Monday, April 7, 2014

Positive Surgical Margins after Partial Nephrectomy: Cause for Concern?

A positive surgical margin implies that cancer is left behind at the time of surgery.  For many cancer surgeries, including prostate and bladder cancer, positive surgical margins are a surrogate for quality of surgery and have implications for additional treatments and cancer survival.  For some cancers, including renal cell cancer (RCC), the implications of a positive surgical margin are less clearly defined.  In this blog, Mohamad E. Allaf, Director of Minimally-Invasive and Robotic Surgery, reviews the data regarding positive surgical margins following partial nephrectomy for the treatment of renal cancer.

Defining Positive Surgical Margins in the Context of the Evolution of Nephron-Sparing Surgery

As kidney surgery evolved from radical to partial nephrectomy (PN), and then from open to minimally-invasive surgery, the definition of a safe margin also evolved. Initially definitions decreased from strict size criteria (i.e. 5mm)[1,2] to any tumor-free margin regardless of size,[2,3] and now consideration of tumor enucleation when possible.  Enucleation is defined by incision of the renal parenchyma within a few millimeters of the tumor, and removal of the tumor by blunt dissection of the plane between the capsule of the tumor  and the healthy renal tissue.[4]  Minervini and colleagues examined oncologic outcomes after standard PN and simple enucleation.  They found a lower rate of positive surgical margins in the patients undergoing enucleation compared to PN (0.2% vs 3.4%) but no difference in recurrence-free or cancer-specific survival.  Interestingly, patients with high-grade disease (Fuhrman Grade 4) who underwent enucleation had worse cancer-specific survival (CSS) compared to those undergoing PN.  Despite these reports , there is still a widespread belief among urologists that enucleation is unsafe with a high risk of incomplete tumor excision, especially for larger lesions.[5]

Rates and Predictors of Positive Surgical Margins

Positive surgical margins have been reported in 0.7-10% of PN series.[6,7]  There are surgical considerations and tumor characteristics that are related positive margins.  Surgical considerations included impaired intraoperative visibility and poor orientation; and can be modified by surgeon experience, intraoperative ultrasound or better clamping techniques.  Tumor characteristics include tumor size, location and invasion;[6] however, due to the relatively low rate of positive surgical margins, parsing out which characteristics are most important remains controversial.


Implications of Positive Surgical Margins

In the case of a positive surgical margins, some surgeons will advocate re-resection or salvage radical nephrectomy.  However, the nephrectomy specimen will only have viable tumor in 6.9% to 15% of cases.[8,9]  The historic CSS after PN is 95% or better.  Several retrospective studies, including one by Besalah and colleagues, fail to demonstrate a difference in survival for patients with positive surgical margins.[10]  A recent large, multi-center study investigated 943 patients undergoing robotic PN; these authors found a low positive surgical margin rate (2.2%), but a higher rate of recurrence and metastases in the patients with positive margins.[11]


Summary


  • Positive surgical margins after partial nephrectomy for renal cell carcinoma are rare.
  • A positive surgical margin may reflect difficulties with a technical aspect of surgery or imply adverse tumor biology.
  • The data regarding recurrence and survival for patients with a positive surgical margin is inconclusive; however the strongest data suggests that: 
    • patients with positive surgical margins are at higher risk for recurrence.
    • this is more evident in patients with high-grade cancer.
    • long-term cancer-specific survival is not affected by margin status.


Recommendations from Dr. Allaf

A "gross" positive margin, meaning a positive margin noticed at the time of initial partial nephrectomy, should be addressed.  This could involve taking additional tumor or completion nephrectomy.

A "microscopic" positive margin, a margin noted by the pathologist under the microscope after the tumor has been removed, warrants careful consideration.  Sometimes the surgeon is certain that all tumor was removed at the time of surgery and can alleviate patient anxiety (frozen margins at the time of surgery can be helpful here).  Regardless, these patients warrant a careful period of active surveillance.  For patients with high-grade or high-stage tumors this should involve frequent imaging and early consideration of a re-operative intervention.

