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Pattern and implication of lymphatic drainage in renal tumors Axel Bex, MD, PhD The Netherlands Cancer Institute FOIU Tel Aviv, July 4, 2018 Financial and Other Disclosures Off-label use of drugs, devices, or other agents: None or FILL IN


  1. Pattern and implication of lymphatic drainage in renal tumors Axel Bex, MD, PhD The Netherlands Cancer Institute FOIU Tel Aviv, July 4, 2018

  2. Financial and Other Disclosures  Off-label use of drugs, devices, or other agents: None or FILL IN HERE; including your local regulatory agency, such as FDA, EMA, etc.  Data from IRB- approved human research is presented [or state: “is not”] I have the following financial interests or Disclosure code relationships to disclose: Pfizer C, S Roche C Genentech C Ipsen C Novartis C BMS C 2

  3. Recommendations from EAU guidelines on RCC – updated 2014 • • For T1 RCCs, nephron-sparing surgery should be performed whenever possible. For T1 RCCs, nephron-sparing surgery should be performed whenever possible. Open partial nephrectomy currently remains the standard. Open partial nephrectomy currently remains the standard. A A • • Laparoscopic radical nephrectomy is recommended in T2 renal cell cancer when nephron- Laparoscopic radical nephrectomy is recommended in T2 renal cell cancer when nephron- sparing surgery is not suitable sparing surgery is not suitable B B • • Extended lymphadenectomy does not improve survival and can be restricted to staging purposes. Extended lymphadenectomy does not improve survival and can be restricted to staging purposes. A A • • Adrenalectomy is generally not recommended except when a normal adrenal gland cannot be excluded Adrenalectomy is generally not recommended except when a normal adrenal gland cannot be excluded by imaging and palpation. by imaging and palpation. B B • • Patients with small tumours and/or signi fi cant comorbidity who are un fi t for surgery should be considered Patients with small tumours and/or signi fi cant comorbidity who are un fi t for surgery should be considered for an ablative approach for an ablative approach (eg, cryotherapy and radiofrequency ablation). (eg, cryotherapy and radiofrequency ablation). A A EAU Guidelines on RCC – 2014 update, Ljungberg et al, Eur Urol 67:913-24, 2015

  4. But…….. • The patient who can potentially be cured by LND has very early lymph node metastasis and no systemic disease Canfield et al., J Urol 175:864-869, 2006

  5. Preoperative nomogram to predict nodal metastases • 1983 patients with cT any cN any cM any • Prevalence of nodal metastases 6.1 % • Accuracy 86.9 % Capitanio et al., BJU Int 112: E59-66, 2013

  6. Is there a template for lymph node dissection in RCC ? N=31 patients with N+ >1 cm Hadley et al, Urologic Oncology 2009

  7. MATERIALS & METHODS • OBJECTIVES: To study the lymphatic drainage of renal tumours • 40 patients • Local cT1-3 (<10 cm) cN0cM0 • US guided p/c injection of 0.4 ml 99m Tc-nanocolloid into the tumour • Preoperative lymphoscintigraphy with SPECT/CT • Surgical treatment with intraoperative SN identification and sampling using a gamma probe and mobile gamma camera • SN and non-SN dissection

  8. Contralateral paraaortic SN location

  9. Supraclavicular lymph node metastases 4/22 patients with SPECT- SN identification (18.2 %) Brouwer et al., Lymph Res Biol 11:233-38, 2013

  10. 65% inside LND templates 35% outside from which 20% in thoracic area Kuusk et al., J Urol 2018

  11. Parker was the first to describe connections to the thoracic duct Parker 1935

  12. 1969 - A lymphographic and histopathological investigation in RCC • N=22 patients undergoing nephrectomy • 7 (32 %) metastasis in lumbar and ipsilateral iliac nodes • 1 supraclavicular node • Poor correlation of lymphography with nodal metastasis but contrast filling of mediastinal nodes observed Hulten et al., Scand J Urol Nephrol 3:129-33, 1969

  13. Direct drainage into the thoracic duct without intervening lymph nodes 5 of 13 right side, 3 of 13 left side Assouad et al., Lymphology 39:26-32, 2006

  14. Distribution of lymph node metastases – an autopsy study • n= 1001 patients with metastatic RCC Location % neck + clavicle 20.7 % mediastinum 10.3 % hilus of lungs 66.2 % hilus of kidney 7 % paraaortal 26.8 % retroperitoneal 36 % mesenterial 14.4 % Saitoh et al. J Urol 1982

  15. Distribution of lymph node metastasis • Imaging study on 28 patients with cN1 identified from 101 with RCC Location Percentage (left/right combined Distant lymphadenopathy 29 % without hilar lymphadenopathy Interaortocaval 42 % retroaortocaval 46 % suprahilar 30 % Hadley et al. Urol Oncol 2009

  16. Paraaortic TD subclavian vein lung mediastinal nodes Brouwer et al, Assoud et al

  17. Implications • The pattern of lymphatic spread in RCC is very unpredictable • The true rate of single early occult LN metastasis is unknown but seems low • The sentinel node concept should be studied in clinically high-risk cN0 patients or used for translational research purposes

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