Long-Term Follow-Up of Yearly Replaced Double Internal Stents for Extrinsic Malignant Ureteral Obstruction

Abstract

Introduction:

To assess long-term outcomes of double internal stents (DIS) for the relief of external malignant ureteral obstruction (MUO).

Materials and Methods:

DIS (7F each; 12-month indwelling time) were inserted under general anesthesia in 62 consecutive patients (75 renal units) with MUO during 2007–2018. Surveillance was performed every 3 months, and stents were exchanged routinely every year. The need for permanent stent retrieval was considered stent failure. Maintenance of stent patency and disease-specific survival (DSS) were estimated (Kaplan–Meier). Risk factors were also assessed (univariate and multivariable Cox regression analyses).

Results:

The median follow-up was 27 months (interquartile range [IQR] 20–27). The most frequent tumors causing obstruction were colorectal and ovarian cancers. Six patients (10%) had stent failure caused by sepsis, creatinine elevation, or hematuria. The average time to failure was 15 months (range 1–27). A history of radiation and an estimated glomerular filtration rate (eGFR) ≤45 mL/(min/1.73 m²) were associated with stent failure (p = 0.038 and p = 0.001, respectively). Thirty-nine patients died with a median DSS of 21 months (IQR 8.6-not reached). Multivariate analysis identified eGFR ≤60 mL/(min/1.73 m²) (hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.1–4.2, p = 0.02) and need for balloon dilation (HR 2.1, 95% CI 1.1–4.1, p = 0.02) as independent predictors for disease-related mortality. Twenty-six patients (42%) had stent-related complications, for example, irritative symptoms, hematuria, and infections, of whom only two failed.

Conclusions:

One-year indwelling DIS provide effective long-term relief of MUO and represent a simple and effective alternative to other methods of urinary diversion. They avoid the need for external tubes and contribute to improved patient satisfaction.

Introduction

Extrinsic malignant ureteral obstruction (MUO) is often caused by incurable advanced disease in a population unsuitable for definitive reconstructive surgery. Its precise incidence has not been well established.¹ New oncologic therapies prolong the survival of patients with MUO² who seek long-term, durable, simple, and low-cost palliative solutions of decompression with minimal negative impact on quality of life (QoL).^3
–5 To date, percutaneous nephrostomy (PCN), polymeric stents, and various metallic stents are used with variable success rates.^4,5 PCN tubes provide effective drainage, but their extracorporeal tubing and bags negatively affect patients' mobility, QoL, and self-esteem. They are also associated with frequent side effects and complications in long-term users, and need to be routinely replaced every 3 months.^1,6,7

Internalization of drainage by means of internal stenting spares patients from extracorporeal devices, but it causes stent-related symptoms, such as flank pain and urinary irritative complaints. Polymeric stents, which are characterized by a relative low-cost and wide availability, are probably the most used by this patient group.^1,5 Double internal stents (DIS) or tandem stenting in which two internal stents are placed in parallel has been shown to provide a more effective and sustained decompression than the single-stent approach.^3,4,8

–11 Developments in stent materials and technology have prolonged the dwelling time warranted by the manufacturers to 12 months,¹ making it more attractive to use in an attempt to avoid external devices and reduce the number of replacements for sustained drainage.

Although many studies have focused on short-term experience with DIS, the long-term experience is less described. In this study, we report the long-term outcomes of patients treated for MUO by means of yearly replaced DIS.

Patients and Methods

Study population

The study was approved by the institutional review board (confirmation: 00531TLV) as a retrospective analysis. It comprised 62 patients (75 renal units) with MUO who received DIS between May 2007 and December 2018. These patients were not suitable for a definitive surgical solution to relieve the obstruction, and they received palliative DIS. The diagnosis of extrinsic obstruction was based primarily on cross-sectional imaging, together with evaluation of the patient's clinical history, physical examination, laboratory results, and functional studies. The study patients presented with either acute manifestations, such as pain, infection or renal function deterioration, or were referred because of significant hydronephrosis. Patients with benign ureteral obstructions—even if the obstruction had been caused by malignant disease (e.g., retroperitoneal fibrosis, postradiation strictures, and iatrogenic ureteral injuries)—were excluded from the study.

