Abstract
Background:
Prophylactic ureteral stents (PUS) are typically placed prior to complex abdominal or pelvic operations at the surgeon’s discretion to help facilitate detection of iatrogenic ureteral injury. However, its usefulness and safety in the setting of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) have not been examined. This study aims to evaluate the potential clinical value and risk profile of prophylactic ureteral stent placement prior to CRS-HIPEC.
Methods:
We performed a single-institutional retrospective analysis of 145 patients who underwent CRS-HIPEC from 2013–2021. Demographic and operative characteristics were compared between patients who underwent PUS placement and those that did not. Ureteral stent-related complications were evaluated.
Results:
Of the 145 patients included in the analysis, 124 underwent PUS placement. There were no significant differences in patient demographics, medical comorbidities, or tumor characteristics. Additionally, PUS placement did not significantly increase operative time and was not associated with increased pelvic organ resection. However, patients who underwent prophylactic ureteral stenting had significantly higher peritoneal carcinomatosis index score (15.1 vs 9.1, p=0.002) and increased rate of ureteral complications (24.2% vs 14.3%, p=0.04), which led to lengthened hospital stay (13.2 days vs 8.1 days, p=0.03). Notably, the sole ureteral injury and three cases of hydronephrosis were seen in patients who underwent PUS.
Conclusion:
PUS placement in patients undergoing CRS-HIPEC may be useful, particularly in patients with predetermined extensive pelvic disease. However, PUS placement is not without potential morbidity and should be selectively considered in patients for whom benefits outweigh the risks.
Keywords: Surgical Oncology, HIPEC, General Surgery
Introduction
Ureteral injuries are a feared but infrequent complication seen in abdominal and pelvic surgery. Several studies report iatrogenic ureteral injury rates of 0.5% - 1.7% in open colorectal and pelvic surgeries1–3. Such a complication can result in significant morbidity, including renal failure and sepsis with consequent increased hospital cost and length of stay4–6. In patients undergoing colorectal or pelvic operations, distorted anatomy due to malignancy, inflammation, adhesive disease from prior operations, or radiation may increase the chance of iatrogenic intraoperative ureteral injury.
The placement of prophylactic ureteral stents (PUS) has long been investigated and discussed as a technique to help facilitate detection of ureteral injury if it occurs. Several studies have documented conflicted results regarding the usefulness of PUS with varying rates of iatrogenic injury and mixed benefit7–9. A recent metanalysis found that iatrogenic ureteral injury occurred in 1.75% of patients with pre-operatively placed PUS and only 0.2% in patients without PUS placement during open colorectal surgery. There was no significant difference in rate of intraoperative recognition of ureteral injury2. Several other studies have also demonstrated increased cost associated with PUS placement and higher rates of acute kidney injury (AKI)10–12. While there are no formal recommendations or guidelines from surgical societies on the use of PUS, individual surgeons weigh the potential benefits against the feared risk of iatrogenic ureteral injury, particularly in patients undergoing large abdominal or pelvic debulking procedures in which the anatomy may be distorted. Such procedures include cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for patients with peritoneal carcinomatosis, which involves peritoneal dissemination of cancer. These patients have frequently undergone a previous cancer resection, have undergone chemotherapy treatment, and many require pelvic organ resections, such as sigmoid colectomies, hysterectomies, retroperitoneal stripping, and pelvic peritonectomies. The potential benefit of routine PUS placement in this patient setting is unknown. This study aims to evaluate the clinical effectiveness of prophylactic ureteral stent placement in patients undergoing CRS-HIPEC and to determine its risk profile.
Methods
Data Sources and Definitions
Data was retrospectively obtained from a prospectively maintained database of all patients who underwent CRS-HIPEC with aim for complete cytoreduction between 2013–2021 at our institution after approval by our institutional review board (approval #200638). Our Patients were divided into two groups: the STENT group consisted of patients who underwent PUS placement prior to CRS-HIPEC based on evaluation of operative reports, while the NO STENT group consisted of patients who did not. Baseline patient demographics, medical history, and operative data were examined between the two groups. Oncologic data, such as peritoneal carcinomatosis index (PCI) and completion of cytoreduction score (CCR) were obtained from the surgeon’s CRS-HIPEC operative note. Tumor histologic data were obtained from the final pathology report from the primary tumor specimen. The presence of ureteral complications was derived from daily progress notes and the patient’s discharge summery. The ureteral complications were defined as follows: iatrogenic ureteral injury requiring intervention, urinary tract infection (UTI) requiring antibiotic treatment, postoperative urinary retention (POUR) requiring re-insertion of urethral catheter, and hydronephrosis requiring intervention.
