Intermediate-term survival of robot-assisted versus open radical cystectomy for muscle-invasive and high-risk non-muscle invasive bladder cancer in The Netherlands.

BACKGROUND: Radical cystectomy with pelvic lymph node dissection is the recommended treatment in non-metastatic muscle-invasive bladder cancer (MIBC). In randomised trials, robot-assisted radical cystectomy (RARC) showed non-inferior short-term oncological outcomes compared with open radical cystectomy (ORC). Data on intermediate and long-term oncological outcomes of RARC are limited. OBJECTIVE: To assess the intermediate-term overall survival (OS) and recurrence-free survival (RFS) of patients with MIBC and high-risk non-MIBC (NMIBC) who underwent ORC versus RARC in clinical practice. METHODS AND MATERIALS: A nationwide retrospective study in 19 Dutch hospitals including patients with MIBC and high-risk NMIBC treated by ORC (n = 1086) or RARC (n = 386) between January 1, 2012 and December 31, 2015. Primary and secondary outcome measures were median OS and RFS, respectively. Survival outcomes were estimated using Kaplan-Meier curves. A multivariable Cox regression model was developed to adjust for possible confounders and to assess prognostic factors for survival including clinical variables, clinical and pathological disease stage, neoadjuvant therapy and surgical margin status. RESULTS: The median follow-up was 5.1 years (95% confidence interval ([95%CI] 5.0-5.2). The median OS after ORC was 5.0 years (95%CI 4.3-5.6) versus 5.8 years after RARC (95%CI 5.1-6.5). The median RFS was 3.8 years (95%CI 3.1-4.5) after ORC versus 5.0 years after RARC (95%CI 3.9-6.0). After multivariable adjustment, the hazard ratio for OS was 1.00 (95%CI 0.84-1.20) and for RFS 1.08 (95%CI 0.91-1.27) of ORC versus RARC. Patients who underwent ORC were older, had higher preoperative serum creatinine levels and more advanced clinical and pathological disease stage. CONCLUSION: ORC and RARC resulted in similar intermediate-term OS and RFS in a cohort of almost 1500 MIBC and high-risk NMIBC.

An Unusual Presentation of Pyelonephritis: Is It COVID-19 Related?

In severe cases of COVID-19, late complications such as coagulopathy and organ injury are increasingly described. In milder cases of the disease, the exact time frame and causal path of late-onset complications have not yet been determined. Although direct and indirect renal injury by SARS-CoV-2 has been confirmed, hemorrhagic renal infection or coagulative problems in the urinary tract have not yet been described. This case report describes a 35-year-old female without relevant medical history who, five days after having recovered from infection with SARS-CoV-2, had an unusual course of acute pyelonephritis of the right kidney and persistent fever under targeted antibiotic treatment. A hemorrhagic ureteral obstruction and severe swollen renal parenchyma preceded the onset of fever and was related to the developing pyelonephritis. Sudden thrombotic venous occlusion in the right eye appeared during admission. Symmetrical paresthesia in the limbs in combination with severe lower back pain and gastro-intestinal complaints also occurred and remained unexplained despite thorough investigation. We present the unusual combination of culture-confirmed bacterial hemorrhagic pyelonephritis with a blood clot in the proximal right ureter, complicated by retinal vein thrombosis, in a patient who had recovered from SARS-CoV-2-infection five days before presentation. The case is suspect of a COVID-19-related etiology.

The BUSCOPAN study: a randomized-controlled non-inferiority trial of a continuous butylscopolamine infusion versus placebo in patients with a renal colic not responding to oral non-steroidal anti-inflammatory drugs.

PURPOSE: To investigate whether placebo is non-inferior to continuous infusion of butylscopolamine in patients with renal colic. METHODS: We conducted a placebo-controlled, multicenter, double-blind randomized clinical trial (RCT) including 128 patients with renal colic (confirmed by ultrasound or CT-scan). Patients were randomized to receive either continuous IV butylscopolamine 100 mg/24 h or placebo (saline). Primary outcome is the amount of opioid escape medication used, measured in doses administered. Secondary outcomes are pain measured on a Numeric Rating Scale (NRS), side effects, and time of drug administration. Non-inferiority was assessed using linear regression with robust standard errors, with non-inferiority limit set at 0.5 units of escape medication. RESULTS: Median number of doses of escape medication was one in both groups. The number of extra doses in the placebo group compared with the butylscopolamine group was 0.05, with a 95% robust confidence interval (CI) of 0.38-0.47. Upper limit of the CI remained below the non-inferiority limit of 0.5 (p = 0.04). No differences in secondary endpoints were seen between the groups. CONCLUSION: Placebo is non-inferior to continuous IV butylscopolamine for pain relief in patients with renal colic. Based on this study and previous evidence, there is no role for continuous butylscopolamine IV in the treatment of renal colic. Trial NL7819.

