Visualization of Tumor Blockage and Rerouting of Lymphatic Drainage in Penile Cancer Patients by Use of SPECT/CT

Leijte, Joost A.P.; Ploeg, Iris M. C. van der; Olmos, Renato A. Valdés; Nieweg, Omgo E.; Horenblas, Simon

doi:10.2967/jnumed.108.059733

Cited by 111 publications

(45 citation statements)

References 29 publications

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“…80). These experimental findings are in agreement with the clinically observed redirection of lymph flow after LN metastasis of penile cancers (82). Bypassing of metastatic LNs with increased intranodal pressure toward the next echelon of nodes with lower intranodal pressure has also been reported in breast cancer (83).…”

Section: Functional Quantitative In Vivo Imaging Of Tumor-draining Lsupporting

confidence: 89%

Mechanisms of lymphatic metastasis

Karaman¹,

Detmar²

2014

J. Clin. Invest.

467

417

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Malignant tumors release growth factors such as VEGF-C to induce lymphatic vessel expansion (lymphangiogenesis) in primary tumors and in draining sentinel LNs, thereby promoting LN metastasis. Surprising recent evidence suggests that lymphatic vessels do not merely represent passive channels for tumor spread, but that they may actively promote tumor cell recruitment to LNs, cancer stem cell survival, and immune modulation. New imaging approaches allow the sensitive visualization of the earliest LN metastases and the quantitative, noninvasive measurement of the function of tumor-draining lymphatic vessels, with potential applications in the development of biomarkers for prognosis and measurement of therapeutic response.Cancer metastasis, the dissemination of cancer cells from the primary tumor to organs, where they initiate malignant growth, is the primary cause of cancer-related deaths. There has been a plethora of studies addressing the mechanisms of tumor metastasis via the bloodstream to distant organs; however, the majority of epithelial cancers first develop metastatic growth by spreading via lymphatic vessels to their draining LNs. Indeed, the detection of metastases within the sentinel LNs (SLNs; the first LNs into which a tumor drains) has major prognostic implications for patient survival and often also determines the choice of adjuvant therapies (1). Despite the obvious clinical importance of LN metastasis, the mechanisms leading to tumor spread via lymphatic vessels have remained unknown for decades. In fact, the prevailing view suggested that lymphatic vessels only play a passive role in tumor metastasis, serving merely as channels for tissue-invading tumor cells. The limited knowledge in this field was due to the relatively low scientific interest in lymphatic vessels as compared to the blood vasculature, the lack of reliable molecular markers to distinguish between lymphatic and blood vessels, the absence of identified growth factors for the lymphatic system, and the paucity of suitable experimental models to study and quantify LN metastasis. During the last 15 years, however, there has been substantial progress in the field of lymphatic vessel biology, which has rapidly lead to the recognition of the lymphatic vascular system as a major player involved in a multitude of human diseases (2). In this article, we will discuss the major discoveries made by our laboratory and many other researchers that have led to the recognition of a major role for the lymphatic vasculature in promoting cancer metastasis and to the new concepts of tumor-associated and LN lymphangiogenesis with a specific focus on the development of new strategies to image and therapeutically target the lymphatic system in cancer.

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Section: Functional Quantitative In Vivo Imaging Of Tumor-draining Lsupporting

confidence: 89%

Mechanisms of lymphatic metastasis

Karaman¹,

Detmar²

2014

J. Clin. Invest.

467

417

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“…Indeed, Kwon et al [26] have reported that lymphatic drainage can occur across the midline of the animal in response to cancer metastasis. In humans, SPECT/CT imaging has shown lymphatic re-routing in response to cancer metastasis [27]. Recently it has been reported that functional intraluminal valves prevent fluid communication between the lymphatic vessels and draining LN [28].…”

Section: Discussionmentioning

confidence: 99%

Visualization of fluid drainage pathways in lymphatic vessels and lymph nodes using a mouse model to test a lymphatic drug delivery system

Kodama

Hatakeyama

Kato

et al. 2014

Biomed. Opt. Express

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Curing/preventing micrometastasis to lymph nodes (LNs) located outside the surgically resected area is essential for improving the morbidity and mortality associated with breast cancer and head and neck cancer. However, no lymphatic therapy system exists that can deliver drugs to LNs located outside the dissection area. Here, we demonstrate proof of concept for a drug delivery system using MXH10/Mo-lpr/lpr mice that exhibit systemic lymphadenopathy, with some peripheral LNs being as large as 10 mm in diameter. We report that a fluorescent solution injected into the subiliac LN (defined as the upstream LN within the dissection area) was delivered successfully to the proper axillary LN (defined as the downstream LN outside the dissection area) through the lymphatic vessels. Our results suggest that this approach could be used before surgical resection to deliver drugs to downstream LNs outside the dissection area. We anticipate that our methodology could be applied clinically, before surgical resection, to cure/prevent micrometastasis in LNs outside the dissection area, using techniques such as ultrasound-guided internal jugular vein catheterization.

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“…The main reason for false negative results is complete sentinel node replacement with tumor cells and identification of non-involved lymph nodes as sentinel nodes. 118 Our systematic review showed that sentinel node mapping is highly successful and accurate in small and low stage cervical cancer tumors. Due to its low accuracy, sentinel node mapping is not well suited for large tumors (>2 cm) and those at a more advanced stage.…”

Section: Tumor Size and Stagementioning

confidence: 98%