Published online Jun 27, 2026. doi: 10.4240/wjgs.117856
Revised: February 6, 2026
Accepted: March 10, 2026
Published online: June 27, 2026
Processing time: 155 Days and 0.4 Hours
Endoscopic submucosal dissection (ESD) is an effective minimally invasive treat
To evaluate the effect of Taishan Codonopsis on outcomes after clip-line traction-assisted ESD.
This single-center, randomized controlled trial enrolled 100 patients with early esophageal cancer at Jiangsu Second Traditional Chinese Medicine Hospital (January 2023-December 2024). Patients were randomly assigned to clipping wire traction-assisted ESD alone or ESD plus oral Taishan Codonopsis extract (250 mg three times daily) from 7 days preoperatively to 14 days postoperatively (n = 50 per group). Between-group comparisons used independent-samples t-tests or χ2 tests; statistical significance was defined as P < 0.05.
There were no significant differences in baseline characteristics or procedural efficiency between the two groups. C-reactive protein levels in the combination group were significantly lower than those in the clipping wire traction group on postoperative day 1, day 3, and day 7 (P < 0.001). Compared with the clipping wire traction group, the combination group exhibited lower peak postoperative pain (P < 0.001), earlier time to first meal (P < 0.001), and shorter postoperative hospital stays (P < 0.001). Four weeks after surgery, gastroscopic reexamination revealed that the ulcer healing rates in the combination group (90.0%) was significantly higher than that in the clipping wire traction group (64.0%; P < 0.05).
Perioperative Taishan Codonopsis significantly suppresses post-ESD inflammation, accelerates recovery, and improves ulcer healing when combined with clipping wire traction-assisted ESD, offering a valuable adjunct to endoscopic resection.
Core Tip: This randomized trial demonstrates that the perioperative administration of Taishan Codonopsis (Codonopsis lanceolata) combined with clipping wire traction-assisted endoscopic submucosal dissection offers significant clinical benefits for early esophageal cancer. This integrative strategy effectively attenuates systemic inflammation (reduced C-reactive protein), mitigates postoperative pain, expedites functional recovery, shortens hospital stay, enhances ulcer healing, and lowers complication rates, providing an effective and safe adjunct to modern endoscopic therapy.
- Citation: Shi D, Zheng L. Synergistic effect of Codonopsis lanceolata and clip-line traction in endoscopic submucosal dissection for early esophageal cancer. World J Gastrointest Surg 2026; 18(6): 117856
- URL: https://www.wjgnet.com/1948-9366/full/v18/i6/117856.htm
- DOI: https://dx.doi.org/10.4240/wjgs.117856
Esophageal cancer (EC) is a common and poorly prognosed malignant tumor. In 2022, there were approximately 600000 new cases and 54000 deaths of EC worldwide[1]. It is the seventh most common cancer globally and ranks sixth in terms of mortality. It remains one of the deadliest malignant tumors globally[2,3]. Many patients with EC show no obvious symptoms in the early stages, so the disease is often diagnosed in the middle or late stages, with a five-year survival rate of less than 20%[4]. Endoscopic submucosal dissection (ESD) is known and used in clinical practice as a complex technique in endoscopy[5]. ESD treatments enable early-stage cancer identification and serve as one of the safest and most effective treatment approaches. ESD can be regarded as one of the most preferred therapeutic options[6]. However, ESD is an invasive procedure that can damage tissue and cause loss of appetite as well as other complications. This can lead to nutrient deficiencies, recurrent issues in hospitalized patients, and deterioration of conditions such as esophageal stricture[7]. Clip-line traction, a crucial and core auxiliary technique for ESD, has been widely applied in the treatment of early gastrointestinal cancers in recent years[8]. This technique typically involves fixing a nylon thread to the lesion mucosa using an endoscopic clip, and then applying continuous traction through external manipulation to expose the submucosal surgical field[9]. A recent systematic review and meta-analysis of 9 randomized controlled trials involving 1477 patients confirmed that traction-assisted ESD significantly shortened mean dissection time in esophageal neoplasms and reduced perforation risk in colorectal cases compared with conventional ESD[10]. By achieving “laparoscopic-like triangulation” through continuous traction on the lesion mucosa, it clarifies submucosal vascular and muscular layers, thereby reducing blind dissection and intraoperative trauma[10].
