Safety and efficacy of transcatheter arterial infusion chemotherapy combined with Lipiodol chemoembolization for advanced colorectal cancer with bleeding: a retrospective single-center clinical study of 119 patients in China

Introduction

Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer-related deaths in both sexes (1). About 40–50% of patients with CRC have distant metastasis at diagnosis and cannot undergo surgery; the 5-year overall survival (OS) rate in these patients is less than 10% (2-5). In advanced CRC, bleeding is one of the most common complications, with 40–93% of patients presenting with bloody stools, black stools (dominant bleeding), or positive fecal occult blood test and anemia (recessive bleeding) (6-10). Long-term bleeding is associated with anemia, infections, tumor progression, poor quality of life, and even death. Endoscopy is widely considered the “gold standard” for diagnosis and achieving hemostasis, with success rates in the range of 65.7–87.4% (11-14); however, bleeding may recur in up to 42% of patients (15).

Transcatheter arterial infusion chemotherapy (TAI) is commonly used in the treatment of liver and lung cancers (14,16-18). In TAI, antitumor drugs are injected directly into the tumor supply artery through a catheter, ensuring exposure of tumor cells to high concentrations of chemotherapeutic drugs without increasing systemic toxicity. Meanwhile, transcatheter arterial embolization (TAE) is a safe and effective method for controlling lower gastrointestinal bleeding due to various colorectal diseases (e.g., diverticulitis, infection, ulcer, malignant tumor, and vascular dysplasia) as well as bleeding following biopsy or segmental resection (16-21). However, there are no studies on the efficacy of TAE with Lipiodol for treating CRC-related bleeding. This study aimed to determine the safety and effectiveness of the combination of TAI and Lipiodol chemoembolization (LCE) for the treatment of CRC with bleeding. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2533/rc).

Methods

Patients

The clinical data of patients with CRC complicated with bleeding who received TAI + LCE treatment at the Interventional Radiology Department of The First Affiliated Hospital of Zhengzhou University from February 2019 to June 2025 were retrospectively analyzed. The inclusion criteria were (I) imaging- and biopsy-confirmed advanced colorectal adenocarcinoma treated by an interventional approach on the recommendation of specialists or because of the patient’s own choice; (II) frank blood in the stool, black stool, or positive fecal occult blood test with moderate anemia, hemoglobin (Hb) ≤70 g/L; and (III) treated with TAI combined with LCE. The exclusion criteria were: (I) lower gastrointestinal bleeding due to other malignant tumor or benign disease; (II) upper gastrointestinal bleeding; (III) aspirin, warfarin or other anti-platelets and anticoagulants use; (IV) history of intestinal obstruction treated with intestinal stents or intestinal obstruction catheters; (V) jaundice or coagulation disorder; (VI) received other anti-tumor treatments during TAI + LCE; or (VII) treatment only with TAE. A total of 119 patients met the eligibility criteria and were included in the study.

Each patient signed an informed consent form for the interventional diagnosis and treatment. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Medical Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No. 2021-KY-0911-004).

Preoperative preparation

Pre-procedure investigations included blood routine examination, liver and kidney function tests, electrolytes, coagulation, tumor markers testing, electrocardiogram, and enhanced computed tomography (CT) of the abdomen and pelvis. The patient should fast for 6 hours before the intervention. Gastric mucosal protective agents, nutritional support, and preventive antibiotics were routinely prescribed.

Interventional treatment

The procedure was performed with the patient lying supine on the digital subtraction angiography (DSA) table, with continuous oxygen supplementation through a mask and electrocardiogram monitoring. The femoral artery was punctured and a 5-F vascular sheath inserted. A guide wire and catheter were introduced through the sheath. Under fluoroscopic guidance, the catheter was placed in the superior mesenteric artery (for right colon cancer) or the inferior mesenteric artery (for left colon cancer and rectal cancer), and angiography was performed to show the distribution of the tumor supply arteries and the lesion volume. A 2.7-F microcatheter (Terumo, Tokyo, Japan) was introduced through the catheter and placed near the tumor supply artery.

The infusion chemotherapy included oxaliplatin 100 mg in 5% glucose solution (150 mL in total) and raltitrexed 4 mg in 0.9% sodium chloride solution (150 mL in total), which were specifically adjusted for intra-arterial administration according to the improved anti-tumor ECF protocol. For patients of advanced age and poor physical condition with Eastern Cooperative Oncology Group (ECOG) performance status rating of 2, the dosage was halved. The chemotherapeutic drugs were administered via a microcatheter, with an infusion rate of 10 mL/min. Then, a uniform mixing emulsion of 10 mg (pirarubicin, THP) in 10 mL Lipiodol was slowly injected into the tumor supply artery through the microcatheter under fluoroscopy until stasis or cessation of antegrade blood flow. The catheter and vascular sheath were then removed. Hemostasis at the puncture site was achieved by femoral artery compression and application of a compression bandage.

