Application of total thoracoscopic ultrasonic scalpel resection in esophageal cancer patients

Authors: Tian-Yi Zhang, Ming-Zhi Ren, Xiao-Kang Gong, Jun Ma

Abstract

BACKGROUND

Esophageal cancer is a prevalent solid malignancy of the gastrointestinal tract. Surgical resection remains an effective intervention for prolonging patient survival. While conventional open surgery demonstrates therapeutic efficacy, it is often associated with significant tissue trauma, high complication rates, and prolonged recovery period. Advances in imaging technology and refined minimally invasive techniques have led to an increasing adoption of total thoracoscopy-assisted resection among patients. However, the efficacy of total thoracoscopic ultrasonic scalpel resection specifically for esophageal cancer patients remains unclear.

AIM

To evaluate the efficacy of total thoracoscopic ultrasonic scalpel resection in esophageal cancer patients.

METHODS

We retrospectively analyzed clinical data from 127 esophageal cancer patients undergoing total thoracoscopy-assisted resection in our hospital from January 2022 to January 2025. Based on surgical technique, 61 patients subjected to total thoracoscopic electrosurgical scalpel esophagectomy were included in the control group, while 66 patients receiving total thoracoscopic ultrasonic scalpel esophagectomy were assigned to the observation group. Perioperative outcomes were compared between the two groups, including pain mediators [5-hydroxytryptamine (5-HT), potassium ions (K^+^), norepinephrine (NE)], immune indices (CD4^+^, CD8^+^, CD4^+^/CD8^+^), inflammatory markers [interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α)], as well as pulmonary function parameters [forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximal voluntary ventilation (MVV)]. Besides, complication rates were also assessed.

RESULTS

Operative time was significantly shorter in the observation group compared to the control group. The observation group demonstrated reduced intraoperative blood loss and lower postoperative chest drainage volume and increased number of dissected lymph nodes (P < 0.05 for all). Preoperatively, no significant differences were observed between the two groups in terms of 5-HT, K^+^, NE, CD4^+^, CD8^+^, CD4^+^/CD8^+^, IL-6, IL-8, TNF-α, FVC, FEV1, and MVV (P > 0.05). Postoperatively, both groups showed improvement in measured parameters, with the observation group exhibiting significantly better outcomes, that is, lower 5-HT, K^+^, and NE levels, higher CD4^+^ levels, lower CD8^+^ levels, and higher CD4^+^/CD8^+^ levels (P < 0.05); reduced IL-6, IL-8, and TNF-α (P < 0.05); superior FVC, FEV1, and MVV measurements (P < 0.05). The total complication rate was significantly lower in the observation group (7.58% vs 21.31%; P < 0.05).

CONCLUSION

Total thoracoscopic ultrasonic scalpel resection demonstrates superior surgical outcomes in esophageal cancer patients compared to electrosurgical techniques. This approach significantly improves perioperative indicators, ameliorates postoperative pain, enhances immune function, alleviates inflammatory responses, and preserves pulmonary function, demonstrating the safety and reliability of this technique in esophageal cancer patients.

Core Tip: Esophageal cancer remains a highly aggressive malignancy with significant implications for patient health. This retrospective cohort study demonstrates superior outcomes with total thoracoscopic ultrasonic scalpel resection vs electrosurgical resection. The ultrasonic scalpel significantly optimizes perioperative indicators, reduces postoperative pain, enhances immune function, suppresses inflammatory mediator release, preserves pulmonary function, while demonstrating a lower complication rate. These advantages support its broader clinical adoption for esophageal cancer resection.

INTRODUCTION

Esophageal cancer represents a significant gastrointestinal malignancy, especially in developed countries, with pathogenesis involving complex interactions between genetic predisposition, environmental exposures, and lifestyle factors[1,2]. Globally, it accounts for approximately 2% of all cancers, with China contributing over 50% of worldwide cases[3]. Anatomically, tumors predominantly arise in the middle and lower esophageal segments, constituting approximately 80% of presentations[4]. The classic clinical triad includes progressive dysphagia, odynophagia, and food regurgitation. Without timely intervention, patients typically develop complete esophageal obstruction, with local tumor invasion into adjacent mediastinal structures and frequent distant metastases[5], hence leading to hematochezia, hematemesis, and other symptoms. In addition to its extremely high mortality rate, patients experience significant suffering in their final stages. While currently, surgical resection remains the cornerstone of potentially curative treatment for esophageal cancer, conventional open surgery involves extensive surgical trauma, severe postoperative pain, and a pronounced systemic stress response[6], which are unfavorable for prognosis.

