Novel Software-Assisted Hemodynamic Evaluation of Pelvic Flow During Chemoperfusion of Pelvic Arteries for Bladder Cancer: Double- Versus Single-Balloon Technique
Approximately 83 % of patients with bladder cancer have achieved a complete response after undergoing a novel bladder preservation therapy involving balloon-occluded intra-arterial infusion chemotherapy (BOAI) using a four-lumen double-balloon catheter, known as the Osaka Medical College regimen. This study aimed to show the quantitative difference in hemodynamics of the bladder arteries using syngo iFlow (Siemens Healthcare, Erlangen, Germany), which provides an automatic tool for quantitative blood flow analysis between double BOAI (D-BOAI) and conventional single BOAI (S-BOAI).
Materials and Methods
Fifty patients were included. The catheters were introduced into both posterior trunks of the internal iliac arteries via contralateral femoral artery access. A side hole between the distal and proximal balloons was placed at the origin of each bladder artery to allow clear visualization of angiographic flow of the injected agent into the urinary bladder. Digital subtraction angiography was used during analysis with the syngo iFlow to evaluate the hemodynamics of the contrast medium in the pelvic arteries during BOAI. The comparative change in the amount of contrast medium in the bladder arteries between D-BOAI and S-BOAI was assessed using syngo iFlow.
One-hundred pelvic sides were analyzed. The amount of contrast medium in the bladder arteries using D-BOAI was more than twice that using S-BOAI (right, 3.03-fold; left, 2.81-fold).
The amount of contrast medium in the bladder arteries using D-BOAI was higher than that using conventional S-BOAI. This may increase the anticancer drug concentration in the affected bladder, leading to a good clinical response.
KeywordsInvasive bladder cancer Double balloon-occluded arterial infusion Syngo iFlow
The gold-standard therapy for locally invasive bladder cancer has long been radical cystectomy with pelvic lymph node dissection. However, approximately 50 % of all patients with invasive bladder cancer die, and the outcome of this disease is closely related to its pathologic stage . A highly effective but minimally invasive therapy that conserves the bladder is therefore needed. Combined treatment involving radical transurethral resection, chemotherapy, and radiation therapy has been attempted as an alternative approach for patients who require cystectomy.
A novel bladder preservation therapy known as the Osaka Medical College (OMC) regimen has resulted in good clinical responses [1, 2, 3, 4, 5, 6, 7, 8, 9]. This regimen adopts double balloon-occluded arterial infusion (D-BOAI) using an original four-lumen double-balloon (4L-DB) catheter. The proximal balloon is located in the internal iliac artery upstream of the bifurcation of the superior gluteal artery. The distal balloon is located at the origin of the superior gluteal artery to isolate the anterior trunk of the internal iliac artery, which lies upstream of the target bladder arteries (BAs) between the balloons. We considered this balloon position suitable, given the variable origins of BAs. It is thought that D-BOAI using the double balloons of the 4L-DB catheter allows for accumulation of a higher concentration of the anticancer agent at the tumor site without flow to other tissues than conventional single balloon-occluded arterial infusion (S-BOAI) using a single-balloon catheter.
Previous studies have angiographically confirmed more accumulation of contrast medium in the tumor site with D-BOAI than with S-BOAI, which might be related to the good clinical response. However, no clinical studies have objectively evaluated the hemodynamics associated with BOAI for patients with bladder cancer. The syngo iFlow (Siemens Healthcare GmbH, Erlangen, Germany) is a software application that uses all of the scenes in a given digital subtraction angiography (DSA) sequence to generate a color map that displays the time of maximum opacification. The further function of iFlow allows retrieval of time–intensity curves for a given point or region of interest (ROI) on the color map. Strother et al. previously described the underlying mathematic model for iFlow . The syngo iFlow has recently enabled analysis of the difference in hemodynamic statuses of the pelvic vessels between D-BOAI and S-BOAI. Therefore, the present study aimed to show the quantitative difference in the hemodynamics of BAs between D-BOAI and S-BOAI in patients with bladder cancer.
