Clinical Effect and Postoperative Pain of Laparo-Thoracoscopic Esophagectomy in Patients with Esophageal Cancer.

Objective: To investigate the clinical effect and postoperative pain of laparo-thoracoscopic esophagectomy in patients with esophageal cancer.
Methods: A total of 90 patients with esophageal cancer who were admitted and treated in our hospital from August 2020 to November 2021 were randomly selected as the research subjects for prospective analysis, and the patients were assigned to the control group and the experimental group according to the time of admission equally, with 45 cases in each group. Patients in the control group underwent conventional open surgery, and those in the experimental group underwent laparo-thoracoscopic esophagectomy. Then, operation-related indicators, postoperative pain, inflammatory factors, and complications were compared between the two groups.
Results: The operation time, intraoperative blood loss, postoperative drainage, and postoperative length of stays of the experimental group were significantly shorter or less than those of the control group (P < 0.05); there was no significant difference in the number of lymph nodes dissected between the two groups (P > 0.05). The number of patients with moderate and severe pain in the experimental group was significantly smaller than that in the control group, and the number of patients with mild pain was significantly larger than that in the control group (P < 0.05). The level of inflammatory factors (TNF-α, IL-6, IL-8, and IL-10) was significantly lower than that in the control group (P < 0.05); the incidence of surgical complications in the experimental group was significantly lower than that in the control group (P < 0.05).
Conclusion: Laparo-thoracoscopic esophagectomy can significantly improve the clinical effect in patients with esophageal cancer. Thoracic-laparoscopic esophagectomy can significantly improve the clinical results of patients with esophageal cancer. With better performance in surgery-related indicators, lower inflammatory factor levels and postoperative pain, and fewer postoperative complications, it will speed up patients' recovery and is worthy of clinical promotion and application.

1. Introduction

Esophageal cancer is one of the most common malignancies in clinical practice [1]. As one of the countries with a high incidence of esophageal cancer, the number of deaths from esophageal cancer in China is over 200,000 per year, accounting for over 46% of deaths worldwide [2]. For patients with esophageal cancer, esophagectomy and regional lymph node dissection are the two commonly used treatments [3]. However, Kunisaki et al. held that conventional thoracotomy is not conducive to the patient's postoperative recovery for its great trauma to patients' bodies, especially the stress and the body's inflammatory response caused by severe postoperative pain would impair the immune function and thus increase the risk of postoperative infection [4]. The injury to patients' lungs during the surgery is one of the key factors triggering postoperative pulmonary complications [5]. In recent years, with the increasing demands of patients for surgery, its impact on the patients' postoperative life has become one of the factors to be considered clinically [6]. In recent years, with the continuous progress and development of laparoscopic technology in China, thoraco-laparoscopic esophagectomy has received widespread attention from surgeons [7]. Laparo-thoracoscopy features small trauma, fast recovery, and high safety, through which the postoperative pain and blood loss of patients can be effectively reduced, and so the recovery can be accelerated [8].

The aim of this study was to collect data from 90 randomly admitted patients with esophageal cancer in our hospital from August 2020 to November 2021, and to investigate the clinical efficacy of laparoscopic esophagectomy and postoperative pain, with a view to providing a clinical reference.

2. Data and Methods

2.1. General Data

Ninety patients with esophageal cancer admitted to our hospital from August 2020 to November 2021 were randomly selected for prospective analysis, and were divided equally and randomly into a control group and an experimental group of 45 patients each according to the time of admission. The experiment was approved by the Ethics Committee of Shengjing Hospital of China Medical University, No. 289711/01., and all included patients and their families were informed and signed the informed consent form.

2.2. Inclusion and Exclusion Criteria

Patients were included if (1) they had been diagnosed with esophageal cancer by clinical examinations, (2) the tumor presents no sign of metastasis or invasion, and (3) they agreed to participate in the study voluntarily after being informed. Patients were excluded from the study if they are living with (1) other serious organ diseases, (2) psychiatric diseases or communication disorders, (3) surgery-related contraindications, and (4) or are possibly unable to cooperate well with the study due to poor compliance.

