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OK. Um Hello everyone, welcome to uh our 24 future Journal Club. Um We're just gonna wait a couple of minutes just to see um the opportunity for everyone to join and then we can start our session. Happy to start, Mr You just uh unmute your microphone. OK. So um good evening everyone and welcome to our 24 ST virtual Journal club. My name is and I will be chatting to tonight's uh session. It's wonderful to have all of you here. Uh And I'm sure you will be an engaging and uh thought provoking discussion. Today's uh session focuses on endocrine surgery and uh with an emphasis on parathyroid pathologies, localization, and management. It is a key topic not only for those clinical practice, but also for our Fr CS exam. Uh Journal discussion will center on a private or randomized controlled trial comparing two imaging modalities. Before we proceed, I would like to thank our sponsors at Advanced Medical Solutions for supporting tonight's event. Um Unfortunately, Mr Thomas wa is unable to join us this evening due to some unforeseen circumstances. We wish him a swift recovery and hope to have him back with us in the future. Um to ensure we uh um the continuity of this important discussion. We will move to our second speaker um Mr San Rajan, who is an uh ST eight in on the breast and endocrine surgery at the Norfolk and Norwich University Hospital and that he brings a wealth of expertise to tonight's session. Please feel free to pause your questions in the chat um And we'll be happy to address all your questions and this session will be recorded as well. So, um let's get started. Um Please join me in welcoming our speaker, Mr uh you Raja over to you. Thanks. Uh Marita. Hi, guys. Uh So I'm sending like, um Marita just mentioned um uh be be before we start the presentation. Can, can, can I just get a shout out to see how many people are endocrine interested over here? Are there any endocrine trainees logged in? Just put it in the chat box if anybody is there? Well, nobody so far. So I've, I've, I've tailored this presentation more uh to help uh Nonendocrine surgical trainee actually, uh go for the exam. Um I'm just going to share my screen. Give me a second. All right. So, um, is it ok, Marita, is it? Yeah, fine. Yeah, presentation is going ok. Yeah. All right. So, um, so like I said, I'm, so I'm, I'm currently a trainee in uh Norfolk nor hospital and uh this is just an endocrine surgery journal club. Uh just a brief disclosure. I'm not an academic trainee. So don't expect me to answer too many questions on statistics. Um uh the learning objectives of this talk really. Um We just review parathyroid and hypoparathyroidism in general with the focus on the F RC is just a few. Um uh ju ju just an update on, on, on the recent stuff as well as well as we'll go through some tricky questions. Um For the part one exam, we'll talk about this paper and we'll analyze it and critically appraise it. We'll focus on the methodology as well. So just, just coming to parathyroidism, I know it's not something we see, we deal with uh daily, but uh it is a very common endocrine disorder and it's the most common cause of hypercalcemia in a nonhospitalized uh patient. Um So, and the incidence is 1 to 4 per 1000 in the UK. And this is probably grossly underreported. And uh you got, you know, you've got the usual painful bones, stones groans. Um We, we, we, we all know, remember that from med school. Um But, but you, but we need to remember that these symptoms are really a feature of endstage hyperparathyroidism. So that's full blown or the natural history of the disease, which we don't really want to see in patients before we treat them. And um as of today, at least, parathyroidectomy is the only definitive treatment for primary hyperparathyroidism for secondary hyperparathyroidism. It's usually medical management. Um but we're gonna talk about primary today. So um we go based on the nice guidelines for referral uh to a tertiary center. And um these are, these are the criteria, of course, most important is the calcium more than 2.85. Um And apart from that, it's any real end stage, like we said, it's a disease. So that means that there's uh you got kidney stones, you got a fracture. And again, these are, we are really treating the patient uh after the patient having a longstanding hyperparathyroidism. Um I just want to compare this in contrast and the, these are the American guidelines, for example. Now, so they are a lot more liberal in who they select for, for surgery with the calcium level, just one above normal. And in fact, the table is, is the, is the guidelines for asymptomatic primary. And um let's just talk about imaging because that's going to be the main focus of our journal club today. So the first thing is why do we need imaging? We, you know, we we we got four parathyroid glands. This is the image that we've been taught uh with the anatomy textbook. But usually it's, it's a lot more complex than that. So we can have the four glands in their Utopic positions and they can enlarge. But you can also have a lot of ectopic locations. And another thing that happens is when the glands do enlarge, they tend to displace in their position, uh especially the superior glands tend to go lower down. So even though it's, it, it might, it and, and they can even