The pathological types of esophageal cancer are mainly divided into squamous cell carcinoma and adenocarcinoma, and in areas with high incidence of esophageal cancer such as Asia and Africa, histologic division is dominated by squamous cell carcinoma, esophageal squamous cell carcinoma accounts for more than 90% of all esophageal cancer tissue classification, and adenocarcinoma is the main in Europe and the United States. Esophageal cancer ranks 8th in the world in the incidence of malignant tumors; In 2020, the number of new deaths from esophageal cancer worldwide was 544,000, ranking sixth in the malignant tumor death spectrum, and the mortality rate of esophageal cancer in 2020 was 7.0 per 100,000 [1]. In addition, gender and region differences can also affect the incidence and mortality of esophageal cancer, among which the incidence rate in rural areas is much higher than in urban areas, and the incidence is higher in men than in women [2]. The high incidence and mortality of esophageal cancer seriously threaten human health. For the treatment of esophageal cancer, there are mainly surgery, radiotherapy, chemotherapy and immunotherapy, which can alleviate the disease to a certain extent, but there are also gastrointestinal reactions, bone marrow suppression and other problems [3]. For chemotherapy, fluorouracil + cisplatin (CF) regimen is often used, which has a certain clinical effect [4], but there are many toxic side effects, and even some patients interrupt treatment because they cannot tolerate its toxic side effects. Patients with intermediate and advanced esophageal cancer are in serious condition and the clinical treatment effect is not good. In order to further improve the treatment effect, based on the combination of traditional Chinese and Western medicine, our research group used antisputum and stasis choking granules combined with channel opening pills combined with CF program to treat stage III.~IV. sputum and stasis internodular esophageal squamous cell carcinoma, systemic differentiation, local disease discrimination, aiming to explore new clinical ideas of combined traditional Chinese and Western medicine in the treatment of advanced esophageal cancer, and achieved positive efficacy, which is reported as follows.
1 Objects and methods
1.1 Study Subjects A total of 99 patients with esophageal squamous cell carcinoma who met the requirements were collected from February 2020 to February 2021 in Henan Provincial Hospital of Traditional Chinese Medicine, Anyang Cancer Hospital and Henan Provincial Cancer Hospital. The patients were divided into control group, treatment I group and treatment II group according to random number table method, and there were 33 cases in all three groups. Inclusion criteria: (1) meet the diagnostic criteria of traditional Chinese and Western medicine for sputum and stasis interconnected esophageal squamous cell carcinoma; (2) Expected survival > 3 months; (3) Inoperable patients with stage III.~IV. esophageal squamous cell carcinoma. Exclusion Criteria: (1) pregnant and lactating women; (2) Those who are allergic to drugs, or patients with acute attacks of other diseases; (3) Those who fail to use drugs in accordance with the provisions to affect the judgment of efficacy. This study has been approved by the Ethics Committee of Henan Provincial Hospital of Traditional Chinese Medicine [2019 Hospital Ethics Review No. 25], and patients have informed consent and signed informed consent.
1.2 Diagnostic criteria
1.2.1 Western Medicine Diagnostic Criteria The pathological diagnosis is esophageal squamous cell carcinoma, and the clinical stage of the tumor TNM is referred to the American Cancer Federation (AJCC) 8th edition [5].
1.2.2 Diagnostic Criteria of Traditional Chinese Medicine The main symptoms include: (1) dysphagia; (2) chest and back pain; (3) Red tongue or ecchymosis. Secondary symptoms include: (1) vomiting sticky strips; (2) skin nail error; (3) Spit such as adzuki bean juice; (4) dry stool; (5) Yellow urine; Diagnosis can be made if there are 2 main symptoms that are the same, or if there is one main symptom plus three secondary symptoms.
1.3 Treatment
1.3.1 Control group was given CF chemotherapy, intravenous infusion of cisplatin (Jiangsu Haosen Pharmaceutical, 20 mg injection, H20040813) 75 mg/m2 on the first day, 1 course of 21 days; On the 1~4th day, intravenous infusion of 5-fluorouracil (Tianjin Jinyao Pharmaceutical, 250 mg injection, H20030105) 250 mg/m2, 21 days for 1 course of treatment, a total of 4 courses.
