Deng Ping (鄧 平)

Department of General Surgery, Cili County People's Hospital, Cili 100700, China

ABSTRACT OBJECTIVE: To investigate the effects of Bazhen Pills on quality of life and immune function of patients undergoing chemotherapy after gallbladder cancer surgery. METHODS: A total of 64 patients with gallbladder cancer treated by surgery and postoperative basic nutritional support and symptomatic treatment in our hospital were selected and randomly divided into the control group and the observation group, with 32 cases in each group.The control group was treated with chemotherapy from 4th to 6th week after surgery. The observation group was treated by Bazhen Pills on the basis of the treatment in the control group. The blood cell count, immune function,TCM symptom scores, KPS scores, quality of life and adverse reactions were compared between the 2 groups.RESULTS: The WBC and PLT in 2 groups were decreased after the treatment, and the data in the observation group were higher than that in the control group (P ＜ 0.05). The levels of CD3+, CD4+ and CD8+ in the 2 groups were increased after the treatment (P ＜ 0.05), and the data in the observation group were higher than that in the control group (P ＜ 0.05). TCM syndrome scores of the 2 groups were decreased after the treatment (P ＜ 0.05),and the KPS scores were increased after the treatment (P ＜ 0.05). The improvement degrees of the 2 scores in the observation group were higher than that of the control group (P ＜ 0.05). The fatigue symptom scores of the 2 groups were decreased while scores of physical function, role function and overall health were increased after the treatment(P ＜ 0.05). The scores of the observation group were better than those of the control group (P ＜ 0.05). The total incidence of grade I-II hematological toxicity and grade I-II gastrointestinal reactions in the observation group was lower than that in the control group (21.88% vs 50.00%) (P ＜ 0.05). CONCLUSION: Bazhen Pills can effectively relieve clinical symptoms of patients undergoing chemotherapy after gallbladder cancer surgery, and improve their immune function and quality of life, with safety.

KEYWORDS: Bazhen Pills; Gallbladder cancer; Chemotherapy; Immune function; Quality of life

Gallbladder cancer is a malignant tumor of the gallbladder, accounting for about 80% to 95% of biliary malignancies, and more women than men[1]. There are no obvious symptoms in the early stage of the disease.Some patients have mild gastrointestinal reactions and are easily misdiagnosed as gastritis and cholecystitis.With the development of the tumor, the patient will have liver enlargement and liver occupying which indicates the middle and late stage of the cancer. Surgical resection is the preferred method for clinical treatment of gallbladder cancer. In addition, chemotherapy is needed to inhibit the continued development of cancer to a certain extent, but it is easy to cause various complications, such as hemocyte reduction and immune dysfunction, which will reduce the quality of life of patients[2,3]. Therefore, relevant measures are required to reduce the adverse reactions caused by surgery and chemotherapy. Bazhen Pills comes from Zhengti Leiyao, which is a Chinese medicine prescription.It has the effects of replenishing qi and nourishing blood[4]. The author used it for patients with postoperative chemotherapy of gallbladder cancer and obtained good curative effects.

MATERIALS AND METHODS

General materials

A total of 64 patients with gallbladder cancer admitted to our hospital from July 2015 to January 2018 treated by surgery were selected. The inclusion criteria: ① they were diagnosed as gallbladder carcinoma by pathological biopsy; ② age70 years old; ③ estimated survival time ＞ 6 months; ④ ECOG score2; ⑤ in line with surgical indications;⑥ patients and their families were informed consent. Exclusion criteria: ① combined with severe dysfunction of heart, liver and kidney; ② multiple metastasis of tumor; ③ lesions showed obvious signs of invasion and perforation; ④ combined with mental system diseases, cognitive impairment;⑤ unwilling to participate in the study. Patients with serious complications due to surgery or with a sharp deterioration in the course of treatment were excluded.The 64 patients were randomly divided into the control group (n = 32) and the observation group (n = 32).The general data of the 2 groups were not significantly different (P ＞ 0.05), which was comparable (See Table 1).

Methods

Patients in the 2 groups were all underwent cholecystectomy, and basic nutritional support as well as symptomatic treatment was given after surgery. Patients in the control group started chemotherapy at 4thto 6thweek after the surgery. The chemotherapy regimen was as follows: an amount of 400-600 mg/m25-fluorouracil(5-FU) by intravenous drip and 60 mg/m2doxorubicin(ADM) by intravenous injection on the 1stday, an amount of 200-400 mg/m25-FU by intravenous drip on the 4thand 26thday, an amount of 400-600 mg/m25-FU by intravenous drip and 45mg/m2ADM by intravenous injection on the 22ndday. An amount of 150 mg/m2Carmustine(Tianjin Jinyao Amino Acid Co., Ltd., SFDA:H12020992, 2g: 125mg) was given by intravenous drip. All patients were given tropisetron hydrochloride(Hangzhou Minsheng Pharmaceutical Co., Ltd., SFDA:H20052664, 5ml: 5mg) to arrest vomiting before chemotherapy. A course of chemotherapy was of 4 weeks, with 2 courses in total. The observation group was given Bazhen Pills (Lanzhou Foci Pharmaceutical Co., Ltd., SFDA: Z62020591, 20g/bag) on the basis of the treatment of chemotherapy in the control group.Bazhen Pills consists of Radix Codonopsis, Rhizoma Ligustici Chuanxiong, Radix Angelicae Sinensis, fried Rhizoma Atractylodis Macrocephalae, Poria, Radix Rehmanniae Preparata, Radix Paeoniae Alba and Radix Glycyrrhizae. 1 bag per time, 2 times per day,taken 1 week before chemotherapy and 1 week after chemotherapy.

