Efficacy and prognostic analysis of carbon nanotracers combined with the da Vinci robot in the treatment of esophageal cancer

Abstract

BACKGROUND

Traditional methods cannot clearly visualize esophageal cancer (EC) tumor contours and metastases, which limits the clinical application of da Vinci robot-assisted surgery.

AIM

To investigate the efficacy of the da Vinci robot in combination with nanocarbon lymph node tracers in radical surgery of EC.

METHODS

In total, 104 patients with early-stage EC who were admitted to Liuzhou worker's Hospital from January 2020 to June 2023 were enrolled. The patients were assigned to an observation group (n = 52), which underwent da Vinci robot-assisted minimally invasive esophagectomy (RAMIE) with the intraoperative use of nanocarbon tracers, and a control group (n = 52), which underwent traditional surgery treatment. The operation time, intraoperative blood loss, postoperative drainage tube indwelling time, hospital stay, number of lymph nodes dissected, incidence of complications, and long-term curative effects were comparatively analyzed. The postoperative stress response C-reactive protein (CRP), cortisol, epinephrine (E) and inflammatory response interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) were evaluated.

RESULTS

Compared with the control group, the observation group had significantly lower postoperative CRP, cortisol, and E levels (P < 0.05) with a milder inflammatory response, as indicated by lower IL-6, IL-10, and TNF-α levels (P < 0.05). Patients who underwent RAMIE had less intraoperative blood loss and shorter operation times and hospital stays than those who underwent traditional surgery. The average number of dissected lymph nodes, time of lymph node dissection, and mean smallest lymph node diameter were all significantly lower in the observation group (P < 0.05). The rate of postoperative complications was 5.77% in the observation group, significantly lower than the 15.38% observed in the control group. Furthermore, the lymphatic metastasis rate, reoperation rate, and 12- and 24-month cumulative mortality in the observation group were 1.92%, 0%, 0%, and 0%, respectively, all of which were significantly lower than those in the control group (P < 0.05).

CONCLUSION

The treatment of EC using the da Vinci robot combined with nanocarbon lymph node tracers can achieve good surgical outcomes and demonstrates promising clinical applications.

Key Words: Nanocarbon tracer, Da Vinci robot, Minimally invasive esophagectomy, Esophageal cancer, Clinical efficacy, Prognostic

Core Tip: Traditional surgical visualization for esophageal cancer (EC) cannot clearly delineate tumor contours and metastases, which limits the accuracy of da Vinci robotic surgery. However, few studies have investigated the effect of nanocarbon tracers combined with da Vinci robotic surgery. This study clarified the therapeutic efficacy of the da Vinci robot system combined with the nanocarbon lymph node tracer in the treatment of patients with EC and confirmed the promising clinical applications thereof.

INTRODUCTION

In China, approximately 180000 people die of esophageal cancer (EC) every year[1]. Because the esophagus is surrounded by complex tissues, conventional open surgery can cause significant trauma, loss of healthy tissue, and poor quality of life postoperatively[2]. The development of medical technology has made minimally invasive procedures possible, which avoid patient trauma and preserve healthy tissues. The da Vinci robotic arm can perform finer and more accurate techniques than conventional surgery, resulting in fewer surgical incisions and less bleeding, higher success rates, and faster patient recovery. The robot has been increasingly used in complex operations[3].

Da Vinci robot-assisted minimally invasive esophagectomy (RAMIE) can implant and preserve tumor margin tissue to the maximum extent, enabling complete resection. Radical resection of EC using RAMIE can improve surgical accuracy and efficiency while minimizing complications[4]. In 2003, da Vinci roboticists announced the first patient in the world to undergo da Vinci robot-assisted EC surgery[5]. However, conventional visualization methods cannot clearly display tumor outlines and metastases, which limits the accuracy of da Vinci robotic surgery.

