Abstract
Objective: This study aimed to determine whether robot-assisted radical cystectomy (RARC) can accelerate recovery, improve pelvic lymph node dissection effects, and reduce serum tumor marker tumor specific growth factor (TSGF) levels in patients with bladder cancer. Methods: A total of 96 patients with bladder cancer admitted to our hospital were recruited as the research participants. Among them, 43 patients who adopted radical cystectomy were enrolled in the control group (CG), and 53 patients treated with RARC were included in the research group (RG). The operation time, intraoperative blood loss, postoperative bowel recovery time, gastrointestinal function recovery, complication rate, clinical efficacy, changes of TSGF levels before and after operation, postoperative satisfaction and quality of life were observed. Results: Compared with the CG, patients in the RG experienced longer operation times (P<0.05), less intraoperative blood loss (P<0.05), and faster time to bowel recovery, anal exhaust, and anal defecation (P<0.05); moreover, the RG had a lower incidence rate of complications (P=0.025) and TSGF levels (P<0.05), higher effective cure rate (P=0.023) and satisfaction degree (P=0.048), as well as superior quality of life scores in six dimensions (P<0.05). Conclusion: The application of RARC can accelerate the recovery of patients with bladder cancer, improve the pelvic lymph node dissection effects, and reduce the serum levels of tumor marker TSGF.
Keywords: Robot-assisted radical cystectomy, bladder cancer, effect of pelvic lymph node dissection
Introduction
Bladder cancer is a malignancy originating from the bladder, which is associated with substantial morbidity, mortality and cost, and is one of the most prevalent cancers worldwide [1]. According to statistics from the World Health Organization, in 2016, there were 770,000 new cases of bladder cancer, and its high prevalence and tendency to recur and relapse has brought a massive burden on health services, as well as a serious threat to patients’ lives [2,3]. Previous data show that carcinogens such as tobacco and environmental or occupational exposure are major risk factors for bladder cancer [4]. The disease can occur at any age, mostly above 50 years of age, and the incidence tends to increase with age [5]. Asymptomatic hematuria is its most common clinical manifestation, and there may also be symptoms such as urinary frequency, urinary urgency, urinary pain and difficulty in urination [6]. Most patients are diagnosed with non-muscle invasive bladder cancer (NMIBC), and transurethral resection of the bladder tumor is the first stage of treatment after diagnosis [7], while radical cystectomy is indicated when NMIBC progresses to high risk or locally advanced stages [8]. Recently, increasing studies have pointed out that although radical cystectomy is effective in treating early-stage patients, it is a complex and invasive procedure that increases the risk of postoperative complications, which seriously affects the prognosis of patient survival [9]. In the meanwhile, clinical research and improvement of surgical skills for bladder cancer have kept pace with the continuous advances in medicine.
Although open surgery remains the most frequently used surgical method, the application of robot-assisted radical cystectomy (RARC) has gained acceptance in patients with bladder cancer in recent years [10]. With the development of Da Vinci robot-assisted Surgical System and surgical techniques, a growing number of urologists are embarking on an in-depth study of RARC [11]. For example, the team of Bochner BH revealed that RARC can effectively improve the perioperative curative effect [12]. Also that RARC has more obvious advantages in treating patients with complicated conditions [13]. However, a large number of studies focus on the success rate of surgery and the long-term survival of patients, while ignoring the recovery of patients’ physical function and the changes of tumor markers. Tumor specific growth factor (TSGF), a peptide produced by tumor cells that is closely related to cell growth, infiltration and metastasis, is also a product of the massive expansion of malignant tumors and surrounding blood vessels [14]. It can be released into the blood at the early stage of malignant transformation, and can be detected at the early stage of malignant tumor formation. Hence, TSGF is not only a specific marker for malignant tumors, but also of great clinical value in the early diagnosis of tumors [15]. Therefore, this time, the effects of RARC on recovery, pelvic lymph node dissection, and serum tumor marker TSGF levels were explored, so as to provide a reliable theoretical basis to optimize surgery and increase patient acceptance.
