ReviewDiagnostic nanocarriers for sentinel lymph node imaging
Graphical abstract
Introduction
The presence of lymph node metastases has major prognostic implications in case of most of the malignancies [1], [2], [3], and is a major criterion for determining the need for adjuvant chemotherapy [4]. Studies concerning the involvement of lymphatic drainage in the treatment of cancer patients and its contribution towards enhancing their survival are not new. Investigation of cancer patients and careful scrutiny of the observations made during their subsequent follow-up sessions have lead to the proposition of various speculations concerning the dissemination of solid tumors.
Sentinel node imaging is the latest concept towards a better understanding and analysis of dissemination of solid tumors. The hypothesis emphasizing the involvement of lymphatic drainage in sequential dissemination of solid malignancies has stemmed from Halsted's theory and research conducted by Gilchrist, Zeidman and coworkers [5].
Cabanas, back in the year 1977, proposed the involvement of lymphatic system in sequential dissemination of primary tumor during his studies in patients with penile carcinoma [6], [7], [8]. He discovered that a specific lymph node in the groin, which remained constant in its location and which he consequently termed as the ‘sentinel node’, was the preferential drainage area of the cells of squamous cell carcinoma of the penis. During his research he realized that sentinel node was the first location of localization of tumor cells through lymphatics before their passage to the other nodes of the lymphatic drainage pathway. Thus he deduced that the status of the entire lymphatic system could be predicted via the identification, surgical dissection and subsequent histological examination of the sentinel node. Thus, the occurrence of metastatic disease in the sentinel node could be used as a possible indicator of spread of the disease in the other nodes of the region and hence dissection of the regional lymph nodes could be recommended. Likewise, absence of disease in the sentinel node would spare the patients of the trauma of dissection of other nodes of the particular region. Since then the sentinel lymph node (SLN), deemed as the first draining site of an anatomical region, has been regarded as a histological indicator of the absence of tumor metastases in the other non-SLNs [9], [10].
The general acceptance and extensive use of SLN imaging was triggered by the initiation of intraoperative lymphatic mapping in 1989. Ever since researchers all over the world have directed their work in this direction and technique validations have now led to SLNs being used as vital tools of providing critical information in patients showing signs of tumor metastasis to superficial lymph nodes. This has facilitated accurate determination of the stage of malignancy, without compromising the local control, at the same time providing the advantage of the patients being spared of regional lymph node dissection.
Section snippets
Lymphatic imaging through SLN biopsy
Visualization of lymphatic drainage began at the end of the eighteenth century when Sappey et al. attempted the imaging of the intricate lymphatic system of the breast using mercury injections. It was later described by Haagensen et al. [11] in ‘The Lymphatics in Cancer’, where he has described anatomical studies using injections of various tracer fluids. The book further described the use of vital dyes and radioactive isotopes being employed by surgeons and nuclear medicine physicians to
SLN imaging: current modalities
The development of a reliable technique for the evaluation of the lymphatic function for cancer patients is one of the most researched areas. Various methods are being practiced for the accurate evaluation of lymphatic function. These imaging modalities are listed in Table 1. The subsequent sections of this review focus on the non-invasive sentinel node imaging modalities and why they have gained a preference over the earlier used invasive techniques of sentinel lymph node mapping.
Liposomes
Liposomes have been used as delivery vehicles since the 1960s and their use for the delivery of imaging agents, for all imaging modalities, has a long history. Liposomes are defined as vesicles in which an aqueous volume is entirely surrounded by a phospholipid membrane. They can vary in size from 30 nm to several micrometers, and can be uni- or multilamellar. Their properties have been extensively investigated and can vary substantially with respect to their size, lipid composition, surface
Implications and future directions
Cancer is known to develop via a multistep carcinogenesis process. Cancer treatments are performed on the basis of clinical and pathologic staging that is determined using morphologic diagnostic tools, such as conventional radiological and histopathological examinations. SLN localization is one the most important parameters considered in cancer diagnosis and therapy. The concept of the sentinel lymph node has earned widespread importance with the advent of the sentinel lymph node biopsy
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