Postoperative care

Postoperatively, all patients routinely received antibiotics, antiemetics, gastric acid suppression drugs, hydration, and symptomatic treatment. This evidence-based practice is a targeted prophylaxis for this high-risk subgroup, not a universal treatment for all bleeding colon cancer patients. One week after LCE, blood was drawn for routine examination, liver and kidney function tests, serum electrolytes, and coagulation series. At follow-up 1 month after treatment, repeat blood routine examination, stool examination for evidence of bleeding, and enhanced CT were performed to evaluate treatment efficacy. When necessary, TAI + LCE treatment was performed 1–2 times, with a 4-week interval between treatments.

Variables and definitions

Dominant bleeding was defined as rectal bleeding and/or black stool, while recessive bleeding was defined as no black stool but positive fecal occult blood test and moderate anemia with Hb ≤70 g/L. Hemorrhage plus intestinal obstruction was considered as the patient with obstruction following bleeding episodes. Acute bleeding was defined as bloody stool within 48 hours of bleeding. Hemodynamic instability (systolic blood pressure <90 mmHg and heart rate >100/min) (16,22-24) was considered as indication of severe bleeding. Bleeding time was defined as the time from the onset of bleeding to LCE.

Technical success was defined as angiographic evidence of stasis or cessation of antegrade blood flow after embolization, without occurrence of serious adverse events such as intestinal perforation or major bleeding. Clinical success was defined as the absence of recurrent bleeding within 30 days after LCE. For clarification, recurrent bleeding encompassed two subtypes: dominant bleeding and recessive bleeding. Clinical failure was defined as sustained bleeding during hospital stay or recurrent bleeding within 30 days after LCE. Hematochezia-free survival (HFS; i.e., time from LCE to recurrence of bleeding, death, or end of follow-up) and OS were the primary outcomes.

CT and DSA images were reviewed by two experienced interventional radiologists. Tumor size and therapeutic effect were assessed on enhanced CT and were based on the RECIST standard. Treatment response was classified as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD). The objective response rate [ORR; (CR + PR)/total number of cases × 100%] and disease control rate [DCR; (CR + PR + SD)/total number of cases × 100%] were calculated.

Adverse events occurring during the peri-interventional treatment period (PITP, defined as within 12 days from the start of TAI) were recorded and classified according to the US Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

Patients were followed up until September 30, 2025, with complete follow-up data achieved before manuscript submission; follow-up was via telephone interview. outpatient examination, or post-hospitalization examination. During the interventional treatment period, patients were reviewed once a month and, thereafter, once every 3 months. Tests for blood in stool and abdominal CT were performed whenever required.

Statistical analysis

Statistical analysis was conducted using IBM SPSS 26.0 (IBM, Armonk, NY, USA). Categorical variables were summarized as percentages and compared using the chi-square test. HFS and OS were analyzed using the Kaplan-Meier method. Variables significantly associated (at P<0.1) with HFS and OS in univariate analysis were entered into a multivariate Cox proportional hazards model to identify the independent predictors of outcomes, and the hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. P<0.05 was considered statistically significant.

Results

The 119 patients (75 males, 44 females) were in the age range of 23–86 years (mean age, 61.16±15.86 years). While 78/119 (65.5%) patients had dominant bleeding, 41/119 (34.5%) had recessive bleeding. There were 33/119 (27.7%) patients who had bleeding combined with intestinal obstruction. There were 16/119 (13.4%) patients with acute bleeding, 9/119 (7.6%) patients with severe bleeding, and 4/119 (3.4%) patients with both acute and severe bleeding. Table 1 shows the clinical characteristics of the patients.

Interventional therapy

TAI and LCE treatments were administered successfully in all 119 patients (technical success rate, 100%). A total of 128 tumor-feeding arteries were identified on angiography (mean, 1.06±0.27 arteries per patient; range, 1–2 arteries). They included six ileocolic arteries, nine right colonic arteries, four middle colonic arteries, nine left colonic arteries, twelve sigmoid colon arteries, twenty-one superior rectal arteries, and one middle rectal artery.

While 53/119 (44.5%) patients received one TAI + LCE treatment, 66/119 (55.5%) patients received two treatments. All patients underwent superselective TAI via a microcatheter (Figure 1). LCE was administered with a mean dose of 2.88±1.65 mL (range, 0.8–6 mL) of Lipiodol, based on the objective procedural or angiographic benchmarks of antegrade blood flow stasis or cessation after embolization. The Lipiodol dose varied widely from 0.8 to 6 mL, and was individually determined according to the objective procedural and angiographic benchmarks of antegrade blood flow stasis or cessation after embolization. Marked heterogeneity in lesion blood supply was observed among individual patients, leading to a right-skewed distribution of the dosage data. Additionally, 27/119 (22.7%) patients with liver metastasis also underwent intrahepatic transcatheter arterial chemoembolization.