With the advancements in thoracoscopic and minimally invasive techniques, thoracoscopy-assisted resection has been widely applied for solid tumor management[7]. Conventional thoracoscopic esophagectomy typically employs high-frequency electrosurgical scalpels, which utilize thermal energy from high-voltage current to achieve tissue separation and hemostasis through protein coagulation[8]. While effective for resection and hemostasis, their clinical utility is constrained by several limitations. Ultrasonic scalpels represent an evolution of this technology, offering superior cutting accuracy and better hemostatic capabilities, demonstrating superior performance in ensuring surgical success and postoperative recovery[9]. While existing clinical studies have reported the application of total thoracoscopic ultrasonic scalpel resection in esophageal cancer, research remains predominantly focused on clinical efficacy, perioperative indicators, pulmonary function, and complications. Few studies have systemically evaluated its impact on surgical trauma, stress response, and immune response. Therefore, our study retrospectively analyzed esophageal cancer patients treated at our hospital and evaluated the clinical outcomes of total thoracoscopic ultrasonic scalpel resection.

MATERIALS AND METHODS

General data

This research retrospectively collected the clinical data of 127 patients admitted to our hospital due to esophageal cancer and subjected to total thoracoscopic resection from January 2022 to January 2025. Inclusion Patients diagnosed with esophageal cancer through clinical pathological examination; patients who met the Union for International Cancer Control/the American Joint Committee on Cancer tumor, node, metastasis staging criteria (7^th^ edition) for esophageal cancer[10], with stages I, II, or III; patients with imaging examination results showing no distant metastasis or invasion; patients with indications for surgery.

Exclusion Patients with a history of thoracic and abdominal surgery; coagulation system disorders; infectious or communicable diseases; immune system or endocrine diseases; concomitant lung lesions. Based on surgical technique, 61 patients subjected to total thoracoscopic electrosurgical scalpel esophagectomy were included into the control group, whereas 66 patients undergoing total thoracoscopic ultrasonic scalpel esophagectomy were set as the observation group. This study was conducted in accordance with the “Declaration of Helsinki”.

Surgical plan

The same experienced surgical team performed all procedures in both study groups to ensure technical consistency. Postoperatively, all patients received standardized care including routine analgesia management, prophylactic antibiotic therapy, correction of pH and water-electrolyte imbalances, and anti-inflammation medication.

**Control ** Thoracoscopy-assisted electrosurgical resection was adopted. The patient was placed in the left lateral position and subjected to endotracheal intubation with general anesthesia. A monopolar high-frequency electrosurgical scalpel and an electrocautery hook were utilized to dissociate the esophagus and stomach, and the large veins dissociated after the procedure were clamped, cut, and subsequently ligated. The anesthesiologist was instructed to inflate the lungs and confirm proper expansion of the right lung without any air leakage before placing an intrathoracic drain. The drain was inserted through the 7^th^ intercostal space along the right midaxillary line, connected to a water-sealed drainage bottle, and fixed in place. The chest was closed in layers after the procedure. The patient was then repositioned to supine, with routine disinfection and draping performed. A 12 cm incision was made along the upper midline of the abdomen to access the stomach and perform lymphadenectomy around the gastric area. The stomach was dissociated, and using a combination of fast and slow speeds, the resection involved a portion of the lesser curvature of the stomach, the cardia, and the tumor-bearing esophagus. The cut edges were sutured and embedded in the seromuscular layer. A 20 cm-long, 2 cm-diameter tubular stomach was created, and a percutaneous catheter was used to pull it up to the patient's neck for digestive tract reconstruction (Figure 1).

