Surgical Outcomes of Fluorescence-Guided Laparoscopic Partial Nephrectomy Using 5-Aminolevulinic Acid-Induced Protoporphyrin IX

Background

To evaluate the clinical performance of photodynamic diagnostic (PDD) after oral administration of 5-aminolevulinic acid (5-ALA) for assessment of tumor type and surgical margins in laparoscopic nephron-sparing surgery.

Materials and Methods

This is a prospective, non-randomized single-center study. A total of 77 patients with a renal mass < 4 cm diameter underwent laparoscopic partial nephrectomy (LPN). For photosentization, 1.5 g 5-ALA was administered orally 4 h prior to surgery. During the operation, the resection site and the outer tumor border were inspected under excitation light for characteristic red fluorescence. The results of PDD were matched up to the histological findings.

Results

Mean operative time was 94.1 min with a mean warm-ischemia time of 23 min. Fifty-eight of 61 (95.1%) renal cell carcinomas showed a positive response when exposed to excitation light. In 16 cases (21%), final pathology revealed a nonmalignant lesion. However, characteristic fluorescence was also detected in 1 angiomyolipoma of 16 nonmalignant lesions. False-negative rate was 3/61 (4.9%) and false-positive rate was 1/77 (1.3%), with these data corresponding to a sensitivity of 95% and a specificity of 94%. Further, PDD with 5-ALA was able to predict the type of the lesion with an accuracy of 94% and with a positive predictive value of 98%. Furthermore, PDD with 5-ALA also identified both cases with positive resection margins, which were confirmed on histological examinations. No side effects of systemic 5-ALA administration were observed.

Conclusions

PDD after systemic administration of 5-ALA is a reliable tool to assess the type and the resection status of a suspected renal tumor during laparoscopic nephron-sparing surgery.

Introduction

The widespread use of routine ultrasound and advances in cross-sectional studies for detection of renal masses have led to a marked shift towards early diagnosis of smaller tumor sizes [1, 2]. Along with this, the indication for organ-preserving surgical therapy, originally reserved for patients at risk of end-stage renal disease, has been expanded. Long-term follow-up data for open nephron-sparing surgery (ONSS) demonstrated excellent results for tumors of 4 cm or less in diameter with local recurrence rates between 0% and 3% [1]. Further, the observation that up to 30% of tumors in this specific subgroup was of benign origin further supported the rationale for an organ-preserving approach.

Recently, minimally invasive strategies have become increasingly popular in the management of renal masses, and various authors have advocated laparoscopic partial nephrectomy (LPN) as a safe procedure for renal tumors of 4 cm or less in diameter [3, 4]. However, similar to the open partial nephrectomy (OPN), complete removal of entire malignant tissue with free resection boundaries is of utmost importance for the final oncological outcome. Therefore, the resection site is usually evaluated by means of frozen section analysis (FSA), which is a time-consuming procedure with a limited reliability and certain probability of false negative results [5]. Thus, alternative methods for intraoperative assessment of resection state during nephron-sparing surgery are currently under investigation.

Over the last decade fluorescence-guided diagnostic, also known as photodynamic diagnostic (PDD) is being used to differentiate healthy from diseased tissue in various medical disciplines. Particularly in urology, fluorescence diagnostic is utilized to visualize plane lesions of the urinary bladder during endoscopic transurethral interventions [6]. Fluorescence-guided diagnostic is based on ability of photosensitive agents to accumulate in malignant cells. The agents can be delivered to the tumor site via intravenous, oral, or topical application. After exposition to light of a specific wavelength—either directly or indirectly through a fiberoptic device—characteristic fluorescence of the photosensitizers occurs. However, the photosensitizer 5-aminolevulinic acid (5-ALA), widely used in urologic PDD, requires endogenous metabolism before it becomes fluorescent. Endogenous 5-ALA is metabolized through several enzymatic catabolic steps into protoporphyrin IX (PPIX) and then finally into the heme radical [7]. Protoporphyrin IX is a fluorescent agent when stimulated by a defined wavelength within its absorption spectrum. When PPIX is irradiated at a wavelength of 390 to 440 nm, it fluoresces at 635 nm (red), and can thus be used to identify tumor cells [8, 9].

In a previous study, we have demonstrated that PDD after oral administration of 5-aminolaevulinic acid (5-ALA) is a reliable tool for assessment of the resection margin in open partial nephrectomy [10]. Whether it also could be used in a laparoscopic setting of partial nephrectomy has not been tested so far. The aim of this study was therefore to evaluate the clinical performance of orally administered 5-ALA for intraoperative assessment of tumor type and resection margins in laparoscopic partial nephrectomy.