ANTICANCER RESEARCH 36 : 6579-6584 (2016) doi:10.21873/anticanres.11262

Videoscopic Inguinal-iliac-obturator Lymph-node Dissection: New Videoscopic Technique for Regional Lymphadenectomy in Patients with Melanoma NICOLA SOLARI1, MARCO GIPPONI2, DI SOMMA CARMINE FRANCO1, FRANCESCA RÈ1, OLCESE SONIA1, SERGIO BERTOGLIO1,3 and FERDINANDO CAFIERO1

1Surgery Unit 1, San Martino Hospital & National Cancer Institute, Genoa, Italy; 2Breast Unit, University of Genoa, School of Medicine, San Martino Hospital & National Cancer Institute, Genoa, Italy; 3Department of Surgical Science (DISC), University of Genoa, School of Medicine, Genoa, Italy

Abstract. Aim: The feasibility of videoscopic inguinal-iliac- National Comprehensive Cancer Network 2016, IIOL is obturator lymphadenectomy (VIIOL) was assessed in 20 indicated for the treatment of clinically positive patients with melanoma and compared with a retrospective superficial nodes or three or more positive superficial sample of 24 patients undergoing standard 'open' technique nodes, if pelvic computed tomographic scan is positive, (IIOL). Results: No postoperative death occurred; the mean or if Cloquet’s node is positive (3). Patients with stage operative time was lower in the IIOL series (190 min vs. 302 III disease after a positive sentinel lymph node biopsy min) but the quality of life was greatly improved in the should be offered a complete lymph node dissection of VIIOL group thanks to earlier bladder catheter removal, no the involved nodal basin because studies have revealed nasogastric suction, less pain, earlier mobilization, lower in- additional metastases in non-sentinel node in 15-20% of hospital stay, and earlier resumption of daily activities (27.6 them (4, 5). Excision of pelvic lymph-node metastases is vs. 83.2 days, p<0.001). Six out of 20 patients in the IIOL reported to yield a 5-year survival rate of 0-35%. series had wound complications (30%) as compared to one Recurrence within the occurs in 9-18% of patients in the VIIOL series (4%) (p=0.035). Conclusion: Staging after superficial lymph-node dissection, and in fewer than and therapeutic efficacy of VIIOL were similar to the 5% after complete IIOL (2). standard technique; the longer operative time of VIIOL was Currently, this surgery is performed using the traditional greatly compensated by less pain, lower wound complication 'open' access, that is through a single long surgical wound rate, and earlier discharge from hospital and recovery of or by means of two separate incisions: in the inguinal- daily activities. femoral area to access the inguinal nodes, and in the iliac fossa for iliac-obturator nodes. The open technique An estimated 6,000 new case/year of melanoma are involves the preparation of the skin flaps, often the diagnosed in Italy, and the incidence of the disease is sectioning of the , muscular fascia and increasing (1). As with nearly all malignancies, the outcome muscle of the lower abdominal wall in order to gain access of melanoma initially depends on the stage at presentation to the lymph nodes. This technique is hampered by (2). It is estimated that 82-85% of patients with melanoma relatively high postoperative morbidity, ranging from 19% present with localized disease, 10-13% with regional disease, to 77% (6). As a matter of fact, lymphatic fistula occur s in and 2-5% with distant metastatic disease. 33% of patients, whereas seroma formation occurs up to Inguinal-iliac-obturator lymphadenectomy (IIOL) is the 34% of patients; the mean in-hospital stay is approximately procedure of choice for patients with regional lymph- 15 (range=3-41) days. Relevant leg edema is observed in node metastases of melanoma in the lower extremities or 13% of patients. The mortality rate is reported to be 1%; lower part of the trunk (2). As recommended by the 30-day wound complications are reported in 77.4% of patients. Risk factors for complications include: body mass index ≥30 kg/m 2, advanced nodal disease, diabetes, and smoking (7, 8). Correspondence to: Marco Gipponi, MD, Breast Unit - IRCCS “San Martino-IST”, L.go R. Benzi, 10, 16132 Genoa, Italy. E-mail: Based on these data, we assessed the feasibility of a new [email protected] surgical approach, namely videoscopic IIOL (VIIOL), and the clinical findings were compared with our historical Key Words: Melanoma, lymphadenectomy, videoscopic technique. experience with the open technique (IIOL).