Observation index

Both groups of patients were tested for blood routine before and after the treatment, including white blood cell count (WBC) and platelet count (PLT).

The 2 groups of patients were tested for immunological function by immunofluorescence before and after the treatment, including the levels of CD3+,CD4+and CD8+.

According to the Guidelines for Clinical Research of New Drugs in Traditional Chinese Medicine, the 2 groups of patients were evaluated for TCM symptoms before and after the treatment, including nausea,vomiting, belching, pain, fatigue, constipation, thirst,etc. The grade 4 (0-3) was used to assess the severity of the symptoms. 0, 1, 2 and 3 respectively indicate no,mild, moderate, and severe. KPS scores were used to evaluate the patient's health condition.

The Chinese version of the Core Scale of Cancer Patients' Quality of Life (EORTCQLQ-C30) was used to assess the quality of life of the 2 groups before and after the treatment. The scale consists of 5 functional aspects (physical, cognitive, role, emotional and social functions), 3 symptoms (fatigue, pain, nausea and vomiting), overall health condition, and 6 single items (shortness of breath, insomnia, loss of appetite,constipation, diarrhea, and financial hardship), among which the higher the scores of functional aspects and overall health condition indicates the better the quality of life, the higher the score of symptom indicates the worse the quality of life.

Table 1. Comparison of the general materials of the 2 groups

Adverse reactions were classified according to acute and subacute criteria of drugs in WHO, including hematological toxicity (decreased white blood cell count, decreased platelet level, etc.), digestive tract reaction (abdominal distension, nausea, vomiting,gastrointestinal discomfort, abdominal pain and hiccup,etc.), fatigue, etc.

Statistical analysis

Data of the 2 groups of patients were analyzed by software SPSS19.0. The measurement data (x–±s)was tested by t value; the count data n (%) was tested by χ2value. P ＜ 0.05 was considered statistically significant.

RESULTS

Comparison of blood cell count of the 2 groups before and after treatment

There was no significant difference in WBC and PLT counts between the 2 groups before the treatment(P ＞ 0.05), while the WBC and PLT counts of the 2 groups were decreased after the treatment, and the decreasing degree in the observation group were higher than that of the control group. The difference was significant (P ＜ 0.05). See Table 2.

Comparison of immune index of the 2 groups before and after treatment

There were no significant differences in CD3+,CD4+, and CD8+between the 2 groups before the treatment (P ＞ 0.05), while the levels of CD3+,CD4+, and CD8+in 2 groups were increased after the treatment, and the improving degree in the observation group were significantly higher than that of the control group (P ＜ 0.05). See Table 3.

Comparison of TCM syndrome scores and KPS scores of the 2 groups before and after treatment

There was no significant difference between the 2 groups in TCM syndrome scores and KPS scores before the treatment (P ＞ 0.05), while the TCM syndrome scores in 2 groups were decreased and the KPS scores were increased after the treatment, and the improvement degree of TCM symptom scores and KPS scores in the observation group were significantly higher than that of the control group (P ＜ 0.05). See Table 4.

Comparison on scores of life quality of the 2 groups before and after the treatment

There was no significant difference in physicalfunction, role function, fatigue symptoms and overall health conditions between the 2 groups before the treatment (P ＞ 0.05). After the treatment, the fatigue symptom scores of 2 groups were decreased, and the scores of physical function, role function and overall health conditions were increased. The improvement degree in the observation group were significantly higher than those of the control group (P ＜ 0.05). See Table 5.

Table 2. Comparison of blood cell count of the 2 groups before and after the treatment

Table 3. Comparison of immune index of the 2 groups before and after the treatment (x–±s, %)

Table 4. Comparison of TCM syndrome scores and KPS scores of the 2 groups before and after the treatment (x–±s)

Table 5. Comparison on scores of life quality of the 2 groups before and after treatment (x–±s, score)

Comparison on adverse reactions of the 2 groups before and after treatment

Chemotherapy was successfully completed in both groups. 2 patients in the observation group developed grade I to II hematologic toxicity reaction, and 5 patients developed grade I to II gastrointestinal reactions with a total incidence rate of 21.88%. In the control group, 4 patients developed grade I to II hematological toxicity reaction, and 12 patients with grade I to II digestive tract reaction, the total incidence rate was 50.00%.There was no serious adverse reactions of grade III-IV occurred in the 2 groups, and the adverse reactions were significantly different (P ＜ 0.05).