2.3. Methods

All procedures were performed by the same surgical team.

Patients in the control group underwent conventional open surgery: preoperative double-lumen bronchial intubation with general anaesthesia combined with epidural anaesthesia. The right side of the posterior lateral 6th intercostal space was opened, and the location and size of the mass was explored and routinely excised free of charge. All mediastinal lymph nodes were cleared, especially the inferior ramus and the bilateral paraglottic lymph nodes, after which the chest was closed and the patient was turned to the supine position. Subsequently, the stomach was opened through the middle of the epigastrium, and the stomach was freed. The lymph nodes in the large and small curves of the stomach, the left paravalvular gastric vessels, the common hepatic artery, the abdominal arterial trunk, and the splenic artery were cleared. The cardia was disconnected, a tubular stomach was created and pulled from the neck region through the esophageal bed, then, the esophagus was disconnected, and the proximal esophagus was anastomosed to the stomach base.

Patients in the experimental group underwent laparo-thoracoscopic esophagectomy: general anaesthesia compounded with epidural anaesthesia through double-lumen bronchial intubation was performed with single-lung ventilation. A 10 mm thoracoscopic hole is made in the 7th intercostal space in the mid-axillary line and three 4 mm surgical holes are made in the subscapularis, the 4th intercostal space in the mid-axillary line, and the 7th intercostal space in the posterior axillary line, respectively. Carbon dioxide is flushed to create an artificial pneumothorax. The patient is placed prone, allowing the right lung to descend ventrally and fully exposing the posterior mediastinum. The mediastinal pleura is opened to determine if the esophageal cancer is resectable. Then, the right recurrent laryngeal nerve was first dissected and exposed, and the lymph nodes adjacent to it were cleared. Next, the entire esophagus and its wall lymph nodes are cleared from the thoracic inlet to the diaphragmatic fissure, and the internal esophageal artery is dissected with an ultrasonic knife. The free esophagus is retracted to the right to clear the subaortic lymph nodes and avoid damaging the patient's bronchus. The trachea is then pulled forward to expose the area between the left side of the trachea and the aortic arch, and the left laryngeal recurrent nerve is located and cleared of its para-acoustic lymph nodes. After the operation, with a drainage tube left in place, the patient was turned to the supine position, an artificial pneumoperitoneum was established, the stomach was freed laparoscopically, and the lymph nodes next to the esophagogastric junction, the perigastric region, the left gastric vessel, the common hepatic artery, the abdominal arterial trunk, and the splenic artery were carefully cleared; the esophagus was cut at the esophagogastric junction, the tube was inserted into the stomach, and the suture between the esophageal cut edge and the base of the tube was used for traction. An incision was made at the anterior border of the sternocleidomastoid muscle in the neck, the cervical esophagus is freed, the cervical lymph nodes are removed, the thoracic segment of the esophagus is pulled out of the neck via the posterior mediastinal esophageal bed, the tubular stomach is elevated to the neck, and a transverse manual anastomosis is performed from the esophagus to the gastric end.

2.4. Control Indicators

Surgery-related indicators include operation time, intraoperative blood loss, number of lymph nodes dissected, postoperative drainage, and postoperative length of hospital stay. All the above indicators were recorded by the medical staff in our hospital.

Pain score indicator: The Visual Analog Scale (VAS) was used to assess the patients' pain. With a full score at 10; 1–3 indicating mild pain, 4–6 indicating moderate pain, and 7–10 indicating severe pain. The higher the score, the more severe the pain patients feel.

Inflammatory factor indicators: 5 ml of fasting venous blood was drawn from patients in the morning before and after treatment, and the supernatant was collected after low-speed centrifugation. The levels of the tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) were measured using an enzyme-linked immunosorbent assay kit from Shanghai Enzyme Biotechnology Co., Ltd. (4Possible complications of patients after surgery include the following: surgical wound infection, pulmonary infection, nerve injury, and pleural effusion.