1.3.2 Treatment Group I was given antisputum and stasis granules (Sichuan New Green Pharmaceutical Technology Development Co., Ltd.) combined with CF chemotherapy, the drug components included: Jiang Banxia 12 g, Sanqi 6 g, Yujin 12 g, Codonopsis 15 g, Baishu 12 g, Angelica 15 g, Gecko 3 g, Poria 15 g, 1 dose/d, 2 times/d, a total of 4 courses.
1.3.3 Treatment Group II was given antisputum and stasis granules combined with channel opening pills combined with CF regimen chemotherapy, and antisputum and stasis granules were taken with warm water, 1 dose/d, 2 times/d, 21 d for 1 course of treatment, a total of 4 courses. Daojie Pill (Henan Provincial Hospital of Traditional Chinese Medicine) is composed of 3 g of borax, 4 g of blood exhaustion, 4 g of plum flakes, 5 g of agarwood, 2 g of soap horn thorn, 4 g of centipede and 1 g of musk, and each course of treatment is taken 7 d, 1 time/d, 1 pill/1 time.
1.4 Observation indicators
1.4.1 TCM Syndrome Points TCM Syndrome Points are evaluated from the aspects of dysphagia, retrosternal pain, nausea and vomiting using the esophageal cancer symptom grading scale, and the lower the score, the milder the symptoms, which can directly reflect the degree of relief of clinical patients' symptoms, and evaluate the improvement of symptoms according to the symptom score [6].
1.4.2 Quality of Life Score The quality of life rating scale (QoL) of tumor patients [7] was used to evaluate the quality of life of patients, and the scale mainly included appetite, spirit, sleep, fatigue, pain conditions, family understanding and cooperation, etc., with a full score of 60 points, the higher the score, the higher the quality of life. Scoring criteria: Compared with before treatment, an increase of more than 20 points after treatment is judged to be effective; An increase of more than 10 points is effective; An improvement of less than 10 points or no change is judged to be stable; Post-treatment scores are lower than pre-treatment if they are considered ineffective.
1.4.3 Functional status (KPS) score [6] Using the KPS score table, the patient's functional status is divided into 11 grades, with the worst state KPS score of 0 and the best state KPS score of 100 points, the higher the KPS score, the better the health status. After treatment, the KPS score increased by ≥10 points compared with before treatment, and the assessment was improved; Increase or decrease < 10 points, rated as stable; The score was reduced by ≥ 10 points, which was rated as reduced.
1.4.4 Tumor markers Before and after treatment, carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC) indexes were observed and recorded.
1.4.5 Lesion remission rate Referring to the efficacy evaluation criteria of solid tumors [8], it was divided into four categories: complete response (CR), partial response (PR), disease stabilization (SD), and disease progression (PD) according to the remission status. Lesion remission rate = [(CR+PR+SD)/(CR+PR+SD+PD)] × 100%.
1.4.6 Evaluation of toxic side effects The effect of sputum elimination and stasis choking granules on safety indicators such as blood routine, liver and kidney function, and digestive tract reaction after treatment was observed. The examination was performed once before and after treatment, and the WHO standard grades (grade 0, I.~II., III.~IV.) were used for evaluation [9].
1.5 Statistical Methods SPSS 22.0 software was used for statistical analysis of the data. The measurement data conforming to the normal distribution were expressed as (x±s), univariate ANOVA ANOVA ANOVA was used for comparison between the three groups, and paired t-test was used for comparison before and after treatment within the group. Count data were presented as relative numbers, and comparisons between groups were either a chi-squared test or a nonparametric rank sum test (ordered data for multi-categorical outcomes). The difference in P<0.05 was statistically significant.
2 Results
2.1 General information There was no significant difference in gender, age, body weight and TNM stage between the three groups (P>0.05), see Table 1.