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Patients and Methods placed in an Endo-Catch bag. The procedure is completed by peritoneal repair with a running suture and by placing a 15-G fluted The clinical data of 20 consecutive patients undergoing IIOL from drain through the lateral 5 mm port site. July 2013 to September 2015 at the Surgical Oncology Unit of the The videoscopic inguinal-femoral dissection technique was Comprehensive Cancer Center San Martino Hospital - National adapted from the original technique described in patients with Cancer Institute of Genoa, Italy, were compared with 24 consecutive genito-urinary malignancies (6, 11). patients with melanoma eligible for VIIOL. Patients were selected The surgeon is positioned between the patient’s legs with the for surgery when a positive sentinel lymph node biopsy, clinical or assistant standing outside the operative limb. A three-incision radiological findings confirmed metastasis in . technique is used, with the first 10 mm port placed 3 cm distally to Absolute contraindications for VIIOL were similar to other the apex of the femoral triangle. A scalpel is used to incise the skin laparoscopy contraindications. (9) Moreover, patients were excluded and sharply dissect down through Camper and Scarpa’s fascias. A when co-morbidities contraindicated VIIOL, such as severe space similar to the one created in the open procedure is then respiratory failure or severe cardiac failure. developed by blunt-finger dissection, extending out 5 cm on each The following parameters were assessed: length of the operation, side from the incision. Initially, the space is insufflated up to adequacy of lymph-node retrieval (lymph-node number, lymph-node 15 mmHg and, under direct visualization with a 30-degree scope, ratio), incidence of postoperative complications, length of hospital 10 mm and 5 mm short bladeless trocars are positioned 3 cm stay, and time-interval to resumption of normal activities of daily outside of the medial and lateral boundaries of the previously life that was assessed at follow-up examinations. delineated femoral triangle. Ultrasonic shears are then used to complete the definition of the anterior working space between the fibro-adipose node-containing Surgical technique. The VIIOL includes two surgical steps: firstly, packet and the superficial tissue. At this time, the pressure is the video-laparoscopic iliac-obturator lymph-node dissection is reduced to 8 mmHg to prevent end-tidal CO elevation. The performed and videoscopic inguinal lymph node dissection is then 2 saphenous vein is readily identified within the apex of the femoral accomplished. The technique described by Picciotto et al. for the triangle, closed with clips and divided with an ultrasonic device. approach to the iliac-obturators lymph nodes was adapted (10). The Anatomical boundaries include: the sartorious muscle, laterally; laparoscopic procedure was performed by means of three/four ports: the abductor muscle, medially; the external oblique fascia and one 10 mm port for the umbilical camera; a second 10 mm inguinal ligament, proximally, and the apex of femoral triangle, sovrapubic operative port; a third 5 mm operative port on the distally (Figure 3). Careful dissection within the femoral triangle pararectal umbilical line, and a fourth optional controlateral enables the identification of the pulse as well as the pararectal umbilical line 5 mm port. The anatomical boundaries of medial . An endoscopic linear cutting stapler with a the limited template included the genito- laterally, the vascular load, or vascular clips, is then used to transect the vein at obliterated umbilical artery medially, the pubic bone distally, and the sapheno-femoral junction (Figure 4). The nodal packet is the bifurcation of the common iliac artery proximally. withdrawn in a laparoscopic specimen bag through the apical port by The procedure is performed under general anaesthesia. The enlarging the skin incision to extract the specimen when necessary. patient is placed in the supine position with the pelvis slightly At the end of inguinal lymphadenectomy, by means of the 30- extended on a split-leg table. Prophylactic antibiotics are degree camera introduced under the inguinal ligament, the administered, and a Foley catheter is placed to empty the bladder; previously skeletonized femoral-iliac vessels are checked in order a transperitoneal 4 port technique is used. to verify the accuracy of the laparoscopic lymphadenectomy, by The patient is tilted 30 degrees up on the pathological side in the removing residual pathological lymph nodes: when residual 30-degree Trendelenburg head-down position. The lateral border of pathological lymph nodes are found, once the internal circumflex dissection is developed along the genito-femoral nerve by dividing vessels, internal pudendal vessels and, if necessary, inferior deep the fibro-areolar tissue and exposing the ilio-psoas muscle. The epigastric vessels are isolated and transected, those nodes are easily lymphatic tissue packet is completely lifted en bloc off the surface removed avoiding the transection of the inguinal ligament. of the ilio-psoas muscle and swept medially. Tissue anterior to the The procedure is completed by placing a 18-G fluted drain external iliac artery and vein is then individually split longitudinally, through the medial port site. A nasogastric tube is never inserted; skeletonizing the two vessels circumferentially, using monopolar, postoperative pain is always managed with non-steroidal anti- bipolar, ultrasound devices (Figure 1). It should be noted that the inflammatory drugs. Patients are given a regular diet and external iliac vein typically appears flat at standard (15 mmHg) encouraged to walk on the first day after the surgery. pneumo-peritoneum pressure; pneumo-peritoneum pressure can be Statistical analysis included the mean, standard deviation, and reduced to 5 mmHg in order to allow re-distension of the vein to mean standard error for numerical variables; continuous variables ease its identification. were analyzed with a two-tailed Fisher’s exact test, and a value of The bifurcation of the common iliac arteries represents the p< 0.05 was considered statistically significant. proximal border. The hypogastric artery is carefully mobilized in order to avoid injury to the internal iliac vein. The released packet is rolled medially on the back side of the mobilized external iliac Results artery and vein, delivering it into the pelvis. The dissection along Overall, 20 patients underwent open IIOL and 24 patients the medial aspect of the packet allows the identification of the obturator nerve (Figure 2). Distally, lymphatic vessels caudal to the VIIOL. Seventeen (85%) primary cutaneous melanomas Cloquet’s node are clipped and transected. Care is taken to avoid were located in the lower extremities, and three (15%) in the any spillage of cancer cells from enlarged lymph node(s) in order trunk. In the VIIOL series, 14 patients (58%) were male and to prevent local seeding, so that the entire specimen is immediately 10 (42%) female; the mean age was 60 years (range=32-86