Researchers have come up with new strategies to avoid challenges during ESD, one of which is integrating a catheter with a clip. This technique is more efficient, less invasive, facilitates enhancements in the visibility of the surgical area, and generally streamlines the surgical approach. This results in improved patient outcomes and ESD effectiveness[11,12]. Within the scope of this discipline, traction methodologies resolve mechanical challenges, yet with regard to the inflammation caused by the surgical trauma, the biological responses resulting from the surgical trauma remain addressed.
The severity of the systemic inflammatory response influences recovery post-surgery. C-reactive protein (CRP) is one of the markers indicating an individual’s inflammatory response[13]. Following ESD, CRP levels rise after certain surgical procedures and injury occur, and post-operative pain and difficulty in eating are correlated with the CRP level increase[14]. Furthermore, post-ESD recovery directly correlates with the likelihood of developing an esophageal stricture[15]. Inadequate recovery increases the chance of the esophagus narrowing due to scar formation and may necessitate additional procedures. Consequently, during the ESD perioperative period, it is important to find strategies to manage inflammation and enhance ulcer healing. This has significant clinical value.
Taishan Codonopsis, also known as Codonopsis lanceolata Benth. Hook.f., is an important herb used traditionally to restore vital energy and bodily resistance, clear away heat, and detoxify. The current phytochemical studies of this plant revealed that the biologically active constituents of this herb, especially saponins and polysaccharides, possess significant antioxidant potential, thus being the basis of its pharmacological action in immune response modulation and mitigation of oxidative stress[16]. Based on this biochemical profile, there is a great likelihood that Taishan Codonopsis will be therapeutically helpful in mitigating inflammation and maintaining integrity within the esophageal mucosa post-esophageal ESD.
As Taishan Codonopsis has a theoretical basis for its anti-inflammatory and wound-healing properties, this study speculates whether its perioperative use along with the refined clip wire traction-assisted ESD method has the ability to influence the response to surgical trauma in patients with early-stage esophageal diseases. In this regard, a prospective, controlled pilot study was undertaken to assess the effectiveness of Taishan Codonopsis and its impact on selected postoperative outcomes, such as aspects of clinical recovery, the relative fluctuations of CRP concentration over time, and the quality of ulcer healing in the postoperative period.
A total of 100 patients with early EC who underwent ESD at the Department of Gastroenterology, Jiangsu Second Traditional Chinese Medicine Hospital between January 2023 and December 2024 were enrolled as study subjects. They were randomly assigned to either the clipping wire traction group (n = 50) or the combination group (n = 50) based on their treatment regimens.
Inclusion criteria: (1) Diagnosis of early EC confirmed by endoscopic biopsy and pathological examination[17]; (2) No lymph node or distant metastasis, as confirmed by chest and abdominal computed tomography and esophageal endoscopic ultrasound; (3) No previous history of esophageal surgery; and (4) Complete clinical and follow-up data available.
Exclusion criteria: (1) Receipt of chemotherapy and/or radiotherapy prior to ESD; (2) Severe cardiac, pulmonary, hepatic, or renal insufficiency; (3) Presence of a coagulation disorder; and (4) Allergy to Taishan Codonopsis or related compounds.
