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World Journal of Surgical Oncology logoLink to World Journal of Surgical Oncology
. 2025 Aug 22;23:316. doi: 10.1186/s12957-025-03972-2

Early application of nanocarbon suspension in gastric cancer patients enhances postoperative lymph node detection

Sheng Li 1,#, Xiaoli Chen 2,#, Xiaoyu Yang 3,#, Zhiyao Chen 4, Jiahui Xiong 3, Yanting Lin 3, Liang Chen 6, Shiyi Lu 1, Lijing Lin 1, Jianan Chen 5, Manbian Lin 6, Xiaoliang Cai 1,✉
PMCID: PMC12372191  PMID: 40847402

Abstract

Background

This retrospective cohort study explores the association between the interval of nanocarbon application before surgery and the detection of postoperative lymph nodes in patients undergoing gastric cancer surgery.

Methods

This retrospective study included eligible patients diagnosed with T1-3NanyM0 gastric cancer at Fuzhou Traditional Chinese Medicine Hospital between March 1, 2020, and March 31, 2023, based on predefined inclusion criteria. Participants were grouped according to the timing of nanocarbon suspension application: either on the same day as surgery or at least 3 days prior. We compared clinicopathological characteristics between these two groups.

Results

Our findings indicate a significant increase in the number of lymph nodes detected postoperatively in patients who received nanocarbon suspension at least 3 days before surgery compared to those who received it on the same day (26.33 ± 3.42 vs. 30.41 ± 2.16, P < 0.05). Early nanocarbon suspension application was found to be safe, with no observed adverse effects or complications.

Conclusions

Early application of nanocarbon suspension may enhance lymph node detection, potentially allowing for more accurate pathological staging. This approach could provide valuable guidance for subsequent comprehensive anti-tumor therapy.

Keywords: Gastric cancer, Nanocarbon application, Postoperative lymph node detection, Surgical timing, Pathological staging

Background

Stomach cancer, known for its significant impact on global health, ranks as the fifth most common cancer and the third leading cause of cancer-related deaths worldwide [1]. In 2022, stomach cancer accounted for approximately 4.9% of all newly diagnosed cancer cases globally, with significant geographical variation in incidence rates. It remains one of the leading causes of cancer-related deaths, contributing to 6.8% of the total cancer mortality, ranking fifth globally in terms of incidence and fourth in cancer-related deaths [2]. The prevalence of this disease shows considerable geographical disparities, with notably higher incidence rates in Asia compared to Europe and the United States [3]. Particularly in China, gastric cancer fatalities represent a significant portion of the global total, underscoring the urgency in addressing this health crisis [4].

Radical surgery stands out as the fundamental treatment option for gastric cancer patients [3]. The advent of laparoscopic techniques marks a significant evolution from traditional open surgery, offering distinct advantages such as enhanced visualization of the surgical field and an increased number of lymph nodes dissected [5–7]. These improvements are crucial, as the extent of lymph node dissection has been directly correlated with patient prognosis, emphasizing the importance of comprehensive lymph node evaluation in gastric cancer staging and treatment planning [8, 9].

The precision in identifying and dissecting lymph nodes during surgery is vital for accurate cancer staging and optimizing patient outcomes [10, 11]. Traditional lymphatic tracers like indocyanine green and methylene blue have their limitations, such as the need for special equipment and rapid diffusion, which can lead to incomplete lymph node detection [12, 13]. In contrast, carbon nanoparticle suspension emerges as a superior alternative, offering stable physical and chemical properties, high affinity for lymphatic tissue, and the ability to enhance the contrast of lymph nodes without the requirement for specialized instruments [14, 15].

Currently, carbon nanoparticles are typically administered within 24 h before surgery—a timing based more on convention than scientific evidence. This study aims to explore the optimal timing for preoperative nanocarbon application, contributing to the development of standardized guidelines for its use in gastric and other gastrointestinal cancers, addressing a significant gap in current surgical practices.

Methods

Study design and population

This retrospective cohort study aimed to investigate the association between the timing of preoperative nanocarbon application and the number of lymph nodes detected postoperatively in patients undergoing gastric cancer surgery. Patients were categorized retrospectively into two groups based on the timing of nanocarbon application: one group received the nanocarbon suspension on the same day as surgery, and the other group received it at least 3 days before surgery. All patients underwent D2 lymph node dissection, with the choice of surgical approach (laparoscopic subtotal gastrectomy or laparoscopic total gastrectomy) based on the tumor’s primary location in the stomach.

