Effect of Traditional Chinese Medicine Combined with Bladder Perfusion with Hydroxycamptothecin on Color Ultrasound and Clinical Efficacy in Patients with Bladder Cancer Surgery

Objective To observe the clinical effect of Xiaozheng Decoction combined with bladder perfusion with hydroxycamptothecin in the treatment of bladder cancer. Methods A total of 92 bladder cancer patients admitted to our hospital from January to December 2018 were selected and divided into an observation group and a control group according to the random number table method, with 46 cases in each group. The observation group was given Xiaozheng Decoction combined with bladder perfusion with hydroxycamptothecin, and the control group was given hydroxycamptothecin. The levels of serum-related factors (intercellular adhesion molecule-1 (ICAM-1), E-cadherin, cell adhesion molecules (CAM), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF)), white blood cell (WBC) level, immune function indexes, short-term total response rate, and incidence of adverse reactions were compared between the two groups before and after treatment. Results After 2 years of postoperative treatment, the levels of ICAM-1, E-cadherin, CAM-1, FGF, and VEGF (a, b, c) in both groups were improved compared with those before treatment and the observation group was better than the control group (p < 0.01). The number of WBCs was significantly higher than in the control group after Traditional Chinese Medicine (TCM) treatment. The observation group was better than the control group in increasing CD3+ and CD4+ levels and decreasing CD8+ level (p < 0.05), indicating that this prescription could improve the immune function of patients. The recurrence rate in the observation group was 6.52% after 2 years of treatment, lower than 17.39% in the control group. Color ultrasound parameters showed that there were no statistically significant differences in arrive time (AT) and time to peak (TTP) between patients with and without recurrence and peak intensity (PI) and washout time (WT) were higher in patients with recurrence than in patients without recurrence (p < 0.01). The incidence of adverse reactions was significantly lower than that of the control group (p < 0.01). Conclusion The clinical effect of Xiaozheng Decoction combined with hydroxycamptothecin on the treatment of bladder cancer was clear and superior to that of hydroxycamptothecin, which could effectively improve the serological indicators of patients with a low incidence of adverse reactions and prolong the survival cycle of patients. Therefore, it is worthy of promotion and application.


Introduction
Bladder cancer is the most common tumor of the urinary system in China [1], and its morbidity and mortality have shown an increasing trend in recent years [2]. Currently, transurethral bladder tumor resection (TUR-BT) is the main treatment method for nonmuscular invasive bladder cancer [3,4]. e surgical technique is mature, and the trauma is small, but still 10%-67% of patients will relapse within 12 months. e recurrence rate is as high as 50%-70% [5][6][7][8][9]. erefore, it is urgent to explore a safe and effective treatment to prevent postoperative recurrence of bladder cancer, which is an urgent topic in this field.
At present, bladder infusion of chemotherapy drugs is still the most commonly used method to prevent postoperative recurrence of TUR-BT [10][11][12].
ere are many chemotherapeutic drugs in bladder infusion, including Bacillus Calmette-Guerin (BCG) vaccine, mitomycin, and hydroxycamptothecin [13,14]. e recurrence rate of bladder cancer treated with BCG and mitomycin was 24.24% and 27.27%, respectively [9]. However, long-term chemotherapeutic drugs often cause chemical cystitis, bone marrow suppression, bladder contracture, and other complications [15]. erefore, there is an urgent need for a safe and effective treatment to prevent postoperative recurrence of bladder cancer.
Any chemotherapy drugs will inevitably cause adverse reactions such as frequent urination, urgent urination, gross hematuria, low fever, and loss of appetite. Traditional Chinese Medicine (TCM) has the effect of reducing toxicity and increasing efficiency, reducing the toxic and side effects of chemotherapy drugs, improving the quality of life of patients, and playing an increasingly important role in the treatment of bladder cancer [16,17]. TCM believes that the pathogenesis of postoperative recurrence of bladder cancer is always characterized by the deficiency of essential qi and the interaction of dampness and toxin [18,19]. erefore, it is suggested that supplementing qi, invigorating dampness, and detoxifying are the basic treatment methods for postoperative recurrence of bladder cancer. On this basis, Xiaozheng Decoction was used to treat postoperative recurrence of bladder cancer.
Color ultrasound examination can be used for early screening of patients with bladder cancer and follow-up observation of patients with bladder cancer. Color ultrasound examination of the urinary system has been widely used in clinical practice because of its advantages of safety, efficiency, noninvasiveness, and low cost. Color ultrasound examination of the bladder can be done by transabdominal ultrasound and transrectal ultrasound. Because of its simple and effective characteristics, it has become an important detection method for bladder cancer after surgery and can accurately determine the recurrence of postoperative tumor, which has an important reference value for the postoperative examination and diagnosis of bladder cancer.
is study was aimed to observe the clinical effect of Xiaozheng Decoction combined with bladder perfusion with hydroxycamptothecin in the treatment of bladder cancer, and results showed that the combination of hydroxycamptothecin and Xiaozheng Decoction could significantly reduce the incidence of side effects such as frequency of urination, urgency of urination, and nausea after bladder perfusion, and improve the quality of life of the patients.

