Evaluation of sentinel lymph node identity in melanoma patients using analysis of antimony by inductively coupled plasma - mass spectrometry

Publication Type:
Thesis
Issue Date:
2010
Full metadata record
Files in This Item:
Filename Description Size
Thumbnail01Front.pdf12.08 MB
Adobe PDF
Thumbnail02Whole.pdf148.53 MB
Adobe PDF
NO FULL TEXT AVAILABLE. Access is restricted indefinitely. ----- The technique of sentinel lymph node biopsy (SLNB) has revolutionised the approach to staging of the regional lymph nodes in Stage I and II melanoma patients. Historically, these patients were subjected to an elective lymph node dissection which is associated with extensive morbidity. In the early 1990’s, Donald Morton and co-workers presented their landmark publication, confirming the bulk of patients can be staged through an assessment of the sentinel lymph node (SLN) which receives direct lymphatic drainage from the primary tumour. Assessment of this node accurately reflects the tumour status of the draining nodal field, sparing many patients a complete lymphadenectomy. Despite the widespread success of SLNB, long term results have indicated that some patients will present with a recurrence of disease in the assessed lymph node field, which is known as a false negative (FN) result. It was hypothesised that a post-operative method to confirm lymph nodes removed by surgeons are true SLNs would reduce potential FN results. The SLNB procedure involves the use of a radiocolloid containing antimony. The use of antimony as a marker for confirming SLN identity was proposed based on the hypothesis it would be preferentially retained compared to non-SLNs. Using solution nebulisation ICP-MS, a method to differentiate SLNs and non-SLNs was developed based on the digestion of nodal material, including lymph node sections and fine needle biopsies. Analysis of the digest concentrations identified a significant difference between the SLN and non-SLN populations. Using a median digest concentration as a threshold, an overall identification accuracy of 83% was achieved for both the lymph node sections and fine needle biopsy samples. The ability to confirm SLN identity using a fine needle biopsy suggested that the combination of proton MRS and ICP-MS analysis sample could represent an accurate, less invasive approach to assessing SLN involvement. A retrospective application of the method was conducted to assess whether the inaccurate removal of SLNs represents a source of FN results. The results indicated that surgical errors may account for up to 30% of FN results, while pathological errors were also prevalent. The method was also applied to a prospective case with the results used to confirm lymph node identity and facilitate a clinical decision. The spatial distribution of antimony in SLNs was also performed using LA-ICP-MS. The results indicated that antimony was not uniformly distributed throughout lymph node sections, with an accumulation around the efferent lymphatic channel observed using 2-dimensional colour maps. The result of subsequent research by other groups has indicated that numerous elemental tumour markers exist. The concurrent acquisition of tumour marker data, together with antimony could represent a viable analytical method for identifying tumour infiltrated nodes while also confirming the identity of the lymph node which was identified as a critical approach to minimising potential FN results.
Please use this identifier to cite or link to this item: