Relevant Surgical Anatomy

The regional lymph nodes of the penis are located in the inguinal region and have been traditionally divided into the superficial and the deep groups. The superficial nodes are located under the subcutaneous fascia in the deep membranous layer of the superficial fascia of the thigh above the fascia lata. The superficial nodes have been divided into 5 anatomic groups: the central nodes around the saphenofemoral junction, superolateral nodes around the superficial circumflex vein, inferolateral nodes around the lateral femoral cutaneous and superficial circumflex veins, superomedial nodes around the superficial external pudendal and superficial epigastric veins, and inferomedial nodes around the greater saphenous vein. The deep inguinal nodes lie in the region of the fossa ovalis where the greater saphenous vein drains into the femoral vein through an opening in the fascia lata. The node of Cloquet is the most cephalad of this deep group and is situated between the femoral vein and the lacunar ligament. Superficial and deep inguinal nodes are considered to be the first draining nodes of the penis; from there, lymphatic drainage is to the second-line regional nodes, which are those in the pelvis around the iliac vessels and in the obturator fossa.

Complications of Inguinal Lymphadenectomy

Surgical morbidity is a significant problem after radical inguinal lymphadenectomy (ILND). Historically, ILND has been associated with a high complication rate of between 80% and 100%). However, more recent surgical series report an overall complication rate of between 42% and 57% for patients undergoing ILND as part of the management for penile cancer. Complications reported in groin dissection series are generally related to disruption of the lymphatics draining the lower extremities and damage to the overlying skin flaps from devascularization. Reported complications include flap necrosis/skin edge necrosis in 2.5% to 64%; wound breakdown in 38% to 61%; seroma in 5% to 87%; lymphorrhea in 33%; wound infection in 3% to 70%; lymphocele in 2.5% to 87%; leg lymphedema in 5% to 100%; deep vein thrombosis/thrombophlebitis in 6% to 9%; myocardial infarction in 9%; femoral neuropraxia in 2%; death in 1.3% to 3%; and an overall complication rate of 24% to 100%.

Wound Infection

Reported rates of wound infections following ILND are between 14% and 17%. Inguinal colonization together with its moist environment predisposes the inguinal region to infection after ILND. Gram-negative rods, Staphylococcus species, diphtheroids, and Peptostreptococcus microorganisms are the organisms most commonly isolated. The use of broad-spectrum antibiotics (eg, ampicillin/gentamicin or ampicillin/ciprofloxacin) before surgery decreases wound colonization before lymphadenectomy. Meticulous hemostasis further reduces the risk of hematoma formation, which could potentially become infected.

Lymphedema

The incidence of lymphedema after ILND is as high as 50%, with severe lymphedema occurring in 35% of patients. Clinically, the affected limb is swollen with enhanced skin creases, increased dermal turgor, hyperkeratosis, and papillomatosis. Lymphedema is traditionally described as nonpitting but, in early cases, pitting may be present. Disabilities from lymphedema include pain, limb heaviness, reduced mobility, impaired function, and recurrent bouts of cellulitis induced by lymphostasis. The surgical removal of lymph nodes and disruption of lymphatic channels during dissection of the inguinal region clearly contribute, but there are other variables that play a role, including treatment-related variables such as use of adjuvant radiation therapy, and patient-related variables. Radiation therapy can promote development of lymphedema by blocking lymph vessels or by compressing lymph vessels through radiation fibrosis. Some of the most frequently reported patient-related variables are increasing age, higher body mass index, weight gain, and infection.

Lymphadenectomy associated with saphenous vein preservation has been shown to reduce lymphedema. In 1988, Catalona published results regarding a modified ILND that targeted the superior medial quadrant, where the highest percentage of positive nodes is found. This modified approach decreased the length of the incision, allowed deeper skin flaps, preserved the saphenous vein, and did not transpose the sartorius muscle, thus decreasing the morbidity associated with the standard groin dissection. In his initial 6 patients, the modified technique did not compromise cancer control, although it was stressed that this method should be used only with clinically negative or minimally positive nodes, and pointed out that preserving the saphenous vein could decrease postoperative complications during ILND. Zhang and colleagues completed a randomized prospective trial of ILND for vulvar cancer comparing saphenous vein sparing ILND with ILND without sparing the vein. Short-term lower extremity lymphedema occurred in 43% in the sparing group and 67% patients in the excision group ( P <.01). However, sparing the saphenous vein is not always possible, particularly in patients with a large burden of metastatic disease.

