Okay, well, what I want to do today is just share a few thoughts about the problem of lower limb lymphedema and the things that have been proposed in the past and going forward into the future to try to reduce this. Now, the status of the groin nodes, as we all know, is the single most important prognostic factor in vulva cancer. The only way to be certain of the status of these nodes is to perform a complete inguinal femoral lymph node dissection. The techniques for the dissection, of course, have improved since the on-block days of Stanley Way to the more separate incision type of approach. But regardless of how you do the operation, if you take out the lymph nodes, then you will get lower limb lymphedema. It occurs in about 40 to 60% of patients. It's a lifelong affliction and it requires a lot of daily massage and support stockings to control. Just briefly, historically over the years, there's been many attempts to reduce this risk of lymphedema. The first was actually to define a category of microinvasive cancer. This was published in the MD Anderson Hospital in 1974. They described 25 patients who had cancers, whammous cancers, 20 millimetres wide and five millimetres deep, and none of these patients had positive nodes. But of course, it soon became clear that in fact, the only group of patients who had negative nodes were those who had one millimetre or less of stromal invasion. If you got up to three millimetres, then more than 25% of patients had positive nodes. So this didn't work. The second attempt was Phil Desire, Bill Creasman, looking at this concept of a superficial inguinal lymphadenectomy. They considered the nodes above the cribriform fascia to be so-called sentinel nodes. And this is the first time we'd heard this term used in gynaecological oncology. They reported 20 patients with cancers 10 millimetres wide and five millimetres deep and all had negative nodes. Again, they obviously got lucky. This was in 1979. I was a second year fellow at that stage at UCLA. And we adopted this approach, but we soon had three patients who had positive nodes. They occurred in the femoral nodes. And in fact, I became aware of four other patients around the Western states of America who also failed this approach. And I reported seven cases to the Western Association of Gynaecologic Oncologists in 1981. And this paper was published in 1983. The Gynaecologic Oncology Group then decided to do a prospective study of this proposed superficial inguinal lymphadenectomy. But they recruited 121 patients and nine groin recurrences occurred and seven of those patients died. And they concluded that this was probably attributable to the decision to leave the femoral nodes. The third approach was to treat the groins with radiation. And again, the GOG conducted this time a randomised trial between groin and pelvic radiation and inguinal femoral lymph node dissection. If the nodes were positive on the dissection, then postoperative radiation was given, which was the standard of care. There were five of 27 recurrences, 18.5% in the radiation arm and none in the groin dissection arm. So, in fact, all of these three modifications clearly failed. And what was worse was that virtually all of the patients that recurred in this undissected groin died of disease. Now, the fourth attempt was to use the sentinel node approach using preoperative lymphocentigraphy and intraoperative mapping together with intraoperative vital blue dye. The original study by Van de Zee had a false negative rate of about 2 or 3%, but most studies in fact reported at least 5 to 10% false negatives. And in addition, there were studies that demonstrated that patients generally were not prepared to trade a small risk of death from recurrent cancer for an opportunity to avoid lymphedema. This was the study that Rhonda Farrell did in my own department, where she looked at 60 patients who had bulbar cancer. They were told there was a 60% risk of lymphedema if they had the groin dissection. There was about a 1 in 100% risk of missing cancer in a lymph node if they had the sentinel node procedure, which would usually result in death. This 1 in 100 was based on a false negative rate of 5% and an incidence of positive nodes of 20%. And as you can see, of the 60 patients that she surveyed, all these patients that had treatment for their bulbar cancer, 53% said they would take no risk at all, and 10% said they would take a 1 in a million risk. Only 15% of patients said they would take a risk of between 1 in 2 and 1 in 100, which was the sort of risk that they were being asked to take. I presented these sort of facts and figures to patients with bulbar cancer, and I found that the only patients that were prepared to take the risk were the elderly patients who felt that they couldn't deal with surgical stockings every day, and the odd young patient who models actresses who felt that they would not be able to pursue their career if they had swollen legs. So the issue is really not about morbidity, it's about risk. And the question that we've got to ask is, what risk is the patient properly informed, prepared to take? Now, these guys are obviously happy to ride bikes around this cliff edge here. It certainly wouldn't be something I would do, and probably most people wouldn't be prepared to take that sort of risk. But the fifth attempt, which I think is ultimately what needs to be done at this point in time, is to look at following patients who have negative sentinel nodes with serial groin ultrasonography. This paper was published in 2018 from the same group, in fact, who did the original