Pharmacological modulation of ureteric peristalsis in a chronically instrumented conscious pig model: effect of adrenergic and nitrergic modulation.

PURPOSE: To evaluate the role of adrenergic and nitrergic signaling on ureteric peristaltic frequency and contraction force in vivo using a large animal model. METHODS: Twelve female pigs (72 ± 4 kg) were chronically instrumented with an electronic pressure-monitoring catheter in the right ureter. Nephrostomy, cystostomy, and arterial and venous catheters were left in situ. Ureteral peristalsis was recorded before and after the administration of propranolol, isoprenaline, doxazosin, urapidil, phenylephrine, LNNA (Nω-nitro-L-arginine), and L-arginine. RESULTS: α1-Adrenergic receptor stimulation resulted in an increased P max and peristaltic frequency. However, α1-inhibition decreased P max alone. Similarly, ß-adrenergic stimulation decreased P max and peristaltic frequency, whereas ß-inhibition increased only P max. LNNA administration increased P max in the distal ureter and hydrostatic pressure in the pyelocalyceal system. L-Arginine did not affect P max or frequency, but resulted in a significantly higher diuresis. Either agonist or antagonist of NO did not affect peristaltic frequency and length of contraction. CONCLUSIONS: Activation of α- and ß-adrenergic receptors, respectively, stimulates and inhibits ureteric peristalsis. The biological effect of NO on ureteric motility is regionally determined and corresponds to the distribution of NOS-positive nerves. Inhibition of NOS activity increases P max in the distal ureter and tonic activity of the ureteric muscle resulting in higher hydrostatic pressure in the renal pelvis.

Pharmacological modulation of ureteral peristalsis in a chronically instrumented conscious pig model. I: Effect of cholinergic stimulation and inhibition.

PURPOSE: We evaluated in vivo the role of muscarinic receptors on ureteral peristaltic frequency and contraction force in a large animal model using pharmacological manipulation. MATERIALS AND METHODS: A total of 12 female pigs weighing a mean +/- SEM of 72 +/- 4 kg were chronically instrumented using an electronic pressure monitoring catheter in the right ureter. Furthermore, nephrostomy, arterial, venous and cystostomy catheters were placed. Ureteral peristalsis was repeatedly recorded before and after the administration of atropine and carbachol. RESULTS: Systemic and local effects of the 2 agents were observed. Compared with controls we recorded an increase in mean ureteral peristaltic frequency (2.0 +/- 0.3 versus 1.6 +/- 0.6 minutes-1, p <0.05) and mean contraction force (50.1 +/- 1.4 versus 45.3 +/- 1.7 cm H(2)O, p <0.05) during renal pelvis perfusion with 0.25 ml per minute saline. Administration of atropine or carbachol modulated neither the force of contraction nor the frequency of ureteral peristalsis in vivo (p >0.05). CONCLUSIONS: Smooth muscle motor activity at the mid and distal ureter is not modulated by muscarinic receptors. Peristaltic frequency is directly related to the pyelocaliceal load during a rate of diuresis not exceeding animal normal diuresis plus 0.25 ml per minute. Ureteral contraction force increases only in the mid ureter with increased diuresis.

Intraluminal pressure changes in vivo in the middle and distal pig ureter during propagation of a peristaltic wave.

OBJECTIVES: To establish the characteristics of mechanical activity during ureteral peristalsis and unidirectional bolus transport, pressure changes in the middle and distal (juxtavesical and ureterovesical junction) porcine ureter were quantified in vivo. METHODS: Five female New Yorkshire pigs (50 to 60 kg) were studied under halothane anesthesia. The endoscopic approach was used to position an 8-channel 6 F perfusion catheter under direct vision into the distal ureter by way of the orifice. Ureteral activity was studied in two separate sessions at 1-week intervals. The pressure, propagation velocity, and length of the peristaltic waves were analyzed. RESULTS: The average maximal pressure in a not previously instrumented ureter amounted to 35.7 +/- 1.2 cm H(2)O in the mid-ureter, and decreased to 19.4 +/- 1.3 cm H(2)O in the juxtavesical ureter (P < 0.001) and further to 7.2 +/- 1.0 cm H(2)O (P < 0.001) in the submucosal segment. The propagation velocity of the peristaltic wave through the ureter was 2.1 +/- 1.3 cm/s. The length of the pressure peak was 5.9 +/- 1.6 cm. CONCLUSIONS: A ureteral peristaltic contraction wave travels at approximately 2 cm/s and is approximately 6 cm long. It is responsible for the unidirectional transport of a urinary bolus and itself acts as an "active" antireflux mechanism. The maximal pressure in the lumen of the ureter decreased from proximally to distally, but remains sufficiently high at the ureterovesical junction to prevent retrograde urine leakage when the ureter empties its urinary bolus into the bladder and the orifice is open.