Inclusion and exclusion criteria

The study included patients diagnosed with T1-3NanyM0 gastric cancer at Fuzhou Traditional Chinese Medicine Hospital between March 1, 2020, and March 31, 2023 (Fig. 1), who met predefined inclusion criteria: (1) Age between 18 and 70 years; (2) Pathologically confirmed gastric cancer (GC) through gastroscopy and biopsy; (3) Signed informed consent for surgery; (4) Clinical staging as advanced T1-3NanyM0 gastric cancer was determined based on preoperative chest CT, abdominal computed tomography, and laparoscopic exploration, in order to exclude distant metastasis and confirm M0 status. Exclusion criteria included: (1) Inability to achieve R0 resection or presence of distant metastasis; (2) History of other malignancies and/or upper gastrointestinal surgery; (3) Other contraindications preventing D2 radical surgery.

Fig. 1.

Fig. 1

This figure shows the gastric tumor site stained with nanocarbon suspension

A total of 160 eligible patients were included in the study. Among them, 80 patients received nanocarbon suspension on the same day as surgery (same-day application group), and 80 patients received it at least 3 days before surgery (early application group).

Primary and secondary outcomes

The primary outcome of this study was the number of lymph nodes detected postoperatively, while secondary outcomes focused on changes in various perioperative indicators, including operative time, postoperative complications, and length of hospital stay. We conducted a post-hoc power analysis using GPower (version 3.1.9.2) to assess whether the available sample size was sufficient to detect a clinically meaningful difference. An effect size of 0.6 was chosen based on clinical experience and the observed difference of approximately 3 lymph nodes detected between groups, with a pooled standard deviation of 5. Using a significance level (α) of 0.05 and a power of 80%, the analysis confirmed that our sample size was adequate for the study.

Ethical considerations

This study was reported in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines to ensure transparency and comprehensiveness in the presentation of observational research findings. Ethical approval was obtained from the Ethics Committee of Fuzhou Traditional Chinese Medicine Hospital (2020-02-017-002). As the study relied on existing medical records, individual informed consent was waived for this retrospective analysis. The study complied with the Declaration of Helsinki and adhered to confidentiality protocols to protect patient data. All data were anonymized before analysis to ensure privacy and data integrity.

Nanocarbon labeling method

Carbon nacoparticles suspension injection (Canaline) with a diameter of 150 nm was purchased from Chongqing LUMMY Pharmaceutical Co, Ltd.(Chongqing, China). The nanocarbon labeling method utilizes a strategic “sandwich” injection approach to enhance lymph node visibility for gastric cancer surgeries [16]. Initially, normal saline is injected around the tumor margin (0.5–1.0 cm away) to elevate the submucosal layer, preparing it for nanocarbon injection. Following the saline uplift, 2.0 mL of nanocarbon suspension is carefully injected into the submucosal layer. This targeted delivery ensures that the nanocarbon enters the lymphatic flow effectively. To facilitate widespread dispersion of nanocarbon within the lymphatic tissue, a subsequent injection of normal saline is administered, enhancing the pressure within the submucosal layer and promoting the distribution of carbon nanoparticles. The injection is systematically performed at four strategic locations surrounding the tumor: the cardia side, the pylorus side, the large curved side, and the small curved side.

In our study, nanocarbon injections were administered either on the day of surgery (same-day group) or endoscopically three days before surgery (early application group), using the same method in both groups. No additional laparoscopic procedures were required. This approach was designed to assess the impact of timing on lymph node visibility while ensuring that the lymphatic marking was optimized without disrupting the surgical plan or field clarity. In the early application group, patients received endoscopic nanocarbon injection three days prior to surgery during the same hospitalization period. They remained admitted throughout the preoperative interval, and no patients were discharged between the injection and the surgical procedure.

Surgical procedure and lymph node examination

The surgical techniques used for both groups followed previously documented methods, with each procedure, including gastrectomy and D2 lymph node dissection, performed laparoscopically [3]. The same group of surgeons performed all gastric cancer surgeries. During surgery, lymph nodes around the gastric cancer, blackened by nanocarbon, are observed. This blackening effect is noted in lymph nodes outside the intended area, such as lateral and retroperitoneal lymph nodes. Despite these observations, our team does not extend lymph node dissection to these areas. Pathological examinations and tumor staging are strictly conducted by expert pathologists, adhering to the eighth edition of the TNM-UICC/AJCC classification and the guidelines of the College of American Pathologists. If fewer than 12 lymph nodes are found initially, a thorough second examination is mandated. Should the lymph node count remain below 12, the report must document the additional examination, ensuring a comprehensive and accurate assessment [17]. The follow-up duration for all patients was set at 30 days post-surgery to monitor early postoperative outcomes and complications. Long-term follow-up was not included in this study as it focused primarily on immediate surgical outcomes.

