Effect of constipation on acute urinary retention following transrectal prostate biopsy

Abstract

Purpose

To evaluate the possible effect of constipation on the acute urinary retention (AUR) after transrectal ultrasound-guided prostate biopsy (TRUS PB).

Materials and Methods

A total of 1,167 patients with prostate-specific antigen (PSA) >4 ng/mL and/or abnormal digital rectal examination underwent a standard 12 core transrectal ultrasound-guided prostate needle biopsy in our hospital and the findings were examined prospectively. Chronic constipation (CC) was defined according to the Rome IV criteria. All cases were well evaluated with respect to clinical-histopathological factors; International Prostate Symptom Score (IPSS), prostate volume, post-void residue, age, body mass index, histopathological inflammation, and AUR.

Results

The mean age of patients was 64.63±8.31 years, the PSA level was 11.60±16.83 ng/mL, and the prostate volume was 54.66±25.44 mL. In 265 cases (22.7%), CC anamnesis was present and AUR developed in 28 (2.4%) of the cases. In the multivariate analysis for the risk of developing urinary retention, prostate volume, pre-operative IPSS, and presence of CC requiring manual maneuvers to facilitate defecation were found to be risk factors (p=0.023, 0.010, and 0.001, respectively).

Conclusions

Our findings demonstrated that CC may be a critical factor in the prediction of AUR formation following TRUS PB.

INTRODUCTION

Prostate biopsy (PB) is considered to be the gold standard in the final diagnosis of prostate cancer since its clinical introduction by Hodge et al. in 1989 [1]. Transrectal ultrasound PB intergrated with multiparametric prostate magnetic resonance imaging (MRI) became the standard diagnostic modality of prostate cancer which seems to be well tolerated by patients [2].

Minor complications such as hematuria, hematospermia, discomfort, and rectal bleeding are commonly encountered after PB and they are usually self-limited. However, although rare, major adverse effects of PB, including prostatitis, infection, and acute urinary retention (AUR) can also ocur [3,4]. Last but not least, published data so far indicates that AUR rates after PB were found to vary between 0.2%–2.6% of patients, undergoing PB [5,6].

Chronic constipation (CC) is a frequent complaint identified during medical outpatient admissions and its prevalence in patients ≥60 years of age is approximately 30% [7,8]. Based on the fact that CC is often associated with bladder dysfunction, a variety of publications indicated that bowel dysfunction is commonly detected in children, middle-aged women, and neuropathic patients suffering from lower urinary tract symptoms (LUTS). However despite adequate number of publication in these populations, number of prospective cohort studies on CC and LUTS in the elderly is highly limited [9]. While rectal distension was found to inhibit bladder contractions in animals, it causes overactive bladder with increased contractions in experimental studies [10,11]. The exact pathophysiological mechanism of the biopsy-related voiding dysfunction has not yet been elucidated. Possible causes of increased bladder outlet resistance after PB are edema/swelling, inflammation, and increased alpha receptor sensitivity in the prostate created by the ultrasound probe and needle [12,13].

In this present study we aimed to evaluate the impact of CC on the formation of urinary retention and define its contributory effect on voiding disruption after PB. To the best of our knowledge, the correlation between CC and AUR formation after PB has not been previously investigated.

MATERIALS AND METHODS

This multicentric prospective study was conducted from May 2019 to March 2021 following approval by the Ethics Committee of Sancaktepe Sehit Prof. Dr. Ilhan Varank Research and Training Hospital (approval no. 162). A sample of 1,167 patients was submitted consecutively to transrectal ultrasound-guided PBs. An informed consent form regarding the procedure and its complications was obtained from the patients.

Inclusion criteria were abnormal digital rectal examination; elevated prostate-specific antigen (PSA) (>4.0 ng/mL in men >55 years old and >2.5 ng/mL in men <55 years old) or positive findings in a multiparametric MRI of the prostate (Prostate Imaging-Reporting and Data System ≥3). People with urinary tract infections diagnosed during biopsy or treatment, an allergic reaction to ciprofloxacin, those who had prostate-related procedures within the last 3 months, patients who refused informed written consent were excluded from the study. Patiens with history of urinary retention and urinary retention at the time of biopsy were also excluded from the study. Among the data parameters, PSA value, International Prostate Symptom Score (IPSS), patient demographics, prostate volume, pre-biopsy Qmax (mL/s), comorbidities, previous prostate disease and post-void residual (PVR) amount, histopathological results and CC, were evaluated.