An in vivo endoluminal ultrasonographic study of peristaltic activity in the distal porcine ureter.

PURPOSE: Experiments were performed to quantify the duration and frequency of ureteric peristaltic activity in the laparotomized and non-laparotomized pig in its virgin and postinstrumented states. MATERIALS AND METHODS: Pigs (n = 10) in a steady state of hydration were studied under halothane anesthesia in two groups. The study was undertaken in two separate sessions at a week's interval. In group I laparotomy and vesicotomy were undertaken to obtain ELUS images. In group II, peristalsis was studied using an ELUS probe introduced through the working channel of a 22F rigid cystoscope. Peristalsis was visualized as a periodic diameter-change of ureter and recorded (for approx. 30 minutes) on videotape after an initial period of adaptation of approx. 30 minutes. RESULTS: The ureter acts like a pump discharging urine into the bladder through peristaltic activity. ELUS imaging of ureteric peristalsis correlated well with "eyeballing" of the passage of peristalsis through a ureter (group I). The shortest peristaltic activity in group I was 6.0+/-2.0 seconds in the non-instrumented- and 5.1+/-1.4 seconds in the instrumented ureter. In group II it was 6.8+/-1.5 seconds in the non-instrumented- and 6.4+/-1.5 seconds in the instrumented ureter. Chronic dilatation of ureter led to decrease in peristalsis frequency. Interestingly, acute dilatation caused an increase in ureteric peristalsis frequency. CONCLUSIONS: Ureteric peristalsis acts as a pump discharging urinary boluses (intraluminal fluid load) unidirectionally into the bladder. ELUS provides us an opportunity to quantify and study ureteric peristalsis.

An electro-myographic study of the distal porcine ureter.

PURPOSE: The accumulation of urine in the renal pelvis causes depolarisation of non-specific muscular pace-maker cells. The wave of depolarisation spreads distally in the ureteric smooth muscle cells via gap junctions. This wave of excitation causes a coordinated peristaltic contraction which transports the urine bolus distally to the bladder. The EMG activity in the distal porcine ureter was studied and analyzed to establish the characteristics of ureteric excitation. MATERIALS AND METHODS: Ten female New Yorkshire pigs (50 to 60 kg.) were studied in two groups under light halothane anesthesia (5% at induction and 1% for maintenance anesthesia). In both groups each pig was studied in two separate sessions at a week's interval. In group I (n = 5), bipolar needle electrodes (o: 0. 09 mm.) were implanted through a lower mid-line abdominal incision in the posterior bladder wall, the trigone and the pelvic ureter at intervals of 3 and 8 cm., respectively, from the ureteric orifice. In group II (n = 5), EMG spike burst activity was studied using a twin bipolar ring-electrode attached to an endoluminal ureteric catheter. EMG complexes were recorded using 0 to 30 Hz filters. The duration of spike burst complexes and their intervals were analyzed using a Nicollet, Pathfinder II(R) machine and a Poly(R) 4.9 digital signal processing program. RESULTS: Two types of spike burst activity could be distinguished between the electrodes: A, the migrating type and B, the non-migrating type. Frequency distribution analysis of spike burst duration revealed two main classes in experimental group II, a short spike burst (96%) which lasted 4.5 +/- 1.8 seconds and a longer one lasting 13.4 +/- 1.5 seconds. The conduction velocity of the migrating spike bursts (n = 177, 42% of total) between the proximal and the distal electrode had an average of 2.3 +/- 1.3 cm./sec. No relationship was found between the duration of the proximal spike burst and the conduction velocity. Data from experimental group I correlated well with data from group II. CONCLUSIONS: The results of our EMG study in the distal ureter reveal an approximately 9 cm. long electrically active zone in >/= 90% of EMG activity recordings. The duration of activity was approximately 5 seconds. Such an excited segment of ureter led to a contraction which occluded the ureter and could prevent retrograde leakage of intraluminal contents.

A study of ureteric peristalsis using a single catheter to record EMG, impedance, and pressure changes.