2.5. Statistical Methods

SPSS 21.0 was used for data analysis, and the T test and the chi-squared test were performed for measurement data () and enumeration data (n (%)), respectively. The difference was statistically significant if P < 0.05.

3. Results

3.1. General Data

The control group: 28 males and 17 females, aged between 40–72 years, with a mean age of 60.72 ± 3.54; tumor sites: 12 in the upper segment, 19 in the middle segment, and 14 in the lower segment; pathological types: 16 of adenocarcinoma, 17 of squamous carcinoma, 12 of adenosquamous carcinoma; TNM staging: 12 in stage I, 23 in stage II, and 10 in stage III. The experimental group: 26 males and 19 females, aged between 41–73 years, with a mean age of 60.82 ± 3.59; tumor sites: 13 in the upper segment, 18 in the middle segment, and 14 in the lower segment; pathological types: 18 of adenocarcinoma, 16 of squamous carcinoma, 11 of adenosquamous carcinoma; TNM staging: 11 in stage I, 24 in stage II, and 10 in stage III. This study was reviewed and approved by the medical ethics committee of our hospital. General data of the two groups were compared, and no significant (P > 0.05) difference was found, as shown in Table 1.

Table 1

Comparison of general data (n (%)).

	Control group (n = 45)	Experimental group (n = 45)	t/X2	P
Gender			0.185	0.667
Male	28	26
Female	17	19
Age (years)	40–72	41–73
Mean age (years)	60.72 ± 3.54	60.82 ± 3.59	−0.133	0.894
Tumor sites			0.067	0.796
Upper segment	12	13
Middle segment	19	18
Lower segment	14	14
Pathological types			0.072	0.788
Adenocarcinoma	16	18
Squamous carcinoma	17	16
Adenosquamous carcinoma	12	11
TNM staging			0.065	0.799
Stage I	12	11
Stage II	23	24
Stage III	10	10

3.2. Surgery-Related Indicators

As can be seen from Table 2, operation time, intraoperative blood loss, postoperative drainage, and postoperative length of stay of patients in the experimental group were significantly shorter or less than those in the control group (P < 0.05). No significant difference was observed in the number of lymph node dissected in the two groups (P > 0.05).

Table 2

Comparison of surgery-related indicators ().

Indicator	Control group (n = 45)	Experimental group (n = 45)	t	P
Operation time (min)	389.47 ± 29.72	253.41 ± 31.59	21.044	<0.001
Intraoperative blood loss (mL)	490.68 ± 28.57	291.17 ± 21.32	37.543	<0.001
Number of lymph node dissection (pieces)	28.18 ± 4.52	27.96 ± 4.27	0.237	0.813
Postoperative drainage (mL)	504.71 ± 70.44	332.69 ± 83.15	10.589	<0.001
Postoperative length of stay (d)	14.12 ± 2.48	9.37 ± 1.35	11.285	<0.001

3.3. Postoperative Pain

The number of patients with moderate and severe postoperative pain in the experimental group was significantly smaller than that of the patients in the control group, and the number of patients with mild pain was significantly larger than that of the patients in the control group (P < 0.05), as shown in Table 3.

Table 3

Comparison of postoperative pain (, n (%)).

Group	VAS score	Pain level grading (cases)
		Mild	Moderate	Severe
Control group (n = 45)	5.87 ± 1.25	17	21	7
Experimental group (n = 45)	4.52 ± 1.13	33	11	1
t/X2	5.374	11.52	4.849	4.939
P	<0.001	0.001	0.028	0.026

3.4. Level of Inflammatory Factors

The level of inflammatory factors (TNF-α, IL-6, IL-8, and IL-10) in the experimental group were significantly lower than that of the control group after treatment (P < 0.05), as shown in Table 4.

Table 4

Comparison of the levels of inflammatory factors ().