Clipping wire traction group: Clipping wire traction-assisted ESD was performed as follows[18,19]: (1) Preoperative preparation: Patients fasted and abstained from fluids for 8 hours prior to the procedure. Routine preoperative assessments - including complete blood count, coagulation profile, electrocardiogram, and other relevant tests - were performed, followed by induction of general anesthesia; and (2) Surgical procedure: The gastroscope was inserted to locate the lesion, and markings were placed approximately 0.5 cm from its margin. A solution (e.g., normal saline with indigo carmine and epinephrine) was injected into the submucosa outside the markings to create a sufficient submucosal cushion. At the mucosal incision site along the lesion edge, a mucosal flap was grasped with biopsy forceps, and an endoscopic clip preloaded with a nylon thread was attached to the flap. External traction was applied to the thread to maintain a clear view of the submucosal layer. Submucosal dissection was then carefully performed using a dual knife along the traction plane. Active bleeding during the procedure was managed with hemostatic forceps under direct vision. After complete resection of the lesion, the post-ESD defect was carefully examined, and any visible vessels or deep injuries were prophylactically treated with hemostatic forceps or clips.
The combination group: Treatment with Taishan Codonopsis combined with clipping wire traction-assisted ESD: Patients in the combination group received the same preoperative preparation, surgical procedure (clipping wire traction-assisted ESD), and postoperative basic care as those in the clipping wire traction group. In addition, the combination group began oral administration of Taishan Codonopsis extract capsules (250 mg per capsule, total saponin content ≥ 50%, supplied by our hospital’s pharmacy) seven days before ESD, taking two capsules three times daily. This administration was continued for 14 days after the operation. Patients in the clipping wire traction group received identically appearing and tasting placebo capsules (containing starch) that were indistinguishable from the Taishan Codonopsis capsules in appea
Surgery-related outcomes: Documentation included the operation time (from initial mucosal incision to complete lesion resection), en bloc resection rate, curative resection rate (en bloc resection with histologically negative margins), and intraoperative blood loss for both groups.
Complication outcomes: The incidence of procedure-related adverse events was recorded, including postoperative bleeding, esophageal stenosis, and infection.
Serial CRP levels: Venous blood samples were collected at baseline (before the procedure) and on postoperative day 1, day 3, and day 7. Serum CRP concentrations were measured using immunoturbidimetry (Roche Diagnostics, Switzer
Postoperative peak pain: The highest pain intensity experienced within the first 72 hours after surgery was assessed using the Visual Analogue Scale (range 0-10)[20].
Time to first meal and postoperative hospital stay: Time to first meal was defined as the interval from the end of ESD to successful ingestion of liquid diet. Postoperative hospital stay was defined as the number of days from the day of ESD to hospital discharge.
Ulcer healing rate at 4 weeks: Healing of ESD-induced ulcers was evaluated by follow-up gastroscopy at 4 weeks postoperatively. Complete healing was defined as full coverage of the ulcer bed by regenerated mucosa or progression to the linear/scar phase (S phase)[21]. The healing rate was calculated as the percentage of patients achieving this endpoint.
All statistical analyses in this study were conducted with SPSS Statistics (version 21.0). Quantitative variables are summarized as means ± SD and underwent intergroup comparison via either the independent-samples t-test or the Mann-Whitney U test. Qualitative data are reported as n (%), with group differences assessed using the χ2 test or Fisher’s exact test. Statistical significance was defined by P value of less than 0.05.
Table 1 indicated that there was no apparent difference in gender, age, body mass index, lesion location, lesion mor
| Indicators | Clipping wire traction group | Combination group | t/χ2 | P value |
| Gender (male/female) | 31/19 | 34/16 | 0.396 | 0.529 |
| Age (years) | 65.23 ± 7.66 | 65.53 ± 5.42 | 0.224 | 0.823 |
| BMI | 21.47 ± 4.29 | 21.16 ± 4.33 | 0.360 | 0.719 |
| Lesion site | 2.763 | 0.251 | ||
| Up | 11 | 14 | ||
| Middle | 28 | 31 | ||
| Lower | 11 | 5 | ||
| Lesion morphology | 0.462 | 0.881 | ||
| Protrusion | 13 | 11 | ||
| Flat | 35 | 36 | ||
| Depression | 2 | 3 | ||
| Depth of the lesion | 1.329 | 0.249 | ||
| Mucosal layer | 45 | 41 | ||
| Submucosa | 5 | 9 |
Table 2 showed that no significant differences existed in surgery-related indicators between the two groups. The ope
| Indicators | Clipping wire traction group | Combination group | t/χ2 | P value |
| Operation time(min) | 57.65 ± 12.81 | 53.39 ± 10.36 | 1.828 | 0.071 |
| En bloc resection rate | 47 (94.00) | 50 (100.00) | 3.093 | 0.079 |
| Curative resection rate | 42 (84.00) | 46 (92.00) | 1.515 | 0.218 |
Table 3 illustrated significantly accelerated postoperative recovery in the combination group. The time to first meal was shorter (1.78 ± 0.39 days vs 2.31 ± 0.48 days; P < 0.001), and the postoperative hospital stay was reduced (6.42 ± 1.18 days vs 8.19 ± 1.34 days; P < 0.001) compared to the clipping wire traction group.
