5 vs. 28.6%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016), and ensuring longer OS (median, 13.0 vs. 10.0 months, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.039). This might be because lipiodol emulsion is a liquid embolic agent, which forms small oil droplets at a diameter that can embolize the capillary bed of the tumor, causing complete tumor necrosis. Conversely, reaching the tumor capillary bed with particle embolic agents is difficult, and the tumor can recover the agents\u0026rsquo; invasiveness by developing collateral branches. Furthermore, lipiodol can carry chemotherapeutic drugs, so in addition to playing an excellent role in embolizing tumor blood vessels, it can continuously exert anti-tumor effects locally. The incidence of postoperative nausea, vomiting, and fever in the TAI-TACE group was higher than in the TAI-BE group, which might be related to faster and more extensive tumor necrosis after TACE. However, overall, the adverse events were mild and controllable.\u003c/p\u003e \u003cp\u003eLocating all tumor blood supply arteries is a prerequisite for a successful treatment. The left gastric arteries and some from lower esophageal branches should be the main arteries of concern for tumors near the gastric fundus and cardia. Patients with advanced tumors are generally older, and the blood vessels are often tortuous, narrow, or even deviated from the normal anatomical position. Choosing appropriate catheters and adopting the coaxial catheter technology to introduce microcatheters can ensure better access and reduced damage to the target blood vessels.\u003c/p\u003e \u003cp\u003eThis study is limited by its single-center retrospective, uncontrolled observational design, the results of which are easily affected by selection and recall bias. In the future, we hope to further illustrate the clinical value of this procedure through more rigorous prospective research.\u003c/p\u003e \u003cp\u003eIn summary, TAI combined with TACE is a safe and effective treatment for patients with advanced gastric fundus and cardia cancer with obstruction, suitable also for patients who had failed chemotherapy. This treatment can quickly shrink the tumor, alleviate the obstruction symptoms, and improve the patients\u0026rsquo; quality of life. TAI-TACE showed a more significant overall effect than TAI-BE.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by The First Affiliated Hospital of Zhengzhou University Ethics Review Committee (Ethics ID: 2021-KY-0910-002). This study was performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients enrolled in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study available from the \u003c/p\u003e\n\u003cp\u003ecorresponding author on reasonable request. \u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo financial grants or other funding have been received in support of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e Gang Zhou participated in the design of the study, data collection and paper writing. Yaozhen Ma and Chunxia Li participated in the design of the study and manuscript editing. Yishu Ma and Wei He participated in the design of the study. Xiaolong Ding and Shuiling Jin participated in the design of the study and data collection. Meipan Yin and Tao Liu participated in the data collection. Gang Wu participated in the design of the study and helped to revise the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e Not applicable. \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eZhao L, Ling R, Chen J, et al. Clinical Outcomes of Proximal Gastrectomy versus Total Gastrectomy for Proximal Gastric Cancer: A Systematic Review and Meta-Analysis. Dig Surg. 2021; 38: 1-13.\u003c/li\u003e\n\u003cli\u003eColquhoun A, Arnold M, Ferlay J, et al. Global patterns of cardia and non-cardia gastric cancer incidence in 2012. 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Cureus. 2022; 14: e27466.\u003c/li\u003e\n\u003cli\u003eLiang M, Liwen Z, Juan D, et al. A case report of endoscopic therapy for radiation-induced hemorrhagic gastritis in patient with recurrent hepatocellular carcinoma. Medicine (Baltimore). 2018; 97: e13535.\u003c/li\u003e\n\u003cli\u003eKokkola A, Louhimo J, Puolakkainen P. Does non-curative gastrectomy improve survival in patients with metastatic gastric cancer? J Surg Oncol. 