The occurrence of urinary retention after the procedure was the primary outcome measure. This was defined as the requirement of urethral catheter insertion due to inability to void, patient discomfort and/or presence of >300 mL PVR urine on bladder ultrasound scan [6]. PVR was measured using the ellipsoid formula (height×width×lenght×0.52) determined by suprapubic ultrasonography.

Patients received a 250-mL phosphate enema on arrival. Sterile urine culture test within 1 month before biopsy was obtained. A prophylactic dose of 500 mg ciprofloxacin was administered 2 hours before and 8 hours after the procedure. Under local anesthesia, 12 core PBs were obtained by using an 18-gauge needle via the transrectal route. The patients were recalled to the clinic 7 days after the procedure. A questionnaire including possible complications such as postprocedure pain, fever, hematuria, dysuria, hematospermia, rectal bleeding, and urinary retention was filled in by the patients.

1. Definition of chronic constipation

CC (also termed functional constipation) was defined by the Rome IV criteria in May 2016. Symptom onset 6 or more months before diagnosis was used as a diagnostic tool, as well as if loose stools were rarely present without the use of laxatives for the previous 3 months. The definition of CC is made according to Rome IV with onset of symptoms 6 months prior to diagnosis and with the presence of at least 2 of the following criteria during the last 3 months: (1) Straining more than 25% of defecations; (2) Lumpy or hard stools more than 25% of defecations; (3) Sensation of incomplete evacuation more than one-fourth (25%) of defecations; (4) Sensation of anorectal obstruction/blockage more than onefourth (25%) of defecations; (5) Manual maneuvers to facilitate more than one-fourth (25%) of defecations; (6) Fewer than 3 spontaneous bowel movements per week [14].

2. Statistical analysis

Analyses were performed using the IBM corporation software released in 2011, IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp.). Student’s t-tests were used to compare normally distributed parameters; to compare non-normally distributed parameters, the Mann–Whitney U-test was used. Pearson’s chi-squared test and Fisher’s exact test were applied to analyze the qualitative data. Variables were subjected to the univariate and multivariate analysis. While using univariate analysis in comparison of all parameters, multivariate analysis was used in 2 different models for CC and its components in terms of risk factors. Statistical significance was considered p<0.05 considered as significant.

RESULTS

One thousand two hundred forty-nine men who underwent PB were included in the study. While 34 patients were excluded from the study, 48 lost to follow-up. The remaining 1,167 patients were evaluated according to the presence of CC criteria.

Group 1 had no CC whereas patients in Group 2 had CC. The distribution of CC with patient characteristics is given in Table 1. The mean age of 1,167 patients was 64.63±8.31 years, the mean PSA level was 11.60±16.83 ng/mL and the mean prostate volume was 54.66±25.44 mL. In 265 cases (22.7%) having constipation, 28 AUR (2.4%) (Table 1).

Table 1. Patient characteristics.

Characteristic	Overall (n=1,167)	Constipation		p-value
		Yes (n=265)	No (n=902)
Age (y)	64.63±8.31	65.91±11.06	64.25±7.30	0.100a
Body mass index (kg/m2)	27.80±6.29	27.61±10.34	27.89±4.47	0.655a
Hypertension	557 (47.7)	157 (59.2)	400 (44.3)	0.294b
Diabetes	177 (15.2)	48 (18.1)	129 (14.3)	0.812b
Cardiovascular disease	242 (20.7)	104 (39.2)	138 (15.3)	0.406b
Serum PSA (ng/mL)	11.60±16.83	12.23±17.55	10.59±17.96	0.344c
Prostate volume (mL)	54.66±25.44	57.78±26.68	53.75±25.02	0.130c
Pre-biopsy PVR (mL)	36.65±45.11	48.78±50.43	33.10±42.85	0.001*c
IPSS	11.67±5.40	14.57 ±5.90	9.60±4.70	0.001*c
Qmax	16.59±4.63	13.51±4.11	16.69±4.72	0.022*c
Prostate Ca	340 (29.1)	91 (34.3)	249 (27.6)	0.259d
Histopathologic inflammation	467 (40.0)	109 (41.1)	358 (39.7)	0.784d
Repeated biopsiese	313 (26.8)	91 (34.3)	222 (24.6)	0.025*b
Hospital admissionf	31 (2.7)	20 (7.5)	11 (1.2)	0.001*d
Rectal bleeding	247 (21.2)	69 (26.0)	178 (19.7)	0.029*g
Hematospermia	212 (18.2)	44 (16.6)	168 (18.6)	0.621g
Macroscopic hematuria	663 (56.8)	163 (61.5)	500 (55.4)	0.050g
Urinary retention	28 (2.4)	15 (5.7)	13 (1.4)	0.002*g