Following the completion of the ILND, it is recommended that a closed suction drain be placed within the inguinal wound to avoid the development of a postoperative fluid collection (ie, lymphocele, seroma, or hematoma). The drain is usually removed when there is minimal drainage (typically <30 to 50 mL per 24 hours). The avoidance of infection is paramount because this promotes increased wound fibrosis and decreased limb drainage. The use of compression stockings, sequential compression devices, early ambulation after 8 hours of bed rest, avoidance of subcutaneous heparin, and physical therapy has been recommended as a method of reducing the incidence and impact of postoperative lymphedema. Early ambulation decreases the risk of deep vein thrombosis (DVT) formation and also assists in moving the patient to a status that is consistent with the level of ambulation required for discharge. Heparin may be avoided because of the concern for an increased risk of lymphocele formation. Strict leg elevation may be maintained in the hospital when the patients are not ambulating.

Skin Flap Necrosis

Skin flap necrosis remains a frequent complication of groin dissection. The blood supply to the skin of the inguinal region is from the superficial branches of the inferior epigastric, external pudendal, and circumflex iliac arteries and these vessels are ligated during groin node dissection. The viability of the skin edge is therefore reliant on anastomotic vessels running in the superficial fatty layer of the Camper fascia parallel to the inguinal ligament.

Several surgical modifications have been developed to minimize skin flap necrosis. Because lymphatic drainage of the penis to the groin is beneath the Camper fascia, this layer can be preserved and left attached to the overlying skin when the skin flaps are fashioned. Straight vertical and S-shaped incisions cut across the anastomotic vessels in the Camper fascia, and postoperative swelling puts traction on these incisions. Smaller operative fields and thick vascular flaps have resulted in decreased skin edge necrosis in patients undergoing prophylactic dissections. Generous use of well-vascularized myocutaneous flaps has decreased skin edge necrosis among patients undergoing therapeutic and palliative dissections. Ornellas and colleagues noted that a Gibson approach provided good exposure to the iliac and inguinal lymph nodes while minimizing morbidity (flap necrosis in 5%) compared with the S-shaped or bi-iliac incisions (72%–82%, respectively). Ravi reported a 0% incidence of skin flap necrosis in a later cohort of 30 patients undergoing therapeutic dissection with myocutaneous flap reconstruction compared with an earlier cohort of patients undergoing lymphadenectomy without flap reconstruction (skin edge necrosis was 61%–78%). Meticulous atraumatic handling of the tissues throughout, limitation of the extent of flap mobilization (superior to the inguinal ligament and inferior to the tip of the femoral triangle) are also helpful in preserving flap viability.

Antibiotics

Antibiotic therapy with broad-spectrum antibiotics for 4 to 6 weeks after treatment of the primary tumor as discussed previously has traditionally been administered to allow resolution of septic lymphadenitis before ILND. In patients with active infection, bacterial cultures should be obtained, and culture-specific antibiotics should be given before surgery. Prophylactic antibiotics are administered at the time of lymphadenectomy and are usually continued for 1 week after surgery or until the wound drains have been removed. The microorganisms isolated from septic ILND wounds have included gram-negative rods, Staphylococcus species, diphtheroids, and Peptostreptococcus .

DVT Prophylaxis

Venous thromboembolism is a serious complication that should be aggressively prevented when possible. Some studies have indicated that the perioperative use of low-dose heparin may be associated with an increased risk of wound hematoma and lymph drainage without reducing the incidence of DVT. It has been suggested that, in patients with a remote history of DVT, perioperative heparin should be continued until postoperative day 28. With a history of DVT or pulmonary embolism in the preceding 6 months, a therapeutic dose of heparin should be restarted when the risk of postoperative hemorrhage is minimal, with subsequent conversion to oral warfarin. The use of antiembolic stockings or intermittent compression devices immediately before anesthetic induction to prevent DVT has also been recommended.