Materials and Methods
Age in years, median (range)
T-stage before TUR-Bt
BOAI Procedure and Imaging Protocol
All angiograms were obtained using the same angiography equipment (Artis zee BA, Siemens AG), and the same injection parameters after bilateral catheters were connected to one high-pressure-resistant extension tube from a contrast medium injector (Mark V ProVis Angiographic Injection System; Medrad, Inc., Warrendale, PA, USA). DSA was performed using the following parameters: 10 mL of iopamidol (370 mgI/mL) injected at a rate of 1.5 mL/s in an anteroposterior position at 4 frames per second. The DSA series were then postprocessed for analysis using the syngo iFlow.
Postprocessing of DSA Images
Data and Statistical Analysis
Changes in CV (CV for the ROI with D-BOAI/CV for the ROI with S-BOAI) for the BA, IGA, and SGA
Change in CV
Average (right) (fold)
Average (left) (fold)
2.01 (range, 0.62–12.00)
1.44 (range, 0.19–10.70)
0.31 (range, 0.09–1.62)
The syngo iFlow system provides a method for extracting more objective and quantitative information when comparing subjective and qualitative evaluations involving the accumulation of contrast medium during standard DSA. The software tool displays dynamic information in a colorful static image in which different-colored scales mark the history of the contrast medium through vessels. The quantitative measurements of the hemodynamic condition are recorded and depicted using syngo iFlow. Previous reports have also described hemodynamic analysis in the head and neck or liver using syngo iFlow [10, 11, 12, 13, 14].
The OMC regimen—a novel therapy for bladder preservation in patients with invasive bladder cancer that involves D-BOAI of an anticancer agent using a 4L-DB catheter—has been used in our hospital for two decades. We have observed improved treatment outcomes using this regimen relative to conventional treatment entailing radical cystectomy with pelvic lymph node dissection [1, 2, 3, 4, 5, 6, 7, 8, 9]. In patients with bladder cancer, several feeding arteries are present as branches of the internal iliac artery. Thus, it is difficult to perform selective arterial infusion into these feeding arteries. D-BOAI presumably delivers an extremely high concentration of anticancer agent to the tumor site. Greater accumulation of contrast medium at the tumor site with D-BOAI than with S-BOAI has been confirmed angiographically. However, no reports have described the use of syngo iFlow to assess the quantitative alterations in pelvic vessel hemodynamics as a result of the introduction of D-BOAI versus S-BOAI.
The use of syngo iFlow provides several advantages . First, the application of syngo iFlow does not require additional X-ray exposure because conventional DSA acquisitions can generate color-coded images and obtain quantitative information. Second, syngo iFlow is a real-time tool. Color-coded images with quantitative measurements are obtained immediately after acquisition of the DSA series. Third, hemodynamic conditions and changes can be quantitatively analyzed using parameters such as the AUC through syngo iFlow. This modality focuses not only on alterations in the flow dynamics of the tumor-feeding vessel but also on tumor perfusion, which is represented by the area under the time–intensity curve.
In the present study, it was quantitatively proved that more contrast medium accumulates in the BAs and less accumulates in the SGAs with D-BOAI than with S-BOAI. We assume that the alteration in the accumulation of contrast medium in the BAs with D-BOAI leads to a higher concentration of the anticancer drug in the bladder tissue using the OMC regimen, resulting in a better clinical response.
In conclusion, compared with S-BOAI, D-BOAI quantitatively increased the amount of contrast medium in the BAs by more than a factor of two. This may result in a higher concentration of anticancer drug in the affected bladder, leading to a good clinical response. However, the long-term clinical outcomes of the patients in this study have not yet been assessed. Further studies are needed to clarify the relation between drug concentration and clinical response.
We thank the members of the Department of Urology and Radiology, Osaka Medical College for technical support. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Compliance with Ethical Standards
Conflicts of Interest
All authors declare that they have no conflicts of interest.
Formal consent is not required for this type of study.
Statement of Informed Consent
Informed consent was obtained from all individual participants included in this study.
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