keep going, going down and even more inferior to the actual inferior gland. So there can be a bit of confusion. And that's why imaging is, is, is, is really important. We, in fact, there's, there's actually a classification called the barrier classification if anybody is interested. And that actually talks about various locations. Uh A to F for are glands located at uh non non Utopic sites. Now again, just sticking with the nice guidelines because I think for the purpose of the exam, if you're nonendocrine trainee, this is pretty much what you need to know. Um We, we've just mentioned that it's um endocrine, it's a pure endocrine disease and the diagnosis is pretty much made on an increased serum calcium and a raised serum PTH. And once that is decided, and the patient actually agrees to undergo surgery, then you offer them preoperative imaging. And this is usually ultrasound. And the N also recommends a second imaging and that's usually a cyst A B scan. So that's a nuclear scan. Um cyst gets up, gets up taken in the parathyroid glands. And this can be combined with something called a spect CT to combine and fuse the functional imaging. That's the nuclear imaging as well as um anatomical imaging in form of a CT scan. Now based on that. If you, if, if, if there's no I adenoma identified, you still offer the patient surgery because like we said, primary hyper is always surgery and that will be a full gland exploration. But if you identify a single adenoma, you can offer them focused parathyroidectomy, which is also called targeted parathyroidectomy. And uh this just means removal of the single gland. It's obviously less mo less morbidity and it can be done as a day case. Um When we look at the modalities available for for imaging. So we talked about ultrasound and we talked about C A maybe or also called maybe. And like I said, it's usually combined with SPECT CT. Uh These two have been available for quite a few decades. Newer modalities that we see are four CT and pet CT scans. Other modalities include MRI which are not done routinely uh done in very few specialist centers where they seem to have a lot of experience and venous sampling is an invasive method um that is done in some centers again, usually for more uh redo cases in patients who have had negative imaging through the other method modalities. But like if, if, if, if we want to shorten it ultrasound and maybe are, are, are, are the trident tested methods and they both have their limitations. Four D CT and Pet CT are the new, let's say kids on the block. Um You're talking about localizing. Now we're treating a disease which sometimes involves all four glands, which sometimes can involve two glands. Um And this is an old article and it actually references an even older article which states that the best way of localizing the parathyroid glands is to localize an experienced parathyroid surgeon. Uh This probably still remains valid. Now, when we um we'll talk, we'll talk a bit more about the surgical approach and I'll, I'll come to that later as well. And speaking of different imaging modalities again, for example, um this was in my previous job in Scotland. And uh we actually have changed our first line imaging over there from ultrasound and maybe the combination to just four DCT upfront in most adults. Um And this had a good sensitivity or uh which was much superior to ultrasound alone and uh superior to ultrasound and maybe combination. So when we talk about surgery, like I said, we, we can offer a patient, a focused Pathom which is just remove of a single gland. Uh and that's also called targeted and that's also called M IP, which is minimally invasive para. It's still done with an open incision, you still see the gland and you remove it. Uh But it's just that you use a much smaller incision and the traditional incision while it, it, it, it, it need not be this long as depicted in this picture, it, you can get away with much smaller incisions as well. So when we WW when you're talking about pure cosmetic part of it. We don't really distinguish between a focused by or a bilateral neck exploration where we look at all four glands. But why do we have these approaches? It's because that we know that 85% of patients are gonna have a single adenoma. 5 to 10% of patients are gonna have multiple adenoma. So they're gonna have multigland disease, but the histology is still gonna come out as adenoma. Now again, another 5 to 10% of patients are going to have hyperplasia and hyperplasia means that all glands are gonna be affected if the patient has four glands, all four, the patient has six glands, all six are gonna be affected. Uh These are frequently, usually associated with some sort of genetic abnormality like men one syndrome uh where you also have pituitary and pancreatic problems. Um and very, very rarely. So, again, less than 0.1% of patients will have parathyroid cancer. Um These typically will be involve only one gland even though it's extremely rare. It's an extremely common FRCS. Uh part one question for some reason. Um Now when we talk, talk and, and, and because of all these problems you can't cure, let's say every patient who walks into your clinic um with the same time with the same surgery, uh you, you might have to change your approach based on, based on individual patients. And there are a lot of adjuncts