Statistical Analysis
Categorical variables were compared using Chi-squared test, and continuous variables were expressed as means and compared using Mann-Whitney U test. Multivariate logistic regression analysis of factors associated with ureteral complications, including placement of a prophylactic ureteral stent, PCI, and pelvic organ resection was performed using Cox regression analysis. All analyses were performed using the IBM Statistical Package for the Social Sciences for Mac, Version XX (IBM Corp., Armonk, N.Y., USA).
Results
Patient and Operative Characteristics
A total of 145 patients who underwent CRS-HIPEC from 2013–2021 at our institution were included in this study. Of these, 86% (124) underwent prophylactic ureteral stent placement, while 14% (21) did not. There were no significant demographic or comorbidity differences between patients in the two groups. Most notably, patients in both groups had undergone a similar number of prior abdominal surgeries, had similar peritoneal surface disease severity scores (PSDSS) and had similar primary tumor locations and grades. The most common primary tumor was appendiceal and the majority were low-grade. Over 80% of patients in each group were able to achieve a CCR score of 0 and most of the patients in each group underwent a colon resection (STENT 75% vs NO STENT 67%, p= 0.7) and a pelvic peritonectomy (STENT 63% vs NO STENT 53%, p=0.4). Patients in the STENT group had significantly higher PCI scores compared to the NO STENT group (15.1 vs 9.1, p= 0.002). While operative times in the STENT group were increased by an average of 29 minutes, this was not significantly higher than the operative times in the NO STENT group (527 vs 497 minutes, p= 0.37). Baseline demographic and operative characteristics are outlined in Table 1.
Table 1:
Demographics and Operative Characteristics
| Variables | Stent % (n) | No Stent % (n) | p Value |
|---|---|---|---|
| Total | 86% (124) | 14% (21) | |
| Gender | 0.92 | ||
| Male | 49% (61) | 47.6% (10) | |
| Female | 51% (63) | 52.4% (11) | |
| Age (years) (mean ± std) | 52.6 years ± 12.1 | 52.3 ± 12.7 | 0.88 |
| Ethnicity | 0.14 | ||
| White | 87% (108) | 73% (15) | |
| Black | 12.% (15) | 27% (6) | |
| Other | 1% (1) | 0% (0) | |
| BMI (mean ± std) | 27. 3± 3.2 | 27.8 ± 6.3 | 0.92 |
| ASA Class | 0.34 | ||
| 1 | 1.0% (1) | 0% (0) | |
| 2 | 15% (18) | 27% (6) | |
| 3 | 80% (100) | 73% (15) | |
| 4 | 4% (5) | 0% (0) | |
| Peritoneal Surface Disease Severity Score (mean ± std) | 7.0 ± 2.1 | 7.4 ± 3.3 | 0.37 |
| Charlson Comorbidity Index (mean ± std) | 7.3 ± 1.4 | 7..1± 2.2 | 0.22 |
| Number of Prior Abdominal Surgeries (mean ± std) | 1.6 ± 0.8 | 1.5 ± 0.6 | 0.76 |
| Primary Tumor Location | 0.07 | ||
| Colorectal Tumor | 30% (37) | 19% (4) | |
| Appendiceal Tumor | 58.8% (73) | 52.3% (10) | |
| Peritoneal Mesothelioma | 5.6% (7) | 14% (3) | |
| Ovarian Tumor | 5.6% (7) | 19% (4) | |
| Tumor Grade | 0.2 | ||
| High-grade | 31.5% (39) | 47.7% (10) | |
| Intermediate Grade | 14.5% (18) | 19% (4) | |
| Low Grade | 54% (67) | 33.3% (7) | |
| Peritoneal Carcinomatosis Index (mean ± std) | 15.1 ± 10.3 | 9.1 ± 6.7 | 0.002 |
| Completion of Cytoreduction Score | 0.08 | ||
| 0 | 87% (108) | 85% (18) | |
| 1 | 13% (16) | 10% (2) | |
| 2 | 0% (0) | 5% (1) | |
| Pelvic Peritonectomy | 63% (78) | 53% (11) | 0.40 |
| Hysterectomy and/or Oophorectomy | 20% (25) | 19% (4) | 0.90 |
| Colon Resection | 0.70 | ||
| Right | 41% (51) | 33% (7) | |
