|Year : 2009 | Volume
| Issue : 1 | Page : 18-21
Sentinel node biopsy in carcinoma penis using methylene blue dye technique
Vinayak S Rohan, Rajen A Tankshali
Department of Surgical Oncology, Gujarat Cancer and Research Institute, Ahmedabad - 380 016, India
|Date of Submission||17-Oct-2008|
|Date of Acceptance||05-Feb-2009|
Vinayak S Rohan
Amrithavarshini, Assaigoli, Mangalagangotri - 574 199
| Abstract|| |
Purpose : Penile carcinoma is a common disease in India. This paper shows the results of sentinel node biopsy using methylene blue and discusses the incidence of false-negative rates.
Materials and Methods: From September 2005 to March 2008, 22 newly diagnosed penile carcinoma patients (T1, T2, N0) were included in this prospective study. Intraoperative lymphatic mapping was done using methylene blue dye and the sentinel node was identified and removed. Lymphadenectomy was performed for positive inguinal lymph node metastasis.
Results : There were 22 patients (mean age 52.7). The tumors were mostly located in the glans (73%). Eighty six percent was T1 lesions and 14% was T2. Ninety one percent of the patients underwent partial penectomy, and 9% underwent total penectomy. Sentinel node was identified in 20 patients (90.9%). In total, 49 sentinel nodes were identified (2.45 nodes per person). Only one patient had a positive pathological lymph node metastasis at the time of the surgery. Additionally, two patients became inguinal lymph node positive at the follow-up. This data yielded a sensitivity rate of 33% and a false-negative rate of 66%. There were no complications due to methylene blue.
Conclusion : Sentinel node biopsy using only methylene blue for penile carcinoma has a very low sensitivity and a high false-negative rate. However, methylene blue can be used as a substitute for lymphazurin.
Keywords: Lymphatic metastasis, methylene blue, penile cancer, sentinel lymph node biopsy
|How to cite this article:|
Rohan VS, Tankshali RA. Sentinel node biopsy in carcinoma penis using methylene blue dye technique. Urol Ann 2009;1:18-21
| Introduction|| |
Carcinoma of penis is primarily a disease of poor countries. Though rare in the West (<0.6/100000), it is a common malignancy in India with incidence as high as 3.1/100000. The standard treatment of penile cancer involves partial or total amputation of the penis, depending on the degree of involvement by the tumor. The management of regional nodes, however, remains controversial. The survival of patients with penile carcinoma depends on the status of the ilioinguinal nodes.  The overall survival is 73-95% for patients with negative nodes and 19-62% for patients with positive nodes.  When the pelvic nodes are involved, the 5-year survival is reduced to <10%.  In patients with metastasis confined to the regional nodes, inguinal lymphadenectomy is often curative with disease free rates of 30-90%. 
Ilioinguinal lymphadenectomy is associated with significant levels of morbidity (30-50%) and up to 3% mortality. , In patients with impalpable nodes, only 20% will harbor metastasis, which leads to 80% of the patients undergoing unnecessary prophylactic bilateral groin dissection. 
The aim of the study was to determine the efficacy and feasibility of methlylene blue as a dye in identifying the sentinel lymph node and to study the safety of methylene blue as a dye.
| Materials and Methods|| |
We studied 22 consecutive patients with penile cancer presenting with N0 groin. All the surgeons at our unit were allowed to do the procedure according to strict procedure guidelines. None of them had any prior experience with sentinel node biopsy procedure. Informed consent was taken from all the patients prior to the procedure.
After induction of anesthesia, commercially available methylene blue dye (aqua fine injecta 1 ml = USB 10 mg) was injected around the tumor [Figure 1]. One milliliter each at 3, 6, 9, and 12 O'clock positions (total 4 ml) was infiltrated about 7-10 min prior to the proposed incision. A 5-cm incision was placed parallel to the inguinal ligament two-finger breaths below and lateral to pubic tubercle. The stained lymphatic draining to the deeply stained blue lymph node [Figure 2] was identified and removed separately and sent for histopathology. Definitive procedure for the penile cancer was performed in the same sitting. Only patients whose sentinel nodes turned out to be positive were subjected to ilioinguinal dissection 1-2 weeks later. All other patients were placed on regular follow up.
| Observation and Results|| |
From September 2005 to March 2008, a total of 22 patients underwent lymphatic mapping with methylene blue and sentinel node biopsy for carcinoma penis.