Ureteric peristalsis transports a urinary bolus from the renal pelvis to the bladder. We developed an intraluminal catheter with a pressure transducer on it to study intraluminal pressure changes and a twin bipolar electrode to record the ureteric EMG and impedance (Z) changes during a peristaltic wave. Five female New Yorkshire pigs (50-60 kg) were studied under light halothane anesthesia (5% at induction/1% for maintenance). A steady state of hydration was maintained using intravenous saline infusion. EMG spike burst activity was studied at a 10-cm interval using low (0-30) Hz filters. Impedance between the same electrodes is measured simultaneously in higher frequencies (1-5 KHz) as a function of ureteric motor activity. Pressure generation in the ureteric lumen was also measured simultaneously by a transducer on the same catheter. A digital signal processing program (Poly 4.9) was used for analysis. Parenteral furosemide was used to induce diuresis. Resting ureteric impedance (Z(R)) decreases to Z(B) (Z bolus) during the passage of the urinary bolus. Passage of a contractile zone during a peristaltic wave increases impedance from Z(B) to its Z(R) level and initiates a pressure rise. Bolus length (the length Z(B)) is not constant and decreases distally. EMG corresponds well in time to impedance. Z(R) disappears after infusion of furosemide because of increased urine load and changes of intraluminal ionic environment. The contractile segment of a ureteric peristaltic wave appears to be represented by an elevated Z segment (Z(C)). Pressure rise is recorded only at the beginning of a contractile zone. A specially adapted intraluminal catheter can be used to study peristalsis in the upper urinary tract. One can study all the three components of ureteric peristalsis (excitation, contraction, and intraluminal pressure rise) using such a catheter.

Anatomy of ureterovesical junction and distal ureter studied by endoluminal ultrasonography in vitro.

PURPOSE: The emerging technique of endoluminal ultrasonography (ELUS) provides a new modality for endoscopic visualization of the urinary tract which needs to be further evaluated. We studied the normal anatomy of distal ureter and ureterovesical junction using ELUS. MATERIALS AND METHODS: An assessment of in vitro ELUS ureteric images undertaken at 1 mm. intervals from 8 fresh human cadaver pelvis blocs of bladder and distal ureter were compared with findings of serial histological sections of the same specimens (stained for cholinesterase isoenzymes) to assess the degree of correlation. Computer-assisted 3D reconstructions were made. RESULTS: The different components (ureteric, detrusor and periureteric tissue) of the UVJ could be identified on the basis of echogenicity and form, but differentiation between the respective muscle layers in the wall of the ureter or of the detrusor was not possible. Nevertheless, ureteric volume measurements and an assessment of transmural ureteric length and the angle of passage through the bladder wall were possible. CONCLUSIONS: ELUS is able to differentiate between the ureteric and detrusor muscle and the UVJ gross anatomy can be reconstructed. ELUS technology, however, fails to differentiate between individual muscular layers of the ureter or the detrusor. Further improvement in ELUS is mandatory.

Functional anatomy of the human ureterovesical junction.

BACKGROUND: The valve function of the ureterovesical-junction (UVJ) is responsible for protection of the low pressure upper urinary tract from the refluxing of urine from the bladder. Controversy about the microanatomy of the human ureterovesical-junction persists. METHODS: Ten (3 male and 7 female) fresh cadaveric bladders (mean age 70 years old) were studied. The bladders were fixed within 24 hours postmortem, frozen, and serially sectioned. Acetyl- and butyryl- (nonspecific) cholinesterase activity were visualised as described by Karnovsky and Roots. The three-dimensional distribution of the different muscle groups participating in the formation of the UVJ was reconstructed. RESULTS: Three different muscle groups were identified: (1) the detrusor muscle and the deep trigone were mainly acetylcholinesterase-positive, (2) the inner and outer layer of the ureteric muscle were butyrylcholinesterase-positive and merged into a single longitudinal layer at the level of the UVJ and form the superficial trigone distally to the ureteric orifices, and (3) the muscularis mucosae is a discontinuous butyrylcholinesterase-positive layer in the bladder that is absent from the trigone. No evidence of any muscular connection was found between the ureter and bladder musculature. CONCLUSIONS: The anatomy of the UVJ as observed by us suggests the following model of the ureteric peristalsis. The urine bolus arrives in the ureteric lumen at the UVJ level. The ureter can only shorten its length, slides freely in its tunnel, and discharges the urine bolus in the bladder cavity. Ureteric constriction due to the peristalsis and thickening of the contracted portion of the ureter prevents the upstream leakage. Distal spreading of the ureteric "peristalsis" in the superficial trigone increases the submucosal ureteric length and prevents reflux.