to surgery as well. And some of the newer questions um ca can be based on this. And as you can see, we've got, we've got a lot of, lot of um, adjuncts and these are just really to help us either identify the glands during the operation or actually tell us if the patient is cured. Uh If we look at the ones that tell us that the patient is cured, it's only intraoperative P th uh which currently can give us a clue whether the patient is cured or not. Because this, we can actually, and, and what how, how we do this is we actually have a machine which can be in theater which gives us a rapid P TH result. And uh we just input three or four samples into it. So that's usually preoperatively postoperatively after five minutes, 10 minutes and 15 minutes depending on a local protocol. Um And that can actually tell us about the biochemical cure, which is what we want to know. Frozen section can tell us if the, the specimen we've taken out has parathyroid tissue or not. It can't really tell us whether that parathyroid tissue is an adenoma or a normal gland ICG angiography can tell us about the vascularity of the parathyroid. But it can't again tell us whether it's it's pathological or not autofluorescence and mass spectroscopy. These are really fairly new. Um um me methods used to identify parathyroid glands. They help more identifying parathyroid glands during thyroid surgery where the aim is to actually preserve the glands. But, um, you know, they need a lot more study to say as whether they can actually distinguish between a normal gland and an abnormal uh gland that's producing more P th. So I'm just going to go a few questions now. Just, just some of the part one questions. Um This is the first question. So, um this is a 29 year old lady who presents to the clinic with symptoms of renal stones and constipation. Um The calcium is quite high 2.79 P th is within the normal limits. So it's 4.7 and the normal range is 1.6 to around seven. Um Vitamin D is normal as well. So, what's the next appropriate steps? Can we uh can we try and see if the polling is working? Marita, I'll try guys. Can you input your a, a ABCD or E just to see if this just get the question up again any more answers? We give it 20 more seconds. Okey doke. So we've got quite a few ES and we've got some Bs and CS. So uh the ES have got it right because this is a bit of a trick question again. So this is really because the patient has got normal P TH level. There is another disorder called familial hypocalciuric and hypocalcemia, which can present as uh hypercalcemia. Uh We can kind of mimic hyperparathyroid, let us say um in these and these are typically younger patients and this is due to a uh defect in the C ASR or the calcium sensing receptor gene. And uh these patients, uh I usually, it's, it's usually a familial disorder and in them, we need to see the urinary calcium creatinine ratio clearance ratio and uh which will show hypocalciuria. And uh another question which they rarely asked is so this is an autosomal dominant disorder in, in one ll. But if the patients get, get it from both, both pa both parents, then it's, it develops something called neonatal severe hypoparathyroidism that's extremely rare. Um And uh and that's, that's actually an indication for an emergency parathyroidectomy in a neonate. Yeah, or, or, or a or a very young child. Yeah. Uh moving to the second question if we can reset the um the poll again, Marita. Um uh So this is a 33 year old male patient who presents to his gp with lethargy, nonspecific abdominal pain. Uh The serum calcium is pretty much through the roof. It's 3.21. Uh P th is also really high 67. Um They, they've had a scan done. A nuclear scan system may be showing a left neck lesion and the ultrasound shows a heterogeneous nodule. The radiology is unable to see whether it's from the thyroid or the parathyroid. And the question really is, what's the next appropriate step? Uh Do you want to do a co biopsy, targeted parathyroidectomy A four D CT scan, staging pet CT scan or a bilateral neck exploration. So you guys want the question up, I'll just put the question up. Yeah. Yeah, we got the answers. I, sorry, I can only see one screen at a time. OK. So we've got a couple of uh mostly A or B. So they, you got a split house. Somebody said C as well. Um Unfortunately, in this, um well, well, somebody said D as well, but it's mainly ABC followed by D. All right. So, um this is a tricky question and unfortunately, they keep asking these questions again and again. So this is actually a case of parathyroid cancer. The correct answer is actually a staging scan over here. Uh And, and, and the reasons are, and honestly some of the, some uh uh you know, many of the um the options can be right in certain situations, but in this question, it's a 33 year old, otherwise healthy man. So we would not normally do a co biopsy uh for anything parathyroid related. Uh parathyroid tissue is uh notorious for, for causing something called parathyromatosis. Um which basically means if you do an FNA or your core biopsy, it can actually see the entire tract uh with pa parathyroid cells and parathyroid cells. They are, you know, quite good at taking a blood supply. Uh That's, that, that's all that, that's the reason when we autotransplant, parathyroid. So if you take a parathyroid out, you mince it, you