Comparison of local infiltration anesthesia and mucous surface anesthesia in trans-rectal ultrasound-guided prostate biopsy

Background: To compare the efficacy and safety of local infiltration anesthesia and mucous surface anesthesia in patients undergoing trans-rectal ultrasound-guided (TRUS guided) prostate biopsy. Methods: Patients with suspected prostate cancer undergoing TRUS guided prostate biopsy were randomly divided into two groups between January 2018 and March 2019. Local infiltration anesthesia was performed in the experimental group with lidocaine; while the control group was treated with mucous surface anesthesia. We collected baseline characteristics. Residual urine volume was measured twice: before biopsy, the first micturition after biopsy. Associated complications, positive rate of biopsy, visual analog pain scale (VAS) and Gleason score were recorded. Results: The study included 78 patients. The pain score of experimental group was significantly lower than the control group. Experimental group had lower rate of urinary retention and catheterization. Both groups had similar positive rate of biopsy, residual urine volume, Gleason score, fever and so on. Conclusion: Comparing with mucous surface anesthesia, local infiltration anesthesia relieved the pain better in patients undergoing TRUS guided prostate biopsy. It was more effective and safer. Trial registration: Chinese Clinical Trial Registry, Trial registration number (TRN): ChiCTR1800016424, Date of registration: 01/06/ 2018.

Third Affiliated Hospital of Sun Yat-Sen University to minimal invasion, good effect, and cost-effectiveness [3]. However, the ideal location, type and number of trans-rectal infiltration anesthesia are unclear. There is no uniform standard for its clinical application [4]. Poor anesthesia can lead to pain and discomfort during biopsy. Anal contraction or lower extremity twitching can cause displacement and inaccuracy of puncture. For elderly patients, severe cases may cause cardiovascular adverse events [5 6]. Poor anesthesia may increase the incidence of complications, hinder the process of puncture and even affect the quality of prostate specimen. Whether transrectal infiltration anesthesia can affect the accuracy of puncture, the degree of pain and the incidence of biopsy complications? Theses questions lack clear research evidence.
Mucous surface anesthesia is easy to perform and can be applied without ultrasound. To compare the two ways of anesthesia , we conducted this prospective randomized controlled trial.

Methods
After obtaining patient consent, 78 patients scheduled for prostate biopsy were included in the study. A sample size was calculated based on the incidence of prostate cancer in Guangzhou and the number of inpatients with prostate cancer in our hospital.

Basic information
Patients who underwent trans-rectal ultrasound-guided prostate biopsy in the Third Affiliated Hospital of Sun Yat-sen University were included in the study.

Biopsy steps and indicators
Prostate volume was obtained assisted by three dimensional measurements computed by MRI calculation. PSA and f-PSA were determined before puncture. Antibiotic prophylaxis was given to these patients (oral metronidazole and levofloxacin 1 day before puncture).
Cleansing enema were administered on the evening before biopsy and on the morning of biopsy. Residual urine volume was determined before biopsy and the first micturation after biopsy with the help of ultrasound. Patients were randomized into two groups using a random number table. The randomization schedule was generated by an independent investigator through a random number table. Another two doctors enrolled participants and assigned body sites to interventions separately. The study protocol was explained to patients, and information was provided about the VAS. In the experimental group, 2% lidocaine guided by color Doppler ultrasound infiltrated the vascular nerve bundle around the angle between the bilateral prostate base and the seminal vesicle, 5 ml on each side.
Patients in the control group were anesthetized around the mucous surface with 10ml lidocaine gel [9,10]. All patients did not know the anesthesia method used for their puncture. Puncture location was guided by a specific B-ultrasound doctor who specialized in prostate biopsy. The puncture was performed by the same doctor with stable technique.
Associated data was obtained by another doctor separately. Liquid gel was applied to the probe to reduce discomfort. In consideration of the filing degree of bladder may cause discomfort and increase the risk of puncture, patients were asked to empty their bladders before biopsy. Usually, twelve cores biopsies were suggested, 6 for each lobe of the prostate (3 for left and right peripheral zone, 1 for left and right transitional zone, 2 for left and right central zone). We adjusted the number of cores according to morphological description of potential pathological features. Patients were asked to grade from 0 to 10 with 0 denoting absence of discomfort, 1-3 mild, 4-6 moderate, and 7-10 severe in the 10-point VAS after biopsy [11,12].