| Indicators | Clipping wire traction group | Combination group | t/χ2 | P value |
| Time to first meal | 2.31 ± 0.48 | 1.78 ± 0.39 | 6.051 | < 0.001 |
| Postoperative hospital stays | 8.19 ± 1.34 | 6.42 ± 1.18 | 6.995 | < 0.001 |
Table 4 revealed a lower overall complication rate in the combination group (8.00%, 4/50) compared to the clipping wire traction group (24.00%, 12/50; χ2 = 4.762, P = 0.029).
| Indicators | Clipping wire traction group | Combination group | t/χ2 | P value |
| Postoperative bleeding | 3 (6.00) | 1 (2.00) | ||
| Esophageal stenosis | 6 (12.00) | 3 (6.00) | ||
| Infection | 3 (6.00) | 0 (0.00) | ||
| Total | 12 (24.00) | 4 (8.00) | 4.762 | 0.029 |
Table 5 detailed the inflammatory, pain, and healing outcomes. While preoperative CRP levels were comparable (P > 0.05), the combination group exhibited significantly lower CRP levels at postoperative day 1 (25.1 ± 5.9 mg/L vs 36.2 ± 7.5 mg/L; P < 0.001), day 3 (38.5 ± 8.7 mg/L vs 60.5 ± 11.3 mg/L; P < 0.001), and day 7 (5.2 ± 2.1 mg/L vs 8.9 ± 2.8 mg/L; P < 0.001). The peak postoperative pain score was also lower in the combination group (5.1 ± 1.2 vs 6.0 ± 1.2; P < 0.001). Furthermore, the 4-week ulcer healing rate was significantly higher in the combination group [90.0% (45/50) vs 64.0% (32/50); χ2 = 9.543, P = 0.002].
| Clipping wire traction group | Combination group | t/χ2 | P value | |
| CRP (mg/L) | ||||
| Preoperative | 3.5 ± 1.2 | 3.3 ± 1.1 | 0.873 | 0.385 |
| Postoperative days 1 | 36.2 ± 7.5 | 25.1 ± 5.9 | 8.229 | < 0.001 |
| Postoperative days 3 | 60.5 ± 11.3 | 38.5 ± 8.7 | 10.913 | < 0.001 |
| Postoperative days 7 | 8.9 ± 2.8 | 5.2 ± 2.1 | 7.483 | < 0.001 |
| Postoperative peak pain (VAS score) | 6.0 ± 1.2 | 5.1 ± 1.2 | 3.732 | < 0.001 |
| 4-week ulcer scar healing rate | 32 (90.00) | 45 (64.00) | 9.543 | 0.002 |
EC is among the most aggressive gastrointestinal malignancies worldwide and is associated with a high mortality rate, largely attributable to late diagnosis. Early EC - defined as carcinoma confined to the mucosa or submucosa - has shown a rising incidence globally and represents a common malignant tumor of the digestive system. In reality, the lesions are usually confined to the mucosa or submucosa of the esophagus; the typical manifestations in the esophagus include lumen narrowing, a thin wall, and lack of serosal protection, which can pose considerable difficulties in subsequent treatment procedures. If patients are not properly managed, they face risk of complications, including bleeding, perforation, esophageal stricture and recurrence of cancer, with the result of poor prognosis and a decrease in quality of life[22]. Treatment methods have improved, but the prognosis for EC patients depends on the stage of the disease at diagnosis. Unfortunately, most early-stage EC present with non-specific symptoms, resulting in delayed diagnosis[23]. Therefore, screening methods for early-stage EC are of paramount importance.