autotransplant it in any muscle, it can actually start functioning if you give it some time. So, uh co biopsy, we tend almost never to do for um, uh endocrine disorders, especially parathyroid. It, it again, if this was a 80 year old patient and uh he was not fit for surgery, let's say, and you're just trying to, trying to, for, uh to do a palliative treatment, then you could do that co biopsy. Um But even even in that case, it's, it, the diagnosis is probably, you know, quite clear that this is likely to be a, a parathyroid cancer, parathyroid cancer compared to other cancers in the body. Very unique because it actually produces uh uh the hormone. So the cells retain the function to produce a hormone and they produce quite a lot of hormone and the calcium also goes up really high. Uh targeted parathyr is not the best answer again because again, when you have a pet CT scan to stage, uh that's, that's probably the better choice because these can actually spread to the lungs. And if they are spread to the lungs, you can't really the the there's no point operating you, it's going to be pal palliative treatment. Um And when we say palliative treatment, we're looking at control of the hypocalcemia with all drugs. Uh you know, that that can be used for, for treating hypocalcemia like Cinacalcet, for example, uh 40 CT scan again, is not going to be of much help because that just localize the lesion, we already seem to have localized the lesion reasonably well. Um and a bilateral neck exploration and targeted paraia again, they, they, they're fairly similar there, there's you, you, you don't want to operate until you've got a pet CT scan and uh uh tell you how common this was. When I gave my Fr CS, there were two questions on parathyroid cancer in the same, in the same paper. Um So they, they do tend to ask a lot about it even though it's exceedingly rare. And most endocrine surgeons who are not in a high volume center would see some of these cases only once or twice in their lifetime. Um The treatment when it comes to surgical treatment, it's on block parathyr. So look out for any answer like that in, in, in the options. And when you say on block, uh you just have to take all adjacent tissue that and that usually means uh hemithyroidectomy. So the answer might also be lobectomy with parathyroidectomy. Okey doke. So uh just move on to the next question. So this is a 61 year old male who's had a renal transplant, referred from the medics for hypercalcemia. The serum calcium is 2.75. Again, it's quite raised. Uh PDH is 22 more than two times the three times the normal level uh limit. So somebody has done a maybe scan and ultrasound. They both show a right lower lesion, um uh parathyroid lesion, the patient has mild symptoms of hypercalcemia. And now what's the next most appropriate state? So, um first choice a pet CT flooring, uh pet CT with all four CT based on the local protocol, a targeted para of the right lower gland, bilateral neck expression and total para, bilateral neck exploration and subtotal para or discharge back to the renal physician and ask them to refer back on the calcium is higher. Could we have the polling again? Ok. Let's leave the question up. OK. So you got mainly some E SA and C. All right. So we've got, we've got mostly es but uh we've got an ASC as well. Uh The correct answer unfortunately is none of the those. It's a, it's actually the best answer here I would give is D as uh uh that's a subtotal parathyr. So if you, if you look at this patient's blood marker, so the calcium is high P th is high and we know this is a renal transplant for KD. Um When you have secondary hypoparathyroidism, you actually have hypocalcemia. Um And that's the stimulus actually for, for increasing the parathyroid hormone. But when you have something called tertiary hypoparathyroid, which is what this question is. Hinting at. You have everything high, you have calcium high, you have phosphatide and you have P TH I. So when you have both calcium and P th high in a, in a, in a renal transplant patient that is um tertiary hypopara. So what that means is that this patient has probably had secondary hyper for a long time, had the renal transplant. And now what's happened is one of those glands has, has, has gone into a bit, you know, uh uh like a, it's, it's gone haywire and it's producing way more PT and that's causing the calcium to go up as well. So this, in, in this scenario, II, think most of you all say discharge back to renal, uh you know, with the intent thinking that it's secondary hyper and that's medical management, which is correct. Um But, but, but in this patient, it's tertiary because you've got raised calcium as well. Uh And the, the best treatment for that would be a subtotal para. Now, some of you all are given total para, that's not a wrong answer and that's definitely what some centers would do. The only uh uh uh the difference between the two is when you do a total parathyr, you kind of achieve 100% cure. But then you render that, render that patient lifelong hypocalcemic and they would need loads of calcium and Vitamin D supplements every day. Um which sometimes can be worse than the disease of hypoparathyroidism. So more and more nowadays, you know, as, as, as we are, um you know, with the less is more concept, uh subtotal para is, is, is a much better