2.2 TCM Syndrome Points Before treatment, the scores of TCM syndrome points (dysphagia, retrosternal pain, nausea and vomiting, mucus, vomit, lack of food, dry stool) and total points of the three groups were not statistically significant (P>0.05). Compared with before treatment, the scores and total scores of retrosternal pain, nausea and vomiting, mucus and vomit were reduced in the three groups, and the scores of dysphagia, less food and dry stool were reduced in the control group and the treatment II. group, and the differences were statistically significant (P<0.05). After treatment, the scores of medical syndrome scores (dysphagia, retrosternal pain, nausea and vomiting, vomiting mucus, vomit, less eating, dry stool) and total scores of the three groups were statistically significant (P<0.05). Among them, the treatment group II had dysphagia, retrosternal pain, nausea and vomiting, vomit, less food, dry stool score and total score were lower than those of the control group and treatment group, and the mucus score of vomiting was lower than that of the control group, and the difference was statistically significant (P<0.05), see Table 2.
2.3 Quality of life score Before treatment, there was no significant difference in quality of life scores between the three groups (P>0.05). Compared with before treatment, the quality of life scores of the three groups were significantly higher (P<0.05). After treatment, the quality of life scores of the three groups were significantly different (P<0.05). The quality of life scores of the two treatment groups were higher than those in the control group, and the difference was statistically significant (P<0.05), as shown in Table 3.
2.4 KPS score Before treatment, there was no significant difference in KPS scores between the three groups (P>0.05). Compared with before treatment, the KPS scores of the three groups were significantly higher after treatment (P<0.05). After treatment, the KPS scores of the three groups were significantly different (P<0.05). The KPS scores of patients in the two treatment groups were higher than those in the control group, and the KPS scores in the treatment II group were higher than those in the treatment I group, and the difference was statistically significant (P<0.05), as shown in Table 4.
2.5 Before the treatment of tumor markers CEA and SCC, there was no significant difference in CEA and SCC levels between the three groups (P>0.05). Compared with before treatment, the levels of CEA and SCC were reduced in the three groups after treatment, and the difference was statistically significant (P<0.01). After treatment, the levels of CEA and SCC were significantly compared between the three groups (P<0.05). Among them, the CEA and SCC levels in the treatment group II were lower than those in the treatment I group and the control group, and the difference was statistically significant (P<0.05), see Table 5.
2.6 Lesion remission rate After treatment, the lesion remission rate of patients in the control group was 72.7%, 78.8% in the treatment I group and 90.9% in the treatment II. group. There was no significant difference in the remission rate of lesions after treatment between the three groups (χ2=3.647, P=0.161), see Table 6.
2.7 Toxic side effects The incidence of leukopenia after treatment in the control group, treatment I group and treatment II group was 60.6% (20/33), 60.6% (20/33) and 57.6% (19/33), the incidence of thrombocytopenia was 51.5% (17/33), 42.4% (14/33), 51.5% (17/33), and the incidence of gastrointestinal reactions was 54.6% (18/33), 69.7% (23/33), 54.6% (18/ 33), the incidence of hair loss was 63.6% (21/33), 72.7% (24/33), 57.6% (19/33), the incidence of neurotoxicity and liver and kidney function abnormalities in the three groups was about 50%, and most of the three groups had skin reactions after treatment; There was no significant difference in the incidence of toxic side effects after treatment between the three groups (P>0.05), as shown in Table 7.
3 Discussion
The etiology of esophageal cancer is complex, and there is no unified understanding, and studies have found that it is mainly closely related to fungal viral infection, lifestyle habits, heredity and other factors [10]. With the development of medicine, endoscopic mucosal dissection [11], immunization and targeted therapy have been gradually promoted and applied in the treatment of esophageal cancer, which has brought new hope to patients. The KEYNOTE-028 study [12] and KEYNOTE-180 study [13] confirmed that the use of immunologics can improve the objective response rate of esophageal cancer patients and prolong progression-free survival. Modern medicine has achieved certain results in the treatment of esophageal cancer, but there are still toxic side effects, and traditional Chinese medicine has a significant effect in the treatment of esophageal cancer, which can significantly relieve the uncomfortable symptoms.