Methods
Patient data
A total of 96 patients with bladder cancer admitted to the Hainan Provincial people’s Hospital from May 2016 to June 2019 were recruited as research participants for prospective analysis. Among them, 43 patients who adopted radical cystectomy were enrolled in the control group (CG), and 53 patients treated with RARC were included in the research group (RG). This study was approved by the Ethics Committee of the Hainan Provincial people’s Hospital, and all patients and their family members were informed and signed the inform consent.
Inclusion and exclusion criteria
The patients included were diagnosed with bladder cancer by cystoscopy, urine and imaging, and received treatment in our hospital, and all of them showed clinical symptoms for the first time, with complete data and high compliance. If patients had serious disorders of heart, lung, liver or kidney function, extreme physical weakness, surgical intolerance, mental disorders, communication disorders or immunodeficiency they were excluded.
Methods
CG: preoperative anesthesia was performed after determining the patient’s posture, and a catheter was indwelled. Then, puncture was performed at 2 cm above the umbilicus of the patient, and the intraperitoneal pressure was maintained at 10-15 mmHg. A laparoscope was placed, and dissection and cystectomy were performed. The ileum was taken as the efferent loops, and the ureteral-ileum anastomosis was performed to form a catheter, which was then fixed. Patients were given routine medication guidance after the operation.
RG: The patient was placed in a satisfactory position for general anesthesia, and a four-arm Da Vinci robot-assisted Surgical System was applied. (1) Establishment of channels: the patient was placed in a Trendelenburg position at 20-30°. After the robot was locked, monopolar electrocoagulation curved scissors and bipolar electrocoagulation forceps were connected to arms 1 and 2, respectively. The first incision was made at the superior margin of the umbilicus, and a 12 mm trocar was placed as the camera lens hole. The pneumoperitoneum pressure was maintained at 12-15 mmHg (1 mmHg =0.133 kPa). The other five operating channels were established under direct vision: the second and third holes were made 2 cm below the umbilicus and the lateral margins of the right and left rectus abdominis muscles, respectively, for the 8 mm channels of the robotic arms 1 and 2; the 12 mm trocar was placed 4 cm below the left costal margin as the first auxiliary hole, and the 5 mm trocar was placed above the left anterior superior iliac spine as the second auxiliary hole; the 12 mm trocar was placed above the right anterior superior iliac spine as the alternate auxiliary hole. (2) Ligation of bilateral ureters: the posterior peritoneum was opened above the iliac vessels, and the bilaterally ureters were first freed to the inner segment of the bladder wall, and then cut off with Hem-o-lok clamping. (3) Dissection of the lateral bladder ligaments: the ligaments were separated downward along the internal iliac vessels to the pelvic floor, and laterally along the medial umbilical ligaments to the pelvic floor, and then the lateral umbilical ligaments and the superior arterial vein of the bladder were ligated in turn with Hem-o-lock. (4) Separation and opening of Denonvillier’s fascia: the peritoneum of the posterior wall of urinary bladder was opened to separate the vas deferens and seminal vesicles. The Denonvillier’s fascia was opened along the seminal vesicles and vas deferens downward, and separated downward to the tip of the prostate. (5) Free of anterior wall of urinary bladder and dissection of prostate ligament: the anterior wall of urinary bladder was lifted to separate the loose tissue of prevesical space. The pelvic fascia was opened to expose the pubic prostatic ligament and severed. The lateral ligaments of the prostate were freed by lifting the seminal vesicles and then dissected by LigaSure electrocoagulation in turn. (6) Dissection of the urethra and resection of the specimen: the penile deep dorsal vein complex was dissected after LigaSure electrocoagulation, the urethra was dissected after Hem-o-lok clamping of the urethra, and the specimen was completely resected. (7) Pelvic lymph node dissection: the external iliac artery, vein, obturator nerve and lymph nodes of internal iliac artery were successively dissected at the iliac vessel bifurcation, and the obturator nerve was carefully protected. (8) Urinary diversion: ureterocutaneous anastomosis was performed [16].
