Indocyanine Green Fluorescence Lymphography: A New Technique to Perform Lymphatic Sparing Laparoscopic Palomo Varicocelectomy in Children

Introduction

Laparoscopic treatment of varicocele according to Palomo technique is probably one of the most common approaches adopted in children to treat high degree varicocele.^1,2 Palomo technique, according to the reports of the literature, gives excellent results in children, with success rates >95% but with a 20%–30% incidence of postoperative hydrocele, requiring redo surgery in most cases.^3–5 For this reason, in recent years, lymphatic sparing procedures have been applied for varicocele repair, to decrease the incidence of secondary hydrocele and ensure a better andrological outcome for children.^6–8

In a recent article, we reported the standardization of lymphatic sparing Palomo technique using preoperative intradartoic/intratesticular injection of isosulfan blue. ⁹ This procedure gives excellent results with the only disadvantage that the patients' urines are blue/green for 2–3 days after surgery and the patients have a blue slick on the scrotum for about 1–2 weeks postoperatively.

Indocyanine green (ICG) has traditionally been used to assess liver function. In recent years, ICG fluorescence has been adopted in adults to perform angiography in case of tumors and to check the anomalies of biliary tract during laparoscopic cholecystectomy.^10,11 More recently, a novel method to measure human lymphatic pumping using a solution of ICG with fluorescence video control has been described.^12,13

Use of ICG angiography has been reported in microsurgical subinguinal varicocelectomy in adult population, resulting in a safer and quicker surgery.^14,15 To date, there are no reports in the international literature regarding application of this technique during laparoscopic varicocele repair in the pediatric population.

This study aimed to evaluate the outcome of ICG-enhanced fluorescence lymphography to perform lymphatic sparing laparoscopic Palomo varicocelectomy in pediatric patients.

Patients and Methods

We retrospectively reviewed the records of 25 patients, who underwent laparoscopic left Palomo varicocelectomy in our unit from March 2017 to March 2018. Patients' age ranged between 12 and 16 years (average 13.7 years). All patients had a high degree varicocele at clinical examination (Grade II or Grade III according to the Dubin clinical classification), all were symptomatic with left testicular pain or discomfort, and all had a left testicular hypotrophy defined as 20% volume or greater differential between testicles. All patients received preoperatively a testicular ultrasound (US) to assess the testicular volume and a testicular venous Doppler to assess the venous reflux.

Regarding the follow-up, all patients were seen 1 week postoperatively for surgical wound check. Clinical controls were performed thereafter at 1, 6, and 12 months after surgery, assessing for varicocele persistence or recurrence or development of new onset hydrocele. Testicular US was repeated when possible. The study received the appropriate Institute Review Board (IRB) approval at Federico II University of Naples.

Surgical technique

All the procedures were performed under general anesthesia with orotracheal intubation. Patients were placed in supine position with slight Trendelenburg and three trocars were always adopted. The first 5- or 10-mm trocar for the 0° optic was placed at umbilical level using open technique and thereafter other two 5-mm working trocars were placed under vision in triangulation with the optic port. After pneumoperitoneum induction, the posterior peritoneum covering the inner spermatic vessels (ISV) was opened performing a 2-cm T-shaped incision with the monopolar hook, at a distance of about 3–4 cm from the internal inguinal ring. After this step, a vial of ICG (5 mg/dL) was diluted with 10 mL of distilled water and only 2 mL of this solution was directly injected into the body of the left testicle using a 23G needle. Using the near-infrared mode, the lymphatic vessels appeared fluorescent and were clearly identified and spared; then the entire spermatic bundle was clipped and divided according to Palomo's principle (Fig. 1). Also using the standard white light mode, the lymphatics were clearly visible because they appeared green (Fig. 2). The ICG is commonly metabolized by the liver; for this reason, the patients' urine was normally colored after surgery and also the injection site on the scrotum presented no sign of the dye. The trocars orifices were closed using resorbable sutures, steri-strips or glue. All steps of the surgical procedure are reproduced in the Supplementary Video S1.

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FIG. 1.

After intratesticular ICG injection, lymphatic vessels appear fluorescent using the near-infrared mode, before (a) and after (b) spermatic vessels' division. ICG, indocyanine green.

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FIG. 2.

After intratesticular ICG injection, lymphatic vessels appear green using the standard white light mode, before (a) and after (b) spermatic vessels' division. ICG, indocyanine green.

Results

All the procedures were completed in laparoscopy with no conversion to open surgery or intraoperative complications. In 2/25 patients (8%), lysis of adhesions of colon covering the ISV was performed as additional procedure during the same surgery. The average operative time was 18 minutes (range 10–25 minutes). All procedures were performed by 1 senior surgeon. About 20–30 seconds after the intratesticular injection of ICG, the fluorescence of the lymphatics was clearly detected in 100% of the patients. The lymphatic vessels appeared fluorescent using the near-infrared mode (Fig. 1) and green using the standard white light mode (Fig. 2). In some patients, after a time interval of about 60 seconds from lymphatic visualization, also gonadal veins were observed using ICG fluorescence, although somewhat dully. In all patients, about two to three lymphatic vessels were identified and spared during the procedure. All patients restarted full oral feeding mean 2 hours postoperatively and the average analgesic requirement was 12 hours (range 8–28 hours). The average length of hospital stay was 36 hours (range 22–48 hours). No allergy or other adverse events induced by ICG were observed in our series. No patients in our series experienced any testicular pain secondary to the intratesticular injection, either early or late after surgery. At a maximum follow-up of 18 months, no recurrence or persistence of varicocele was recorded and no postoperative hydrocele was observed. One patient (4%) presented postoperatively umbilical port-site infection, treated with oral antibiotics and local therapy (II Clavien). All patients were highly satisfied with the postoperative cosmetic appearance of the umbilicus.