 
Mohamad E. Allaf, M.D. 
Associate Professor of Urology, Oncology, and Biomedical Engineering
Johns Hopkins Medical Institutions
Director, Minimally Invasive and Robotic Surgery
Johns Hopkins Hospital






[1] Li Q-L, Guan H-W, Zhang Q-P et al. Optimal margin in nephron-sparing surgery for renal cell carcinoma 4 cm or less. Eur Urol. 2003; 44: 448.
[2] Castilla EA, Liou LS, Abrahams NA et al. Prognostic importance of resection margin width after nephron-sparing surgery for renal cell carcinoma. Urology. 2002; 60: 993.
[3] Timsit MO, Bazin JP, Thiounn N, et al: Prospective study of safety margins in partial nephrectomy: intraoperative assessment and contribution of frozen section analysis. Urology. 2006; 67: 923.
[4] Minervini A, Ficarra V, Rocco F, et al. Simple enucleation is equivalent to traditional partial nephrectomy for renal cell carcinoma: results of a nonrandomized, retrospective, comparative study. J Urol. 185:1604-1610
[5] Touijer K, Jacqmin D, Kavoussi LR et al. The expanding role of partial nephrectomy: a critical analysis of indications, results, and complications. Eur Urol. 2010; 57: 214.
[6] AnI, Finelli A, Alibhai SMH, et al. Prevalence and impact on survival of positive surgical margins in partial nephrectomy for renal cell carcinoma: a population-based study. BJU Int. 2013;111: E300–E305.
[7] Marszalek M, Carini M, Chlosta P et al. Positive surgical margins after nephron-sparing surgery. Eur Urol. 2012; 61: 757.
[8] Raz O,Mendlovic S, Shilo Y, et al. Positive surgical margins with renal cell carcinoma have a limited influence on long-term oncological outcomes of nephron sparing surgery. Urology. 2010;75:277–80.
[9] Sundaram V, Figenshau RS, Roytman TM, et al. Positive margin during partial nephrectomy: does cancer remain in the renal remnant? Urology. 2011;77:1400–3.
[10] Besalah K, Pantuck AJ, Rioux-Leclercq N, Thuret R, et al. Positive surgical margin appears to have negligible impact on survival of renal cell carcinomas treated by nephron-sparing surgery. Eur Urol. 2010;57:466-473.
[11] Khalifeh A, Kaouk JH, Bhayani S, et al. Positive surgical margins in robot-assisted partial nephrectomy: a multi-institutional analysis of oncologic outcomes (leave no tumor behind). J Urol. 2013;190:1674-1679.

9 comments:

  1. God bless Dr.Ekpiku for his marvelous work in my life, my name is Joyce Benson from USA, I was diagnosed of HERPES since 2013 and I was taking my medications, I wasn't satisfied i needed to get the HERPES out of my system, I searched about some possible cure for HERPES i saw a comment about Dr Ekpiku how he cured HERPES with his herbal medicine, I contacted him and he guided me. I asked for solutions, he started the remedy for my health, he sent me the medicine through UPS delivery company. I took the medicine as prescribed by him and 11 days later i tested negative for HERPES, Dr.Ekpiku truly you are great, do you need his help also? Why don't you contact him through email (ekpikuspellhomeofgrace@gmail.com) or call him on +2348073673757 and you can also contact me to know more about him on my email Joycebenson731@gmail.com or text me +16506538578. DOCTOR Ekpiku CAN AS WELL CURE THE FOLLOWING DISEASE:- 1. HIV/AIDS 2. HERPES 3. CANCER 4. ALS 5. Hepatitis B 6. Diabetes 7. Athrux, 8. hydrophobia 9.hpv 10 pregnancy spell and bring back your ex back 11 scabies 12. STD.