Inclusion and Exclusion Criteria. (1) Inclusion Criteria.
(1) Patients in this study were clearly diagnosed with bladder cancer. (2) All patients underwent TUR-BT. (3) Patients have normal heart, lung, liver, and kidney functions. (4) ey participated voluntarily and signed informed consent forms.

Control Group (Hydroxycamptothecin Bladder Infusion
Group). Hydroxycamptothecin injection (Shenzhen Wanle Pharmaceutical Co., Ltd., approval no. 20043063) was used as a recurrence prevention infusion drug. 40 mL of normal saline was added into 40 mg of hydroxycamptothecin and injected into the bladder by catheterization. e hydroxycamptothecin was placed in the left, right, supine, and prone positions for 30 minutes each and retained for 2 hours in total. e course of treatment is as follows: once a week, a total of 8 times, and once a month thereafter, up to 2 years after surgery.

Observation Group (Chinese Medicine Xiaozheng Decoction Combined with the Bladder Perfusion Group).
On the basis of the bladder infusion of hydroxycamptothecin, Chinese Medicine Xiaozheng Decoction was added: Huijiaren 30 g, Astragalus membranaceus 20 g, Huang Jing 15 g, Hedyotis wilsa 15 g, Zhu Ling 15 g, Zedoary zedoary 9 g, and Tubei 9 g. Chinese medicine decoction is 1 dose per day, and the course of treatment was 2 years after surgery. Evidence-Based Complementary and Alternative Medicine

Ultrasound Examination.
Philip-iu22 color ultrasonic diagnostic instrument with probe frequency of 3.5 MHz was applied. Before the examination, the patient was properly filled with the bladder, and the supine position was routinely taken, or the side decubitus position or the knee bend decubitus chest position was taken if necessary, fully exposing the lower abdomen to the symphysis pubis. e probe was carried out through multisection and multiangle scanning in the bladder region, and the lesions were carefully observed. Two-dimensional ultrasound was used to observe tumor location, morphology, size, and tumor diameter (maximum diameter and minimum diameter). During the examination, the interference of the artifact in the bladder should be avoided as far as possible, and the same patient was examined by the same physician before and after chemotherapy. e examination results were compared and analyzed and then compared with the postoperative pathological results.

Serum-Related Factors.
e levels of serum-related factors (ICAM-1, E-cadherin, CAM, FGF, and VEGF) in the two groups were compared before and after treatment.

VEGF Levels.
Serum VEGF levels were detected by enzyme-linked immunosorbent assay (ELISA) before and 12 months after treatment.

Indicators of Immune Function.
e levels of CD3+, CD4+, CD8+, CD4+/CD8+, and NK were detected by flow cytometry before treatment and 12 months after treatment. Before and after treatment, 5 mL of fasting venous blood was taken from the patients and placed on the automatic blood centrifugation machine in our hospital for centrifugation. e speed of centrifugation was adjusted to 3000 r/min for 10 min. e supernatant was taken and placed in a refrigerator at −20°C for examination. e relative indexes of T lymphocyte subsets in serum were detected by flow cytometry. T lymphocyte subsets (CD3+, CD4+, CD8+) and NK levels were detected by Beckman Coulter EpicsXL flow cytometry, and CD4+/CD8+ was calculated.

Follow-Up Recurrence Rate.
e recurrence cases were recorded at 6, 12, 18, and 24 months after the operation, and the percentage was calculated. Reexamination was performed by color ultrasound.

Incidence of Adverse Reactions.
A number of adverse reactions such as nausea and vomiting, frequent urination, urgent urination, abnormal urine routine, hematuria, and low fever were recorded during the treatment period, and the percentage was calculated.

Statistical
Methods. Independent repetitions of experiments were 3 times. SPSS 20.0 software (IBM, NY, USA) was used for statistical analysis of the data. e measurement data were expressed as x ± s, and t-test was used for comparison between groups. Count data were expressed as frequency/rate (%), and χ2 test was used for comparison between groups. p < 0.05 was considered statistically significant.