| Transverse | 4% (5) | 10% (2) | |
| Low Anterior Resection | 18% (22) | 14% (3) | |
| Previous Anastomosis | 12% (15) | 10% (2) | |
| None | 25% (31) | 33% (7) | |
| Operative Time (minutes) (mean ± std) | 526 ± 118 | 497 ± 149 | 0.37 |
Ureteral Complications
Within the STENT group, more patients were diagnosed with a ureteral complication compared to the STENT group (24.2% vs 14.3%, p=0.04). The most common ureteral complication was UTI (STENT 13% vs 4.7%, p= 0.02). There were similar rates of post-operative urinary retention requiring foley catheter reinsertion. In 3 patients, all within the STENT group, postoperative hydronephrosis and acute kidney injury occurred requiring ureteral re-stenting. Furthermore, the sole patient with a ureteral injury was in the STENT group. This injury was diagnosed intra-operatively and repaired over the prophylactically placed ureteral stent. In a multivariate analysis including placement of a prophylactic ureteral stent, PCI, and pelvic organ resection (pelvic peritonectomy, hysterectomy and/or oophorectomy, or low anterior resection), placement of a ureteral stent was independently associated with a ureteral completion (HR 3.2, 95% CI 1.4 – 4.1, p=0.04). Among patients who sustained a ureteral complication after PUS placement, their hospital length of stay was significantly increased (13.2 days vs 8.1 days, p= 0.03) compared to patients who underwent PUS placement and did not sustain a ureteral complication A review of ureteral complications seen in our patient cohort is presented in Table 2.
Table 2:
Ureteral Complications Associated with Prophylactic Ureteral Stents
| Variables | Stent % (n) | No Stent % (n) | p Value |
|---|---|---|---|
| Ureteral Complication | 24.2% (30) | 14.3% (3) | 0.04 |
| Ureteral Injury | 0.8% (1) | 0% (0) | 0.7 |
| Urinary Tract Infection | 13% (16) | 4.7% (1) | 0.02 |
| Urinary Retention | 8% (10) | 9.5% (2) | 0.6 |
| Hydronephrosis (Ureteral re-stenting) | 2.4% (3) | 0% (0) | 0.4 |
Discussion
In this retrospective study, we observed that the rate of iatrogenic ureteral injury after placement of prophylactic ureteral stents prior to cytoreductive surgery with hyperthermic intraperitoneal chemotherapy was 0.8% and 0.7% overall, despite the high number of pelvic and colorectal resections. Our data is consistent with previously published literature. However, our data suggests that the clinical benefit of PUS placement may not be clearly evident. Patients requiring an extensive pelvic dissection and resection of pelvic organs can potentially benefit the most from placement of PUS. Nonetheless, patients in both groups underwent similar rates of pelvic peritonectomies, left colon resections, and hysterectomies without any increased risk of iatrogenic ureteral injury in the NO STENT group.
Patients in the STENT group had significantly higher PCI scores, which is indicative of more widespread peritoneal dissemination and larger peritoneal disease burden. Despite having higher PCI scores, patients in the STENT group were able to achieve CCR 0 scores at a similar rate to the NO STENT group and had no patients with a CCR score of 2, while 5% of patients in the NO STENT group did. This constellation of findings suggest that the placement of PUS may help facilitate pelvic dissection to achieve a complete cytoreduction in the setting of more extensive disease. Thus, PUS placement may be of benefit in patients with known extensive burden of peritoneal disease preoperatively.