    ReplyDelete
    Replies
    1. Hello I'm Gladness buff by name, I'm giving a testimony about Dr. Emmanuel the great Herbalist, he has the cure to all manner of diseases, he cured my Herpes virus, though I went through different website I saw different testimonies about different spell casters and herbalist, I was like: 'Many people have the Herpes Virus cure why are people still suffering from it?' I though of it, then I contact Dr. Emmanuel via email, I didn't believe him that much, I just wanted to give him a try, he replied my mail and Needed some Information about me, then I sent them to him, he prepared it (CURE) and sent it to Airfreight Online Courier Service for delivery, he gave my details to the Courier Office, they told me that 3-5 days I will receive the package and i took the medicine as prescribed by him and I went for check-up 2 weeks after finishing the medicine, I was tested Herpes Virus negative, if you are Herpes Virus positive do me a favor for you to contact him and I will try my possible best to make sure you get cured, when you contact him, make sure you tell him that I referenced you.. contact him via: nativehealthclinic@gmail.com or WhatsApp/Call him +2348140073965
       he have cure to HIV/AIDS,diabetes,cancer,copd,hepatitis,hpv etc//..

      Delete
  2. My names are HARRY MARY I’m a citizen of United Kingdom, My younger sister was sicking of breast cancer and her name is HARRY Sandra I and my family have taking her to all kind of hospital in UK still yet no good result. I decided to go to the internet and search for cancer cure so that was how I find a lady called peter Lizzy she was testifies to the world about the goodness of a herbal man who has the root and half to cure all kind of disease and the herbal man email was there. So I decided to contact the herbal man for my younger sister help to cure her breast cancer. I contacted him and told him my problem he told me that I should not worry that my sister cancer will be cure, he told me that there is a medicine that he is going to give me that I will cook it and give it to my sister to drink for one week, so I ask how can I receive the cure that I am in UK, he told me that I will pay for the delivery service. The courier service can transport it to me so he told me the amount I will pay, so my dad paid for the delivery fee. two days later I receive the cure from the courier service so I used it as the herbal man instructed me to, before the week complete my sister cancer was healed and it was like a dream to me not knowing that it was physical I and my family were very happy about the miracle of Doctor so my dad wanted to pay him 5 million us dollars the herbal man did not accept the offer from my dad, but I don't know why he didn't accept the offer, he only say that I should tell the world about him and his miracle he perform so am now here to tell the world about him if you or your relative is having any kind of disease that you can't get from the hospital please contact drsujuherbalhome@gmail.com or call him and whatsApp him <+2348168259521> he will help you out with the problem.

    ReplyDelete
  3. My names are HARRY MARY I’m a citizen of United Kingdom, My younger sister was sicking of breast cancer and her name is HARRY Sandra I and my family have taking her to all kind of hospital in UK still yet no good result. I decided to go to the internet and search for cancer cure so that was how I find a lady called peter Lizzy she was testifies to the world about the goodness of a herbal man who has the root and half to cure all kind of disease and the herbal man email was there. So I decided to contact the herbal man for my younger sister help to cure her breast cancer. I contacted him and told him my problem he told me that I should not worry that my sister cancer will be cure, he told me that there is a medicine that he is going to give me that I will cook it and give it to my sister to drink for one week, so I ask how can I receive the cure that I am in UK, he told me that I will pay for the delivery service. The courier service can transport it to me so he told me the amount I will pay, so my dad paid for the delivery fee. two days later I receive the cure from the courier service so I used it as the herbal man instructed me to, before the week complete my sister cancer was healed and it was like a dream to me not knowing that it was physical I and my family were very happy about the miracle of Doctor so my dad wanted to pay him 5 million us dollars the herbal man did not accept the offer from my dad, but I don't know why he didn't accept the offer, he only say that I should tell the world about him and his miracle he perform so am now here to tell the world about him if you or your relative is having any kind of disease that you can't get from the hospital please contact drsujuherbalhome@gmail.com or call him and whatsApp him <+2348168259521> he will help you out with the problem.