Color Ultrasound Image of a Patient with Preoperative Bladder Cancer.
e staging of bladder tumors was based on the TNM staging method (6 th edition, 2002) of the International Union against Cancer: Stage Ta: noninvasive, superficial tumor; T1: tumor invasion into subepithelial connective tissue; Stage T2a: tumor invasion of the superficial muscle layer; Stage T2b: tumor invasion of deep muscle layer; and >Stage T2: tumor invasion of the peribladder tissue. Imaging features of bladder tumor stage were determined by 3D-CEUS: Ta stage: the bladder wall at the base of the tumor was clear, and the angiography showed continuous and bright lines of the bladder wall; T1: the contrast agent perfusion was slightly stronger in the mucosa layer of the bladder wall than in the muscle layer. T2a stage: <1/2 bladder wall and tumor contrast agent perfusion synchronous, consistent degree of enhancement; T2b stage: >1/2 bladder wall and tumor contrast agent perfusion synchronous, consistent degree of enhancement; and >Stage T2: full bladder wall or surrounding tissue perfusion time, intensity, and characteristics of bladder tumor.
Among the 46 cases of bladder cancer in the control group, 27 tumors were located in the trigone, 18 cases were located in the lateral wall, and 1 case was located at the top. Among the 46 cases of bladder cancer in the observation group, 28 cases were located in the trigone region, 17 cases were located in the lateral wall, and 1 case was located at the top. e characteristics of two-dimensional ultrasonography of patients in both groups were improved after surgery.

Short-Term Efficacy Evaluation.
According to the Guideline for the evaluation of TCM Clinical Efficacy in bladder cancer [20], TCM curative effect of bladder cancer was defined as clinical benefit, which was divided into obvious benefit, benefit, and no benefit. A significant benefit is as follows: effective or stable tumor evaluation + significant effect of symptom evaluation + effective or stable quality of life evaluation + effective or stable body weight evaluation. Benefits are as follows: stable tumor evaluation + effective symptom evaluation + effective or stable quality of life evaluation. No benefit is as follows: those who do not meet the above targets. All patients observed in this study were Evidence-Based Complementary and Alternative Medicine post-TUR-BT patients, so tumor evaluation was not used as the criteria for clinical efficacy.
After 2 years of postoperative treatment, the total effective rate in the observation group was 91.30%, which was higher than 67.39% in the control group (p < 0.05), as shown in Table 1.

Comparison of Serum-Related Factor Levels.
Before treatment, there was no significant difference in the levels of ICAM-1, E-cadherin, CAM-1, FGF, VEGF (a, b, c) between the two groups (p < 0.05). After 5 courses of treatment, the levels of ICAM-1, E-cadherin, CAM-1, FGF, and VEGF (a, b, c) in both groups were improved compared with before treatment, and the observation group was better than the control group (p < 0.01), as shown in Table 2. Table 3 shows 11 (23.91%) patients with leukocyte suppression in the observation group and 27 (58.70%) patients in the control group.

Changes in White Blood Cell Values.
e observation group has significantly better efficacy than the control group.
According to Figure 1, there was no significant difference between the two groups before treatment (p > 0.05), and the internal comparison between the two groups after treatment was statistically significant (p < 0.05). ere were still significant differences between the two groups after treatment (p < 0.05), indicating that the number of WBC in the observation group after treatment was significantly higher than that in the control group.

Comparison of Immune Function Indexes between the Two Groups before and after Treatment.
e level of CD4+/CD8+ in the control group was significantly increased after treatment (p < 0.05). CD3+ and CD4+ levels were higher (p < 0.05) and CD8+ level were lower than those before treatment (p < 0.05). CD3+, CD4+, and CD4+/CD8+ levels and NK level in the observation group were significantly increased after treatment (p < 0.05). CD8+ level were significantly decreased (p < 0.05). After treatment, the increase of CD4+/CD8+ level in the observation group was significantly better than that in the control group (p < 0.05). After treatment, the observation group was superior to the control group in increasing the levels of CD3+, CD4+, and NK and decreasing CD8+ level (p < 0.05), as shown in Figure 2, suggesting that this formula can improve the immune function of patients.