approach. And what that would mean is that you do something like a 3.5 gland. If you identify four abnormal glands, you take out the three most abnormal looking glands, you definitely take out the gland that's causing. Um, um, you know, in this question is the right, lower, lower gland. Uh and you take out two of the most abnormal looking glands and the most normal appearing glands, the smallest gland you take away probably half or most of it and you probably mark that remaining um normal gland with like an absorbable proline stitch or a clip like a clip, for example. Uh So that because we know that's abnormal tissue that's, that might cause problems later on and then we can always go back and take it. Ok. So, um these three questions are a bit tricky and um honestly, I've chosen them because they're a bit tricky. Now, uh most of the questions you guys will get in the exams are not gonna be this tricky. But for some reason, you know, even though though these, these scenarios are quite rare, FH H very rare, you're not gonna see it as a, as a, as, as a surgeon. Uh parathyroid cancer is extremely rare and the same with tertiary as well. Tertiary hyper is quite rare. Um But, but the uh F RC is party examiners really like these. All right. So, moving forward to the journal club. So this is the article that we've chosen and the, the, the, the title of the article is uh FA and C PCT or maybe E CT in the surgical management of primary HEPA. Uh And this was a RCT. It was published in uh Jama, the uh and Jama as you know, is, is Jama Surgery is, is, is the top rated surgical journal today. Um This was by uh uh published in one of the assisted journals at Jama had a neck surgery ent uh So, uh whenever you in the, in the exam, they always ask you to, to know the impact factor. So before the exam, uh week before you'd probably be going and checking the impact factor of most journals because when they give you a paper, they will, they expect you to know the impact factor and they, they usually going to give you a paper um of from one of the top top 10 channels. Um And as you know, the impact factor definition, they're gonna ask you that it's the ratio of um a number of publications uh that year. And then the with the denominator being number of citations over the last two years. So the authors, as you can see, there are a lot of authors, but again, just some things to look at, most of them are um, the lead authors actually for a nuclear physician from the Department of Nuclear Medicine and and, and they're all from France um introduction for this paper. And I'm just going to talk about the paper and, but we'll also, we'll also branch out and talk a bit about the methodology um as we discussed localization or, or, and these, all these, all these imaging techniques technologies, we have uh the, the main advantage of it. The only reason they exist really is to offer the patient a smaller procedure day case, a minimally invasive pa or a focus pa a conventional bilateral neck exploration. And um we we know that, you know, based on, on, on many studies that it can, it, it offers faster recovery, less hospital stay and more cosmetic outcomes. Um And this was the paper su suggest suggest for cure rate. Now when it comes to cure rate, like I said, there have been other studies and you can quote other studies which actually say that a bilateral leg explanation has a better cure rate than uh focused parathyr. Um But it, I think most publications would say that the complication rate of bi bilateral neck expression is going to be higher. You're doing a much more uh bigger dissection. Uh You can't really discharge the patient as a day case because there's always gonna be a risk of uh uh lifethreatening hematoma. And there's also a risk of because you've damaged the blood supply to a lot of the glands, you're going to get hypocalcemia POSTOP. Um This ef 818 Choline Pet CT. So this is a fairly new technique for preoperative localization. Uh Previous studies have shown that it's got a superior detection rate versus the older scans that we have talked about. Um And the advantage is perceived advantage is that it's got superior spatial resolution, which is something really important. Um If, if, if, if you look at the, the accuracy of, of something like a maybe scan or an ultrasound scan, if you're gonna look at patients who have got, you know, two centimeter or larger uh parathar adenomas, which is a very rare, nobody really has a two centimeter adenoma. The the you're going to get sensitivity rates of more than 95%. But if you're looking at smaller lesions that's gonna drop drastically. So that's a big uh advantage probably of pet CT as as well as uh other uh uh other modalities like MRI of four DCT. Um So currently, the authors stated that this is not a first line imaging te technique, it is only used for patients who have had other imaging and that imaging was negative. Um It is cost clear there's no market authorization in even in France for that matter, definitely not in the UK. For first line imaging, it is generally less available. Of course, it needs your pet CT scanner to be there in house. Um And even though even though it has previously shown better diagnostic accuracy, whether this actually impacts on clinical impact for the patients and the patients, what they need is cured, they need cure of the