Antibiotics

Antibiotic therapy with broad-spectrum antibiotics for 4 to 6 weeks after treatment of the primary tumor as discussed previously has traditionally been administered to allow resolution of septic lymphadenitis before ILND. In patients with active infection, bacterial cultures should be obtained, and culture-specific antibiotics should be given before surgery. Prophylactic antibiotics are administered at the time of lymphadenectomy and are usually continued for 1 week after surgery or until the wound drains have been removed. The microorganisms isolated from septic ILND wounds have included gram-negative rods, Staphylococcus species, diphtheroids, and Peptostreptococcus .

DVT Prophylaxis

Venous thromboembolism is a serious complication that should be aggressively prevented when possible. Some studies have indicated that the perioperative use of low-dose heparin may be associated with an increased risk of wound hematoma and lymph drainage without reducing the incidence of DVT. It has been suggested that, in patients with a remote history of DVT, perioperative heparin should be continued until postoperative day 28. With a history of DVT or pulmonary embolism in the preceding 6 months, a therapeutic dose of heparin should be restarted when the risk of postoperative hemorrhage is minimal, with subsequent conversion to oral warfarin. The use of antiembolic stockings or intermittent compression devices immediately before anesthetic induction to prevent DVT has also been recommended.

Radical Prostatectomy

Pelvic lymphadenectomy is frequently performed simultaneously with radical prostatectomy to determine lymph node status. Current radical retropubic prostatectomy series indicate that the incidence of lymph node metastasis is less than 10%. The presence of lymph node metastasis in men diagnosed with clinically localized prostate cancer is a poor prognostic finding and has important implications on the initiation of adjuvant therapy. The original staging lymphadenectomy approach was transperitoneal with biopsies of the para-aortic, common iliac, hypogastric, external iliac, and obturator lymph nodal basins guided by pedal lymphangiography. This approach provided excellent exposure, although it increased perioperative morbidity compared with an extraperitoneal approach. For PLND in prostate cancer, the anatomic boundaries (ie, extent) of dissection remain controversial because of a lack of standardization. Currently standard pelvic lymphadenectomy involves the dissection and removal of lymphatic tissue from the level of the external iliac vein to the obturator nerve, extending proximally to the common iliac artery bifurcation and distally to the proximal femoral canal to include the node of Cloquet. An extended lymphadenectomy is the extension of resection to include the lymphatic tissue surrounding the internal iliac vein and presacral region.

The therapeutic benefit of pelvic lymphadenectomy for disease clearance in the era of prostate cancer stage migration and lymph node micrometastasis is still largely unknown. Bhatta-Dar and colleagues retrospectively examined the role of pelvic lymphadenectomy in 336 men who underwent radical prostatectomy. Patients had a prostate-specific antigen (PSA) level of less than 10 ng/mL, Gleason score of less than 7, and clinical stage T1 or T2 disease. Only 140 men underwent pelvic lymphadenectomy, according to the discretion of the operating surgeon who performed the radical prostatectomy. Both groups were matched in terms of age, family history of prostate cancer, race, clinical stage, and PSA level. The pelvic lymphadenectomy boundaries included the external iliac vein, pelvic side wall, obturator nerve, bifurcation of the common iliac artery, and the inguinal ligament.

The pelvic lymphadenectomy group had a 0.7% metastasis rate. The results showed no statistically significant difference in biochemical relapse rates after 60 months. On multivariate analysis, pelvic lymphadenectomy also did not seem to be an independent predictor of outcome. The 6-year biochemical relapse-free survival did not show any statistical significance between the 2 groups.

The advent of PSA screening has led to considerable stage migration and a low incidence of lymph node involvement in contemporary radical prostatectomy series. The incidence of lymph node metastasis has decreased in the last decade from 20% to 40% in the 1970s and 1980s to the present rate of about 6%. Some investigators have suggested that PLND may be omitted in patients deemed to be at low risk for lymph node metastasis. The Partin tables, Memorial Sloan-Kettering Cancer Center Prostate Nomogram, and the Hamburg Algorithm have been developed as methods of identifying patients who are at increased risk of lymph node metastasis before surgery. These tools have proved to be useful guides in clinical decision making, and their performance has been established.