Values are presented as mean±standard deviation or number (%).

PSA, prostate-specific antigen; PVR, pre-biopsy post-void residual; IPSS, International Prostate Symptom Score.

^a:Student’s t-test.

^b:Pearson’s chi-squared test.

^c:Mann–Whitney U-test.

^d:Yates’ continuity correction test.

^e:Patients with a history of previous prostate biopsy.

^f:Patients who admit to hospital due to complications after prostate biopsy

^g:Fisher’s exact test

^*Statistically significant p<0.05.

In univariate analysis, prostate volume (p=0.003), IPSS (p=0.001), diabetes mellitus (DM) (p=0.007), CC (p=0.002) (Table 2) and CC components; straining, lumpy or hard stools, manual maneuvers to aid defecation and <3 defecations a week were found to be statistically significant for AUR after PB (p=0.025, p=0.011, p=0.001, and p=0.014, respectively) (Table 3). However, all factors in multivariate logistic regression analysis indicated that the prostate volume (OR, 6,810; 95% CI, 2.32–11.41; p=0.023), pre-operative IPSS (OR, 3.310; 95% CI, 1.270–8.43; p=0.010), constipation (OR, 9.641; 95% Cl, 3.898–23.84; p=0.001) and manual maneuvers for defecation greatly increased the predictors of AUR (OR, 103.420; 95% CI, 6.249–1,711.57; p=0.001) (Table 4).

Table 2. Evaluation of possible risk factors comparing patients with vs. without urinary retention.

Variable	Overall (n=1,167)	Urinary retention		p-value
		Yes (n=28)	No (n=1,139)
Age (y)	64.63±8.31	68.42±5.76	64.54±8.34	0.086a
Body mass index (kg/m2)	27.80±6.29	26.32±8.74	27.84±6.33	0.379a
Hypertension	557 (47.7)	14 (50.0)	543 (47.7)	0.881b
Diabetes	177 (15.2)	11 (39.3)	166 (14.6)	0.007*b
Cardiovascular disease	242 (20.7)	7 (25.0)	235 (20.6)	0.406b
Constipation	265 (22.7)	16 (57.1)	249 (21.9)	0.002*b
Serum PSA (ng/mL)	11.60±16.83	7.14±5.14	11.15±17.05	0.410c
Prostate volume (mL)	54.66±25.44	76.05±37.07	52.46±29.24	0.003*c
Pre-biopsy PVR (mL)	36.65±45.11	51.90±49.92	36.31±45.02	0.201c
IPSS	11.67±5.43	15.95±4.71	10.71±7.42	0.001*c
Qmax	16.59±4.63	16.62±4.59	14.43±3.62	0.078c
Prostate Ca	340 (29.1)	11 (39.3)	329 (28.9)	0.437c
Histopathologic inflammation	467 (40.0)	8 (28.6)	459 (40.3)	0.204c
Repeated biopsiesd	313 (26.8)	7 (25.0)	306 (26.9)	0.194e

Values are presented as mean±standard deviation or number (%).

PSA, prostate-specific antigen; PVR, pre-biopsy post-void residual; IPSS, International Prostate Symptom Score.

^a:Student’s t-test.

^b:Yates’ continuity correction test.

^c:Mann–Whitney U-test.

^d:Patients with a history of previous prostate biopsy.

^e:Pearson’s chi-squared test.

^*Statistically significant p<0.05.

Table 3. Evaluation of constipation alone and its components with respect to their possible impact on the risk of urinary retention after biopsy procedure.