**Observation ** Thoracoscopy-assisted ultrasonic scalpel resection was performed. In a left lateral position, the patient was subjected to endotracheal intubation with general anesthesia. Under left lung ventilation, a 1.5 cm incision was made at the 7^th^ intercostal space along the right midaxillary line, and a thoracoscope was inserted for chest cavity exploration. The lung was retracted forward and upward to fully expose the mediastinum. The azygos vein was dissociated and clamped at both ends. The arch of the azygos vein was transected using the ultrasonic scalpel in slow mode. The surface of the esophagus was incised through the mediastinal pleura, and the tumor-bearing esophagus was separated from the chest portion, from the esophageal hiatus to the apex of the chest. The mediastinal pleura was quickly cut with the ultrasonic scalpel, and the esophagus was dissociated. When large vessels were not encountered, a high-speed sharp blade was used for cutting. In the presence of nourishing vessels downstream of the aortic arch, a slow-speed blunt blade was employed for coagulation and then slightly retracted. Next, the high-speed mode was used for cutting. Lymph nodes around the upper and middle esophageal segments, near the trachea, bilateral recurrent laryngeal nerves, and below the carina were cleared. The esophagus was transected above the tumor, and the stump was ligated with double-stranded 7-0 silk sutures and secured with sterile gauze tape. Distilled water was taken to flush the chest cavity. After confirming the absence of active bleeding, the thoracic duct was clearly identified and prophylactically ligated with 7-0 silk. The remaining steps were the same as in the control group (Figure 2).

Observation of indicators

(1) Surgical Operative duration, intraoperative blood loss, chest drainage volume, and total dissected lymph nodes were recorded for both groups; (2) Pain Fasting venous blood samples were collected from all patients at 00 AM preoperatively (day of surgery) and postoperatively (day 1). After centrifugation, the supernatant was collected. Immunoturbidimetry[11] was performed to detect the levels of 5-hydroxytryptamine (5-HT), potassium ions (K^+^), and norepinephrine (NE) in the serum; (3) Immune Fasting venous blood samples were collected from all patients at 00 AM before surgery (day of surgery) and after surgery (day 3). Following centrifugation, the serum was obtained. The percentages of CD4^+^ T lymphocytes and CD8^+^ T lymphocytes and the CD4^+^/CD8^+^ ratio were assessed by flow cytometry; (4) Inflammatory Serum samples were collected before surgery (day of surgery) and after surgery (day 3) using the method mentioned in (3). The levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) in the serum was determined by enzyme linked immunosorbent assay[12]; (5) Pulmonary A spirometer was utilized to examine the forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximal voluntary ventilation (MVV) in the two groups of patients preoperatively (day of surgery) and postoperatively (day 3); and (6) Complications: We documented incidence rates of iatrogenic injuries, chylothorax, anastomotic fistula, massive hemorrhage, pleural effusion, and pulmonary and other system infections.

Statistical analysis

All study data were processed and analyzed using SPSS22.0 software. Measurement data were represented as mean ± SD. One-way ANOVA was employed for multi-group comparisons, and t-tests were used for inter-group comparisons. Enumeration data were expressed as percentages, with the χ^2^ test adopted for analysis. If P < 0.05, differences were considered statistically significant.

RESULTS

Comparison of general data between the two groups

The observation group included 37 males and 29 females (mean age 62.33 ± 5.78 years; range 41-87 years). Tumor characteristics comprised 42 mid-thoracic and 24 upper thoracic lesions. Pathologic staging revealed 35 cases of stage I and 31 cases of stage IIa, with histological subtypes distributed as squamous carcinoma (n = 17), adenocarcinoma (n = 25), and others (n = 24). The control group consisted of 33 males and 28 females aged 41-87 years [mean age of (61.54 ± 6.40) years]. Tumor locations comprised the mid-thoracic portion (36 cases) and upper thoracic portion (25 cases); disease staging comprised 39 stage I and 22 stage IIa cases. The histological classification showed 15 cases of squamous carcinoma, 30 cases of adenocarcinoma, and 16 cases of others. No significant differences were found in the general data such as the sex, age, tumor location, tumor staging, and histological classification (P > 0.05; Table 1).