Figure 1 TAI + LCE angiography of the patients. Angiography, after placement of microcatheters in the branches of the inferior mesenteric artery and sigmoid colon artery, showed abnormally enhancing lesions (A) in the sigmoid colon area. Oxaliplatin (100 mg) and raltitrexed (4 mg) were perfused successively through microcatheters to implement TAI, and 3.5 mL of Lipiodol emulsion (10 mL of Lipiodol + 10 mg of THP) was injected for LCE. Post-procedure imaging showed the disappearance of the abnormally enhancing lesions and cessation of blood flow (B). LCE, Lipiodol chemoembolization; TAI, transcatheter arterial infusion chemotherapy; THP, pirarubicin.

Adverse events during PITP

No patient experienced severe adverse events such as perforation or necrosis during the PITP.

All 119 patients experienced intermittent abdominal pain after LCE, but only 25/119 (21.0%) required pain relief treatment. Of the 119 patients, 39 (32.8%) patients developed mucinous stools and tenesmus within 1–3 days following LCE. All these gastrointestinal events were categorized as Grade 1–2 adverse events in accordance with Common Terminology for Adverse Events (CTCAE) version 5.0, and were considered to be associated with prominent mucosal irritation or mild ischemic alterations. These events were well tolerated, required no specific treatment, and underwent spontaneous remission within one week.

Other complications during PITP were nausea I–II (58/119 patients), thrombocytopenia I–II (29/119 patients) and fever (24/119 patients) (Table 2). In all cases, the symptoms finally improved.

Short-term efficacy of interventional therapy

Clinical success was achieved in 99/119 (83.2%) patients. In 5/119 (4.2%) patients, bleeding stopped after two interventional treatments. One patient with a lesion in the hepatic flexure needed embolization of the middle colon artery and of the right colon artery. The other patient showed no abnormalities in the middle rectal artery on the first angiography, but a repeat angiography was performed because of continued bleeding, which revealed that a branch of the artery was involved in the blood supply of the tumor; this artery was then successfully embolized. Clinical failure was recorded in 20/119 (16.8%) patients. Seven of these patients had intestinal obstruction that was not relieved by treatment, and the other 13 had continued bleeding with deterioration of overall condition, and further interventional treatment was not attempted.

Among the 33 patients with bleeding plus intestinal obstruction, 29 experienced relief in intestinal obstruction symptoms after interventional treatment and recovered the ability to pass flatus and stools. The other 4 patients experienced relief in abdominal distension after insertion of intestinal obstruction catheters, and some ability to pass flatus and stools; all four patients withdrew from the study, which met the predefined exclusion criterion.

One month after the end of TAI + LCE, we evaluated the patient’s tumor response. Treatment response was classified as CR in 19/112 (17.0%) patients, PR in 55/112 (49.1%), SD in 23/112 (20.5%), and PD in 15/112 (13.4%). The ORR and DCR were 68.5% and 90.7%, respectively (Figure 2).

Figure 2 Tumor response in patients after LCE. A 62-year-old man presented with intermittent bloody stools for more than 4 months. His bowel habits had changed, and he occasionally experienced abdominal pain and bloating. CT showed significant thickening and enhancement of the sigmoid colon wall, and the white line segment represented the maximum meridian of the lesion (A-C). Colonoscopy showed a nodule in the sigmoid colon 14–20 cm away from the anus; the nodule’s surface showed erosion, necrosis, and bleeding (D). One month after LCE, the patients had no blood in their stools, indicating clinical success. CT reexamination showed a significant decrease in the wall of the sigmoid colon (E-G), and colonoscopy showed a significant reduction in lesion size (H). The treatment response was graded as complete remission, and the response grading just refers to the treated lesions. CT, computed tomography; LCE, Lipiodol chemoembolization.

Additional therapy after LCE included targeted therapy, interstitial radioactive particle implantation, chemotherapy, radiotherapy, and/or PD-1 therapy (Table 1).

Factors associated with HFS

Three patients were lost to follow-up as they could not be contacted. The 109 patients who completed follow-up were followed up for a median of 11.5 months (range, 1–79 months). Among the 96 patients who achieved clinical success, the median HFS was 11.0 months (95% CI: 8.34–13.66 months; Figure 3).

Figure 3 Survival curve for (A) HFS and (B) OS. HFS, hematochezia-free survival; OS, overall survival.

Table 3 shows the association of different factors with HFS. In univariate analysis, age and bleeding time were significantly associated with HFS, but sex, type of bleeding, lesion location, and TNM stage were not related to HFS. In multivariate analysis, the factors independently associated with the risk of recurrent bleeding were age (HR 2.31, 95% CI: 1.09–4.862, P=0.028) and bleeding time (HR 2.62, 95% CI: 1.18–5.84, P=0.018).

Survival

During the follow-up period, 95/109 (87.1%) patients died (88 died of cancer progression, 5 of lung infections, and 2 of heart failure); 14/109 (12.9%) patients survived. The median OS was 13.0 months (95% CI: 10.86–15.14; Figure 3). Median OS was significantly longer in the clinical success group than in the clinical failure group [13.0 months (95% CI: 9.97–16.03) vs. 5.0 months (95% CI: 2.85–7.15); P=0.002]. For the multivariate OS analysis adjusting for disease stage, ECOG performance status, and post-treatment systemic therapy, ECOG performance status and post-treatment systemic therapy were significantly influencing factors of OS (Figure 4).