disease. And that difference remains to be investigated. So this trial, which had a name, they gave the name as a APAC H two trial uh P trial perhaps. And um this was to compare a first line pet CT versus the traditional maybe scan uh to assess optimal care in patients with primary hyperparathyroidism uh as a first line imaging modality resulting in a successful ectomy and normalization of calcium. So these are the two key words in, in, in, you know, when they look at the aim of when you look at the aim of the study, um you have, I think around 30 minutes to look at the paper, the most important thing in the introduction, what you want to pick up is actually the aim. So this was the objective of the aim of the study going to the methods. This was a randomized controlled trial done over three years in four French hospitals. So, Multicenter um it was two arm and we'll come to that. It included all adults. So 18 years and older and the primary eval diagnosis confirmed by laps and this is all fairly standard. They excluded patients who had previous surgery. Um A N One syndrome and special groups like pre like pregnancy. Um they have, they go, they have, you know, they got their local ethics clearance. All these things have to be noted down. If they, if they are not mentioned, then obviously these are red flags. Uh The trial was registered. Um And um it was performed in accordance with the ethical standards of Declaration of Helsinki. This, this question, suddenly the examiner can ask you what is, what, what you know, what do you mean by that? And that's the World Medical Association. They just laid out the ethical principles for all research that involves humans. Um And uh it's, it's, it's got there, there, there are a lot of points which you can't tell the exam. But I think they usually just ask for the definition um or they can ask you what, you know, what ethical principles would you follow? And then you say the declaration of Helsinki. Um This study was reported in line with concert. And again, this is a very common uh exam during the academic vi a uh what is concert concert is a consolidated standards for reporting trials. Um And um that's just a internationally agreed upon um transparent reporting criteria. So if this is this is a typical concert uh diagram which we'll see later on as well. Uh Apart from concert, you've got Strobe for observational studies most for meta analysis. Um and Prisma for um we, we call that a big, big, big mistake, but Prisma is usually for more observational studies don't. So that that's probably wrong over there. Sorry about that. Uh But yeah, the, you will you will, you will, you guys will get questions on this, this for sure. Um And it's just important to know what they are. Of course, each one of them have got like more than 10 points. So you can't remember everything um a a all their individual criteria. Um So looking at the randomization in, in this study, this was patients were assigned as a uh one is to one ratio and they just use electronic randomization. Uh The you, you can get a couple of questions on randomization. So as we know that in our ct, the um you know, you take a sample population, you have a control treatment in one group and you put a new treatment in another group in in the other group, randomize them. So to eliminate bias, and um this is another question that's commonly asked, that's the phases of the trial. So um your question could be asked. So if, if it's not mention in the paper. So what phase trial is this? Uh this would be a phase three trial because it's comparing a new treatment to the standard treatment. Um And this is a bit more different because we are actually looking at imaging rather than actual treatment which can be in the form of medicine or you know, medication or surgery. Um So why do we randomize again to eliminate bias, specifically the selection bias? Um It allows blinding and we definitely use the probability theory to, to express chance and not choice. Uh There are different types of randomization. So what they've used, they can, you can be asked what type of randomization was used in the study. And uh this, this was a sa simple randomization which they use using the computer software. Uh You do have other different types of randomization. We just briefly to touch up on them. Simple randomization is like flipping a coin and it's usually done by a computer software nowadays. Uh It's very simple and easy to use. Uh The only disadvantage is that you're going to get an unequal number of participants in each group. So if you have, if you're doing a study on 20 patients, you might get, you know, 12 patients in one group and eight patients in the other group. And that's gonna cause you problems. Um So when you, when you have smaller groups like that, you can do something called restricted randomization block randomization is one way to do that where you actually assign patients into blocks. So even though there are 40 patients here on, on this image, the first block has got four and 44 and four and four and, and, and, and, and, and so on. So you just keep having 44444 until you. Um and, and you have equal number of patients in each block. Um Stratified randomization is when you also address covariate. So that's all baseline characteristics oo of patients and these are potential confounding factors. Um