Statistical analysis

Statistical evaluations were performed with SPSS software v24.0 (IBM, Armonk, NY, USA) and GraphPad Prism (version 8, GraphPad Prism Software Inc.). Data following a normal distribution were expressed as Mean ± SD and analyzed via t-tests or ANOVA, while categorical variables were analyzed using Chi-squared or Fisher’s exact tests as appropriate. Non-normally distributed data were analyzed using the Mann-Whitney test. Statistical significance was set at p < 0.05 for all analyses.

Results

Patient demographics

A cohort of 160 gastric cancer patients was enrolled, adhering to the established inclusion and exclusion criteria. The average age at diagnosis was 51.4 years with a standard deviation of 6.4. The sex distribution between male and female patients was equal in both groups. Participants were retrospectively divided into two groups based on the timing of nanocarbon application: 80 patients in the same-day application group and 80 patients in the 3-day early application group. There was no significant disparity between the groups in terms of age, sex, ASA score, body mass index, method of anastomosis, tumor grade, pathological T stage, pathological N stage, perineural invasion, or tumor size (Table 1).

Table 1.

Baseline characteristics of gastric cancer patients between march, 2020 and march, 2023

Characteristics All patients Same day application group Early application group P-value
(n = 160) (n = 80) (n = 80)
Age at diagnosis, year, (n%) 51.4 ± 6.4 50.2 ± 7.1 52.6 ± 8.3 0.803
21–60 97 (60.6%) 48 (60%) 49 (61.3%)
60–79 63 (39.4%) 32 (40%) 31 (38.7%)
Sex, n (%) 0.548
 Female 82 (51.3%) 40 (50%) 42 (52.5%)
 Male 78 (48.7%) 40 (50%) 42 (52.5%)
ASA score 0.617
 I 53 (33.1%) 26 (32.5%) 27 (33.8%)
 II 105 (65.6%) 54 (67.5%) 51 (63.8%)
 III 2 (1.3%) 0 (0%) 2 (2.5%)
BMI, kg/m2 (mean ± SD) 23.5 ± 2.4 22.5 ± 2.5 24.5 ± 1.9 0.699
Anastomosis method, (n%) 0.731
 Esophagojejunostomy 88 (55%) 44 (55%) 44 (55%)
 Esophagogastrostomy 72 (45%) 36 (45%) 36 (45%)
Tumor grade, (n%) 0.592
 Poor or moderately 112 (70%) 56 (70%) 56 (70%)
 Mucinous or signet cell 48 (30%) 24 (30%) 24 (30%)
Pathological T staging, (n%) 0.785
 T1 24 (15%) 11 (13.7%) 13 (16.3%)
 T2 56 (35%) 30 (37.5%) 26 (32.5%)
 T3 80 (50%) 39 (48.8%) 41 (51.2%)
Pathological N staging, (n%) 0.729
 N0 17 (10.6%) 7 (8.8%) 10 (12.5%)
 N1 63 (39.4%) 33 (41.3%) 30 (37.5%)
 N2 77 (48.1%) 38 (47.5%) 39 (48.8%)
 N3 3 (1.9%) 2 (2.5%) 1 (1.3%)
Perineural invasion, (n%) 0.667
 Yes 108 (67.5%) 53 (66.3%) 55 (68.8%)
 No 52 (32.5%) 27 (33.8%) 25 (31.3%)
Tumor size, cm, (n%) 0.764
 0–5 110 (68.8%) 52 (65%) 58 (72.5%)
 >5 50 (31.2%) 28 (35%) 22 (27.5%)

Surgical and postoperative outcomes

The occurrence of surgical conversion from laparoscopic to open procedure was comparable between the early application group (5%) and the same-day application group (3.8%), without statistical significance (p = 0.523). The mean operative time was slightly longer in the early application group (179 ± 43.2 min) compared to the same-day application group (170 ± 40.8 min), though the difference did not reach statistical significance (p = 0.214).