Variable	Overall (n=1,167)	Urinary retention		p-valuea
		Yes (n=28)	No (n=1,139)
Straining	351 (30.1)	17 (60.7)	334 (29.3)	0.025*
Lumpy or hard stools	317 (27.2)	14 (50.0)	303 (26.6)	0.011*
Sensation of incomplete evacuation	198 (17.0)	7 (25.0)	191 (16.8)	0.241
Sensation of blockage	135 (11.6)	6 (21.4)	129 (11.3)	0.240
Manual maneuvers	40 (3.4)	14 (50.0)	26 (2.3)	0.001*
3 defecations/wk	193 (16.5)	14 (50.0)	179 (15.7)	0.014*

Values are presented as number (%).

^a:Yates’ continuity correction test.

^*Statistically significant p<0.05.

Table 4. Logistic regression analysis predicting the risk of urinary retention after prostate biopsy.

Variable		p-value	Odds ratio	95% Confidence interval
				Lower	Upper
Model 1
	Diabetes	0.883	0.874	0.145	5.25
	Constipation	0.001	9.641	3.898	23.84*
	Prostate volume (mL)	0.023	6.810	2.320	11.41*
	IPSS	0.010	3.310	1.270	8.43*
Model 2
	Straining	0.747	0.441	0.003	63.69
	Lumpy or hard stools	0.754	0.215	0.000	3,218.28
	Manual maneuvers	0.001	103.420	6.249	1,711.57*
	<3 defecations/wk	0.685	2.197	0.049	98.64

IPSS, International Prostate Symptom Score.

^*Statistically significant p<0.05.

DISCUSSION

Transrectal radiology guided PB is accepted as the current gold standard method for detecting prostate cancer. Although it is considered safe, a wide variety of complications, including sepsis and AUR, may occur to a certain extent. Unlike severe infectious and bleeding complications, as a temporary short lasting problem insertion of a short-term urethral catheter to drain the bladder is sufficient the patients presenting with AUR without any need for the other invasive procedures. The incidence of AUR among our patients undergoing PB in the present study was 2.4%, which is in accordance with previously reported rates of AUR following PB ranging from 0% to 3.1% [15,16].

Evaluation of our findings have clearly demonstrated that AUR following a successful PB tends to be more common in patients with CC, higher IPSS values and relatively larger prostate volume than the ones who do not present with these features. Regarding this issue highly limited data is present in the current literature and high baseline IPSS values, the ratio of transition zone volume to total prostate volume, previous biopsies, sampling of multiple cores were reported to be predictors of post PB AUR in a couple of the studies published [17] so far. The results of our study correspond well with the parameters reported in former studies focusing on the possible impact of IPSS values and prostate volume on the formation of AUR after PB. In their original study, Aktas et al. [13] found that post PB AUR rate is higher in patients with larger prostate based on the requirement of maneuvers causing more vigorous trauma to reach the prostate base in a such high volume prostates. On the other hand, Zisman et al. [18] reported that presence of higher baseline IPSS values and larger prostate volume were thye possible predictors of LUTS and AUR after PB. Klein et al. [19] investigated the effect of saturation PB and 10 core biopsy on voiding function and AUR. They observed that saturation biopsy inhibited voiding function over 12 weeks vs. 10-core biopsy. The authors did not detect any correlation between increased IPSS and prostate volume. In contrast to Klein et al. [19], Berger et al. [3] reported no link between the risk of AUR and the number of biopsy cores. Since we took 12 biopsy cores in each case, sampling of multiple cores was not the case in our study.

Although systemic illnesses, such as obesity, diabetes, and cardiovascular disease, which are more common in older patients and presumed as predictors of worsening urinary obstruction after PB [20], we found that only DM significantly increased the occurrence of AUR. It seems obvious that PB provokes prostate swelling with mechanical trauma and inevitable inoculation of rectal flora through biopsy needle causes prostatitis. Post PB edema and inflammation constricts the urinary tract; therefore, the already impaired voiding in patients with enlarged prostate worsens, leading to a severe increase in bladder outlet resistance [21]. Increased alpha receptor sensitivity was another explanation for increased bladder outlet resistance after PB [13].

