Radio-isotope guided surgery
I wish to share a few lessons learned at a course on “minimally invasive radio-isotope guided surgery”- at the Moffit Cancer Center/USF, Tampa, Florida. For the sake of brevity the topics covered will be divided into four:
- malignant melanoma
- carcinoma of the breast
- parathyroid adenoma
- colonic cancer
Malignant melanoma
The aim is to reach a low morbidity and low cost compromise between routine lymphnode dissection (LND) and observation in patients with clinical stage II disease (non palpable nodes).
Patients with lesions of less than 0.76 mm may be sparred the procedure as their chance to have involved nodes are remote; patients with lesions thicker than 4 mm are known to harbor disseminated disease-and therefor may not benefit from the procedure.
At a certain time prior to the operation-depending on one’s local facilities-the melanoma site or the site of its previous excision are injected with the radioisotope and the potential lymphnode basins are scanned to locate the position of the first node taking the radioisotope-called the SENTINEL NODE. Lesion of the trunk and head and neck may drain to LN basins remote from the lesion or to more than a one basin. Thus, we were showed patients with melanoma of the back draining to both axillas and one groin, and lesion on the left chest draining to the right axilla!
The approximate location of the “hot” LN is then tattooed on the corresponding skin. On the morning of surgery the original injection site is re-injected with the radioisotope. In the OR before the surgeon scrubs he injects the primary tumor site or its scar with a blue dye.
At the sentinel node biopsy the surgeon is guided by the tattoo on the skin, the blue dye which stains the lymphatics converging on the sentinel node, and by a hand-hold radioisotope counter (probe) which guides the surgeon onto the hottest spot. Best results are obtained by using together all 3 modalities.
Finding a negative sentinel node means that in 99% there are no other involved “skip lesions” at the dissected LN basin.
The procedure is performed under local anesthesia and is relatively easy-less so, however, in fat patients. It saves the patient the morbidity of “full’ LND which at the groin situation is relatively severe- i.e. limb edema and wound complications. Obviously, in cases with multiple sentinel nodes ;i.e. a scalp lesion with “hot” nodes on both sides of the neck-both nodes are dissected.
If the sentinel LN is positive the patient is subjected to a full LND at another day. Currently, positive LN in melanoma means systemic therapy with interferon- which has been showed to improve survival.
Having seen the relative ease of the procedure at the animal lab and OR , its role in malignant melanoma is convincing to me.
Carcinoma of breast
The technique is the same as in melanoma. Let us take for example a T1b lesion at the LLQ. The patient comes to the OR with her axilla tattooed over the assumed sentinel LN. You inject 5 ml of blue dye around the palpable lump. In cases of a non-palpable lump you inject the dye around the localizing needle -that is if you believe that such patients need axillary staging (see below). After the lumpectomy you go and search for the sentinel node through a small axillary incision (local anesthesia) again guiding yourself using the blue dye and radioisotope sensing probe.
Should the LN turn positive the patient will require formal LND. The Tampa guys use “touch cytology” technique to immediately evaluate the adequacy of the lumpectomy margins and assess whether the sentinel node is positive. The excised lump in divided and marked into 5-6 “surfaces” -each “touched” with a slide. their results show that negative cytology for malignant cells excludes positive margins and secure a local recurrence rate of 2 % after radiotherapy). When malignant cells are seen on the slide the corresponding lumpectomy field is immediately re-excised. But obviously you must have a well trained cytologist.
I was impressed by the easiness of this technique and am convinced that sentinel node biopsy may spare formal axillary LND in numerous women. I was concerned however with the rather wide indications as practiced in Tampa.
We were shown a pre-menopausal lady with a scar following a needle guided biopsy of an in situ ductal carcinoma. The scar was injected and the sentinel node dissected. Many would argue that in such a case the axilla needs no attention at all.
Then a 70 yo lady with a 1cm’ lesion; in many places such a patient would receive a lumpectomy, radiotherapy +/- tamoxifen. Dissection of the axilla has no staging and surely no therapeutic benefits here.
And, in view of the recent studies of radiotherapy we all heard about, perhaps in 5 years or so from now most patients will be managed by local excision of the lesion and wide -field radiotherapy+/- chemotherapy and “to hell with the axilla”.