Endoscopic mucosal resection (EMR) and ESD are the principal techniques of endoscopic resection. ESD, which has developed as a technique originally in Japan from EMR, has become the procedure of choice for the treatment of early neoplasm of the esophagus, stomach and colon. Compared to EMR, ESD offers more effective treatment, as demonstrated by higher en bloc resection rates, lower local recurrence rates, lower long-term morbidity, and probably overall treatment costs are lower, too[24]. The ESD technique involves the use of the endoscope which renders it technically difficult. Thus, compared to EMR, ESD involves longer operative times, greater risks and more complications (bleeding, pain, perforation and stenosis etc.)[25].
To enhance this process further, scientists have also developed techniques for mucosa lifting, including the use of traction with the help of clips and threads. This approach utilizes a long thread fixed with a clip to apply traction in the direction of a target area. Such an approach provides for good localization of the defect and distinctly visualizes various types of tissues of the body, like submucosal vessels and muscular layers, thereby facilitating the performance of surgery with precision. This enables detailed investigation and visualization of body organs and blood vessels, which can reduce the duration of the surgery and minimize the possibility of injury[26]. Thus, wires can efficiently solve the mechanical problems; however, do not ensure significant biological improvement for erythrocyte sedimentation rate, including cell damage and further inflammatory response. The inflammation after surgery causes not only patient discomfort and prolonged recovery but also becomes a critical point for such long-term complications as esophageal stricture.
By addressing this clinical challenge, our research aims to innovatively combine the traditional Chinese herb Taishan Codonopsis with modern endoscopic techniques. Our goal is to explore whether this herb, when used in conjunction with line traction, can produce significant protective effects. As one of the four famous medicines of Taishan, Taishan Codonopsis is historically recorded in the “Concise Table of Chinese Herbs” with traditional uses including reducing swelling and detoxifying, resolving phlegm and relieving cough, as well as strengthening the body. According to recent pharmacological studies, Taishan Codonopsis is rich in saponins, polysaccharides, flavonoids and other bioactive compounds, and has been shown to have pharmacological effects such as anti-inflammatory, antioxidant, immune system protection, and energy restoration[27]. Based on these pharmacological properties, we assess that Taishan Codonopsis may regulate the inflammatory response after ESD surgery and enhance mucosal repair, thereby optimizing the effects of milder treatments for EC.
In this study, a randomized controlled trial method was used to scientifically analyze 100 patients with early-stage EC undergoing clip wire traction-assisted ESD. The participants were divided into two groups: The clipping wire traction group received only clip wire traction-assisted ESD, while the combination group also took oral Taishan Codonopsis during the treatment. In the study findings, there was a systematic comparison made between the two groups with respect to the various clinical parameters: The plateau of the inflammatory response as indicated by the blood depression of serum constituents, the clinical improvement as indicated by the relief of symptoms, the healing of the ulcers as indicated by the endoscopy, and the data convenient with respect to safety from the clinical point of view as determined by the report of adverse phenomena were considered. The results given above show that there is marked difference in these important points between the two groups, and they will be given in three main features as being indications of the efficiency of the treatment.