Comparison of Serum VEGF Levels between the Two Groups before and after Treatment.
ere was no significant difference in serum VEGF levels between the two groups before treatment (p > 0.05). After three months of treatment, there was no significant difference in serum VEGF levels between the two groups (p > 0.05). After six and twelve months of treatment, VEGF levels in both groups were significantly decreased, and VEGF levels in the observation group and control group were significantly decreased after treatment (p < 0.05). Compared with the two groups after treatment, the observation group was superior to the control group in reducing VEGF level (p < 0.05), as shown in Table 4.

Recurrence Rate.
All patients in this study were treated with perfusion and followed up for 24 months. Specific results: the recurrence rates of bladder tumors in the observation group were 23.91%, 17.39%, 10.86%, and 6.52% at 0.5, 1, 1.5, and 2 years, respectively, while those in the control group were 28.26%, 26.09%, 23.91%, and 17.39% at 0.5, 1, 1.5, and 2 years, respectively. e recurrence rate of bladder tumor in the observation group was 4.35%, 8.70%, 13.05%, and 10.87% lower than that in the control group, respectively. After statistical treatment, there was no significant difference in recurrence rate between the two groups at 0.5 years and 1 year (p > 0.05). e recurrence rate in the observation group was significantly lower than that of the control group at 1.5 and 2 years (p < 0.05). In conclusion, compared with the control group, the effect of the observation group on reducing the recurrence rate of bladder tumor was increasingly obvious over time, as shown in Figure 3.

Comparison of Parameters of Contrast-Enhanced Ultrasound in Bladder Cancer Patients with and without Recurrence at Two Years.
In the observation group, 3 of the 46 patients were positive by ultrasonography, the maximum tumor size was 0.9 cm × 0.5 cm, and the minimum tumor size was 0.6 cm × 0.4 cm. e tumor was broad base, papillary, triangular, mound, or corrugated protruding into the bladder with regular or irregular protruding edges. ere was no boundary or fuzzy boundary between the base edge and the bladder wall, and the internal echo was uneven low, equal, or slightly strong. e bladder wall in the tumor area had thickening, stiffness, or no hierarchical sonographic changes. e recurrence of bladder cancer was confirmed by surgical pathology.
In the observation group, preoperative ceUS showed rapid filling of contrast agent in arterial phase in the mass, with arrival time earlier than the bladder wall, prostate, or cervix, and the intensity of contrast agent filling was higher than the bladder wall, prostate, or cervix. In the delayed stage, the internal mass was gradually cleared of contrast media. ere was no significant difference in AT and TTP between recurrent and nonrecurrent patients (p > 0.05). PI and WT in recurrent patients were higher than those in nonrecurrent patients, and the differences were statistically significant (p < 0.05), as shown in Table 5. In patients with recurrence, 66.7% (2/3) showed fast forward and slow regression in contrast enhancement mode, and 33.3% (1/3) showed fast forward and slow regression in pathological grading. Among the patients without recurrence, 86.0% (37/ 43) showed fast forward and fast regression in contrast enhancement mode, and 14.0% (6/43) showed fast forward and slow regression in pathological grading.

Adverse Reactions.
In the control group, 31 cases had frequent urination, 28 cases had nausea or loss of appetite, and 22 cases had abnormal urine routine. In the observation group, 12 cases of frequent urination, 11 cases of nausea or anorexia, and 11 cases of abnormal urine routine, Chinese medicine combined with hydroxycamptothecin can significantly reduce the incidence of frequent urination, urgent urination, nausea, and abnormal urine routine after bladder perfusion, and the difference was significant (p < 0.05). Meanwhile, there were 20 cases of low fever in the control group, 12 cases of low fever in the observation group, 16 cases of hematuria in the control group, and 11 cases of hematuria in the observation group. ere was no significant difference between the two groups (p > 0.05). No other adverse reactions such as myelosuppression were found during the treatment (Figure 4).