Surgical procedure and follow-up protocol

With the patient under general anesthesia, the obstructed segment was assessed by either antegrade, retrograde, or combined ureterography. A 0.035 in composite guidewire with a hydrophilic floppy tip (Sensor™, Boston Scientific, Natick, MA) was introduced through the obstruction. In most of the patients, this maneuver necessitated reinforcing of the guidewire by either 5F ureteral or angled hydrophilic catheters (Imager II™, 40 cm, Boston Scientific) passed through an 8/10 coaxial introducer (8/10 Dilator/Sheath set, Boston Scientific). The ureteral narrowing was dilated, as needed, by a pressure balloon up to 15–18F with a 5F/10 cm high-pressure balloon (UroMax Ultra™, Boston Scientific), and a second 0.038 in nitinol kink-resistant guidewire (Zebra™, Boston Scientific) was inserted. Two 7F/26–28 cm hydrophilic low-friction 12-month dwelling time commercially available Double-J stents were then placed under fluoroscopy (Percuflex Plus™, Boston Scientific). A 14F Foley catheter was left in place overnight, and the patients were discharged on the following day. Large-spectrum perioperative antibiotics were administered in cases with a negative urine culture or according to the antibiogram findings in those with a positive urine culture.

The stents were placed with the intention to be maintained for their maximal 1 year indwelling time. The patient follow-up consisted of assessment of symptoms, measurements of creatinine levels, urinary cultures, and imaging tests every 3 months. The patients were electively referred for routine stent replacement annually.

Outcomes and statistical analysis

The primary outcomes of our study were stent failure and mortality. Stent failure was defined as the need to convert DIS to another method of drainage. Patients were free to choose other methods of drainage at any time during the study period. Patient survival and stent failure were estimated with Kaplan–Meier curves. The length of follow-up was measured by means of the reversed censoring method. The log-rank test and Cox regression analysis (univariate and multivariate) were applied to study the association between the primary outcomes and the categorical and continuous variables. Statistical significance was defined as p < 0.05. Analyses were performed with SPSS v.23 (IBM).

Results

General results

Demographics and by-entry clinical data are presented in Table 1. The mean age of the cohort was 60 years (standard deviation 13.9), and the median follow-up was 27 months (interquartile range [IQR] 20–31). Forty-five patients (72.6%) had distal obstruction and 13 (21%) had bilateral obstruction. The primary malignancy was colorectal in 19 (30%) patients, ovarian in 11 (18%), caused by a retroperitoneal sarcoma in 7(11%), gastric in 4 (6%), cervical in 4 (6%), and uterine in 3 (5%). Twenty-eight patients (45%) had acute presentation, including flank pain (13%), renal function deterioration (30%), and sepsis (8%). The by-entry median estimated glomerular filtration rate (eGFR) calculated by the modification of diet in renal disease equation was 63 mL/(min/1.73 m²) (IQR 38–68). Sixteen patients (26%) had a history of abdominopelvic radiation and 29 patients (46%) had been previously drained [14 (22%) with PCN and 15 with a single Double-J stent (24%)]. DIS was feasible in all cases although 30 patients (48%) had required balloon dilation in the first procedure. There were no intra- or postoperative complications related to balloon dilation. Redilation was not needed at the time of DIS replacement. Five patients developed a urinary infection within 30 days after the procedure, and they all were treated with antibiotics. Mild stent encrustations, especially on the distal edge of the stents, occurred in one patient. This was resolved by holmium laser cystolithotripsy and diagnostic ureteroscopy at the planned time of stents replacement. This patient had no previous history of urolithiasis. No obstruction occurred on this patient as assessed by creatinine level and PET-CT performed 2 weeks before the procedure for oncologic stage follow-up.

Table 1.

Study Population Demographics and By-Entry Data (N = 62)

Variable	Value
Age, years, mean	60 (SD 13.9)
Gender
Male	13 (20.9%)
Female	49 (79.1%)
Side of obstruction
Left	27 (43.6%)
Right	22 (35.5%)
Both	13 (20.9%)
Level of obstruction
Proximal	17 (27.4%)
Distal	45 (72.6%)
Cause of obstruction
Colorectal cancer	19 (30.6%)
Ovarian cancer	11 (17.7%)
Sarcoma	7 (11.3%)
Cervical cancer	4 (6.5%)
Gastric cancer	4 (6.5%)
Uterine cancer	3 (4.8%)
Other	14 (22.6%)
Presentation
Hydronephrosis^a	34 (54.8%)
Pain	8 (12.9%)
Renal function deterioration	19 (30.6%)
Sepsis	5 (8.1%)
eGFR, mL/(min/1.73 m²), median (IQR)	63 (38–68)
History of abdominopelvic radiation	16 (25.8%)
PCN at presentation nephrostomy	14 (22.5%)
Single Double-J stent at presentation	15 (24%)
Balloon dilation in first procedure	30 (48%)

Significant hydronephrosis diagnosed by cross-sectional imaging.

eGFR = estimated glomerular filtration rate; IQR = interquartile range; PCN = percutaneous nephrostomy; SD = standard deviation.