Nanocarbon tracers comprise a new type of nanomaterial consisting of carbon-based materials, such as carbon nanotubes or graphene[6]. These tracers are highly biocompatible and safe and can be quickly metabolized and cleared from the body without inducing toxicity. Nanocarbon tracers can achieve precisely targeted delivery and controlled release by modifying or coating the surface of drugs, thereby enhancing pharmacological efficacy and lowering the risk of adverse drug reactions[7]. In terms of biological imaging, nanocarbon tracers can achieve high-sensitivity and high-resolution imaging of specific biomolecules or tissues through surface modification or doping with fluorescent dyes and other substances. Nanocarbon tracers can enhance the visualization of EC by computed tomography or positron emission tomography/computed tomography, which can accurately locate tumors and define tissue boundaries[8]. In addition, nanocarbon tracers can indicate lymph nodes, which is beneficial in lymph node dissection. The nanocarbon lymph node tracer, a new type of lymphoid tissue active dye, provides fast staining and helps improve lymph node detection and resection rates[9]. However, few studies have explored the utility of combining nanocarbon tracers with da Vinci robotic surgery. Therefore, this study aimed to investigate the therapeutic efficacy of nanocarbon tracers in combination with da Vinci robots for the treatment of EC and its influence on prognosis.

MATERIALS AND METHODS

Patients

This study included 104 patients with early-stage EC admitted to Liuzhou worker's Hospital from January 2020 to June 2023. The patients were divided into an observation group (n = 52), which underwent RAMIE with the intraoperative use of nanocarbon tracers, and a control group (n = 52), which underwent traditional surgery. The two groups did not differ significantly in sex, age, pathological type, lesion diameter, or body mass index (P > 0.05).

Surgical method

The control group underwent traditional surgery. The patient was assisted by single-lumen endotracheal intubation in both lungs, and a 15–20-cm incision was made in the fourth intercostal space on the anterolateral side of the right chest. Through this incision, the surgical area was examined in detail to identify the location, size, and shape of the tumor. During the procedure, the thoracic esophagus was mobilized, and the chest lymph nodes were dissected. Another arc-shaped incision, approximately 5 cm long, was created at the sternum, below the neck, and an anastomosis was performed on the esophageal ends of the cervical segment and gastric fundus.

The observation group underwent radical surgery with the da Vinci robot as the auxiliary system. Anesthesia was induced by intravenous inhalation, and endotracheal intubation was established using a single-lumen tube combined with a bronchus or double-lumen tube capable of collapsing a fully joined artificial pneumothorax. The procedure consisted of three parts and was performed as described previously[10]. A corresponding change in body position was required for each part of the operation: (1) When the thoracic esophagus was being mobilized by the robot, the patient was placed in the left decubitus position to facilitate lymphatic cleaning of the corresponding region; (2) When the robot was being used to free the stomach, the patient was placed in a supine posture with the head in a high position, the feet in a low position, and the body tilted 15° to the right; and (3) When the neck was being anastomosed mechanically or at the end of surgery, the pillow was removed from under the patient’s head so the patient can lie down completely.

Preparation and injection of nanocarbon lymph node tracers

A 1-mL nanocarbon suspension injection was prepared using 0.1 mL of nanocarbon suspension (specification: 1 mL, 50 mg; Laimei Pharmaceutical, Chongqing, China; national drug approval: H20041829) and 0.9 mL of 0.9% normal saline (total nanocarbon content: 5 mg). The suspension was injected 2 h preoperatively after confirming the location of the tumor through a gastroscope, with the patient in the lateral position. In total, 4–6 points that were approximately 1 cm away from the tumor were chosen. A fine needle was inserted approximately 5 mm into the tissue, and 0.1-0.3 mL of the tracer was slowly injected at each point.

Observation indicators

Stress response: Anticoagulant test tubes were used to collect fasting venous blood from all patients preoperatively and postoperatively. The collected blood samples were centrifuged at 3000 rpm for 15 min, after which the serum was collected off the top into sterile test tubes. The test tubes were frozen at -70 °C until use. Enzyme-linked immunosorbent assay (ELISA) kits (Bohu Bio, Shanghai, China) were used to determine C-reactive protein (CRP), cortisol, and epinephrine (E) levels following the manufacturer’s instructions.