The assessment of intraoperative blood loss revealed no significant difference between the early application group, with an average of 83.2 mL, and the same day application group, with an average of 79.5 mL (p = 0.381). Likewise, the duration of hospital stay post-surgery was not significant between the groups, averaging 7.3 days for the early application group and 7.0 days for the same day application group (p = 0.432).

In terms of postoperative complications, the rates of anastomotic leakage were 5% in the early application group and 6.3% in the same day application group, a difference that was not statistically significant (p = 0.698). The early application group experienced a slightly higher occurrence of delayed gastric emptying (16.3%) compared to the same day application group (11.3%), yet this difference did not reach statistical significance (p = 0.089). No statistically significant differences were found in the incidence of other postoperative complications such as bowel obstruction, surgical wound infection, bleeding, pleural effusion, lung infection, and fever, with all p-values exceeding 0.05. There were no instances of 30-day postoperative mortality reported in either group. The incidence of postoperative complications in both the same-day and early application groups was higher than expected (Table 2).

Table 2.

Perioperative data of patients

Characteristics Same day application group Early application group P-value
(n = 80) (n = 80)
Conversion to open, n (%) 3 (3.8%) 4 (5.0%) 0.523
Operation time in min, mean ± SD 170 ± 40.8 179 ± 43.2 0.214
Estimated blood loss in mL, mean ± SD 79.5 ± 24.3 83.2 ± 23.7 0.381
Hospital stay after operation (d, mean ± SD) 7.0 ± 1.1 7.3 ± 0.9 0.432
30 d post-operative mortality, n (%) 0 0 1
Time to first flatus, day (mean±SD) 2.4 ± 1.3 2.6 ± 1.6 0.345
Time to Regular diet, day (mean±SD) 5.4 ± 2.0 5.2 ± 2.4 0.678
Postoperative complications (grades II, III)
Pleural Effusion 1 (1.3%) 0 0.315
Anastomotic Leakage 5 (6.3%) 4 (5.0%) 0.698
Bowel Obstruction 2 (2.5%) 3 (3.8%) 0.451
Surgical Wound Infection 6 (7.5%) 4 (5.0%) 0.381
Bleeding 3 (3.8%) 2 (2.5%) 0.678
Delayed gastric emptying 9 (11.3%) 13 (16.3%) 0.089
Lung infection 0 1 (1.3%) 0.099
Fever 6 (7.5%) 7 (8.8%) 0.604

Related results of retrieved lymph nodes

In examining the results of retrieved lymph nodes (Fig. 2), the early application group had a statistically significant increase in the mean number of harvested lymph nodes (30.41) compared to the same day application group (26.33) (p = 0.021). However, no significant differences were found in lymph node metastasis (p = 0.749), stained lymph nodes (p = 0.29), or stained lymph node metastasis (p = 0.344) between the two groups.

Fig. 2.

Fig. 2

Intraoperative carbon nanoparticles and black-stained lymph nodes are depicted in this figure

When assessing lymph nodes dissected at each station, significant differences were observed at Station 1 (Right cardia) (p = 0.034), Station 8 (Common hepatic artery) (p = 0.03), and Station 11 (Splenic artery) (p = 0.02), with the early application group showing higher lymph node retrieval in these stations compared to the same day application group. Although there were trends toward differences in Station 3 (Lesser curvature) (p = 0.056) and Station 12a (Hepatoduodenal ligament - proximal) (p = 0.06), these did not reach statistical significance. No significant differences were noted for the other stations. Additionally, the lymph node noncompliance rate was similar between the two groups, with 5% in the same day application group and 4% in the early application group (p = 0.76). A stratified analysis was conducted to evaluate the impact of different surgical methods on lymph node dissection outcomes. For patients undergoing subtotal gastrectomy, the early application group had a significantly higher mean number of harvested lymph nodes (25.34 ± 2.59) compared to the same day application group (22.6 ± 4.41) (p = 0.041). However, for patients undergoing total gastrectomy, there was no statistically significant difference in the mean number of harvested lymph nodes between the early application group (29.41 ± 3.67) and the same day application group (28.73 ± 4.25) (p = 0.28) (Table 3.).

Table 3.