Stent failure and patient mortality

During the study period we performed 94 renal units DIS replacements, 77 (82%) of them at 12 months as planned according to the study protocol. Six patients experienced stent failure of them two after initial placement, three after first year replacement, and one after second year replacement (Fig. 1a). The average time to failure was 15 months (range 1–27) (Fig. 1a). The causes for stent failure were renal function deterioration in three patients, uncontrollable urosepsis in two patients, and intractable severe hematuria in one patient. Thirty-nine (63%) patients died during the study period, with a median disease-specific survival of 21 months (IQR 8.6-not reached, Fig. 1b). The median number of yearly replacements per patient was 1 (range 0–7). Twelve (19%) patients accomplished more than two elective replacements (Fig. 1). Balloon dilation (hazard ratio [HR] = 2.1, p = 0.02, 95% confidence interval [CI] 1.1–4.1) and eGFR ≤60 mL/(min/1.73 m²) (HR = 2.1, p = 0.02, 95% CI 1.1–4.2) were independent risk factors for mortality (univariate and multivariate Cox regression analysis, Table 2). An eGFR value ≤45 mL/(min/1.73 m²) and a history of abdomen/pelvic radiation were significantly associated with stent failure (both p < 0.05, Table 2).

FIG. 1.

Kaplan–Meier curves showing (a) stent failure and (b) disease-specific survival.

Table 2.

Univariate and Multivariate Cox Regression Model Predicting Stent Failure and Mortality of Patients Treated by Double Internal Stents for External Malignant Ureteral Obstruction During the Study Period (2007–2019)

Variables	Univariate analysis			Multivariate analysis
Variables	p	HR	95% CI	p	HR	95% CI
Stent failure
Age	0.8	—	—
Gender	0.5	—	—
History of radiation	0.05	5.06	01/27/07
Cause of obstruction	0.8	—	—
Side	0.2	—	—
Level	0.16	—	—
eGFR ≤45 mL/(min/1.73 m²)	0.01	16.07	01/08/39
Presenting with drainage^a	0.7	—	—
Balloon dilation	0.8	—	—
Disease-specific mortality
Gender	0.8	—	—	1.2	0.5–2.6	0.6
Age	0.6	—	—	1	0.9–1	0.8
eGFR ≤60 mL/(min/1.73 m²)	0.01	2.1	1.2–4.3	0.02	2.1 1.1–4.2	1.1–4.2
Balloon dilation	0.01	2.2	1.1–4.3	0.02	2.1	1.1–4.1

PCN or single Double-J stent.

95% CI = 95% confidence interval; HR = hazard ratio.

Secondary outcomes

Twenty-six patients (42%) sustained DIS-related complications and side effects. Seven patients (11%) underwent early interventions, including stent replacement or temporary concurrent PCN caused by urosepsis in five patients and creatinine elevation in two patients. Nineteen patients were treated conservatively for urinary tract infections (UTIs) in 10 patients, irritative symptoms or pain in 10 patients, and hematuria in 3 patients. All patients in this group treated either invasively or conservatively were satisfied with the treatment and wished to continue with the stenting method; only two patients who sustained complications eventually failed.

Discussion

PCN is often recommended by oncologists as the first-line solution for patients with MUO who present with renal function deterioration or urinary infection. It is also recommended for patients with MUO and significant hydronephrosis to preserve kidney function for future therapies or to prevent chronic kidney disease. These patients are usually not suitable for reconstructive procedures because of comorbidities and advanced oncologic stage, whereupon simple palliative means are needed. PCN, however, significantly affects the patient's QoL because of external tubes and bags as well as frequent complications, such as tube obstruction, displacement, skin irritation and/or inflammation, hematuria, and UTIs.^6,7,12
–14 In addition, it requires routine replacement every 3 months under sedation or local anesthesia. Internalization of kidney drainage may potentially be more advantageous in such cases.