Figure 4 Overall survival analysis adjusting for disease stage, performance status, and post-treatment systemic therapy. In (A), 1 indicates ECOG 0–1 or age <65 years, and 2 indicates ECOG 2 or age ≥65 years. In (B), 1 indicates receipt of systemic therapy and 2 indicates no systemic therapy. ECOG, Eastern Cooperative Oncology Group; OS, overall survival.

Discussion

Bleeding is a common problem in patients with advanced CRC and can be difficult to manage. Bleeding is often due to erosion of blood vessels by the tumor. Further, tumor neovascularization is fragile and prone to rupture and bleeding. In addition, tumor-induced inflammatory response increases the risk of vascular rupture and bleeding. The complex pathological mechanism makes treatment of bleeding difficult and recurrence common. Control of bleeding requires a combination of hemostatic therapy and antitumor therapy.

Surgery is a definitive treatment for CRC-related bleeding, but surgical resection has strict indications, and emergency surgical resection is associated with high incidence of complications and poor prognosis (25-27). Intravenous chemotherapy and bevacizumab is an effective palliative treatment for advanced CRC but is associated with risk of gastrointestinal bleeding (28-32), probably due to treatment-related dysfunction of vascular endothelial cells and reduced regeneration ability.

In recent years, there has been increased interest in the use of vascular embolization to treat colon and rectal bleeding (17-19,33-36). However, there are no studies on CRC-related bleeding. Various embolic materials such as N-butyl-2-cyanoacrylate (NBCA), gelatin sponge, blood clot, spring coil, and polyvinyl alcohol (PVA) have been used as embolic agents. The therapeutic effect of TAE is limited, and the bleeding caused by the treatment of CRC with the above-mentioned embolic materials is prone to recurrence. Clinical studies on various types of lower gastrointestinal bleeding have shown a 17.4–28.0% probability of re-bleeding after TAE (24,37-39).

Lipiodol is an oily contrast medium consisting of a mixture of long-chain (C16 and C18) di-iodinated ethyl esters of fatty acids derived from poppy seed (Papaver somniferum var. nigrum) oil, which contains 98% unsaturated fatty acids (40). Lipiodol, similar to NBCA, is a liquid embolic agent. Lipiodol has several advantages. First, it is a radiopaque, controllable delivery method, and can be transported further than the spring coil or PVA through microcatheters (41), and thus achieve microcirculation embolism. Second, Lipiodol has unparalleled tumor affinity and drug-carrying capacity (42); in our patients, we exploited this characteristic of Lipiodol, using it to carry THP to the tumor. However, there are no reports of the use of Lipiodol. Further, the use of the combination of antitumor treatment and embolization for control of CRC-related bleeding has not been reported.

The combination of TAI and LCE was able to achieve a satisfactory therapeutic effect. Lipiodol blocked the tumor supply artery and achieved immediate hemostasis, while also acting as a “slow-release” system for chemotherapy drugs, thereby prolonging the antitumor treatment effect. Meanwhile, infusion of chemotherapy drugs into the feeding artery achieved high chemotherapy drug concentration within the tumor for more rapid killing of tumor cells and control of tumor neovascularization (43).

According to literature, the incidence of intestinal ischemia after TAE is in the range of 0–25% (17,24,44,45). In this study, Lipiodol embolization did not result in any serious adverse events. The 39/119 (32.8%) patients who developed mucinous stools and tenesmus 1–3 days after LCE improved spontaneously. This was related to tumor necrosis and local exudation after embolization. There are several possible explanations for the demonstrated safety of Lipiodol. First, Lipiodol does not stay in the colorectal tissue for a long time, so it only causes brief local ischemia. Previous studies have shown that Lipiodol droplets can enter the hepatic vein through hepatic sinuses with a diameter of only 5–8 µm (46,47). Capillaries have diameters similar to those of the hepatic sinuses. Arterial pressure drives Lipiodol through the capillaries of the colon and rectum and into the draining veins. Second, Lipiodol causes little foreign body reaction. Inflammatory granulomas have been reported in the pelvic cavity, diaphragm, and inguinal hernia sac after salpingography (48,49), but they only appeared after many years. As shown in this study, the duration of retention of Lipiodol in colorectal tissue is not long enough to cause a significant foreign body reaction. Third, embolization articles such as coils, gelatin sponges, or PVA rely on thrombus formation to block blood vessels, rather than the embolic material itself. Lipiodol does not cause thrombosis or exacerbate colorectal tissue ischemia. Fourth, the use of microcatheters effectively reduces the risk of complications such as vasospasm and dissecting aneurysm (24,50-52).