Comparison of surgical indicators between the two groups

The observation group exhibited significant shorter surgical duration (165.48 ± 20.44 minutes vs 194.63 ± 22.78 minutes), significant reduced intraoperative blood loss (89.08 ± 10.23 mL vs 123.62 ± 15.28 mL), and significant lower chest drainage (256.34 ± 31.61 mL vs 310.29 ± 35.72 mL), significant increased total number of dissected lymph nodes of (8.44 ± 0.75 vs 6.23 ± 0.61; P < 0.05; Table 2). These findings suggested that total thoracoscopic ultrasonic scalpel resection, compared with electrosurgical scalpel resection, brought about a more substantial improvement in perioperative indicators.

Comparison of pain mediator levels between the two groups

No significant differences were detected in preoperative levels of 5-HT, K^+^, and NE between the two groups (P > 0.05). Following treatment, both groups exhibited a dramatic increase in the levels of pain mediators in both groups (P < 0.05). Postoperatively, the observation group showed 5-HT levels of (0.41 ± 0.04) nmol/L, K^+^ levels of (33.69 ± 2.58) nmol/L, and NE levels of (3.03 ± 0.48) ng/L, all significantly lower than those in the control group during the same period (P < 0.05; Table 3). These findings demonstrated that ultrasonic scalpel resection mitigated surgical pain responses more effectively than conventional electrosurgical techniques.

Comparison of immune response between the two groups

Preoperative CD4^+^ levels, CD8^+^ levels, and CD4^+^/CD8^+^ ratios showed no significant intergroup differences (P > 0.05). Both surgical approaches triggered significant postoperative immunosuppression, characterized by decreased CD4^+^ percentages, elevated CD8^+^ percentages, and reduced CD4^+^/CD8^+^ ratios (P < 0.05). However, the ultrasonic scalpel group demonstrated significantly better-preserved immune parameters postoperatively, that is, significantly higher CD4^+^ levels (31.73% ± 2.12% vs 27.49% ± 2.98%), lower CD8^+^ levels (29.46% ± 3.55% vs 33.95% ± 3.96%), elevated CD4^+^/CD8^+^ ratio (1.07 ± 0.10 vs 0.81 ± 0.07; P < 0.05 for all; Table 4). These results indicated that ultrasonic scalpel resection induced less immunosuppression and better maintains immune homeostasis compared to electrosurgical techniques.

Comparison of inflammatory markers between the two groups

Preoperative serum levels of IL-6, IL-8, and TNF-α showed no significant differences between the two groups (P > 0.05). Following surgery, the levels of the inflammatory markers showed a significant increase (P < 0.05). Notably, the observation group exhibited IL-6 Levels of (268.75 ± 25.48) ng/L, IL-8 Levels of (221.43 ± 20.38) ng/L, and TNF-α levels of (132.05 ± 15.43) ng/L, all of which were significantly lower than those in the control group during the same period (P < 0.05; Table 5). These findings confirmed that thoracoscopic ultrasonic scalpel resection, compared with electrosurgical scalpel resection, was more effectively in dampening the body’s inflammatory response in the treatment of esophageal cancer.

Comparison of pulmonary function parameters between the two groups

No significant differences were observed in preoperative levels of FVC, FEV1, and MVV between the two groups (P > 0.05). After surgery, both groups displayed a significant decline in the levels of pulmonary function parameters compared with preoperative levels (P < 0.05). Of note, the observation group demonstrated FVC of (78.28 ± 7.75) mL, FEV1 of (76.68 ± 6.41) mL, and MVV of (68.49 ± 7.11) mL, all of which were better than those in the control group during the same period (P < 0.05; Table 6). Our findings revealed that while thoracoscopic surgery inevitably impaired respiratory function, ultrasonic scalpel resection provided significantly greater protection against surgical pulmonary compromise compared to electrosurgical techniques.