Inflammatory response: Blood samples were collected and processed in the same manner as above to evaluate serum levels of interleukin (IL)-6, IL-10, and tumor necrosis factor α (TNF-α) by ELISA.

Observation of relevant clinical indicators: Surgery-related indicators were recorded, including the total and average numbers of dissected lymph nodes and the average duration of lymph node dissection.

Complication rate: The safety of the procedure was evaluated based on the incidence of complications, such as gastrointestinal emptying disorder, anastomotic leakage, empyema, lung infection, and incision infection.

Medium and long-term curative effect: Telephone follow-ups of all patients were conducted for 2 years to evaluate the disease recurrence rate, transfer rate, and mortality rate.

Statistical analysis

SPSS version 19 was used to analyze the data of this study. Measurements (expressed as mean ± SD) and count data (expressed as number and percentage) were compared between the observation and control groups using the independent sample t-test and the χ² test, respectively.

RESULTS

Application of nanocarbon lymph node tracers

Nanocarbon materials have a small particle size and a large specific surface area, enabling them to enter lymphatic vessels and flow to the lymph nodes. However, nanocarbon materials cannot enter the capillaries and interstitial systems. In lymph nodes, carbon nanomaterials can be taken up by phagocytes or be otherwise retained. Therefore, after the nanocarbon material is injected into the body, it is quickly taken up by the lymphatic system and spread along the lymphatic vessels to the lymph nodes, enabling the visualization and tracking of the lymphatic system (Figure 1).

Figure 1  Schematic diagram of the visualization process using the nanocarbon lymph node tracer.

Clinical indicators

The observation group had shorter operation times and less intraoperative blood loss than the control group (Figure 2A). The observation group also showed a shorter recurrent laryngeal nerve lymph node (RLNLN) dissection time, smaller mean number of minimal lymph nodes, and greater total and average numbers of left and right RLNLNs dissected than the control group (Figure 2B–D).

Figure 2 Comparison between the observation and control groups. A: Operation time; B: Recurrent laryngeal nerve lymph node dissection time; C: Intraoperative blood loss; D: Number of dissected lymph nodes. ^aP < 0.05, indicates statistically significant difference between the two groups; ^bP < 0.01, indicates statistically significant difference between the two groups.

CRP, cortisol, and E levels

Both groups showed elevated postoperative CRP, cortisol, and E levels, with those in the observation group being lower than the control group (P < 0.05) (Figure 3).

Figure 3 Comparison between the observation and control groups. A: C-reactive protein (CRP); B: Cortisol; C: Adrenaline levels. ^aP < 0.05; ^bP < 0.01; ^cP < 0.001. E: Epinephrine.

Observation of inflammatory indicators

After radical surgery for EC, the relevant inflammatory indexes increased in both groups, with the most significant increase observed in TNF-α levels. The control group showed higher postoperative IL-6, IL-10, and TNF-α levels than the observation group (Figure 4).

Figure 4 Comparison between the observation and control groups in pre- and postoperative results. A: Interleukin (IL)-6; B: IL-10; C: Tumor necrosis factor-alpha levels (TNF-a). ^aP < 0.05; ^bP < 0.01.

Efficacy and prognosis evaluation

The incidence of adverse events, such as postoperative gastric emptying disorder, anastomotic leakage, and pulmonary infection, was 5.77% in the observation group, which was significantly lower than the 15.38% observed in the control group (Figure 5A). The lymphatic metastasis and reoperation rates and the 12 and 24-mo cumulative mortality rates in the observation group were 2.5%, 0%, 0%, and 2.5%, respectively, all of which were lower compared with those in the control group (Figure 5B).

Figure 5 Comparison between the observation and control groups. A: Occurrence of complications; B: Patient prognosis. ^aP < 0.05; ^bP < 0.01.