DISCUSSION

The cause of gallbladder cancer is unclear for present. Due to the easily occurrence in the neck of the gallbladder that is easily hit by gallstone, and about 80% of patients have a long-term history of gallstones,it is considered that chronic stimulation of gallstones is an important factor in the development of gallbladder cancer[5,6]. The histological classification of gallbladder carcinoma showed that the adenocarcinoma occupies the highest proportion, followed by squamous cell carcinoma, with highly malignant degree and prone to metastasis with poor prognosis[7]. For now, surgery,radiotherapy and chemotherapy are the main methods to control the development of the disease and prolong patients' survival time. However, the moment the tumor cells have been removed or killed, different degrees of damage also been caused to normal cells and tissues, leading to serious adverse reactions in human body, and affecting the quality of life. After a large number of clinical practice and related literature review, the author found that traditional Chinese medicine as an adjuvant treatment of postoperative chemotherapy for gallbladder cancer can better reduce the incidence of adverse reactions and improve patients' quality of life.

Gallbladder cancer belongs to the category of hypochondriac pain and jaundice in traditional Chinese medicine. Its pathogenesis is the deficiency of vital qi and blood, plus external evils entering the body, and the joint actions caused cancer. Inner Canon of Yellow Emperor records that the fight of cold evil and defensive qi makes the qi away from home while the pathogens staying inside of the body,which causes the increasing of evil qi and furthering grows the polyp. After the surgical treatment, the patient's body functions are affected in many aspects,especially the loss of transportation in digestive tract, the related symptoms including the loss of appetite, tiredness and fatigue, sallow complexion,and deficiency of qi and blood[8]. Therefore, for postoperative chemotherapy patients with gallbladder cancer, treatment should focus on benefiting qi and replenishing blood, invigorating the spleen and benefiting the stomach. In Bazhen Pills prescription,Radix Codonopsis has a function of invigorating spleen-stomach and replenishing qi, Rhizoma Ligustici Chuanxiong and Radix Angelicae Sinensis can promote blood circulation for removing blood stasis as well as activating qi flowing and relieving pain. Fried Rhizoma Atractylodis Macrocephalae and Poria can invigorate the spleen and benefit vital energy as well as diuresis and remove dampness.Radix Rehmanniae Preparata has the effects of nourishing yin and tonifying blood, as well as benefiting the essence. Radix Paeoniae Alba can nourish blood and soften the liver as well as relieve the pain, and Radix Glycyrrhizae regulates the middle warmer and relieves the acute symptoms, recovers yang and blood flows, and harmonics all medicines.Modern pharmacological studies have confirmed that Radix Codonopsis can enhance immunity, expand blood vessels, improve microcirculation, enhance the body's hematopoietic function and the decline of WBC caused by chemotherapy[9]. Rhizoma Ligustici Chuanxiong has the effects of reducing vascular resistance, relaxing the arteries and increasing coronary flow[10]. Radix Angelicae Sinensis can improve the body's immune function and effectively replenish blood[11]. Poria contains active ingredients such as choline and Poria cocos mushroom polysaccharide, which can improve the activity of body tissues, activate T cells and Th cells, improve immune system function, and induce the production of WBC regulator[12]. Fried Rhizoma Atractylodis Macrocephalae has the function of regulating the spleen and the stomach, enhancing hematopoietic function and immunity. Radix Rehmanniae Preparata can increase the amount of peripheral WBC and enhance immune function[13].

Chemotherapy can damage the WBC, due to the decreasing of WBC and its bone marrow suppression, patients will experience different degrees of PLT reduction[14,15]. The results of this study showed that both groups of patients had lower WBC and PLT counts after the treatment, which also demonstrated the effects of chemotherapy on blood cells. The WBC and PLT counts in the observation group were higher than that of the control group,which indicating that Bazhen Pills can improve the blood cell count and improve the recovery of the patient. During the formation of gallbladder carcinoma, T lymphocyte proliferation is inhibited;immune regulation is disordered, which makes it more difficult to effectively kill tumor cells. As continuously development of the tumor, cancer cells will metastasize and spread, and leading to further exacerbation of immune imbalance[16]. This study showed that the CD3+, CD4+, and CD8+levels in the observation group were higher than that in the control group after the treatment, which indicating that Bazhen Pills can repair the damaged immune cytokines and improve the immune function of patients. After treatment, the TCM syndrome score of the observation group was lower than that of the control group, and the KPS score was higher than that of the control group, indicating that the addition of Bazhen Pills can alleviate the clinical symptoms of patients and improve the health of the body. The comparison on the quality of life of the 2 groups shows that the scores of fatigue symptoms in the observation group were lower than that in the control group. The scores of physical function, role function and overall health conditions were higher than those of the control group, indicating that Bazhen pills adjuvant therapy can effectively improve patients'quality of life. The total incidence of hematological toxicity and grade I to II digestive tract reaction in the observation group was lower than that in the control group, suggesting that Bazhen Pills has positive effects on reducing adverse reactions after the surgery and chemotherapy.

In summary, the treatment of patients with postoperative chemotherapy for gallbladder cancer by Bazhen Pills can reduce the clinical symptoms, improve the blood cell count and immune function, promote the recovery of body function,reduce adverse reactions, and improve patients' quality of life,which is worthy of clinical promotion.