Related results of retrieved lymph nodes, n (%)

Characteristics Same day application group Early application group P-value
(n = 80) (n = 80)
Harvested lymph nodes, mean ± SD 26.33 ± 3.42 30.41 ± 2.16 0.021
Lymph node metastasis, mean ± SD 2.21 ± 3.44 2.04 ± 3.28 0.749
Lymph nodes stained, mean ± SD 11.52 ± 4.37 12.2 ± 3.7 0.29
Stained lymph node metastasis, mean ± SD 1.0 ± 1.1 1.3 ± 0.9 0.344
Lymph nodes dissected at each station: 
 Station 1 (Right cardia) 4.54 ± 3.64 5.11 ± 2.04 0.034
 Station 2 (Left cardia) 2.11 ± 0.63 2.21 ± 1.11 0.48
 Station 3 (Lesser curvature) 3.29 ± 2.19 2.82 ± 1.39 0.056
 Station 4sa (Greater curvature - upper) 1.06 ± 0.92 1.31 ± 0.77 0.16
 Station 4sb (Greater curvature - lower) 1.05 ± 1.29 1.33 ± 0.57 0.08
 Station 5 (Suprapyloric) 2.82 ± 1.46 2.39 ± 1.58 0.19
 Station 6 (Infrapyloric) 3.10 ± 0.96 3.41 ± 1.50 0.15
 Station 7 (Left gastric artery) 0.86 ± 0.61 0.76 ± 0.06 0.12
 Station 8 (Common hepatic artery) 5.12 ± 2.14 4.21 ± 0.57 0.03
 Station 9 (Celiac axis) 0.82 ± 0.74 0.94 ± 0.63 0.27
 Station 11 (Splenic artery) 1.03 ± 0.96 2.49 ± 1.55 0.02
 Station 12a (Hepatoduodenal ligament - proximal) 3.55 ± 2.67 4.39 ± 2.88 0.06
 Station 12b (Hepatoduodenal ligament - distal) 2.67 ± 1.33 2.83 ± 1.59 0.49
 Station 14v (Superior mesenteric vein) 1.09 ± 0.94 1.04 ± 0.67 0.7
Lymph node noncompliance rate 5% 4% 0.76
Subtotal Gastrectomy 22.6 ± 4.41 25.34 ± 2.59 0.041
Total Gastrectomy 28.73 ± 4.25 29.41 ± 3.67 0.28

Discussion

Gastric cancer ranks as one of the most prevalent malignancies worldwide and stands as the leading gastrointestinal cancer in terms of incidence. Despite favorable outcomes for early-stage gastric cancer, the low early diagnosis rate contributes to high mortality rates, particularly in China [18, 19]. A significant factor in the poor prognosis is the potential for lymph node metastasis at the time of diagnosis, with literature reports indicating rates up to 70% in advanced stages [20]. Consequently, the thorough eradication of metastatic lymph nodes during surgery is crucial.

Several studies emphasize the importance of extensive lymph node dissection in gastric cancer surgery for improved prognosis. Baxter et al. [21] established a correlation between the number of resected lymph nodes and patient outcomes. Similarly, data from the American Surveillance, Epidemiology, and End Results (SEER) database suggests that every additional 10 lymph nodes retrieved can improve prognosis, even for patients initially diagnosed as lymph node negative [22]. This concept extends to accurate pathological staging. Researchers recommend a minimum lymph node yield of 10–15 for N0 stage (no lymph node involvement), 20 or more for N1-3 stages (positive lymph node involvement), and ideally 30 or more for optimal staging accuracy [23]. International guidelines, such as the 8th Edition of the UICC/AJCC TNM staging system, recommend a minimum of 16 lymph nodes, while Japanese regulations advocate for at least 15 [24, 25]. Despite the inability of the naked eye to accurately determine lymph node metastasis during surgery, increasing the number of resected peritumoral lymph nodes potentially enhances the removal of metastasis-harboring nodes. Studies further demonstrate a significant correlation between insufficient lymph node dissection and poorer 5-year survival rates [26]. The rationale behind extensive dissection is clear: a higher number of examined lymph nodes increases the likelihood of detecting metastasis and reduces the risk of staging errors [27].