TAI and LCE work together through multidimensional mechanisms in tumor and bleeding control, forming a dual strike strategy of “embolization + chemotherapy” (53). The core mechanism is the synergistic enhancement of embolization and chemotherapy. On the one hand, by directly blocking the tumor’s blood supply artery with embolic agents, oxygen and nutrient supply are cut off, leading to tumor ischemic necrosis (54,55). On the other hand, Lipiodol, as a carrier of chemotherapy drugs, not only embolizes microvessels through its viscous properties, but also selectively retains in tumor tissue, slowly releasing chemotherapy drugs, creating a local high concentration drug environment, and prolonging the duration of action (56,57). In addition, in the combination of embolization and chemotherapy, local blood flow slows down after embolization blocks tumor blood vessels. At the same time, Lipiodol slowly releases chemotherapy drugs, maintaining high local concentrations while reducing systemic toxicity and enhancing anti-tumor and hemostatic effects. Therefore, embolization directly stops bleeding, while chemotherapy drugs reduce tumor volume and inhibit angiogenesis, which would reduce the risk of subsequent bleeding. The combined application of them is expected to achieve the dual goal of “hemostasis + anti-tumor”.

However, bleeding control is a core aspect of clinical management of severe cases, especially tumors, trauma, gastrointestinal diseases, etc. (58). Direct hemostasis contributed to the improved survival in our study, while the interruption of the “bleeding-systemic exhaustion” vicious cycle also played a pivotal role (59,60). Supported by our clinical data, a virtuous cycle was constructed through systemic therapy, nutritional improvement and functional enhancement, leading to prolonged survival and better quality of life. Systemic therapy (such as chemotherapy, targeted therapy, immunotherapy, anti-infective therapy, etc.) is the key means of controlling the primary disease, but the bleeding state can directly hinder the implementation of treatment; effective hemostasis provides a safe window for subsequent systemic therapy, ensuring treatment continuity and improving oncological outcomes. Gastrointestinal bleeding may impair nutrient intake and absorption and exacerbate malnutrition. However, the underlying mechanisms are complex and beyond the scope of the present study; therefore, they are not elaborated further here.

This study has obvious limitations. It is a single-center retrospective study without a control group. Large-scale multicenter controlled clinical trials are needed to confirm our findings. In the future, we hope to further illustrate the clinical value of this procedure through more rigorous prospective research. We should expand the sample size and multi-centre studies, and use strategies such as clear inclusion and exclusion criteria, multivariate adjustment, propensity score matching, sensitivity analysis, standardized data collection tools, and multiple data source validation to minimize these biases. We should have a long-term follow-up to evaluate the long-term effects of treatment and further improve the scientific and reliable nature of the research.

In addition, all participants in this single-center study were enrolled in China and were of Chinese ethnicity, representing a relatively homogeneous Asian cohort. As such, the direct generalizability of our findings to other racial and ethnic populations may be limited. Accordingly, our results primarily reflect the efficacy and safety of LCE in Chinese patients with advanced CRC with bleeding. Although the fundamental hemostatic mechanisms and technical principles of LCE are universal, potential differences in genetic background, lifestyle, tumor biology, and clinical practice patterns should be acknowledged when extrapolating these findings to other ethnic groups or geographic regions. Future multi-ethnic and international validation studies are warranted to enhance the global generalizability of our conclusions and to quantify the potential impact of ethnicity on clinical outcomes.

Conclusions

TAI combined with LCE appears to be a safe, effective, and well-tolerated treatment for advanced CRC with bleeding. It is a feasible palliative treatment plan in clinical practice that provides a new treatment method for patients with CRC combined with bleeding.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2533/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2533/dss