Parathyroid adenoma
The Tampa guys argue against the conventional credo that localization tests are not necessary prior to parathyroid surgery for primary adenoma. They claim that it is indicated to permit a minimally invasive surgery.
The Sestamibi scan permits a very precise localization of the adenoma; in fact -one “hot” site means that there is ONE adenoma in almost 99% of the cases. At operation, the surgeon places the incision over the tattoo, previously placed by the isotope-guys. The surgeon then zooms directly on the adenoma guided by the isotope probe. After the adenoma is removed the field becomes “radioactively silent”. While conventional parathyroid surgery requires bilateral anatomical dissection averaging 2.2 hours the Tampa team does it under local anesthesia in the average of 40 minutes. The patient diagnosed as having hyperparathyroidism (based on elevated PTH levels) comes to the surgeon’s office, undergoes the scan and the operation – all in the same day. Makes sense.
Colonic cancer
RIGS or radio-isotope guided surgery in colonic ca is not new but has never really caught on. Only a few centers in this country continue evaluating this technique. During this course we were not exposed to such cases but the topic has been mentioned. As I understand it now- perhaps the only practical indication for RIGS would be prior to a planned hepatectomy for colonic met’s. A day before operation the patient is injected with anti-CEA radio-tagged antibodies. During laparotomy the abdomen is explored with the isotope sensing probe and any “hot” spots are biopsied- when positive- hepatectomy is FUTILE. “Hot” spots are commonly present along the duodenohepatic ligament.
In conclusion:
it appears that sentinel node biopsy guided by radioisotopes and blue dye has a real role in patients with melanoma and breast ca. Radioisotope scan guided “minimal’ surgery may proof the ideal way to deal with parathyroid adenomas RIGS in colonic ca has a limited but still under evaluation role.
A nice synopsis of your radioisotope course and a few prejudices of my own:
RE: breast cancer, I fully agree with you that sentinel node technology will be a thing of the past in a few years, as the next change in breast cancer Rx will be avoidance of axillary dissection altogether in clinically negative axillae–i.e. in most cases of breast cancer–reserve it only for palpable nodes, in which case a full dissection must be done regardless of the status of the sentinel node–the arguments for this are very powerful.
I disagree with you about radioisotope imaging for primary cases of hyperparathyroidism–as numerous studies have documented, it is superfluous and dangerous to the patient–I’m sure the guys at Tampa failed to mention their cases in which a second andf/or third adenoma was missed by this technique, as it is well established that its false negative rate is much higher than a surgeon’s hands–after all, it’s hard to improve on a 95% accuracy of the latter, so why try? Multiple adenomas occur in up to 22% of cases of primary hyperPTH, according to a classic study by Wells a few years back. Also, as a purist in this area, I greatly object to deleting from resident’s training the proper surgical approach to this disease, which is the only way they, or any surgeon, comes to realize that the diagnosis and treatment is totally and optimally possible on the basis of 2 or three very simple tests, a knowledge of the pathophysiology(and here is where it is just easier to get a test than understand a disease process!), and your own gross assessment at the time of surgery. This si the way it’s been done succe4ssfully–95% reliability–for decades, so why this fascination with a test that every study to date documents to have a clearly lower accuracy? Well, my answer is above, in that it’s perceived to be easier and quicker for the surgeon, the heck with the patient.
Your contention that operative time is shortened is not based on any quality evidence, as studies of this have documented no significant time difference, but HAVE documented missed disease in upwards of 10- 15% or more of cases in which pre-op imaging was used (as opposed to 5% using the standard and more cost effective approach) Certainly, in persistent or recurrent hypercalcemia after initial operation, this and methylene blue staining (another great technique which selectively stains only pathologic glands a brilliant blue and makes them easier to find) are valuable adjuncts–but this should come up only 5% of cases!
Where do you inject the methylene blue?
It is isosulfan blue. Inject 5 ml at the periphery of the lesion or the excised skin; multiple small dermal injections around.
The advanced thinking about axllary dissection (AD) is unfortunately not accepted by the “community” where AD is considered “the standard of care”. Surgeons in this country-as opposed to the UK and Europe-will be terrified to avoid AD even in T1B lesions unless the so called “leaders in the field” will establish uniform guidelines.