Statistical methods
Data analysis was done by SPSS 20 software. Normal distribution data was represented by the mean±SD, and the mean was compared by the independent sample t test. Non-normal distribution data were expressed as median and inter-quartile range, and the median was compared by the Mann-Whitney test. The count data was compared using a chi-square test. A p value of less than 0.05 was considered statistically significant( Fig. 1 2 ).

Results
Baseline characteristic 78 patients were recruited during January 2018 and March 2019, 39 in Group1 and 39 in Group2. The two groups were evenly matched. There was no significant difference among the two groups in terms of demographic data (Table 1 ).

Major research indicators
The pain score of the experimental group after puncture was significantly lower than the control group. There was no statistical difference in residual urine volume between the two groups ( Table 2 ).
Complications and positive rate of biopsy There was no difference in positive rate of biopsy between the two groups. Most of them are self-limiting [13]. The experimental group had lower rate of urinary retention and catheterization. No significant difference was seen in other complications (Table 3).

Discussion
Prostate cancer is the most common cancer among men in the world [14,15]. To improve cancer detection rate, needle aspiration of 12 or more needles is recommended for clinical use to obtain the maximum cancer detection rate and avoid repeated puncture [16,17].
However, the increase of needles brings discomfort such as pain and anxiety. Local infiltration anesthesia, topical anesthesia and intravenous anesthesia are used for prostate biopsy [18]. To be effective, local anesthesia anaesthesia should block all possible routes of painful stimuli. One region requiring blockade is the prostatic sac which has rich autonomic innervation conveying visceral pain to the spinal cord via fibers that run with the vascular pedicles basolaterally [19]. Without local infiltration anesthesia, most patients cannot stand puncture again. With the administration of local infiltration anesthesia, patients describe the perception of pain similar to pinching of skin with fingers softly.
Factors like benign prostatic hyperplasia, enlargement of prostate, and bladder outlet obstruction are responsible for lower urinary tract symptoms [20]. Residual urine volume is a good indicator to assess the risk of urinary retention. No difference was found in residual urine volume between the two groups which indicated that pain was not a primary risk factor for the increase of residual urine volume. Some patients failed to urinate and had to be catheterized even though they had defecated. Therefore the gauze inside the anus is possibly not a influence factor for the increase of residual urine volume. The increase of residual urine volume is very complicated. Acute inflammation reaction induced by inflammatory factors is related to it. The pathway of inflammation reaction may vary among patients.
All patients included completed the biopsy process. Perineal puncture is a better choice for sampling of the anterior and apical regions, especially when the prostate is large [21].
However, combination of both tans-rectal and perineal puncture could not improve cancer detection rate compared to tans-rectal solely [22].
Gross hematuria and gross blood stool are common complications of prostate biopsy, but are generally self-limiting [24]. Infection is a serious adverse event of prostate biopsy with an increasing incidence [25] . Trans-rectal biopsy has an increasing rate of infection because of increasing multi-drug resistant rectal flora compared with perineal biopsy [26].
Perineal biopsy was rarely associated with infection but more commonly with urinary retention[27].
One of the inadequacy of our study is that only 70 patients were included in this trial.
Besides, sub-group analysis was not performed as the subsamples of different age group were relatively small. Our results only applied to prostate cancer without distant metastasis.

Conclusion
In short, local infiltration anesthesia was more effective and safer than mucous surface anesthesia. It should be recommended for TRUS guided prostate biopsy.

Consent for publication
We obtained consent for publication from patients.

Availability of data and material
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors claim that they have no conflict of interest.

Supplementary Files
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