It's a bit more complex and you need to uh identify what co covariate you have before that. So if you want to do males and females separately, for example, young and old separately, and you do get a bit more complex problem. And the biggest difficulty in this, you need to identify patients, uh identify the coma, please, before you randomize, which is kind of impossible when you're doing a real world randomized trial. Uh there is um um an option to do that and that's covariate adaptive randomization. That's when you um once the randomization begins, there is, you know, you can use software to place patients in, in, in different groups based on the imbalances in each group, let's say. Um but I think you mainly just, you guys need to know the names of different type of randomization and where they can be used. So, like we said, this was uh give you a simple randomization in, in the study that we're talking about. Um No, in the baseline evaluation of all the patients in this study before the randomization was performed. Um clinical examination was done. Standard neck ultrasonography was done and all blood tests were done. Now, if you look at this, this slide and this is directly verbatim from the paper, there's, there's something glaring that's standing out and that's that they've, they've, they have done ultrasound for all patients before randomization. Um Now, clearly this is this this can introduce a, a bit of bias because if you get a positive ultrasound, um you know, you can, you, that, that, that, that is going to influence, influence the outcome. Um But anyway, moving on in this paper, so that, that, that's one point noted on. So when you're, when you're doing, when you're reading the paper, you get good time, like almost half an hour to do. So you just need to note on all these points towards the end and then we'll uh discuss the critical appraisal at the end. Um The regarding what, what happened to imaging. So we, they randomized patients in the experimental arm with the new modality. That's the pet CT. The standard arm was the maybe. So patients who had negative first line imaging had crossover imaging the second time. So if you had a negative pet CT, you had a maybe if you have a negative, maybe you then get a pet CT uh which was an interesting uh trial design, but it's a very pragmatic and practical trial design. Um That's actually quite fairly ethical. So if you have a negative imaging, you give the patient the option of the other one. Um So uh they had blinded their nuclear medicine physicians who interpreted a scan and they were, they were, it was positive and it was clear negative and there was no, no uptake and inconclusive when you WW when they saw a faint uptake and faint uptake is something we do very commonly seen with the, with the nuclear scans because there can be a lot of false positives that give you a bit of an uptake. So a hyperactive thyroid gland, for example, uh can also give you a slight uh you know, higher uptake. You have thyroid nodules just in front of the parathyroid adenoma that can give you a bit more uptake. And when there was discordance, they reviewed the images of the MDT. Um Now regarding the treatment, so whenever they had a positive imaging, the patient just underwent um a focused parathyroidectomy. When there was a negative results, the patient underwent a bilateral exploration and even an inclusive inconclusive result. Patient underwent a bilateral neck expression. So far, all this seems to be fairly um you know, straight standard standard treatment that, that, that we would offer as well. Um They did use frozen section which is something that most centers in the UK do not use it routinely. Um But definitely that's a, that, that, that's a useful adjunct to identify whether you remove the right tissue or not. Um And the primary outcome again, this is a very important bit of the study and this is something you want to note down really uh in, in, in, in your notes. When you before you go for the um for the vi as such, um the primary outcome that they measured was the true positive first line imaging image guided. Um minimally invasive para. So the the the primary outcome was not whether the test was sensitive or not, it wasn't the sensitivity of this. Rather, it was whether the imaging actually resulted in a patient undergoing a focused parathyroidectomy. Um And they also looked at the uncorrected serum calcium at one month after surgery. So they, they also looked at cure. So they looked at a surgical cure as well as a biochemical cure. Um um and that, that's a bit interesting choice of a primary outcome. Um It is, it, it, it's, it's a bit contentious because you would only do a minimally invasive pater me if your sensory was good. So that's if you had a positive imaging. So it's a bit of a convoluted way of getting to the same point, but it is admirable that they have chosen this as a primary outcome because this is probably a bit more harder to achieve. Um It, it must be impressed that they did follow up the patients with uh biochemistry at one and six months after surgery. Um sample size calculation. Now this is another question that that's commonly asked. Now you need to see how they have calculated their sample size. So they have previously published a phase two trial and they found that their pet c had a sensitivity of 