Outcome measures
The operation time, intraoperative blood loss, postoperative bowel recovery time, gastrointestinal function recovery and complication rate of two groups of patients were observed, as well as the clinical efficacy. The clinical efficacy was assessed as follows: complete response: patients with clear urine color, no visible hematuria, and urine routine showing red blood cells (-) or (+), and their clinical symptoms and lesions completely disappeared and maintained for more than 4 weeks. Partial response: patients with significantly reduced hematuria, no visible hematuria, routine urine tests showing red blood cells (++) or (++++), and their tumor lesion reduced (the sum of the longest diameter reduced ≥30%) and maintained for more than 4 weeks. Stable disease: patients with no significant change in hematuria, and the sum of the longest diameter was reduced less than 30%. Progressive disease: the increase of the sum of the longest diameters of tumors ≥10%. The effective cure rate = (complete response + partial response) cases/total number of cases ×100%. The levels of tumor marker TSGF before and after operation, postoperative satisfaction were recorded, and the quality of life scores were calculated (the higher the score, the higher the quality of life).
Statistical analysis
All results were recorded as (mean ± standard deviation) and were statistically analyzed by SPSS 22.0 software. Comparison between groups was performed with t test. Comparison among multiple groups was done by one-way analysis of variance and LSD post-hoc test. P<0.05 was considered as statistically significant.
Results
Clinical data
The two groups of patients were compared in terms of general information of age, body mass index (BMI), gender, course of disease, smoking history, hypertension history, obesity, living environment, and ethnicity, and the results showed no statistical difference (P>0.05) (Table 1).
Table 1.
Comparison of general data
| Research group (n=53) | Control group (n=43) | χ2 or t/p | |
|---|---|---|---|
| Age (years) | 49.7±8.9 | 50.2±9.1 | 0.271/0.787 |
| BMI (KG/cm2) | 23.2±2.4 | 23.5±2.1 | 0.644/0.521 |
| Gender | 0.038/0.845 | ||
| Male | 31 (58.49%) | 26 (60.47%) | |
| Female | 22 (41.51%) | 17 (39.53%) | |
| Course of disease (year) | 1.1±0.5 | 1.2±0.6 | 0.891/0.375 |
| Smoking history | 0.089/0.766 | ||
| Present | 38 (71.70%) | 32 (74.42%) | |
| Absent | 15 (28.30%) | 11 (25.58%) | |
| Hypertension history | 0.151/0.698 | ||
| Present | 35 (66.04%) | 30 (69.77%) | |
| Absent | 18 (33.96%) | 13 (30.23%) | |
| Obesity | 0.058/0.809 | ||
| Present | 32 (60.38%) | 27 (62.79%) | |
| Absent | 21 (39.62%) | 16 (37.21%) | |
| Living environment | 0.084/0.772 | ||
| Town | 36 (67.92%) | 28 (65.12%) | |
| Countryside | 17 (32.08%) | 15 (34.88%) | |
| Ethnicity | 0.211/0.646 | ||
| Han | 45 (84.91%) | 35 (81.40%) | |
| Minority | 8 (15.09%) | 8 (18.60%) |
Operation time and intraoperative blood loss in the two groups
The statistical comparison of the operation time and intraoperative blood loss between the two groups revealed that patients in the RG experienced longer operation times (P<0.05, Figure 1A) and had less intraoperative blood loss than those in the CG (P<0.05, Figure 1B).
Figure 1.
Operation time and intraoperative blood loss in the two groups. A. Operation time of the two groups of patients. B. Intraoperative blood loss of the two groups of patients. Note: *denotes P<0.05.
Postoperative bowel recovery time and gastrointestinal function recovery
The comparison of postoperative bowel recovery time and gastrointestinal function recovery showed that patients in the RG experienced faster bowel recovery (P<0.05, Figure 2A), time of anal exhaust (P<0.05, Figure 2B), and anal defecation (P<0.05, Figure 2C) than those in the CG.
Figure 2.
Postoperative bowel recovery time and gastrointestinal function recovery. A. Bowel recovery time of the two groups of patients. B. Anal exhaust time of the two groups of patients. C. Anal defecation time of the two groups of patients. Note: *denotes P<0.05.