6580 Solari et al : Videoscopic Ilio-inguinal Dissection

Figure 1. Iliac-obturator lymph node dissection. Figure 3. Inguinal lymph node dissection.

Figure 2. Obturator lymph node dissection. Figure 4. Inguinal lymph node dissection.

years). Nineteen (79%) primary melanomas were located in abdominal muscle or fascia transection was performed the lower extremities, and five (20%) in the trunk. The (excluding the 1-cm port incision). Patients were usually able clinical and histological features of patients are reported in to walk on the first postoperative day, and bowel movements Table I. The median length of follow-up was 42.5 months occurred within 2 days of surgery. (range=4-171 months) after IIOL, and 16 months (range=3- The mean in-hospital stay was 6 (range=4-8) and 2 29 months) for VIIOL. (range=1-3) days in the IIOL and VIIOL series, respectively. The surgical procedure was well tolerated in both series, There were six wound complications (6/20; 30%) in the IIOL with no intraoperative or 30-day operative death. The mean series, with four wound infections and two of wound length of the operation was 190 min vs. 302 min with IIOL dehiscence, as compared to one wound infection in the and VIIOL, respectively; no conversion from videoscopic to VIIOL series (1/24: 4%) ( p=0.035; two-tailed Fisher’s exact open surgery was required. test). Lymphatic fistula occurred in 13% and 8% in the IIOL In the VIIOL group, the quality of life was greatly and VIIOL series, whereas inguinal seroma resulted in 20% improved thanks to the earlier postoperative removal of the and 12.5%, respectively. No port-site recurrence occurred. bladder catheter, and by avoiding use of a nasogastric tube. Patients resumed normal daily and working activities on Moreover, pain was moderate and always managed with average after 83.2 days in those who underwent IIOL and minor analgesic (1,500 paracetamol mg/day) because no after 27.6 days ( p< 0.001) in patients treated with VIIOL.