Our findings should be understood in the context of PUS-associated morbidity. 24.2% of patients who underwent PUS placement experienced stent-related complications, the most common being urinary tract infection and urinary retention. Urinary tract infections are a major source of postoperative morbidity and is a costly yet preventable complication13. Such infections are likely due to contamination secondary to urethral instrumentation that occurs with PUS placement and with the indwelling urinary catheter that remains postoperatively. The risk of developing a UTI is increased with prolonged urinary catheterization and thus must be balanced with the risk of POUR, which can occur after discontinuation of an indwelling urinary catheter14,15. In patients who underwent PUS placement, ureteral mucosal edema may develop which can lead to POUR and even hydronephrosis16. The development of post-operative hydronephrosis is likely due to ureteral stenosis due to spasm, tissue edema, scar formation, or related to the thermal and chemical pressures of CRS-HIPEC17,18. In the STENT group, 2% of patients developed hydronephrosis requiring ureteral stent reinsertion, while no patients in the NO STENT required another intervention. This suggests that, although the nature of CRS-HIPEC may impact hydronephrosis, the placement of ureteral stents is likely the driving factor in the development of hydronephrosis. Furthermore, the development of postoperative hydronephrosis is generally accompanied with AKI. Although the exact pathophysiology of AKI after PUS placement is unknown, it is likely related to traumatic mucosal edema due to stent placement and removal as well as CRS-HIPEC17. Regardless of the specific complication associated with PUS placement, patients who experienced PUS-related morbidity had significantly increased hospital length of stay compared to patients who did not have a stent-related complication. Such a consequence underscores the risk profile associated with PUS placement and should encourage surgeons to selectively consider which patients would incur the most potential benefit and accumulate the least risk with PUS placement.
The limitations of this study revolve mainly around its retrospective nature and sample size. Although this is the largest analysis of routine PUS placement in patients undergoing CRS-HIPEC, ureteral injuries are rare in open abdominopelvic operations. This retrospective study describes the risk profile of routine PUS placement in patients undergoing CRS-HIPEC and identifies patients who could derive potential benefit rather than recommend for or against the routine placement of PUS. To further elucidate the benefit of PUS placement in CRS-HIPEC, prospective studies with matched patient cohorts or randomized control trials should be conducted. The authors recognize that preoperative diagnostic imaging is at times unreliable in defining the extent and location of peritoneal carcinomatosis, thus identifying patients who would benefit from PUS difficult19,20. Nonetheless, the data in this large retrospective study suggests that selective use of PUS in patients with known high PCI scores or significant pelvic disease based on preoperative imaging or diagnostic laparoscopy may facilitate complete cytoreduction, while minimizing risk of stent-related complications in patients who are least likely to benefit from PUS placement.
In this retrospective analysis, we demonstrate that prophylactic ureteral stent placements in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should be selective given its associated morbidity. Patients who derive the most potential benefit are those with known or anticipated extensive disease burden in the pelvis with expected pelvic organ resection based on preoperative imaging or diagnostic laparoscopy.
Table 3:
Multivariate Analysis of factors associated with Ureteral Complications
| Variables | HR | 95% CI | p Value |
|---|---|---|---|
| Prophylactic ureteral stent placement | 3.2 | 1.4 – 4.1 | 0.04 |
| Peritoneal carcinomatosis index | 0.04 | 0.97 – 1.09 | 0.64 |
| Pelvic organ resection (pelvic peritonectomy, | 1.9 | 0.19 – 3.82 | 0.85 |
Key Take-Aways.
Patients who undergo prophylactic ureteral stent placement prior to cytoreductive surgery with hyperthermic intra-peritoneal chemotherapy are at increased risk for ureteral complications, which is associated with increased hospital length of stay.
Prophylactic ureteral stenting should be selectively considered in patients for whom the benefits outweigh the risks.
Acknowledgements
We would like to acknowledge our funding source, the National Cancer Institute (T32CA106183).
Contributor Information
David Hanna, Vanderbilt University Medical Center, Section of Surgical Sciences.
Andrew Hermina, Meharry Medical College.
Emma Bradley, Vanderbilt University Medical Center, Section of Surgical Sciences, Department of Surgery, Division of Surgical Oncology and Endocrine Surgery.
Muhammad Ghani, Vanderbilt University Medical Center, Section of Surgical Sciences, Department of Surgery, Division of Surgical Oncology and Endocrine Surgery.
Alexander Mina, Vanderbilt University School of Medicine.
Christina Bailey, Vanderbilt University Medical Center, Section of Surgical Sciences, Department of Surgery, Division of Surgical Oncology and Endocrine Surgery.
Kamran Idrees, Vanderbilt University Medical Center, Section of Surgical Sciences, Department of Surgery, Division of Surgical Oncology and Endocrine Surgery.
Deepa Magge, Vanderbilt University Medical Center, Section of Surgical Sciences, Department of Surgery, Division of Surgical Oncology and Endocrins Surgery.
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