Indicator	Time	Control group (n = 45)	Experimental group (n = 45)	t	P
TNF-α (ng/L)	Preoperative	105.23 ± 41.59	103.78 ± 35.79	0.177	0.86
	Postoperative	170.37 ± 62.58	130.72 ± 79.82	2.622	0.01
IL-6 (ng/L)	Preoperative	191.23 ± 18.35	189.75 ± 18.96	0.376	0.708
	Postoperative	296.70 ± 21.57	281.74 ± 21.35	3.307	0.001
IL-8 (ng/L)	Preoperative	170.03 ± 16.42	167.38 ± 16.34	0.767	0.445
	Postoperative	265.47 ± 24.62	227.61 ± 23.99	7.388	<0.001
IL-10 (ng/L)	Preoperative	54.82 ± 6.47	55.68 ± 6.52	−0.628	0.532
	Postoperative	82.15 ± 7.68	66.83 ± 7.23	9.743	<0.001

3.5. Complications

The incidence of surgical complications in the experimental group was significantly lower than that in the control group (P < 0.05), as shown in Table 5.

Table 5

Comparison of complications (n (%)).

	Control group (n = 45)	Experimental group (n = 45)	X 2	P
Wound infection	5	2
Pulmonary infection	4	1
Nerve damage	2	1
Pleural effusion	2	1
Incidence	13 (29%)	5 (11%)	4.444	0.035

4. Discussion

China is one of the countries with a high incidence of esophageal cancer worldwide. Its clinical mortality rate is high [9]. At present, the pathogenesis of esophageal cancer in clinical practice is not fully understood. Some studies suggest that it is closely related to excessive intake of tetranitrate, lack of trace elements and inorganic salts in food, and poor living habits [10]. At present, the common treatment methods for malignant tumours include radiotherapy, surgery, and other conventional treatments, among which surgical resection is still the mainstay [11]. Clinical studies showed that conventional open esophagectomy caused greater trauma to patients' bodies, including more tubes left in the postoperative period, which would seriously affect postoperative recovery [12]. With the continuous development of laparoscopic surgery and the maturation of minimally invasive techniques in China, laparoscopic esophagectomy has received widespread attention from surgeons in recent years [13]. Related studies have shown that thoracic-laparoscopic esophagectomy is less traumatic and causes less bleeding than conventional open surgery, and it significantly accelerates patients' postoperative recovery and reduces the incidence of postoperative complications [14].

Laparoscopy is a medical device with a miniature camera and with it comes laparoscopic surgery, a minimally invasive surgical method that has developed rapidly in recent years [15]. Using a laparoscope, a hole is made in the patient's abdomen and the laparoscope is subsequently placed inside the patient's abdomen; using the miniature camera carried by the laparoscope the inside of the abdomen can be viewed [16]. Once the laparoscope is inside the patient, the light source at the head of the laparoscope emits light to provide light for the surgical field of view, and the camera transmits images from the abdominal cavity to the screen via optical fibres, allowing the operator to see the patient's abdominal cavity clearly on the screen of the camera [17]. Laparoscopy is now widely used in minimally invasive laparoscopic surgery, therefore, minimally invasive surgery in gynaecology, gastrointestinal surgery, hepatobiliary surgery, and urology all require laparoscopic assistance [18]. Compared to traditional open surgery, laparoscopy can reduce the trauma and blow of surgery and is a major trend in the future development of surgery [19].