Comparison of complications between the two groups

Common complications following total thoracoscopic esophagectomy include intraoperative iatrogenic injuries, chylothorax, anastomotic fistula, massive hemorrhage, pleural effusion, and infections in the lungs and other systems in esophageal cancer patients. Here, we found that the observation group displayed no intraoperative iatrogenic injuries or massive hemorrhage, but there were 2 patients with chylothorax, 1 patient with anastomotic fistula, 2 patients with pleural effusion, as well as 1 patient with infections in the lungs and other systems. The overall incidence of complications reached 7.58%, significantly lower than 21.31% in the control group (P < 0.05; Table 7). These results demonstrated that total thoracoscopic ultrasonic scalpel resection served as a safe and reliable surgical method for treating esophageal cancer.

DISCUSSION

The incidence of esophageal cancer in China demonstrates a concerning upward trajectory, with pathogenesis closely linked to shifting dietary patterns, excessive nitrate intake, deficiencies in trace elements, and tobacco/alcohol use. With an annual mortality exceeding 150000 cases, this malignancy predominantly affects males aged > 40 years[13,14]. Surgical resection, radiotherapy, and chemotherapy remain the mainstream methods currently, among which surgery is the primary option. While conventional open surgery demonstrates efficacy, it shows limitations such as larger surgical trauma, more indwelling catheters, and higher pain levels, which all impact patient recovery[15,16]. With the development of minimally invasive and endoscopic technology, total thoracoscopic surgery has been widely applied in surgical treatment for esophageal cancer. It addresses the shortcomings of conventional open surgery, ensuring the visualization of the surgical area, thus enhancing surgical precision, and contributing to smaller trauma and less bleeding, eventually improving postoperative recovery[17].

Electrosurgical scalpel resection and ultrasonic scalpel resection are two predominant techniques in total thoracoscopy. Our comparative study demonstrates that ultrasonic scalpel resection significantly optimizes perioperative outcomes relative to electrosurgical approaches. Specifically, the observation group, which adopted total thoracoscopic ultrasonic scalpel resection, had a shorter operative time, lessened intraoperative blood loss and chest drainage volume, more lymph nodes dissected, and lowered complication rates compared with the control group, indicating substantial clinical advantages over conventional electrosurgical techniques for esophageal cancer patients. These superior outcomes stem from fundamental technological differences. Electrosurgical scalpel cuts lesion tissues using high-frequency current, but its thermal energy has a wide propagation range, which can damage nearby tissue cells, causing char and smoke[18], which affects intraoperative visualization and surgical outcomes. Moreover, the imprecise cutting can result in poor closure of larger blood vessels, requiring additional time during surgery for vessel clamping and ligation. Conversely, ultrasonic scalpel uses mechanical vibrations with wavelengths below 0.5 mm during energy transmission, resulting in minimal thermal damage and allowing for precise removal of the lesion, while clearing lymph nodes as many as possible[19]. It boasts a rapid hemostatic effect, reducing surgical time and blood loss, and offers significant protection to adjacent tissues. Furthermore, it can effectively lower the incidence of postoperative complications.

The detrimental stimuli triggered by surgical trauma are transmitted to the central nervous system through sensory neurons, thereby releasing a large number of pain mediators, that amplify clinical pain perception. Previous studies found that pain perception manifested through complex neurohumoral mechanisms involving dysregulation of serum biomarkers such as 5-HT and NE[20]. 5-HT, K^+^, and NE function as critical neurotransmitters and pain mediators. K^+^ primarily generates physical stimuli in the body, and by regulating the secretion of 5-HT, it induces second messenger effects on local tissues, which in turn stimulate peripheral nerves to generate pain. This cascade ultimately activates peripheral nociceptors through multi-receptor mechanisms[21,22]. Our biomarker analysis demonstrated that the levels of 5-HT, K^+^, and NE in both groups were all higher than those before surgery, with the observation group showing lower levels of these indicators compared with those in the control group during the same period, confirming that the ultrasonic scalpel, compared with the electrosurgical scalpel, has a better effect on alleviating subjective pain perception in esophageal cancer patients.

