Intraoperative damage to ureter in rectal cancer – no fear with fluorescence

       Medically induced ureteral injury is a serious complication of colorectal cancer surgery, with an incidence ranging from 0.7% to 10%. In cases of inflammation, previous surgical history, and radiation therapy, the ureter is difficult to identify in surgical patients. In this case, the ureter can be placed preoperatively with a double J-stent, but this in turn will present other complications.  Fluorescent image-guided surgery has the potential to reduce the risk of surgical ureteral injury in patients. Intravenous methylene blue is excreted by the kidneys and concentrated in the urine. Methylene blue can be excited by 660 nm wavelength light and emits far-red/near-infrared light. Therefore, a fluoroscopic device can be used intraoperatively to locate the deep and superficial ureters.  Recent studies have reported that intraoperative fluoroscopy with methylene blue can be used for open pelvic surgery. Animal studies have demonstrated that methylene blue and other fluorescent dyes can visualize the ureter laparoscopically. Yeung et al, from the University of Oxford, reported the application of this technique to patients with intraoperative localization of the ureter. The article was published in the recent Annals of surgery.  The group recruited eight consecutive subjects, six of whom underwent laparoscopic surgery and two of whom were open. Inclusion criteria were all adult patients who underwent open or laparoscopic surgery for colorectal cancer. Exclusion criteria included non-signed consent forms, pregnancy, severe renal and or hepatic dysfunction, and all patients at potential risk for pentraxin syndrome.  Indications for surgery included colorectal cancer, endometriosis involving the rectum, with inflammatory bowel disease. Patients were between 27 and 76 years of age with a BMI range of 23 to 34 kg/m2. 0.25 to 1 mg/kg of methylene blue was administered slowly intravenously at a concentration of 10 mg/ml. Background and peak fluorescence intensities were measured at multiple time points. The excitation light wavelength was 660 nm and the emission light wavelength was 672-850 nm, while white light imaging was acquired.  Ten of the 11 ureters in the fluorescence group were successfully visualized (Figure 1). The strongest confidence was found at the dose of 1 mg/kg. The strongest signal was obtained between 9 and 20 minutes after drug administration, with an average time of 14.4 minutes. The fluorescence was still detectable 75 minutes after injection.  During surgery, hypoxia artifacts are caused by methylene blue interference affecting the pulse oximetry probe. This symptom disappears within a few minutes after methylene blue clearance. In this group of patients, no intraoperative hemodynamic changes or methylene blue-related complications occurred.  Figure 1. Ureter seen in the white field (A and C) and 660 nm excitation fluorescence field (false color, B and D) after intravenous methylene blue injection (1 mg/kg) in a 73-year-old male patient undergoing laparoscopic perineal colectomy (APER) for low-grade rectal cancer. The large amount of intra-abdominal fat in this patient makes it difficult to clarify the location of the ureter. The left ureter (A and B) is clearly visible under fluorescence; the right ureter is not visible under white light (C), but is clearly visible in situ on fluorescence imaging. This technique is particularly useful in patients whose ureter is not visible under white light, such as those with previous pelvic radiation or retroperitoneal fibrosis, and those who have undergone reoperation.  In conclusion, small doses of methylene blue administered intravenously are effective in determining the location of the ureter under fluorescence and can be detected by laparoscopy and wide-field fluoroscopy. However, large sample clinical studies are still needed to determine the subset of patients who will benefit.