Various methods for internal relief of MUO have been reported for the past decade.^3,7 DIS was first introduced by Liu and Hrebinko⁹ in 1998 based on the rationale that in comparison with a single stent this concept may provide an additional extraluminal flow between the stents.¹⁵ The available literature suggests that insertion of DIS is feasible, safe, and superior to a single-stent approach (polymeric or metallic) in the short term.^3,4,11 A recently published study on 81 patients treated by DIS reported a 72.9% success rate after a short-term median follow-up of 32 weeks (IQR 24–67).¹⁵ Other short-term studies^{9
–11,14,16} exhibited similar results. Elsamra et al.³ reported a success rate of 59% (20/34) in a series of 34 patients with DIS, using Double 6F stents, who were followed for a median period of 17 months. However, the mean replacement time was only 4.3 months in this series. It is possible that size (6F) and type (which is not mentioned by authors) of stents as well as therapeutic concept led to the relative early replacement reported by these authors. As such, it appears that this study using 7F advanced polymeric stents with 12 months dwelling time is the first to report real long-term outcomes in a large series of patients. Our rationale was that long-term success should be measured by uninterrupted drainage and adherence of patients to treatment, and we propose the use of this definition for consistency in future studies on long-term solutions for MUOs.

Our study findings demonstrated a 100% feasibility of DIS and suggest that it does not carry risks for major complications. The 12-month 7F dwelling stents permitted long-term effective drainage with annual replacement in most of the patients, low rates of permanent failures, and a significantly reduced number of procedures per patient (median 1 replacement/surviving patient).

We are aware of the DIS disadvantages that are related to symptoms of irritation, pain, and hematuria. However, none of the patients, including the 14 (22%) patients who presented with PCN before the procedure, wished to convert to PCN, which we believe is indicative of good tolerance, adherence to treatment, and satisfaction. As expected, most of the complications were infectious and explainable by the presence of foreign bodies in the urinary tract. However, because of the risk of promoting resistant species, we, nevertheless, recommend reserving antibiotic therapies only when clinical signs of infection appear and concur with others who object to prolonged prophylactic antimicrobial therapy.^17,18 Our statistical analysis by means of Cox regression model pointed out some independent predicting factors for stent failure and mortality. First, eGFR ≤45 mL/(min/1.73 m²) was associated with stent failure, and ≤60 mL/(min/1.73 m²) doubled (HR = 2.1) the risk for mortality. An eGFR value ≤60 mL/(min/1.73 m²) represents moderate to severe kidney damage, which is well recognized as a general risk factor of mortality.¹⁹ However, most of our patients improved their eGFR to the normal or mildly elevated ranges after receiving DIS. Therefore, we suggest that the association between low eGFR and mortality or stent failure is rather explained by the extent of the underlying malignant disease and the severity of the obstruction, which elevated the creatinine levels. Moreover, a history of abdominopelvic radiation predisposes a patient for stent failure. This finding is supported by reports on radiation-induced tight ureteral strictures as a late radiation complication.^20,21 Finally, the need for balloon dilation in the first procedure reflects the severity of the MUO resulting from the aggressive nature of the disease, and may explain the association between balloon dilation and mortality (HR = 2.1). Several predictors for single-stent failure, including severe hydronephrosis and preoperative high serum creatinine levels, have been reported.^22
–24 Haifler and colleagues found that metastasis and prior PCN predicted the failure of DIS for the short term.¹⁵ All these predicting factors, including ours, share the presumption that disease extent and obstruction severity probably determine the DIS prognosis.

The limitations of our study are derived mostly from its retrospective nature. We believe that the consecutive and standardized procedures as well as long-term follow-up mitigate this limitation and provide important information for urologists dealing with MUO. Additional limitations include lack of comparison with other methods of drainage and no quantitative assessment of QoL.

Conclusions

A 12-month indwelling DIS provides durable long-term relief of MUO. It represents a valuable alternative to other methods of urinary drainage by prolonging interprocedural intervals and avoiding external tubes and bags. Patient adherence to the DIS approach suggests its advantages in terms of QoL.

Ethical Statement

Institutional Review Board (IRB) approval was obtained for this study and patient informed consent was obtained before undergoing the procedures.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Abbreviations Used

References

Kouba

, Wallen

, Pruthi

. Management of ureteral obstruction due to advanced malignancy: Optimizing therapeutic and palliative outcomes. J Urol, 2008; 180:444–450.