Discussion

Varicocele is a frequent pathology in pediatric population, with an incidence of ∼15%–20% ¹⁶ and is associated with testicular damage and subsequent testicular hypotrophy. Several reports stated that varicocele is related to sperm DNA disorders and male infertility, which are improved by surgical repair.^17–19 Three different surgical techniques have been described for the treatment of pediatric varicocele: high ligation (suprainguinal), microsurgical low ligation (subinguinal), and laparoscopy. ¹⁵ In recent years, several authors have reported the safety and efficacy of laparoscopy for the surgical correction of pediatric varicocele.^1,2

Laparoscopic Palomo technique is the most common approach adopted in children.^1,16 According to the reports of the international literature, the laparoscopic Palomo procedure resulted in a significant decrease of the operative failure rate compared with the artery-sparing procedures, with no increase in the incidence of testicular hypotrophy/atrophy.^1,16 The main disadvantage reported with Palomo procedure was the high rate of postoperative hydrocele (10%–30%) since during this technique no attempt is made to preserve the lymphatic vessels that are difficult to identify, because they are similar to small veins.^3–5 Therefore, lymphatic sparing procedures have been applied for varicocele repair to decrease the incidence of postoperative hydrocele.^6–9 Different vital dyes have been applied to perform lymphography during lymphatic-sparing varicocelectomy, including methylene blue, patent V, or its isomer isosulfan blue.^19–23

In a recent article, we reported the standardization of lymphatic sparing Palomo technique using preoperative intradartoic/intratesticular injection of isosulfan blue. ⁹ This procedure reported excellent results with a 0% rate of postoperative hydrocele.^9,16 No adverse event related to isosulfan blue injection such as orchitis, allergy, or anaphylactic shock was reported in our series.^9,16

In recent years, ICG-enhanced fluorescence has been introduced in laparoscopic surgery to improve visualization and provide detailed anatomical information during surgery.^24,25 The ICG dye can be injected into the human blood stream with practically no adverse effects. ¹² ICG becomes fluorescent once excited with light of a specific wavelength in the near-infrared spectrum delivered by a Xenon light source. ²⁶ After intravenous injection, ICG is rapidly bound to plasma proteins, especially lipoproteins. ICG is rapidly extracted unaltered through the liver and almost completely excreted without conjugation in bile about 8 minutes after injection. ¹² Fluorescence can be detected using specific scopes and cameras and then transmitted to a video screen, thus enabling the observer to visualize areas of anatomical interest where the dye has accumulated (biliary ducts, vessels, and lymph nodes). For visualization of efferent lymphatic vessels, ICG is injected in the peritumoral area, commonly reaching the nearest draining lymph node within 15 minutes. ¹¹ ICG-enhanced fluorescence imaging has been used in the past few years for improved visualization of the biliary duct system during laparoscopic cholecystectomy, intraoperative evaluation of lymphatic drainage, sentinel lymph node mapping in case of tumors, identification of vascular anatomy and for perfusion control of solid organs, colon, and rectum.^{10–12,24–26} To date, no data about use of ICG to perform lymphography in pediatric patients affected by varicocele have been reported. We decided to adopt intratesticular injection of ICG to visualize lymphatic vessels during lymphatic-sparing laparoscopic Palomo varicocelectomy. We also standardized the technique of injection of ICG, as we already reported for isosulfan blue, ⁹ and we outlined the differences between the two vital dyes. The main difference is that isosulfan blue is metabolized by the kidney and consequently the urines appear blue for 1–2 days after surgery, whereas ICG is metabolized by the liver and the urines remain normal after surgery. Isosulfan blue injection leaves a blue slick on the scrotum for about 1–2 weeks postoperatively, whereas the scrotum appears normally colored after ICG injection.

After ICG injection, there are two modalities of visualization of lymphatics: they appear fluorescent using the near-infrared mode (Fig. 1), whereas they appear green at the standard white light mode (Fig. 2). Switching from standard white light mode to near-infrared mode is simply done through foot-pedal control. The onset of fluorescence of lymphatics is about 20–40 seconds after ICG injection, and the duration of fluorescence is about 15 minutes. In this way, it is sufficient a single injection to allow completion of the entire procedure with no loss of the fluorescence. In addition, the modality of administration of ICG, which is directly injected into the testicular parenchyma, is technically easier compared with the intradartoic/intratesticular injection previously described for isosulfan blue.

We also standardized the amount of product to be injected to optimize the visualization of lymphatics, as we already reported in the methods. As for disadvantages related to the use of ICG, special equipment, including a camera system that can be operated in dual mode for both white light and fluorescence imaging and an ICG laparoscope equipped with a special filter for optimal reproduction during INC-enhanced fluorescence and standard white light imaging, are needed in the operative theatre.

In conclusion, our preliminary experience showed that lymphatic sparing laparoscopic Palomo varicocelectomy using ICG fluorescence lymphography is a feasible and versatile technique to adopt for treatment of children and adolescents with varicocele. The intratesticular injection of ICG and use of fluorescence vision resulted in a safe and effective method, allowing identification of lymphatic vessels in 100% of cases in our series. In addition, no allergy to ICG or postoperative hydrocele was reported after a mid-term follow-up.