Anatomy of Lymphatic Drainage of the Bladder

The anatomy of bladder lymphatic drainage has traditionally been divided into 6 distinct areas: (1) the visceral lymphatic plexus within the bladder wall, originating inside the submucosa and extending into the muscular layer of the organ; (2) the intercalated lymph nodes, which are juxtavesical lymph nodes located within the perivesical fat arranged into anterior, lateral, and posterior groups; (3) the pelvic collecting trunks, which are lymph nodes medial to the external iliac and hypogastric lymph nodes; (4) regional pelvic lymph nodes, which include the external iliac, hypogastric, and presacral lymph node groups; (5) lymphatic trunks leading from the regional pelvic lymph nodes; and (6) common iliac lymph nodes on the common iliac vessels. The primary drainage starts from the external and internal iliac and obturator sites, secondary drainage is from the common iliac sites, and tertiary drainage is from the trigone and posterior bladder wall is to the presacral nodes.

Pelvic Lymphadenectomy in Bladder Cancer

Presence or absence of lymph node involvement has been shown to be predictive of outcome in patients who undergo RC and PLND. Present guidelines for the pretreatment assessment of lymph node status are mainly based on cross-sectional imaging techniques like computed tomography (CT) and magnetic resonance imaging (MRI) with contrast enhancement. The assessment of nodal status based simply on size is limited by the inability of both CT and MRI to identify metastases in normal-sized or minimally enlarged nodes. The overall sensitivity for detection of lymph node metastases is low and ranges from 48% to 87%. Specificities are also low because nodal enlargement may be caused by benign conditions. Pelvic nodes greater than 8 mm and abdominal nodes greater than 10 mm in maximum short-axis diameter (MSAD) should be regarded as enlarged on CT and MRI.

The curative value of lymph node dissection is still unknown and a standardized lymph node dissection has yet to be defined. Standard PLND includes the whole primary lymphatic drainage of the bladder. The standard PLND has been defined as having the following boundaries: common iliac bifurcation (cephalad extent), genitofemoral nerve (lateral), circumflex caudal iliac vein and lymph node of Cloquet (distal), and hypogastric vessels (posterior), including the obturator fossa. Extended PLND has been defined to include nodes in the boundaries of the aortic bifurcation and common iliac vessels (proximal/cephalad), genitofemoral nerve (lateral), circumflex (distal) and caudal iliac vein and lymph node of Cloquet, hypogastric vessels (posterior), including the obturator fossa, presacral lymph nodes anterior to the sacral promontory. In some cases, an extended dissection may extend more superiorly to the level of the inferior mesenteric artery and include paracaval and para-aortic areas.

Pelvic Lymphadenectomy in Bladder Cancer and Survival

Herr and Donat analyzed the outcome of patients with grossly node-positive bladder cancer after PLND and RC. Included in this study were 83 patients treated with surgery alone (no neoadjuvant or adjuvant chemotherapy), presenting with N2 to 3 disease, and with a follow-up of up to 10 years. Twenty patients (24%) survived, and 64 patients (76%) died of the disease. This finding would suggest that some patients with grossly node-positive bladder cancer have a chance of cure with RC through PLND. In a multivariate analysis, the extent of the lymph node dissection, number of lymph nodes removed, and number of cases performed by the individual surgeon were found to be the most significant factors influencing survival in patients undergoing cystectomy for bladder cancer. In this prospective trial, 270 patients underwent cystectomy, and half were randomized to receive neoadjuvant chemotherapy. In a separate analysis of this trial, various surgical factors were analyzed. In this cohort of patients, 24 had undergone no lymph node dissection, 98 had undergone a limited dissection (obturator lymph nodes only), and 146 underwent a standard (not extended) PLND. The 5-year survival rates for these groups were 33%, 46%, and 60%, respectively. The median number of lymph nodes removed for the cohort was 10. The survival rate for patients with less than10 lymph nodes removed was significantly lower compared with patients with more than 10 lymph nodes removed (44% vs 61%, respectively).