Siegel

, Miller

, Jemal

. Cancer statistics, 2016. CA Cancer J Clin, 2016; 66:7–30.

Elsamra

, Motato

, Moreira

, et al. Tandem ureteral stents for the decompression of malignant and benign obstructive CHNe uropathy. J Endourol, 2013; 27:1297–1302.

Elsamra

, Leavitt

, Motato

, et al. Stenting for malignant ureteral obstruction: Tandem, metal or metal-mesh stents. Int J Urol, 2015; 22:629–636.

Fiuk

, Bao

, Calleary

, Schwartz

, Denstedt

. The use of internal stents in chronic ureteral obstruction. J Urol, 2015; 193:1092–1100.

Monsky

, Molloy

, Jin

, et al. Quality-of-life assessment after palliative interventions to manage malignant ureteral obstruction. Cardiovasc Intervent Radiol, 2013; 36:1355–1363.

Allen

, Longhorn

, Philp

, Smith

, Choong

. Percutaneous urinary drainage and ureteric stenting in malignant disease. Clin Oncol, 2010; 22:733–739.

Liatsikos

, Kallidonis

, Stolzenburg

. Ureteral stents: Past, present and future. Expert Rev Med Devices, 2009; 6:313–324.

Liu

, Hrebinko

. The use of 2 ipsilateral ureteral stents for relief of ureteral obstruction from extrinsic compression. J Urol, 1998; 159:179–181.

10.

Rotariu

, Yohannes

, Alexianu

, et al. Management of malignant extrinsic compression of the ureter by simultaneous placement of two ipsilateral ureteral stents. J Endourol, 2001; 15:979–983.

11.

Varnavas

, Bolgeri

, Mukhtar

, Anson

. The role of tandem Double-J ureteral stents in the management of malignant ureteral obstruction. J Endourol, 2016; 30:465–468.

12.

Efesoy

, Saylam

, Bozlu

, Cayan

, Akbay

. The results of ultrasound-guided percutaneous nephrostomy tube placement for obstructive uropathy: A single-centre 10-year experience. Turk J Urol, 2018; 44:329–334.

13.

Soto Delgado

, Varo Solís

, Bachiller Burgos

, Beltrán Aguilar

. Percutaneous nephrostomy as management technique of obstructive uropathy: Review of 105 cases. Actas Urol Esp, 2000; 24:568–572.

14.

Fromer

, Shabsigh

, Benson

, Gupta

. Simultaneous multiple double pigtail stents for malignant ureteral obstruction. Urology, 2002; 59:594–596.

15.

Haifler

, Shvero

, Zilberman

, et al. Tandem ureteral stents for malignant ureteral obstruction. J Endourol, 2019; 34:222–226.

16.

Chen

, Shen

, Wang

, et al. Parallel second stent placement for refractory ureteral stent malfunction in malignant ureteral obstruction. J Vasc Interv Radiol, 2011; 22:1012–1016.

17.

Hyams

, Shah

. Malignant extrinsic ureteral obstruction: A survey of urologists and medical oncologists regarding treatment patterns and preferences. Urology, 2008; 72:51–56.

18.

Davey

, Marwick

, Scott

, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev, 2017; 2:CD003543.

19.

Webster

, Nagler

, Morton

, Masson

. Chronic kidney disease. Lancet, 2017; 389:1238–1252.

20.

Green

, Kirwan

, Tierney

, et al. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: A systematic review and meta-analysis. Lancet, 2001; 358:781–786.

21.

Elliott

, Malaeb

. Long-term urinary adverse effects of pelvic radiotherapy. World J Urol, 2011; 29:35–41.

22.

Chow

P-M

, Hsu

J-S

, Huang

C-Y

, et al. Metallic ureteral stents in malignant ureteral obstruction: Clinical factors predicting stent failure. J Endourol, 2014; 28:729–734.

23.

, Ryu

, Jeong

, et al. Predicting factors for stent failure-free survival in patients with a malignant ureteral obstruction managed with ureteral stents. Korean J Urol, 2013; 54:316–321.

24.

Matsuura

, Arase

, Hori

. Ureteral stents for malignant extrinsic ureteral obstruction: Outcomes and factors predicting stent failure. Int J Clin Oncol, 2019; 24:306–312.