Postoperative complications in the two groups
Postoperative complications such as incision infection, intestinal obstruction, thrombosis, ileostomy ischemia, and catheter blockage were counted in both groups. The total incidence of postoperative complication was 5.66% in the RG, which was notably lower than that in the CG (20.93%), with a statistically significant difference (P=0.025) (Table 2).
Table 2.
Postoperative complications in the two groups
| Research group (n=53) | Control group (n=43) | χ2 | p | |
|---|---|---|---|---|
| Incision infection | 0 (0.00%) | 1 (2.33%) | ||
| Intestinal obstruction | 0 (0.00%) | 2 (4.65%) | ||
| Thrombosis | 1 (1.89%) | 2 (4.65%) | ||
| Ileostomy ischemia | 1 (1.89%) | 2 (4.65%) | ||
| Catheter blockage | 1 (1.89%) | 2 (4.65%) | ||
| Total incidence | 3 (5.66%) | 9 (20.93%) | 5.061 | 0.025* |
denotes P<0.05.
Comparison of clinical efficacy
The effective cure rate of patients in the RG was 86.79%, which was higher than that in the CG (67.44%) (P=0.023), as shown in Table 3.
Table 3.
Comparison of clinical efficacy between the two groups
| Research group (n=53) | Control group (n=43) | χ2 | p | |
|---|---|---|---|---|
| Complete response | 27 (50.94%) | 15 (34.88%) | ||
| Partial response | 19 (35.85%) | 14 (32.56%) | ||
| Stable disease | 3 (5.66%) | 6 (13.95%) | ||
| Progressive disease | 4 (7.55%) | 8 (18.60%) | ||
| Effective cure rate (%) | 86.79% | 67.44% | 5.201 | 0.023* |
denotes P<0.05.
Changes of tumor marker TSGF levels before and after operation in the two groups
We detected the levels of tumor marker TSGF in the two groups, and found no marked difference in TSGF level between the two groups before operation (P>0.05). After operation, TSGF level decreased significantly in both groups, and was lower in the RG than in the CG (P<0.05) (Figure 3).
Figure 3.
Changes of tumor marker TSGF levels before and after operation in the two groups. Note: *denotes P<0.05.
Comparison of postoperative satisfaction
The postoperative satisfaction of the two groups was counted. The total satisfaction was 94.34% in the RG, which was notably higher than that in the CG (81.40%) (P=0.048), as shown in Table 4.
Table 4.
Comparison of postoperative satisfaction
| Research group (n=53) | Control group (n=43) | χ2 | p | |
|---|---|---|---|---|
| Satisfied | 38 (71.70) | 19 (44.19) | ||
| Basically satisfied | 12 (22.64) | 16 (37.21) | ||
| Dissatisfied | 3 (5.66) | 8 (18.60) | ||
| Total satisfaction (%) | 50 (94.34) | 35 (81.40) | 3.921 | 0.048* |
denotes P<0.05.
Quality of life of the two groups
Postoperative quality of life of patients was assessed from the six dimensions of physiology, psychology, interpersonal relationship, social function, independence, and environmental impact. The RG exhibited higher scores in all aspects than the CG, with statistical differences (P<0.05), as shown in Figure 4.
Figure 4.
Quality of life of the two groups. A. Postoperative physiological scores of the two groups of patients. B. Postoperative psychological scores of the two groups of patients. C. Postoperative interpersonal relationship scores of the two groups of patients. D. Postoperative social function scores of the two groups of patients. E. Postoperative independence scores of the two groups of patients. F. Postoperative environmental impact scores of the two groups of patients. Note: *denotes P<0.05.
Discussion
Bladder cancer is the first and second most common urological malignancy in China and the United States, respectively [17]. It is characterized by painless hematuria, and its diagnosis is determined by urine cytology and transurethral resection of the bladder tumor [18]. Intravesical treatment was applied for carcinoma in situ and other non-muscular invasive tumors [19]. The standard treatment for muscle-invasive disease is radical cystectomy and several urinary diversion services [20]. With the popularization of minimally invasive techniques and the continuous advancement of medicine, robot-assisted laparoscopic techniques have gradually become increasingly popular in clinical practice [21]. This study, compared the value of RARC in patients with bladder cancer, and is of great significance for clinical practice.