Characteristics of the patients undergoing the procedure are presented in [Table 1]. The mean age of the patients was 52 years, the range being 33-74 years.
Most of the patients had T1 tumors, with the glans being the commonest site of involvement. Fourteen of the 22 tumors were well differentiated. Twenty patients underwent partial penectomy and two patients total penectomy.
Sentinel nodes were identified by following the stained lymphatics.
Sentinel nodes were identified in 90% of the patients (20/22).[Table 2]. In 19 patients, it was identified bilaterally, in one patient unilaterally. In two patients, sentinel nodes could not be identified.
A single sentinel node was positive in one person for malignancy (5%). On subsequent dissection, three more nodes were found to be positive in the groin of the same side, the opposite groin being negative.
In all, 49 sentinel nodes were identified in 22 patients, 2.45 nodes per person or 1.225 nodes per groin.
The duration of follow-up ranged from 2-17 months. Five patients were lost to follow-up. One patient died of myocardial infarction after five months of follow-up.
During the follow-up, two patients developed unsalvageable groin metastases with distant metastasis, giving a false-negative rate of 66%. The sensitivity rate in this study was found to be 33% and the specificity was 100%. The positive predictive value was 100% and negative predictive value was 85.7% with an overall accuracy of staging of 86.7%.
| Discussion|| |
The concept of sentinel node was originally described by Cabanas in 1977.  He used lymphangiography performed via the dorsal lymphatics of the penis to identify the lymph node close to the superficial epigastric vein as the sentinel node. However, this fell into disfavor due to the high false-negative rates. Morton et al. described lymphatic mapping using isosulfan blue with a high success rate. 
The study of sentinel node biopsy for carcinoma penis so far has yielded conflicting results. The false-negative rates in different studies have varied from 42.5-4.5%.
Hornables et al. using DSNB achieved a low false-negative rate of 4.5%.  Perdona et al. had a false negative rate of 11%. 
Gonzanga-Silva et al. using isolated gamma probe technique had a sensitivity of 25% and a false-negative rate of 42.8%. 
Pettaway et al. at M.D Anderson did extended sentinel node dissection in 20 patients which were all negative for metastasis, but five patients developed inguinal metastasis at a median of 10 months with a false-negative rate of 25%. 
Our study shows a false-negative rate of 66% which indicates that lymphatic mapping with methylene blue is not a reliable method of detecting the sentinel node.
Spiess et al. compared sentinel node biopsy by isosulfan blue to combined techniques and found the sensitivity be 55% and 71%, respectively. 
Hornables et al. using DNSB with preoperative USG and USG guided FNAC with a strict pathology protocol including IHC have brought down the false-negative rate from 16 to 4.5%.  On its own, USG-guided FNAC has sensitivity of only 39%, so it is best used as an adjunct to DSLB.
The theoretical reasons for false-negative nodes include:
- Improper site of the injection.
- Insufficient tracer injection.
- Obstruction of lymphatic channels or nodes by the tumor and the tracer going to the uninvolved node.
- A false-negative histopathology.
Complications associated with the study were mostly minor. One patient had a major wound infection which needed treatment with intravenous antibiotics. Three patients had minor wound infections. All the patients had bluish discoloration of urine for 2t-3 days. There were no hypersensitivity reactions.
The study shows that methylene blue can be safely administered for intraoperative lymphatic mapping, but is unreliable as a single modality of investigation. Currently, DSNB is the method of choice for sentinel node biopsy. Lymphatic mapping with only methylene blue was done due to lack of availability of gamma probe. Methylene blue can be used as a substitute for lympazurin because of easier availability and lower cost.
Patients undergoing sentinel node biopsy need to be followed up rigorously. In our series, five patients were lost to follow-up which affected the result. The duration of follow-up in our study was also short. Patients of carcinoma penis are known to develop metastasis in the groin as late as three years from the time of diagnosis.  Hence, a longer duration of follow up is required to arrive at more definitive conclusions.
| Conclusions|| |
Our findings show that sentinel node biopsy using only methylene blue is associated with a low sensitivity and a high false-negative rate, hence this procedure cannot be recommended. Methylene blue because of its safety and cost can be used as a substitute to lymphazurin during dynamic sentinel node biopsy, which is the more accurate method of sentinel node detection.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]