CC is a symptom-based disorder characterized by hard consistency and infrequent and difficult passage of stool, as well as abdominal pain, palpable stool in the abdomen and in the rectal vault [22]. The prevalence of CC varies from 0.7% to 79%, and approximately 21% of people experience problems with fecal evacuation [7]. Incidence increases with age; 26% of womenand 30% of men over 65 years old have CC [7,23]. Although some studies reported that the presence of CC is among factors increasing the incidence of LUTS in elderly people of both sex, the correlation between CC and post PB AUR has not been yet reported [24,25]. Treatment of CC in the age on these parameters and they were able to show that significant improvement could be noted with respect to the urological symptoms like frequency, urgency, urinary stream disturbance and decrease in residual volume and urinary tract infection rates [25].

Effective treatment of CC improved not only the LUTS but also the patient’s mood, sexual activity, and quality of life in the elderly cases. It is possible that any pathology or dysfunction in one of the organs could affect the other as the urinary bladder and rectum are the neighboring organs which develop from common embryological structures in the cloaca. The following theories have been proposed in some studies investigating the co-existence of bladder and bowel dysfunction together in pediatric patients and these may also be adapted to elderly patients suffering from CC; The first suggests that rectal distention in the constipated patient compresses bladder outlet and urethra, leading to impaired bladder emptying [26]. The second theory assumes that urethral and anal sphincteric neural input is a single functional unit being innervated by parasympathetic nerves originating from S2 to S4. The external anal and external urethral sphincter also have motor innervation via the pudendal nerve originating from S2-S4. Persistence of a large amount of stool in the rectum with permanent external anal sphincter contraction may lead to excessive pelvic floor muscle contraction resulting in concomitant disturbed urethral sphincter relaxation [9,27].

From a pathophysiological perspective, Cajal’s interstitial cells located in the colon wall generate electrical waves which may probably be responsible for colonic motor activity and it is high likely that these waves may be absent or inadequate in cases with CC. Disordered or degenerated Cajal cells may slow or cease pacemaker activity causing subsequent disturbed peristaltic activity. In experimental studies, urinary bladder smooth muscle was shown to generate electric activity likewise. They are in the form of slow waves and action potentials [28]. Previous studies also demonstrated the presence of Cajal cells in the urinary bladder wall as well [29]. An unidentified disturbance in electrophysiologic activities causing CC may also occur concomitantly in urinary bladder smooth muscle, causing voiding disturbance apart from neuropathic and mechanic effects. However, furthere experimental research studies are certainly required to clarify this hypothesis.

Based on the facts stated above we aimed to evaluate the possible effects of constipation status on the bladder function and outflow status in cases undergoing transrectal US guided biopsy for the detection of cancer. Evaluation of our findings in this study carried out with a reasonably large case number did clearly show that in addition to the well-known factors like prostate volume and IPSS values, presence of a CC status could help the surgeon to predict the likelihood of complications related with infravesical outflow obstruction namely AUR formation. Surgeons should be aware of the negative effects of CC, take the necessary measures both for the treatment of this problem and also closely follow these cases for possible AUR formation which may disturbe patients’ life quality by compromising the early post-procedureal phase of PB.

There are some limitations of this present study; First of all, AUR formation can be influenced by a variety of other certain factors. In our current study however as an important factor which could be responsible for this complication, we mainly focused on the possible impact of CC on the prediction of AUR formation after PB. A parameter that has not be considered and studied so far by other authors. On the other hand, CC is also affected by many conditions and its diagnostic criteria are subjective. Furthermore it is clear that the presence or absence of CC can vary according to the patient's condition for only 6 months of life. Despite the limitations mentioned above however, in the light of the highly limited information reported on this issue we believe that severe CC requiring auxiliary maneuvers could be regarded and treated as acritical risk factor for AUR formation in a certain per cent of the patients undergoing PB.

CONCLUSIONS

CC could be regarded as an important and reliable predictive factor of AUR formation in patients undergoing PB. CC and its well-defined components (especially severe CC requiring manual maneuvers to aid defecation) need to be well questioned prior to every PB procedure. More importantly, necessary measures under close follow-up of the cases should be taken in order to minimize the risk of AUR after PB, a common procedure performed almost in all urology clinics worldwide.