The results of this experiment showed that patients in the RG who had RARC experienced longer operation time and less intraoperative blood loss than patients in the CG who received radical cystectomy, suggesting that RARC causes smaller incision and less bleeding, which can effectively reduce postoperative pain and accelerate wound healing. Operation time has always been an important indicator for surgeons [22]. However, it is worth noting that RARC requires a lot of instrument docking and position adjustment [23], which we speculate may also be an important factor affecting the duration. Previous studies have shown that the average operation time for radical cystectomy has been continuously shortened with the development of minimally invasive surgical techniques and the increase in the volume of robotic bladder cancer procedures [24]. The team of Tang JQ [25] showed that the operation time of RARC was within the acceptable range and did not cause poor prognosis of patients, which can prove our results. Then, the postoperative bowel recovery time and gastrointestinal function recovery of the two groups were statistically compared. Patients in the RG experienced faster recovery time of bowel, and shorter time of anal exhaust and defecation than those in the CG, indicating that RARC is effective in treating patients with bladder cancer, which reduces the amount of intraoperative blood loss, causes less damage to the patient’s body, and promotes the recovery of the patient’s bowel and other functions. It is also suggested that the gastrointestinal function of patients undergoing RARC recovers quickly after operation [26], which is similar to the results of this experiment. Furthermore, postoperative complications such as incision infection, intestinal obstruction, thrombosis, ileostomy ischemia and catheter blockage were statistically analyzed. The total incidence of complications in the RG was 5.66%, which was notably lower than that in the CG (20.93%), indicating that RARC can effectively reduce the incidence of adverse reactions and is of great significance to improve the clinical efficacy. We speculate that its value lies in the fact that the procedure takes advantage of the robotic system, its anatomical precision, its ability to maintain a sufficient length of urethral stump intraoperatively, and its reduced use of opioid analgesics during surgery [27], which reduces complications and accelerates patient recovery. Further, we found an effective cure rate of 86.79% in the RG, which was higher than that of CG (67.44%), suggesting that RARC has an extremely high application value for bladder cancer. Such results are also in line with the team of Hussein AA [28] on RARC in bladder cancer, which can support the results of this experiment. TSGF, a tumor-specific growth factor, is the result of the expansion of malignant tumor and its peripheral capillaries [29]. According to previous studies, TSGF, secreted by tumor tissues during vascular proliferation, will be released into the peripheral blood along with the formation and growth of tumors, resulting in increased serum levels, which has been therefore used as a tumor marker in clinical screening of tumor diseases [30]. In this experiment, there was no significant difference in the TSGF levels between the two groups before operation. After operation, TSGF level decreased notably in both groups, especially in the RG. This suggests that RARC can clean the tumor tissue thoroughly, which is beneficial to reduce the level of tumor marker TSGF, and has a positive effect on promoting patients’ self-confidence and increasing their satisfaction degree. We also counted the postoperative satisfaction of the two groups. The total satisfaction was 94.34% in the RG, which was notably higher than that in the CG (81.40%). Such results were consistent with the above, proving its application value. At the end of the study, the postoperative quality of life scores were compared from the six dimensions of physiology, psychology, interpersonal relationship, social function, independence, and environmental impact. The RG exhibited higher scores in all dimensions than the CG, indicating the obvious advantages of RARC in enhancing the surgical efficacy and prognosis.
There are many clinical treatments for bladder cancer, while in this study, only radical cystectomy was used as a control for comparison. Therefore, there is a possibility that RARC may not differ so significantly in all aspects compared with other treatment methods, which is a key direction of our future research. Besides, due to the short experimental period, we cannot determine the influence of RARC on the long-term prognosis of patients. Hence, we will follow up the participants in this study for a longer time to improve our results.
To sum up, the application of RARC can accelerate the recovery of patients with bladder cancer, improve pelvic lymph node dissection effect, and reduce the serum levels of tumor marker TSGF.
Disclosure of conflict of interest
None.
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