DISCUSSION

EC is a clinical gastrointestinal malignancy that can directly endanger the physical and mental health of patients. It can be treated by diverse surgical methods. Traditional open radical resection of EC involves right thoracotomy and laparotomy; however, this approach is relatively harmful to the patient[11], with high postoperative morbidity and mortality. Furthermore, prognosis decreases with recurrence[12]. The da Vinci robotic surgery system is being increasingly used in multidisciplinary applications. The magnified vision of its lens can provide three-dimensional images that clearly differentiate anatomical structures and allow the surgeon an ample visual field. This clear visual field, excellent surgical operation, and stable surgical platform enable highly precise and minimally invasive surgery for EC. These advantages help reduce intraoperative blood loss, reduce tissue damage, and shorten the postoperative recovery time[13]. Yang et al[14] compared various surgical methods for esophageal squamous cell carcinoma and observed significantly improved long-term quality of life among patients after RAMIE. Boone et al[15] showed that da Vinci robotic esophagectomy has great advantages in lymph node dissection, with the degree of dissection reaching or even exceeding that of traditional thoracotomy. Furthermore, the incidence of lymphatic fistula and chylothorax is lower than that in laparoscopy. The present study also found that, compared with traditional surgical methods, RAMIE significantly reduced operation time, intraoperative blood loss, and postoperative complications in patients with EC. The 2-year follow-up revealed that the lymphatic metastasis rate, reoperation rate, and 24-mo cumulative mortality rate were also significantly reduced with RAMIE compared with traditional surgery.

The use of nanocarbon tracers in the diagnosis and staging of EC has great potential. Carbon nanoparticles have high biocompatibility and stability and are the ideal tracers[16]. Compared with conventional methods, such as capsule endoscopy, nanocarbon tracers can provide higher resolution and contrast, thereby facilitating the early detection and accurate staging of EC[17]. In addition, nanocarbon tracers can be combined with other imaging techniques, such as fluorescence imaging, to further improve diagnostic and staging accuracy[18]. After it is injected into the tissues surrounding the tumor, the nanocarbon tracer is engulfed by macrophages, allowing the nanocarbon group to quickly penetrate the capillary lymphatic vessels and accumulate in the lymph nodes, giving them the indicative black stain that facilitates lymph node tracing[19]. Our study demonstrates the significant advantages of carbon nanotracers in combination with da Vinci robotic surgery for the treatment of EC. In the observation group, significantly more lymph nodes were dissected, and the dissection time was also significantly reduced, indicating greater efficiency in lymph node dissection compared to the control group. Lymph node detection by inspection with the naked eye and palpation increases the likelihood of overlooking small lymph nodes with a diameter of < 5 mm[20]. The use of carbon nanotracers in this study demonstrated that the smallest diameter of lymph nodes detected was significantly smaller than that in the control group.

CRP is a common acute response protein that can indicate the degree of injury. Cortisol and E are also indicators of the body’s stress response, as well as the extent of damage to the body’s immunologic function and overall status. Thoracoscopic treatment of EC has previously been reported to reduce traumatic stress responses in the patient[21]. Similar conclusions were drawn in this study. After radical esophagectomy using the da Vinci robot, significantly lower CRP, cortisol, and E levels were noted in the observation group than in the control group. Analysis of relevant inflammatory indicators before and after surgery also revealed that postoperative IL-6, IL-10, and TNF-α levels increased in both groups but were significantly lower in the observation group than in the control group. This may be because RAMIE requires smaller surgical incisions, which can effectively reduce the degree of stretching of various tissues and organs, thereby minimizing trauma and stress response by mitigating the secretion of inflammatory factors[22].

Although the carbon nanotracers combined with the da Vinci robotic surgical system have obvious advantages in treating EC, there are still some limitations. First, the high cost of production and use of carbon nanotracers may limit their widespread clinical application. Second, the high cost of the da Vinci robotic surgical system may limit its adoption in low-income settings. With regards the limitations of the present study, the retrospective design may have introduced selection and information biases.

CONCLUSION

This study demonstrated that, compared with traditional surgical methods, carbon nanotracers combined with da Vinci robotic surgery have significant curative effects and a good prognosis for EC. The advantages of the two technologies should be explored further in a multicenter prospective study with a larger dataset to screen suitable patient groups. Such studies would help optimize comprehensive treatment plans and improve therapeutic efficacy and quality of life in patients with EC.