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2533/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Medical Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No. 2021-KY-0911-004), and informed consent was obtained from all individual participants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin 2023;73:233-54. [Crossref] [PubMed]
2. Chakedis J, Schmidt CR. Surgical Treatment of Metastatic Colorectal Cancer. Surg Oncol Clin N Am 2018;27:377-99.
3. Zacharakis M, Xynos ID, Lazaris A, Smaro T, Kosmas C, Dokou A, Felekouras E, Antoniou E, Polyzos A, Sarantonis J, Syrios J, Zografos G, Papalambros A, Tsavaris N. Predictors of survival in stage IV metastatic colorectal cancer. Anticancer Res 2010;30:653-60.
4. Zellweger M, Abdelnour-Berchtold E, Krueger T, Ris HB, Perentes JY, Gonzalez M. Surgical treatment of pulmonary metastasis in colorectal cancer patients: Current practice and results. Crit Rev Oncol Hematol 2018;127:105-16. [Crossref] [PubMed]
5. Hernandez Dominguez O, Yilmaz S, Steele SR, Stage IV. Colorectal Cancer Management and Treatment. J Clin Med 2023;12:2072. [Crossref] [PubMed]
6. Del Giudice ME, Vella ET, Hey A, Simunovic M, Harris W, Levitt C. Systematic review of clinical features of suspected colorectal cancer in primary care. Can Fam Physician 2014;60:e405-15.
7. Hreinsson JP, Jonasson JG, Bjornsson ES. Bleeding-related symptoms in colorectal cancer: a 4-year nationwide population-based study. Aliment Pharmacol Ther 2014;39:77-84. [Crossref] [PubMed]
8. Majumdar SR, Fletcher RH, Evans AT. How does colorectal cancer present? Symptoms, duration, and clues to location. Am J Gastroenterol 1999;94:3039-45. [Crossref] [PubMed]
9. Lasson A, Kilander A, Stotzer PO. Diagnostic yield of colonoscopy based on symptoms. Scand J Gastroenterol 2008;43:356-62. [Crossref] [PubMed]
10. du Toit J, Hamilton W, Barraclough K. Risk in primary care of colorectal cancer from new onset rectal bleeding: 10 year prospective study. BMJ 2006;333:69-70. [Crossref] [PubMed]
11. Nigam N, Patel P, Sengupta N. Outcomes of Early Versus Delayed Colonoscopy in Lower Gastrointestinal Bleeding Using a Hospital Administrative Database. J Clin Gastroenterol 2018;52:721-5. [Crossref] [PubMed]
12. Saleepol A, Kaosombatwattana U. Outcomes and performance of risk scores in acute lower gastrointestinal bleeding. JGH Open 2023;7:372-6. [Crossref] [PubMed]
13. Chang A, Ouejiaraphant C, Akarapatima K, Rattanasupa A, Prachayakul V. Prospective Comparison of the AIMS65 Score, Glasgow-Blatchford Score, and Rockall Score for Predicting Clinical Outcomes in Patients with Variceal and Nonvariceal Upper Gastrointestinal Bleeding. Clin Endosc 2021;54:211-21.
14. Omori J, Kaise M, Nagata N, Aoki T, Kobayashi K, Yamauchi A, et al. Characteristics, outcomes, and risk factors of surgery for acute lower gastrointestinal bleeding: nationwide cohort study of 10,342 hematochezia cases. J Gastroenterol 2024;59:24-33.
15. Mourad FH, Leong RW. Role of hemostatic powders in the management of lower gastrointestinal bleeding: A review. J Gastroenterol Hepatol 2018;33:1445-53.
16. Bua-Ngam C, Norasetsingh J, Treesit T, Wedsart B, Chansanti O, Tapaneeyakorn J, Panpikoon T, Vallibhakara SA. Efficacy of emergency transarterial embolization in acute lower gastrointestinal bleeding: A single-center experience. Diagn Interv Imaging 2017;98:499-505.
17. Hur S, Jae HJ, Lee M, Kim HC, Chung JW. Safety and efficacy of transcatheter arterial embolization for lower gastrointestinal bleeding: a single-center experience with 112 patients. J Vasc Interv Radiol 2014;25:10-9.
18. Pannatier M, Duran R, Denys A, Meuli R, Zingg T, Schmidt S. Characteristics of patients treated for active lower gastrointestinal bleeding detected by CT angiography: Interventional radiology versus surgery. Eur J Radiol 2019;120:108691.
19. Seyferth E, Dai R, Ronald J, Martin JG, Sag AA, Befera N, Pabon-Ramos WM, Suhocki PV, Smith TP, Kim CY. Safety Profile of Particle Embolization for Treatment of Acute Lower Gastrointestinal Bleeding. J Vasc Interv Radiol 2022;33:286-94.
20. Frost J, Sheldon F, Kurup A, Disney BR, Latif S, Ishaq S. An approach to acute lower gastrointestinal bleeding. Frontline Gastroenterol 2017;8:174-82.
21. Hosse C, Moos M, Becker LS, Sieren M, Müller L, Stoehr F, Schaarschmidt BM, Barbone G, Collettini F, Fehrenbach U, Hinrichs JB, Kloeckner R, Geisel D, Tacke F, Gebauer B, Auer TA. Trans-arterial embolization for treatment of acute lower gastrointestinal bleeding-a multicenter analysis. Eur Radiol 2025;35:2746-54. [Crossref] [PubMed]