Esophageal cancer mostly belongs to the category of "hiccup" in traditional Chinese medicine, and since ancient times, hiccups have been treated from qi, phlegm and stasis. Professor Ma Chunzheng has extensive research on esophageal cancer, and has rich experience in clinical treatment of esophageal cancer [14], and has achieved remarkable results in the treatment of sputum and stasis intertwined esophageal cancer [15]. In this study, the drug composition was further optimized for the treatment of sputum and stasis choking granules with channel opening pills. Eliminate phlegm and dissolve stasis tongtong granules with Banxia and Panax notoginseng as the medicine, playing the function of drying and humidifying phlegm, dispersing and removing stasis; Gecko anti-cancer and swelling, with the liver thinning and depression of the tulip as a medicine; Party ginseng and white art are beneficial to qi and spleen, and Wu angelica and Zhu Ling are used as adjuvant medicines. Modern studies have shown that anti-tumor effects in anti-phlegm and stasis granules in Banxia [16], gecko [17], Panax notoginseng [18], and Yujin [19]. Channel opening pills are topical chemicals, among which musk, agarwood, and ice chips are more pain-relieving; Musk can reduce swelling and pass menstruation; Agarwood Qi; Ice chips improve penetration; Borax soft and firm disaccumulation; Centipedes, their sex is smuggling, omnipresent, so it can search for evil spirits, remove poisonous evil, relieve pain, disperse knots and reduce swelling; Equipped with soap horn thorn and blood exhaustion to increase the effect of swelling. Modern studies have shown that musk [20], centipede [21], agarwood [22], ice chips [23], blood exhaustion [24], and soaphorn thorn [25] in channel kaijie pills can inhibit tumor cell proliferation and promote apoptosis.
The results of this study showed that the scores of medical symptoms in both treatment groups were improved compared with the control group, and the treatment group II had a more significant effect than the treatment group I in alleviating dysphagia, nausea and vomiting, vomit, and lack of food. In terms of improving the quality of life scores of esophageal cancer patients, the two treatment groups were significantly higher than the control group, indicating that the elimination of sputum and stasis choking granules combined with channel opening pills could improve the quality of life of patients. The KPS score is an indicator to assess the patient's physical condition, and the improvement of the score indicates the improvement of the patient's mental state and the recovery of body functions. The KPS score of treatment group II was higher than that of treatment I group, and the treatment group I group was higher than that of the control group, indicating that the combination of antisputum and stasis choking granules combined with channel opening pills combined with CF regimen had more therapeutic advantages. The remission rates of lesions in the three groups were 72.7%, 78.8% and 90.9%, respectively, and although the remission rates of lesions in the two treatment groups were higher than those in the control group, the results were not statistically significant. In addition, in terms of improving tumor markers, the combination of antisputum and stasis granules combined with channel opening pills combined with CF regimen has significant advantages over chemotherapy alone, among which oral combined with local inclusion of CEA index is better than oral medication alone, suggesting that traditional Chinese and Western medicine treatment can inhibit tumor progression to a certain extent. In terms of improving the toxic side effects of chemotherapy, there were no significant differences in the incidence of myelosuppression and abnormal liver and kidney function after treatment between the three groups (P>0.05).
In summary, the combination of sputum and stasis granules combined with channel opening pills combined with CF program can significantly reduce the clinical symptoms of esophageal cancer patients, improve the quality of life of esophageal cancer patients, improve physical strength, reduce the level of tumor markers, and improve the remission rate of lesions to a certain extent, but has no obvious effect on alleviating toxic side effects, suggesting that the combination of TCM systemic differentiation and local disease differentiation therapy with Western medicine treatment can further benefit patients. However, this study also has limitations, on the one hand, the sample size is relatively small, and only a single symptom type is studied; On the other hand, this study did not conduct long-term follow-up and observation of indicators such as overall survival and progression-free survival, so it needs to be further verified by multi-center, large-sample randomized trials.
There is no conflict of interest in this article.
Bibliography
Source: LI Jilei, LI Honglin, XU Yanchao, et al. Clinical efficacy of antisputum and stasis tong granules combined with channel opening pills in the treatment of esophageal cancer[J]. Chinese Journal of General Practice, 2023, 26(30): 3759-3764. DOI: 10.12114/j.issn.1007-9572.2023.0185.