sentinel node study, van der Zee, de Hoola, etc. It was a multi-centre Dutch study, followed 79 patients who had negative sentinel nodes. They did physical examination and ultrasound every three months for two years. They found two asymptomatic isolated groin recurrences, both were treated with groin dissection and adjuvant radiation, and both were alive at 39 and 120 months respectively. It's important, I think, to note that both these positive nodes were detected within eight months, but one of the nodes was actually clinically palpable at the time that it was detected. So the sensitivity of the ultrasound, they said, was 100% and the specificity 92%. And in my opinion, sentinel node biopsy and serial groin ultrasonography for patients with negative sentinel nodes should now be considered the treatment of choice for those with cancers four centimetres or less in diameter. Now, is it possible to use serial ultrasonography alone in selected patients with vulva cancer? In other words, not even do the sentinel node biopsy? Well, in 2009, I was first confronted with a young woman with a six by six millimetre cancer, 1.2 millimetres deep. So if you work out the volume of this tumour, it was 43 cubic millimetres. And if you talk about a tumour two by two by one millimetre, that's 400 cubic millimetres. So I felt that it was reasonable to just do some serial ultrasounds on this patient. And I got ethical committee approval to do this. And I subsequently did this on a total of 13 patients, and there was one patient on whom we couldn't identify a sentinel node, so we followed her with ultrasound. And of those 14 patients, we identified three positive nodes. One of them was alive at eight years, one died at six months in spite of groin dissection and subsequent radiation, and the other one was alive at three years. I also used this technique for patients who had a fairly large ipsilateral tumour, some of them up to 60 centimetres, but the tumour came to the midline. Now, clearly, there would be some small risk of nodes on the other side. But I did a groin dissection on the side of the tumour and followed the contralateral side with ultrasound. And as you can see, of 10 patients here, none developed a positive contralateral node with plenty of follow up for that to occur, if it were going to occur. But three of these patients did have positive ipsilateral nodes, including one patient who had two positive nodes. The third situation where I've used ultrasound is for patients who had small multifocal cancers. Now, these are cancers that occur within in situ squamous or Paget's disease of the vulva. So this is the sort of situation here. You can do multiple biopsies there and it's usually just in situ Paget's disease. But when you actually resect this, you find that there and do serial sections of it, you find that there are one or two or more sites of invasive cancer. And you can see that this one here, for example, eight by three was the largest focus, 2.8 millimetres deep. Here's one 16 by 16, three millimetres deep. So I followed five of those patients. They all with bilateral groin ultrasound, they all did well between about 32 and 72 months. And then the fourth group of patients are those who either refused groin ultrasound or were considered one patient, 87 with multiple other comorbidities we considered not really suitable for ultrasound. We treated the primary, we followed the groins with ultrasound and she was fine at 34 months. In one of these patients who refused, we had a false positive at 20 months and we removed two nodes, but they were negative. So of the 32 patients that we followed, occult nodes were detected in 9.4% of them. One of the patients died, so 3.1% mortality. The sensitivity for the ultrasound was 100%, the specificity 96% and 39 groins were preserved intact. So between this study and the Dutch study by Poyer, there were five recurrences in an undissected groin and only one death, 20%, which is certainly a lot better than the 90% that we've experienced without ultrasonic surveillance. But I believe the ultrasound should be done every two months for 12 months, not every three months for 24 months. All of these five recurrences occurred within eight months. And so I think that there's no need to continue this beyond 12 months, but I think it does need to be done more frequently than every three months because two of the five patients actually had a palpable node. They had a positive ultrasound and the patient themselves was not aware of the node there, but it was actually palpable when you examine the groin. And so I think the idea of course, is to pick it up while it's still macroscopic, the patient that died certainly had a palpable node that she wasn't aware of, but it was there. Now, is there anything that can be done to decrease the incidence in patients with lesions greater than four centimetres? Well, this was a paper that we had published last year, medial inguinal ephemeral lymphadenectomy, an approach to decrease lymphedema without compromising survival. Classical textbooks of anatomy, such as Gray's Anatomy, give a detailed description of lymph nodes in the groin, but they don't indicate specifically which nodes drain the vulva and which nodes drain the leg. Since 2007, studies of sentinel lymph node mapping have demonstrated that 85% of sentinel nodes are situated in the superficial medial and intermediate inguinal chains and about 15% are in the ephemeral nodes. In 2020, a study using CT lymphangiography on 130 lower limbs from 83 fresh cadavers reported that about 75% of lymphatic drainage from