    ReplyDelete
  4. Am really happy that i and my husband are cured of (HIV VIRUS) with the herbal medicine of Dr Marko , i have been suffering from this disease for the past 3 years without solution until i came across this doctors who have cured so many people with his herbal medicine, i also choose to give him a chance to help me and my husband, he told me what to do and i kindly did it, and he gave us his herbal medicine and direct me on how to use it, i also follows his instruction for use and he ask us to go for a check up after 3 weeks and which i did, to my greatest surprise our result came out as negative, we are really happy that there is someone like this DR Marko who is ready to help anytime any day. to all the readers and viewers that is doubting this testimony stop doubting it and contact this Dr and see if he will not actually help you. i am not a stupid woman that i will come out to the public and start saying what someone have not done for me .contact him now if you are also in need of help via email templeofsuccessandlove@gmail.com or whatsapp number +2348075705225 may God bless you sir for all your good works. contact Dr Marko today for your following diseases below

    HEPATITIS,
    CÁNCER,
    HERPES

    ReplyDelete
  5. Hello I'm Gladness buff by name, I'm giving a testimony about Dr. Emmanuel the great Herbalist, he has the cure to all manner of diseases, he cured my Herpes virus, though I went through different website I saw different testimonies about different spell casters and herbalist, I was like: 'Many people have the Herpes Virus cure why are people still suffering from it?' I though of it, then I contact Dr. Emmanuel via email, I didn't believe him that much, I just wanted to give him a try, he replied my mail and Needed some Information about me, then I sent them to him, he prepared it (CURE) and sent it to Airfreight Online Courier Service for delivery, he gave my details to the Courier Office, they told me that 3-5 days I will receive the package and i took the medicine as prescribed by him and I went for check-up 2 weeks after finishing the medicine, I was tested Herpes Virus negative, if you are Herpes Virus positive do me a favor for you to contact him and I will try my possible best to make sure you get cured, when you contact him, make sure you tell him that I referenced you.. contact him via: nativehealthclinic@gmail.com or WhatsApp/Call him +2348140073965
     he have cure to HIV/AIDS,diabetes,cancer,copd,hepatitis,hpv etc//..

    ReplyDelete
  6. My Name is Faith, and am really grateful and thankful for what Dr voodoo
    has done for me and my family. I Was having HIV/AIDS for good three years
    with no solution, the diseases almost took my life and cause I was unable
    to work and I was also loosing lots of money for medication, but one
    faithful day when I went online, I met lots of testimonies about this great
    man so I decided to give it a try and to God be the glory he did it. he
    cured me of my diseases and am so happy and so pleased to Write about him
    today. if you need his help of you also want to get cured just the way I
    got mine, add Dr voodoo on whatsApp: +2348140120719 or just contact Dr
    voodoo via email, voodoospelltemple66@gmail.com

    ReplyDelete
  7. I'm 40 years old female I tested genital herpes (HSV1-2) positive in 2002. I was having bad outbreaks. EXTREMELY PAINFUL. I have try different kinds of drugs and treatment by the medical doctors all to know was avail. Six months ago I was desperately online searching for a helpful remedies for genital herpes (HSV1-2) cure, which i come across some helpful remedies on how Dr OYAGU have help so many people in curing genital herpes (HSV1-2) with the help of herbal treatment because I too believe there is someone somewhere in the world who can cure herpes completely. At of the past 2 months, however, I've been following his herpes protocol Via oyaguherbalhome@gmail.com or +2348101755322 and it stopped all outbreaks completely! To my greatest surprise I was cured completely by following the protocol of his herbal medicine . Don't be discouraged by the medical doctors. There is a cure for HSV with the help of herbs and roots by a herbalist Dr call Dr OYAGU he is so kind and truthful with his herbal treatment, kindly contact him for more information Via oyaguherbalhome@gmail.com or WhatsApp DR on +2348101755322 you will be lucky as i am today

    ReplyDelete