22. Valek V, Husty J. Quality improvement guidelines for transcatheter embolization for acute gastrointestinal nonvariceal hemorrhage. Cardiovasc Intervent Radiol 2013;36:608-12. [Crossref] [PubMed]
23. Ierardi AM, Urbano J, De Marchi G, Micieli C, Duka E, Iacobellis F, Fontana F, Carrafiello G. New advances in lower gastrointestinal bleeding management with embolotherapy. Br J Radiol 2016;89:20150934. [Crossref] [PubMed]
24. Yu Q, Funaki B, Ahmed O. Twenty years of embolization for acute lower gastrointestinal bleeding: a meta-analysis of rebleeding and ischaemia rates. Br J Radiol 2024;97:920-32. [Crossref] [PubMed]
25. Bin Traiki TA, AlShammari SA, AlRabah RN, AlZahrani AM, Alshenaifi ST, Alhassan NS, Abdulla MH, Zubaidi AM, Al-Obeed OA, Alkhayal KA. Oncological outcomes of elective versus emergency surgery for colon cancer: A tertiary academic center experience. Saudi J Gastroenterol 2023;29:316-22. [Crossref] [PubMed]
26. Baer C, Menon R, Bastawrous S, Bastawrous A. Emergency Presentations of Colorectal Cancer. Surg Clin North Am 2017;97:529-45. [Crossref] [PubMed]
27. Weixler B, Warschkow R, Ramser M, Droeser R, von Holzen U, Oertli D, Kettelhack C. Urgent surgery after emergency presentation for colorectal cancer has no impact on overall and disease-free survival: a propensity score analysis. BMC Cancer 2016;16:208. [Crossref] [PubMed]
28. Zou Y, Liu S, Wu J, Sun Z. Severe ileum bleeding following adjuvant capecitabine chemotherapy for locally advanced colon cancer: a case report and review of the literature. World J Surg Oncol 2021;19:332. [Crossref] [PubMed]
29. Moriwaki T, Bando H, Takashima A, Yamazaki K, Esaki T, Yamashita K, Fukunaga M, Miyake Y, Katsumata K, Kato S, Satoh T, Ozeki M, Baba E, Yoshida S, Boku N, Hyodo I. Bevacizumab in combination with irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) in patients with metastatic colorectal cancer who were previously treated with oxaliplatin-containing regimens: a multicenter observational cohort study (TCTG 2nd-BV study). Med Oncol 2012;29:2842-8. [Crossref] [PubMed]
30. Yokoyama T, Kondo H, Yokota T, Tokue Y, Saito D, Shimada Y, Sugihara K. Colonoscopy for frank bloody stools associated with cancer chemotherapy. Jpn J Clin Oncol 1997;27:111-4. [Crossref] [PubMed]
31. Ross WB, Morris DL, Clingan PR. Major upper gastrointestinal haemorrhage associated with hepatic arterial chemoperfusion. Aust N Z J Surg 1996;66:816-9. [Crossref] [PubMed]
32. Koucky K, Wein A, Konturek PC, Albrecht H, Reulbach U, Männlein G, Wolff K, Ostermeier N, Busse D, Golcher H, Schildberg C, Janka R, Hohenberger W, Hahn EG, Siebler J, Neurath MF, Boxberger F. Palliative first-line therapy with weekly high-dose 5-fluorouracil and sodium folinic acid as a 24-hour infusion (AIO regimen) combined with weekly irinotecan in patients with metastatic adenocarcinoma of the stomach or esophagogastric junction followed by secondary metastatic resection after downsizing. Med Sci Monit 2011;17:CR248-58. [Crossref] [PubMed]
33. Kodani M, Yata S, Ohuchi Y, Ihaya T, Kaminou T, Ogawa T. Safety and Risk of Superselective Transcatheter Arterial Embolization for Acute Lower Gastrointestinal Hemorrhage with N-Butyl Cyanoacrylate: Angiographic and Colonoscopic Evaluation. J Vasc Interv Radiol 2016;27:824-30. [Crossref] [PubMed]
34. Koo HJ, Shin JH, Kim HJ, Kim J, Yoon HK, Ko GY, Gwon DI. Clinical outcome of transcatheter arterial embolization with N-butyl-2-cyanoacrylate for control of acute gastrointestinal tract bleeding. AJR Am J Roentgenol 2015;204:662-8. [Crossref] [PubMed]
35. Kwon JH, Kim MD, Han K, Choi W, Kim YS, Lee J, Kim GM, Won JY, Lee DY. Transcatheter arterial embolisation for acute lower gastrointestinal haemorrhage: a single-centre study. Eur Radiol 2019;29:57-67. [Crossref] [PubMed]
36. Nykänen T, Peltola E, Kylänpää L, Udd M. Transcatheter Arterial Embolization in Lower Gastrointestinal Bleeding: Ischemia Remains a Concern Even with a Superselective Approach. J Gastrointest Surg 2018;22:1394-403. [Crossref] [PubMed]
37. Huang CC, Lee CW, Hsiao JK, Leung PC, Liu KL, Tsang YM, Liu HM. N-butyl cyanoacrylate embolization as the primary treatment of acute hemodynamically unstable lower gastrointestinal hemorrhage. J Vasc Interv Radiol 2011;22:1594-9. [Crossref] [PubMed]