2012; 106: 193-196.\u003c/li\u003e\n\u003cli\u003ePeng D, Zhang B, Yuan C, et al. Gastric transcatheter chemoembolization can resolve advanced gastric cancer presenting with obstruction. Front Surg. 2022; 9: 1004064.\u003c/li\u003e\n\u003cli\u003eSchuhmacher C, Gretschel S, Lordick F, et al. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol. 2010; 28: 5210-5218.\u003c/li\u003e\n\u003cli\u003eWu ZF, Cao QH, Wu XY, et al. Regional Arterial Infusion Chemotherapy improves the Pathological Response rate for advanced gastric cancer with Short-term Neoadjuvant Chemotherapy. Sci Rep. 2015; 5: 17516.\u003c/li\u003e\n\u003cli\u003eWang S, Yin M, Ma Y, et al. Transcatheter arterial chemoembolization with lipiodol for advanced gastric fundus and cardia cancer. Eur J Cancer Prev. 2023; 32: 305-306.\u003c/li\u003e\n\u003cli\u003eNagamitsu A, Konno T, Oda T, et al. Targeted cancer chemotherapy for VX2 tumour implanted in the colon with lipiodol as a carrier. Eur J Cancer. 1998; 34: 1764-1769.\u003c/li\u003e\n\u003cli\u003eIkoma A, Kawai N, Sato M, et al. Ischemic effects of transcatheter arterial embolization with N-butyl cyanoacrylate-lipiodol on the colon in a Swine model. Cardiovasc Intervent Radiol. 2010; 33: 1009-1015.\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":"gastric cancer, obstruction, transcatheter infusion chemotherapy, lipiodol, chemoembolization","lastPublishedDoi":"10.21203/rs.3.rs-5402538/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5402538/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eGastric fundus and cardia cancer are increasingly common, diagnosed at a late stage, often with severe obstruction, and have a poor prognosis. Transcatheter arterial lipiodol chemoembolization (TACE) is rarely used for gastric cancer. This single-center retrospective study aimed to analyze the efficacy and safety of transcatheter arterial infusion chemotherapy (TAI) combined with TACE in advanced gastric fundus and cardia cancer with obstruction and compare it to bland embolization (BE).\u003c/p\u003e\u003ch2\u003eMaterials and Methods\u003c/h2\u003e \u003cp\u003eThe clinical efficacy of TAI-TACE was evaluated through technical and clinical success rates, obstruction relief, tumor response, overall survival (OS), and postoperative adverse events. TAI-TACE and TAI-BE efficacies were compared.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe study included 53 patients (age 70.0\u0026thinsp;\u0026plusmn;\u0026thinsp;11.1 years, 38 males). Thirty-two patients underwent TAI-TACE, and 21 underwent TAI-BE. The cohort\u0026rsquo;s technical success rate was 100%. The pre- and post-intervention median Stooler grades were 4 and 2 in the TAI-TACE group and 3 and 3 in the TAI-BE group, respectively. Compared to the TAI-BE group, the TAI-TACE group had a higher clinical success rate (78.1%, 25/32 vs. 42.9%, 9/21; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009), a better objective response rate (53.1% vs. 38.1%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016), and a longer median OS (13.0; 95% confidence interval (CI), 3.2\u0026ndash;22.8 vs. 10.0; 95% CI, 8.5\u0026ndash;11.5; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.039) months. All adverse events were grade 1.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe TAI-TACE interventional therapy scheme was safe and effective, achieving rapid tumor shrinkage, obstructive symptom alleviation, improved quality of life, and a significantly better overall effect than TAI-BE.\u003c/p\u003e","manuscriptTitle":"Transcatheter arterial infusion chemotherapy combined with lipiodol chemoembolization for advanced gastric fundus and cardia cancer with obstruction","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-18 10:17:55","doi":"10.21203/rs.3.rs-5402538/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":"d9bcbd79-cfae-44f9-8db8-317a31137722","owner":[],"postedDate":"December 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-28T16:38:35+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-18 10:17:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5402538","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5402538","identity":"rs-5402538","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}