This retrospective study investigated the impact of the timing of nanocarbon application on lymph node detection during laparoscopic surgery for gastric cancer. The study aimed to determine the optimal timing for nanocarbon application to enhance surgical outcomes, particularly in terms of lymph node retrieval. Our findings demonstrate that administering the nanocarbon suspension on the three days before surgery (early application group) yielded a statistically significant increase in the mean number of harvested lymph nodes compared to the group receiving the treatment at the same day with surgery (same day application group) (26.33 ± 3.42 vs. 30.41 ± 2.16, P < 0.05). Notably, there were no significant difference in lymph node metastasis (2.21 ± 3.44 vs. 2.04 ± 3.28, P = 0.749), stained lymph nodes (11.52 ± 4.37 vs. 12.2 ± 3.7, P = 0.29), or stained lymph node metastasis (1.0 ± 1.1 vs. 1.3 ± 0.9, P = 0.344) between the two groups. These results suggest that early application of nanocarbon may improve lymph node detectability during surgery.

A key question arising from our findings is why earlier injection of nanocarbon led to a significantly higher number of harvested lymph nodes, despite no significant difference in the number of stained nodes. One possible explanation is that injecting nanocarbon three days before surgery allows more time for the particles to effectively permeate the lymphatic system, reaching smaller or more peripheral lymph nodes that may otherwise be challenging to detect [28]. This longer absorption time enhances the efficiency of lymphatic mapping, aiding surgeons in identifying and harvesting additional nodes. Nanocarbon staining helps highlight the lymph nodes and their afferent lymphatic vessels, which facilitates precise tracing of lymphatic drainage. With better visualization, the surgeon can more effectively target nodes that might be overlooked with a shorter time between injection and surgery [29]. This advantage may lead to a more comprehensive lymph node dissection, thus increasing the total number of nodes retrieved. Additionally, early application may minimize variability caused by lymphatic flow changes occurring near surgery time, allowing for a more consistent distribution of the nanocarbon particles [30]. This stability helps in creating uniform staining across nodes, supporting a more standardized and efficient identification process during dissection. Prolonged staining may also improve identification of nodes located in anatomically variable areas, thus enhancing overall node retrieval [31].

This study found no significant differences in the rates of surgical conversion, operative duration, intraoperative blood loss, or hospital stay lengths between the early application and same day application groups. These results indicate that the timing of nanocarbon application does not negatively impact immediate surgical outcomes. Additionally, similar rates of postoperative complications, such as anastomotic leakage and delayed gastric emptying, further affirm the safety of preoperative nanocarbon labeling, regardless of when it is administered.

It is worth noting that the total number of postoperative complications reported may appear higher than expected. This may be attributed to our method of reporting each complication individually, even in cases where a single patient experienced multiple complications. Nonetheless, this approach reflects the thoroughness and transparency of our reporting methodology.

While our findings suggest a positive effect of early nanocarbon application, this study has certain limitations inherent to its retrospective design. Selection bias may exist due to the non-random assignment of patients to different nanocarbon application timings. Additionally, unmeasured confounding factors could influence the observed associations. Future prospective studies are needed to confirm these findings. Also, our study is lack of long-term follow-up data, particularly regarding patients with nanocarbon staining outside the D2 field. We acknowledge that such data would be valuable in evaluating whether these findings carry prognostic significance or represent false-positive staining.

Conclusions

In conclusion, our study indicates that administering nanocarbon suspension three days before surgery may enhance lymph node detection during laparoscopic surgery for gastric cancer. By potentially improving diagnostic yield without compromising surgical safety, this approach shows promise as a preoperative strategy. However, given the retrospective nature of our study and the lack of long-term follow-up, prospective studies, especially randomized controlled trials, are necessary to confirm the clinical benefits and assess long-term oncologic outcomes.

Abbreviations

GC

Gastric cancer

CT

Computed tomography

OS

Overall survival

DFS

Disease free survival

SPSS

Statistical Package for the Social Sciences

LNR

Lymph node ratio

UICC

Union for International Cancer Control

AJCC

American Joint Committee on Cancer

Authors’ contributions

SL, XC and XY: acquisition of data. ZC, JX, YL, JC, LC, SL and LL: analysis and interpretation of data. SL, XC, ML and XY: drafted the manuscript. XC: critical revision of the manuscript and funds collection. All authors reviewed the manuscript.

Funding

This work was supported by the Scientific Foundation of Fuzhou Municipal Health Commissio (2021-S-wp3) and Training Project of Fuzhou Traditional Chinese Medicine Hospital 2022-3.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Fuzhou Traditional Chinese Medicine Hospital (No. 2020-02-017-002). As a retrospective analysis using anonymized medical records, the requirement for informed consent was waived.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Sheng Li, Xiaoli Chen and Xiaoyu Yang contributed equally.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

No datasets were generated or analysed during the current study.


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