Discussion
Bladder cancer is one of the most common solid tumors in the genitourinary system and the second most common malignant tumor in the genitourinary system, with more than 400,000 new cases occurring every year [21]. At present, more than 2 million people in China suffer from bladder      Evidence-Based Complementary and Alternative Medicine cancer [22]. ere were 430,000 new cases of bladder cancer in 2012, making it the ninth most common cancer worldwide. In recent decades, there has been little success in reducing the incidence of bladder cancer for many reasons [23]. Bladder cancer has a high postoperative recurrence rate due to being multifocal, implantable, and urinary-derived [24]. 50%∼70% of patients have recurrence after bladdersparing surgical treatment, and 20%∼30% of superficial bladder cancer develops into invasive or metastatic cancer after surgery, with poor long-term efficacy [25,26]. All bladder cancer patients who underwent bladder preservation had a higher risk of recurrence. erefore, postoperative local perfusion chemotherapy should be performed to kill the remaining tumor cells as much as possible, prevent tumor progression, reduce the probability of recurrence, and delay recurrence. At present, although there are many chemotherapeutic drugs available for postoperative bladder infusion chemotherapy, about 30% of patients still have a recurrence.
Previous studies have found that hydroxycamptothecin is basically not absorbed by the bladder mucosa. It inhibits DNA replication, transcription, and mitosis by acting on DNA topoisomerase I and has an inhibitory effect on the development of tumors [27,28]. e adverse reactions are relatively small, and the patient's recurrence rate is low, which is better than the preventive effect of mitomycin and BCG. In our hospital, hydroxycamptothecin has been used for adjuvant chemotherapy after bladder preservation in patients with bladder cancer, and good efficacy has been achieved for many years. However, because most patients are older at the onset of the disease, and the body constitution is in the decline stage, and the return of surgical treatment, the body's resistance is significantly reduced, and it can also be seen in the clinic that the patient has severely reduced white blood cells and decreased body immunity due to myelosuppressive reaction after perfusion, resulting in severe infections and a poor prognosis for the patient.
TCM can enhance the curative effect of chemotherapy drugs and the immune function of the body.
is study explored the effect of hydroxycamptothecin bladder perfusion (control group) and Xiaozheng Decoction combined with hydroxycamptothecin bladder perfusion (observation    group) to prevent bladder cancer recurrence after surgery. e recurrence rates at 1.5 years and 2 years after surgery were lower than those in the control group (p < 0.05), and with the passage of time, the recurrence rate of patients in the observation group gradually decreased.
Long-time bladder perfusion chemotherapy can cause different degrees of adverse reactions. is study showed that the adverse reactions in the treatment of the two groups were mainly manifested as anorexia, nausea and vomiting, hematuria, low fever, frequent urination and urgent urination, and abnormal urine routine. Pharmacological experiments showed that Xiaozheng Decoction can inhibit tumor formation, enhance immunity, and reduce adverse reactions caused by chemotherapy drugs. is present study indicated that Xiaozheng Decoction combined with hydroxycamptothecin bladder infusion can reduce the incidence of anorexia, nausea and vomiting, frequent and urgent urination, and abnormal urine routine and improve the quality of life of patients to a certain extent. VEGF is highly specific and can induce the proliferation of vascular endothelial cells and promote the angiogenesis of tumor cells, which plays an important role in the occurrence and development of bladder tumor and has a certain relationship with tumor recurrence [29,30]. erefore, the detection of VEGF level can be used to determine the status of tumor metastasis and treatment effect. In this present study, that the levels of VEGF in the two groups showed a downward trend after treatment. At 6 and 12 months after treatment, the VEGF levels in the observation group were lower than those in the control group (p < 0.05). ese results indicated that the combination of Chinese and Western drugs can reduce the level of VEGF in postoperative patients with bladder cancer, which is beneficial to reducing the recurrence and metastasis of tumor. e application of chemotherapeutic drugs is often accompanied by serious gastrointestinal reactions, bone marrow suppression, nerve damage, and other toxic and side effects, and many patients often end treatment halfway because they cannot tolerate the toxic and side effects of chemotherapy [31]. e results of this study showed that the white blood cells count in the observation group was significantly higher than that of the control group after TCM treatment. In addition, the observation group was superior to the control group in increasing the levels of CD3+, CD4+, and NK and decreasing the level of CD8+ (p < 0.05), indicating that this prescription could improve the immune function of patients.
ese results suggested that TCM combined with hydroxycamptothecin infusion in the treatment of bladder cancer had a significant protective effect on white blood cells, which was worthy of popularization and application.

Conclusion
In conclusion, Xiaozheng Decoction combined with hydroxycamptothecin bladder perfusion can significantly reduce the recurrence rate after TUR-BT; reduce the incidence of frequent urination, urgency, nausea, and abnormal urine routine after bladder perfusion; and improve the quality of life of patients. erefore, the combination of TCM and Western medicine treatment can improve the clinical efficacy and alleviate the suffering of patients, which is worthy of clinical promotion. However, the mechanism of Xiaozheng Decoction remains to be further studied.
Data Availability e datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request. Disclosure e funding body had no role in the design of the study, collection, analysis, interpretation of data, or writing of the manuscript.

Conflicts of Interest
e authors declare that they have no conflicts of interest.