But the “leaders” ever busy fighting for more grants and power are busy generating more and more studies which make management more complicated. Dr. Reintgen for example samples axillas of any tumor stage, looking-among other-for MICRO-MET’s dedected by molecular methods. Their rational- patinets without micro-met’s may not require chemotherapy while all the others do…
So the wagon is being pulled in many direction- but where shall we go?
You present the conventional main – stream wisdom that bilateral exploration is the standard of care and that selective -imaging-guided exploration is not good.
I am far far from being an expert in the field and therefore do not wish to enter in any discussion with experts as yourself. I do not think he was trying to hide all these adenomas he missed. Why don’t you drive across to see what he is doing – it is quite cool. Did you ever look for land mines with a metal detector- this is how they find the adenoma with the Neoprobe. Easier than searching for 25 cent coins on the beach.
And BTW, what should I do with the ? Ca pancreas case I presented yesterday?
Isosulfan blue or lymphozuran blue is used instead of methylene blue. Methylene blue does not accumulate in the lymphatics. Incidentally, you have to tell all patients that will have greenish blue urine for 1-2 days postop!
One ml is injected, typically in four quadrants, around the melanoma primary site.
Currently, three ml is injected around the breast lesion. Earlier studies used one ml, but the latest protocol from Moffitt and other places uses 3 ml. The lymphatic drainage in the breast seems to concentrate dye and radioactivity less efficiently than from the skin.
Regarding parathyroid surgery, I will state that Wells himself has expressed interest in the non-invasive technique espoused by Dr. Norman, at a recent conference here at Wash U. This was surprising, given his previous publications, which have been cited already. However, one could take the approach that almost all patients with non-familial primary hyperparathyroidism would be spared a full neck dissection, and only that small minority (?10-20%) with multi-gland disease would need a “redo” that would really only be a primary surgery, since the other tissue planes would be undisturbed. I think that non-invasive parathyroid surgery will find its place over time and will become important in selected (?which ones) patients.
Another thing that he did not mention is the need for close cooperation between the nuclear medicine and surgical physicians. We have found here over the past year that there is a learning curve for all involved, and the procedure becomes infinitely easier from multiple perspectives, right down to scheduling, with experience. There are also some issues about pathologic examination of the lymph node that he alluded to . Pathologists typically examine lymph nodes by bisecting them and taking a few sections (H&E only) from each half. The most recent sentinel node literature suggests that this is inadequate, that more micrometastases will be found with more serial sections and more advanced (and expensive) immunohistochemistry, specifically S-100 and HMB-45. This has not been shown in randomized prospective fashion, although there is emerging *almost* published data from MD Anderson and Moffitt where almost all of their lymph node recurrences in melanoma patients with “negative” sentinel nodes predate this more aggressive pathologic examination, and would have been found with their current aggressive examination protocol. At our institution and others, the pathologists have balked at changing their protocol, pending further publicaitons. Dr. Reintgen is also a champion of PCR examination of lymph nodes for tyrosinase, an enzyme in the melanin pathway, but the prognostic implications of this test are speculative at this point, and are not used to change therapy outside of protocols.
Thank you very much for the update. The approach to parathyroid adenoma removal is certainly fascinating. As a paediactric surgeon I am very fortunate not to have deal with the other problems much.
I will be attending the same conference on December 4th. I have come to the same conclusionsn as you regarding the usefulness of this procedure for melanoma and breast cancer. Obviously, the potential role of sentinel node biopsy for breast cancer will have a greater impact on our practices than in melanoma because of the higher volume of patients.
Reintgen at Moffett is currently enrolling his breast ca pts in a study where only the sentinel node is dissected out, and only positive nodes are followed by a full axillary dissection. There are other studies looking at the same thing in the country. There will soon be an NSABP study as well, I am told.
I have begun doing a preliminary sentinel node biopsy ( with vital blue dye only) in my breast cancer pts who are having axillary dissections. This allows me to identify a sentinel node in most cases, so that the pathologist can concentrate his efforts on evaluating for nodal mets. In the process, I am gaining needed experience in doing the sentinel node dissection. At this point I am always following immediately with a full dissection.
For those surgeons who participate in the clinical trials, I think one must have had a certain number of cases in which a full axillary dissection is done regardless of the sentinel node findings, in order to “validate” the technique in his/her own hands. I think it would be worthwhile for others to consider beginning the process of learning the technique.