the leg goes to the lateral inguinal nodes. Our study separated lymph nodes into these three groups, inguinal nodes medial to the femoral artery, these over here, inguinal nodes lateral to the femoral artery over here, and femoral nodes medial to the femoral vein within the fossar ovalis. So, the hypothesis was that lymphatic drainage from the vulva would go to the medial inguinal ephemeral lymph nodes, and if these nodes were negative, then the inguinal nodes lateral to the femoral artery would also be negative, so it could be left in situ. This procedure should be applicable to cancers of any size or histological type which extend laterally, which don't extend onto the thigh, such as here. We wouldn't guarantee that that would go to a medial node up onto the mons pubis here or down onto the buttocks. So, suitable cases would be Bartholomew's cancers. Cancers, doesn't matter how big they are, as long as they're spread medially up the vagina or involving the urethra, and as I said, any histological type, this was a melanoma. So, we did this study between March 2010 and April 2018. We enrolled 76 patients, 112 groins. The mean age was 71 years, and the patient stage ranged from 1B to 4B. Most, of course, were squamous cancers, but we had three melanomas, two Bartholomew's cancers, and an invasive Paget's disease. So, all the nodes, when we did the groin dissection, we separated them into medial inguinal, lateral inguinal, and femoral nodes before we sent them off to pathology. Groin dissections are either complete inguinal femoral lymphadenectomy, which was the majority of them, lymph node debulking. If we had a patient with bulky nodes, then we would simply take out those nodes, note where they were in relation to the femoral artery, get a frozen section to make sure they were positive, and we would not then proceed to a full groin dissection or a sentinel node biopsy. As I said, we didn't do a lot of sentinel nodes because, in my experience, patients did not like sentinel nodes if they were trading that for lymphedema. So, there were a total of 9.4 nodes removed in patients who had a complete lymphadenectomy, 5.3 in the medial inguinal group, 3.2 in the lateral inguinal group, and 1.5 in the femoral group. So, in other words, you can see that about a third of the nodes are actually lateral to the femoral artery. Now, five patients actually had positive lateral nodes. So, 6.6% actually had nodes laterally. Four of these five had had a debulking procedure, and as you can see, in two cases, there were three nodes, three bulky nodes medially and only one laterally. In two cases, there was one lateral and one medial, but the medial node was always the bigger node, 12 versus 6.5, 55 versus 18. We had one patient on whom we did a completing one-olefemoral lymph node dissection, and she had one out of five medial nodes, which was six millimeters, and one out of four lateral nodes, 0.6 millimeters. So, again, clearly the medial node was the first involved. So, in this study then of 76 patients, the incidence of positive groin nodes was 38.2%. All lymphatic spread was initially to the medial, inguinal, or femoral lymph nodes. If these nodes were negative, the lateral inguinal nodes were also negative in 100% of cases. So, the likelihood of having a positive lateral node and a negative medial node is less than one in 10,000. About one-third of groin nodes are located lateral to the femoral artery. So, leaving these nodes, if the medial nodes are negative, should decrease the incidence and severity of lymphedema without compromising survival. We've shown in another study that the incidence of lymphedema is basically proportional to the number of nodes you take out. So, if you leave a third of the nodes, then you should decrease the incidence and the severity by about a third. I think if these results can be reproduced, medial, inguinal, femoral lymphadenectomy would be appropriate management for all vulva cancers without extension to the inner thigh, buttocks, or mons pubis, as long as these nodes were negative. So, in conclusion, I think for unifocal cancers, four centimeters or less in diameter, sentinel node biopsy and post-operative groin ultrasound for patients with negative sentinel nodes should, at this point in time, be regarded as the treatment of choice. The ultrasonography, in my opinion, should be performed every two months for 12 months in order to detect these nodes before they become clinically palpable. For patients with bulky positive nodes, all palpably enlarged nodes should be removed and the patient treated with post-operative bilateral groin and pelvic radiation. We've previously reported this approach, but it hasn't been subjected to any prospective study. For patients with cancers greater than four centimeters without extension to the thigh, mons pubis, or buttocks, the role of medial inguinal femoral lymphadenectomy, I think, warrants further investigation. And the role of serial groin ultrasonography alone warrants further investigation for primary cancers two centimeters or less in diameter, with greater than one millimeter of stromal invasion, small multifocal cancers, and to follow the contralateral groin in patients with a large unilateral cancer that extends to the midline. Thanks very much. Can, okay. Thank you. Thank you so much. Thank you, Professor Hacker. What is considered abnormal? Do they look at the size? So do they look at the size of the body?

lower limb lymphedema

vulva cancer

lymph node dissection

inguinal femoral lymphadenectomy

sentinel node biopsy

medial inguinal femoral lymphadenectomy