In this study, we compared the differences between laparoscopic esophagectomy and conventional open surgery in terms of clinical outcomes and postoperative pain [20]. The results showed that the operative time, intraoperative bleeding, postoperative drainage, and postoperative hospital stay of patients in the experimental group were significantly shorter than those in the control group; the number of patients with moderate to severe postoperative pain in the experimental group was significantly less than that in the control group, and the number of patients with mild postoperative pain scores was significantly more than that in the control group. The levels of inflammatory factors (TNF-α, IL-6, IL-8, and IL-10) were significantly lower in the experimental group than in the control group; the number of lymph nodes cleared in the two groups was not statistically significant; the incidence of surgical complications was significantly lower in the experimental group than in the control group. There was no significant difference between laparo-thoracoscopic esophagectomy and conventional open surgery concerning the number of lymph nodes cleared [21]. In addition, laparoscopic esophagectomy performs better in terms of intraoperative indications, effectively alleviating postoperative pain symptoms and inflammatory response in patients [22], thus, effectively reducing the incidence of complications, and ultimately speeding up their postoperative recovery. The reason behind this may be that laparoscopic esophagectomy provides an open and nonblinded view, allowing the same anatomical results as conventional open surgery [23].

In conventional open surgery, the internal organs will be exposed for a long time due to the large wound, and the lung will be further compressed and contused, which will cause a serious impact on patients' bodies and circulatory system function [24]. Damage to the body then leads to an increase in the level of serum inflammatory factors. TNF-α, IL-6, and IL-8 are common proinflammatory factors that have been shown by Xing et al. to exacerbate the inflammatory response of patients by promoting the expression of T-lymphocytes and hypersensitive C-reactive protein [25]. The levels of these three proinflammatory factors increase with the degree of damage to the patient's body, and the interaction of multiple inflammatory factors in the patient's body can lead to a circulatory effect, leading to a series of adverse reactions and complications. IL-10, on the other hand, is an anti-inflammatory factor that effectively suppresses the immune response of the patient's body and antagonises a number of factors to alleviate the inflammatory response. Laparoscopic esophagectomy is known to be minimally invasive and can effectively reduce the damage to the patient, thereby alleviating the inflammatory response and reducing serum inflammatory factor levels. At the same time, there is a close relationship between the body's pain and the inflammatory response. Therefore, the decrease in the inflammatory response predicts the relief of pain the patients feel. Chen et al. found that there is a close correlation between the occurrence of tumors and the immune system [26]. Once a tumor develops in patients' bodies, cancer cells will seriously affect the immune function. At the same time, the damage caused by surgical trauma can cause a series of stress reactions that further compromise the immune system, leaving the patient's body susceptible to various infections and ultimately creating a vicious cycle. The results showed that minimally invasive surgery can significantly reduce damage to the patients' bodies, thus effectively reducing the impact on the immune function and so reducing the occurrence of complications.

For patients with mid-to late-stage esophageal cancer who cannot undergo surgery or for whom surgery is not feasible, a combination of radical radiotherapy and chemotherapy may improve survival [27]; for patients with recurrent or distant metastatic esophageal cancer, a combination of chemotherapy or targeted therapy-based treatment may prolong survival [28]. The general treatment of esophageal cancer is mainly to maintain water and electrolyte balance, and nutritional support [29]. As esophageal cancer can lead to swallowing obstruction and difficulty in eating, patients in advanced stages suffer from malnutrition and wasting, so nutritional support therapy is very important for patients' survival and subsequent antitumour treatment [30]. Nutritional support therapy for patients with esophageal cancer can be divided into two forms: enteral nutrition and parenteral nutrition, with enteral nutrition being the mainstay as far as possible because it can be administered through a nasal feeding tube or gastrostomy to avoid the obstructed esophageal segment. Parenteral nutrition is administered as an infusion of glucose, electrolytes, amino acids, and fatty milk, depending on the patient's condition.

There are some limitations to our experiments. First of all, because the sample size is too small, it will cause a certain deviation of the results. Moreover, we need to conduct a large number of follow-up visits in the follow-up period to prove the prognostic effect of laparoscopy and the improvement effect on long-term quality of life.

5. Conclusion

In conclusion, thoracic-laparoscopic esophagectomy can significantly improve the clinical results of patients with esophageal cancer. With better performance in surgery-related indicators, lower inflammatory factor levels and postoperative pain, and fewer postoperative complications, it will speed up patients' recovery, and is worthy of clinical promotion and application.