First, it has been shown that Taishan Codonopsis significantly reduces breakdown in the body during inflammation. As a result, CRP, an important protein produced by the liver under the influence of factors such as interleukin (IL)-6, is used to indicate inflammation and is helpful in assessing the severity of metabolism and inflammation[28]. The results re
Second, the suppressed inflammatory state is directly associated with patient-centered outcome improvements. In terms of pain management, the peak Visual Analogue Scale score was lower in the combination group (5.1 ± 1.2 vs 6.0 ± 1.2, P < 0.001). This difference can be attributed to the reduction of local and systemic inflammation, as inflammatory mediators such as prostaglandins and bradykinin are key sensitizing factors in pain pathways. Pain management brings a series of successes in the rehabilitation process. Specifically, it prevents postoperative ileus by reducing intra-abdominal inflammatory responses and patient discomfort, thus promoting better pain control and earlier oral intake (1.78 ± 0.39 days vs 2.31 ± 0.48 days, P < 0.001). Better pain control and early nutritional support reasonably shorten postopera
Third, key Impacts on ulcer healing quality and long-term benefits. It should be noted that the ulcer scar healing rate in the combination group was significantly increased at 4 weeks after the operation (90.0% vs 64.0%, P < 0.05). The quality and speed of ESD ulcer healing are of vital importance; incomplete epithelial regeneration is an important high-risk factor for esophageal stenosis[32]. Through effectively controlling the initial inflammatory response, Taishan Codonopsis may promote a more orderly and efficient healing process. Besides, previous studies have demonstrated that Codonopsis extract promotes angiogenesis and proliferation of fibroblasts[33], which is important in the course of the formation of granulation tissue and regeneration of the mucosa. Improvement in the quality of ulcer healing means reduction in the risk of esophageal stenosis and a guarantee for long-term quality of life in patients. Improvement in the quality of ulcer healing means reduction in the risk of esophageal stenosis and a guarantee for long-term quality of life in patients. Experimental studies indicate that Codonopsis polysaccharide preparations significantly accelerate wound closure[34]. Its healing mechanism involves upregulating key repair-related genes, particularly enhancing vascular endothelial growth factor and miRNA-21 expression, which play crucial roles in angiogenesis and tissue remodeling[34]. Furthermore, Codonopsis polysaccharide treatment promotes new capillary formation and increases collagen deposition[34], while improving the ordered arrangement of collagen fibers in regenerated tissue[35]. This formulation also effectively suppresses the high expression of pro-inflammatory factors in damaged skin, significantly enhances the activity of antioxidant enzymes (such as glutathione peroxidase and superoxide dismutase) and total antioxidant capacity, and reduces levels of lipid peroxidation products[35]. These multidimensional effects collectively promote efficient and orderly tissue repair.
This study ensured the reliability of its results through a rigorously controlled design, random selection, clipping wire traction, and objective CRP measurement. However, there are certain limitations: Firstly, the single-center design may limit the generalizability of the findings, thus multi-center clinical trials are needed to confirm these results. Secondly, using CRP as the primary anti-inflammatory target does not cover significant changes in a broader range of inflammatory mediators - such as IL-6, tumor necrosis factor-α, and IL-10 - which may hinder a comprehensive understanding of the anti-inflammatory mechanism of Taishan Codonopsis. Furthermore, the follow-up period for assessing esophageal stricture was relatively short (4 weeks). To determine whether the observed positive trend is long-term and stable, the observation period needs to be extended to 6 months or 1 year. This guideline also indicates directions for future research: Preliminary studies have confirmed its efficacy, but the optimal dosage, treatment course, and combination therapy regimen of Taishan Codonopsis need to be clarified, and small-scale laboratory work is required to track the mechanism of action - that is, to identify the cell types involved in key processes under animal or in vitro conditions.
In conclusion, this study confirms that the perioperative use of Taishan Codonopsis provides significant additional benefits to patients undergoing ESD. It effectively alleviates postoperative inflammation (as reflected by reduced CRP levels), reduces pain, accelerates functional recovery, shortens hospital stay, and enhances long-term healing quality. The integrative model of “traditional Chinese medicine combined with modern endoscopic technology” offers a novel strategy for minimally invasive oncology and underscores the value of harmonizing traditional and contemporary medical approaches. As a safe and effective natural agent, Taishan Codonopsis merits inclusion in enhanced recovery protocols following ESD and is poised for broader clinical adoption, ultimately offering patients a less aggressive therapeutic pathway with improved quality of life.
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