Pain induces stress-associated stimuli in the body that disrupt immune homeostasis, and amplify the inflammatory mediators release[23]. In our study, both groups of patients displayed a decline in CD4^+^ and the CD4^+^/CD8^+^ ratio, as well as an increase in CD8^+^ postoperatively compared with preoperative levels. Nevertheless, the observation group showed heightened CD4^+^ and CD4^+^/CD8^+^ ratios and lowered CD8^+^ levels vs the control group. Meanwhile, serum inflammatory factors IL-6, IL-8, and TNF-α were higher postoperatively than preoperatively, but the observation group exhibited lower levels than the control group, suggesting that ultrasonic scalpel more effectively mitigated immune dysfunction and suppressed inflammatory cascades compared to electrosurgical techniques. These findings are consistent with the research of Kalari et al[24]. Given that ultrasonic scalpel directly acts on local tissues, rapidly increasing the temperature of adjacent tissues through high-frequency oscillations, accelerating water vaporization and coagulation, and allowing for timely vessel closure, the precision maintains superior surgical field visualization, minimizes unnecessary surgical damage, suppresses systemic stress responses, attenuates pain mediators release and limits subsequent immune and inflammatory dysregulation[25,26], which is beneficial for postoperative recovery in patients. Unlike electrosurgery’s diffuse thermal conduction, ultrasonic scalpel cuts through mechanical vibration, which can reduce thermal damage, decrease the release of pain mediators, and alleviate the inflammatory response. By minimizing pleural irritation and maintaining airway patency, it significantly better preserves pulmonary function parameters[27].

FVC, FEV1, and MVV are known as critical indicators directly reflecting pulmonary function status, with their alterations closely correlated with the degree of lung injury[28,29]. It has been reported that total thoracoscopic surgery can reduce cardiopulmonary damage and preserve pulmonary function compared with conventional open surgery[30]. Here, we further found that ultrasonic scalpel resection provided superior pulmonary protection compared to total thoracoscopic electrosurgical scalpel resection. Although both cohorts exhibited expected postoperative declines in pulmonary function, the ultrasonic group maintained significantly better FVC, FEV1 and MVV than electrosurgical controls. Considering that pulmonary function depends on the integrity and compliance of the thorax and lung tissues, and the degree of airway patency[31], Electrosurgical scalpel resection, due to excessive current and overheating, inevitably affects the integrity of the diaphragm and exacerbates pulmonary function impairment. In contrast, the precise cutting effect of the ultrasonic scalpel minimizes damage to surrounding tissues such as the heart and lungs, demonstrating remarkable lung-protective effects[32], making it a highly efficient, safe, and fast-recovery surgical approach for the clinical treatment of esophageal cancer.

As a retrospective analysis utilizing real-world clinical data, this study inevitably faces potential selection bias concerns. The non-randomized assignment of surgical approaches, where patients self-selected either ultrasonic or electrosurgical resection based on personal preference, introduces inherent confounding risks. Factors including differential healthcare costs, institutional technical capabilities, or surgeon-specific preferences could systematically influence both technique selection and postoperative outcomes, thereby compromising causal inference. To avoid the limitation, patients and their families are told that that both ultrasonic scalpels and electrosurgical scalpels are thoracoscopic techniques with similar functions, and the selection had a certain degree of randomness in clinical practice, without other significant clinical preference issues.

Based on our findings, surgeons should prioritize the total thoracoscopic ultrasonic scalpel resection for suitable candidates, leveraging its tissue-preserving properties to enhance oncological precision and staging accuracy. Perioperative management requires comprehensive preoperative preparation including psychological support and nutritional optimization. Moreover, it is essential to develop strict intraoperative protocol. Postoperatively, management of pain, immune function, and pulmonary function should be performed. Besides, future research should address long-term follow-up on patients who have undergone ultrasonic scalpel resection, and compare their long-term survival and recurrence rates with those of patients who received other surgical methods.

CONCLUSION

To conclude, total thoracoscopic ultrasonic scalpel resection significantly outperforms electrosurgical techniques across multiple perioperative domains for esophageal cancer patients, including improved surgery-related indicators, reduced postoperative pain, enhanced immune function, decreased inflammatory response, and better pulmonary function, demonstrating its safety and reliability for the treatment of esophageal cancer.