38. Gillespie CJ, Sutherland AD, Mossop PJ, Woods RJ, Keck JO, Heriot AG. Mesenteric embolization for lower gastrointestinal bleeding. Dis Colon Rectum 2010;53:1258-64. [Crossref] [PubMed]
39. Tan KK, Wong D, Sim R. Superselective embolization for lower gastrointestinal hemorrhage: an institutional review over 7 years. World J Surg 2008;32:2707-15.
40. Wolff J. Physiology and pharmacology of iodized oil in goiter prophylaxis. Medicine (Baltimore) 2001;80:20-36.
41. Frodsham A, Berkmen T, Ananian C, Fung A. Initial experience using N-butyl cyanoacrylate for embolization of lower gastrointestinal hemorrhage. J Vasc Interv Radiol 2009;20:1312-9.
42. Idée JM, Guiu B. Use of Lipiodol as a drug-delivery system for transcatheter arterial chemoembolization of hepatocellular carcinoma: a review. Crit Rev Oncol Hematol 2013;88:530-49.
43. Anteby R, Kemeny NE, Kingham TP, D’Angelica MI, Wei AC, Balachandran VP, Drebin JA, Brennan MF, Blumgart LH, Jarnagin WR. Getting Chemotherapy Directly to the Liver: The Historical Evolution of Hepatic Artery Chemotherapy. J Am Coll Surg 2021;232:332-8. [Crossref] [PubMed]
44. Kwak HS, Han YM, Lee ST. The clinical outcomes of transcatheter microcoil embolization in patients with active lower gastrointestinal bleeding in the small bowel. Korean J Radiol 2009;10:391-7. [Crossref] [PubMed]
45. Kuo WT, Lee DE, Saad WE, Patel N, Sahler LG, Waldman DL. Superselective microcoil embolization for the treatment of lower gastrointestinal hemorrhage. J Vasc Interv Radiol 2003;14:1503-9. [Crossref] [PubMed]
46. Kan Z, Sato M, Ivancev K, Uchida B, Hedgpeth P, Lunderquist A, Rosch J, Yamada R. Distribution and effect of iodized poppyseed oil in the liver after hepatic artery embolization: experimental study in several animal species. Radiology 1993;186:861-6. [Crossref] [PubMed]
47. Kan Z, Ivancev K, Hägerstrand I, Chuang VP, Lunderquist A. In vivo microscopy of the liver after injection of Lipiodol into the hepatic artery and portal vein in the rat. Acta Radiol 1989;30:419-25.
48. Grosskinsky CM, Clark RL, Wilson PA, Novotny DB. Pelvic granulomata mimicking endometriosis following the administration of oil-based contrast media for hysterosalpingography. Obstet Gynecol 1994;83:890-2.
49. Miyazaki Y, Yamamoto T, Hyakudomi R, Taniura T, Hirayama T, Takai K, Hirahara N, Tajima Y. Case of inflammatory granuloma in inguinal hernia sac after hysterosalpingography with oily contrast medium. Int J Surg Case Rep 2020;72:215-8. [Crossref] [PubMed]
50. Pham T, Tran BA, Ooi K, Mykytowycz M, McLaughlin S, Croxford M, Skinner I, Faragher I. Super-Selective Mesenteric Embolization Provides Effective Control of Lower GI Bleeding. Radiol Res Pract 2017;2017:1074804. [Crossref] [PubMed]
51. Moss AJ, Tuffaha H, Malik A. Lower GI bleeding: a review of current management, controversies and advances. Int J Colorectal Dis 2016;31:175-88. [Crossref] [PubMed]
52. Chan DK, Soong J, Koh F, Tan KK, Lieske B. Predictors for outcomes after super-selective mesenteric embolization for lower gastrointestinal tract bleeding. ANZ J Surg 2016;86:459-63. [Crossref] [PubMed]
53. Zhang J, Zhou G, Yin M, Ma Y, He W, Bi Y, Wu G. Transcatheter arterial infusion chemotherapy combined with lipiodol chemoembolization for advanced gastric fundus and cardia cancer with obstruction. J Cancer Res Clin Oncol 2025;151:183. [Crossref] [PubMed]
54. Gao F, Rafiq M, Cong H, Yu B, Shen Y. Current research status and development prospects of embolic microspheres containing biological macromolecules and others. Int J Biol Macromol 2024;267:131494.
55. Hu J, Albadawi H, Chong BW, Deipolyi AR, Sheth RA, Khademhosseini A, Oklu R. Advances in Biomaterials and Technologies for Vascular Embolization. Adv Mater 2019;31:e1901071.
56. Zhu S, Gu C, Gao L, Du S, Feng D, Gu Z. Lipiodol emulsion as a dual chemoradiation-sensitizer for pancreatic cancer treatment. J Control Release 2024;374:242-53.
57. Konno T, Maeda H. Targeting cancer chemotherapy using lipiodol as a carrier of anticancer drugs for hepatocellular carcinoma. Gan To Kagaku Ryoho 1988;15:1043-50.
58. Foley A, Hannity J. Advancing Basic Bleeding Control. J Emerg Nurs 2018;44:210-1. [Crossref] [PubMed]
59. Aoki T, Hirata Y, Yamada A, Koike K. Initial management for acute lower gastrointestinal bleeding. World J Gastroenterol 2019;25:69-84. [Crossref] [PubMed]
60. Kate V, Sureshkumar S, Gurushankari B, Kalayarasan R. Acute Upper Non-variceal and Lower Gastrointestinal Bleeding. J Gastrointest Surg 2022;26:932-49. [Crossref] [PubMed]