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Table I. Clinical features of inguinal-iliac-obturator lymphadenectomy (IIOL) and videoscopic (VIIOL) series.

IIOL (n=20) VIIOL (n=24)

Mean age (years) 53.3 60 Gender, n (%) Male 11 (55%) 14 (58.3%) Female 9 (45%) 10 (41.7%) Stage, n (%) T1 2 (10%) 1 (pTis) (4.2%) T2 9 (45%) 2 (8.3%) T3 2 (10%) 11 (45.8%) T4 7 (35%) 10 (41.7%) Median Breslow thickness (range), mm 3.23 (1.15-24) 3.84 (1.18-11.30) Median mitotic rate (range) 8 (1-39) 6.1 (0-25) Median Clark level of invasion (range) 3.9 (3-5) 3.8 (1-5) Anatomic site, n (%) Leg 17 (85%) 19 (79.2%) Trunk 3 (15%) 5 (20.8%) Ulceration, n (%) Absent 12 (60%) 8 (33.3%) Present 8 (40%) 16 (66.7%) Median no. of excised lymph nodes (range) 15.5 (11-28) 24.1 (8-38) Median no. of positive lymph-nodes (range) 3.15 (15.75%) 1.58 (6,58%) Positive lymph-node ratio 20.3% 6.56%

Regarding pathological staging, an average removal of 15 hospital costs, including the management in the Outpatient lymph nodes was reported in the IIOL series, while in the Clinic notwithstanding the longer duration of the operation VIIOL series, an average of 24 lymph nodes (range=8-38) (approximately 302 min vs. 190 min in the VIIOL and IIOL were removed: 14 (range=8-23) pelvic lymph nodes, and 10 series, respectively). (range=4-25) inguinal lymph nodes. With regard to pathological staging, at least 10 to 15 lymph nodes are usually removed in the IIOL procedure. (12-18). Discussion Our historical control group had an average removal of 15 lymph nodes; in the current VIIOL series, an average of 24 Even with proper perioperative and precise wound care lymph nodes (range=8-38) were removed: 14 (range=8-23) management, almost one out of three patients undergoing pelvic lymph nodes, and 10 (range=4-25) inguinal lymph radical -iliac-obturator lymphadenectomy has nodes. In other clinical series, traditional open ileo-inguinal postoperative complications requiring medical or radical dissection had a mean lymph-node retrieval of 21.5 interventional treatment (6). Furthermore, literature data lymph nodes (range=17-25), whereas inguinal dissection had report an average in-hospital stay of approximately 15 days an average of 11 (range=10-14) (19-22). (range=3-41 days) and a median postoperative morbidity of With regard to seroma formation and lymphatic fistula, a 4 months (range=1.5-2.4 months) (7). small but consistent advantage was appreciated in the VIIOL In our experience, patients in the VIIOL series had a series. No lymphedema occurred by the time of writing, significant reduction of postoperative wound complication likely due to the short follow-up interval. Therefore although rate (4% vs. 30%; p=0.035); they were able to walk within VIIOL has only a moderate advantage regarding lymphatic 24 hours of the operation; their postoperative pain was drainage and rate of lymphocele, it greatly reduces moderate and easily managed with non-steroidal anti postoperative morbidity and complication rate with fewer inflammary drugs; a nasogastric tube was never required, nor postoperative wound complications, less postoperative pain, a central venous catheter, while the bladder catheter was early discharge from the hospital and early recovery of daily removed soon after surgery. Finally, patients were usually and working activities. discharged on the second postoperative day, although with a suction drain closed circuit, and they experienced a faster Conclusion return to normal daily and working activities (27.6 days vs. 83.2 days in the VIIOL and IIOL series, respectively). The staging and therapeutic efficacy of transperitoneal Hence, VIIOL achieved an important reduction of the overall VIIOL was similar to the standard IIOL technique. The

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