90% compared to the maybe scan, which only had a sensitivity of 60%. So they use that that difference, which is, that's a 30% difference in sensitivity. And that's you, you can be asked, what do you need um to, to, to calculate the sample size. So you need that difference between the two tests, the perceived difference um and the, the risk and power. And so based on that, the, they decided that a sample size of 50 was um was needed. And uh when they adjusted for a 15% rate of patients po possibly lost a follow up or patients lost uh in, in the, in the trial, they planned to enroll 58 patients overall. Um Now there's, there's nothing wrong the way they've, they've, they've calculated their power all that. But if you look at this, they've, they've given a fairly high sensitivity based on their own trial for pet city and uh a low, low, low, low sensitivity for maybe if we look at the international data, the sensitive for maybe spec is around, let's say 70%. I would say if you want to look at all trials in some centers even higher, maybe up to 80%. And Pet C is of course a new uh technique. But you, but what you need to understand is if this was closer. So if that if, if it was 90% and 80% you need a lot more patients in this trial. Um So it's definitely helping them uh coming to the results. So the, the, the, the, the first, the first um table that you see is actually the consort diagram. And um it's, it's very common in the exam for the examiners just to ask you, um please look up table two and tell me what you see. Uh So just describe the findings of, of the, of a table. For example, this, this paper didn't have that many tables, but this consult diagram could be asked as well. And you can see from 59 patients uh where they started, 57 patients were randomized. And at the end, if you look lower down, only 25 and uh 25 or 28 were were accessible for primary endpoint analyses. Uh So they did lose a few patients. Um And that, that, that's uh a bit of the, the loss of follow up. It's very important that follow up at six months was missing for quite a few patients, seven patients uh in one group, in the, in the pet CT group and five patients. So that's 12 patients who are missing follow up at six months. Now, again, now the c the clinical relevance of this is of this is when we talk about cure following parathyr, we really look at more um checking the biochemistry a bit later. And when I say a bit later, it's usually six months. So even our National guidance is mainly the nice guidance. If you go through it, it's mainly looking at six months because after one month, you can get a normalization of calci calcium and maybe you've removed the wrong gland or maybe the patients just got multigland disease and that calcium can, can creep up over the next four or five months. And then at six months, you actually realize the patient is not cured. So their primary outcome measure that they have chosen is, is, is, is a, is a bit of a, uh, it, it's, it's, it's debatable. I would say it, it will definitely raise a few eyebrows where they just chose the one serum calcium one month after surgery. Um So when they looked at their primary outcome, they found that in the pet C group, 85% of patients had normal calcium at one month uh versus 56% there's a difference of 29% that's definitely clinically significant. Um So, but I mean, by, by the, the inference they're trying to tell us is that you're using your pet CT, you're more likely to remove the correct gland uh following a minimally invasive parathyr. Um And again, the secondary outcome was actually looking at uh the sensitivity and, and again, the sensitivity of the pet CT was 82% versus maybe 63%. Again, showing superiority of the pet scan. Um And even in WW when they use a second line scan, when the maybe scan was negative, the pet C was positive in 80% of the patients, which is pretty remarkable. Now, must add that this is the indication most UK centers uh would use uh for a pet city. It is being used in a few centers, especially in London, some of the high volume centers. Uh and, and, and you don't see that reciprocation when you, when you have a negative pet, um it's only about 40% who will have a positive maybe scan. So, um out of the 66 specimens they explored during the surgery, um seven were, were, you know, were, were inspected visually, but the frozen section did not correspond to parathyroid tissue. Uh Out of the 59 resected specimens, they had 56 out of 59 were adenomas and there was only one parathyroid hyperplacia. Uh Again, this can be a bit of a and you know, when you look, when you look at the paper, like we discussed, para hyperplasia is definitely a cause of failure of, of a single gland exploration. Um because, you know, you've got more abnormal glands, you need to go back in and, and, and usually do uh a completion surgery. You do, you might not need to do it immediately because um uh you know, again, we're looking at biochemical cure and these patients, maybe you have removed the most uh the most, the most dominant gland and you can do a redo surgery months or years later. Uh important to see that the, the lesion size was 11 millimeters, uh which is fairly small and again, very standardized lo looking at most studies around the world and the UK, that's the size you'd see. Um And like, like we talked about the follow up. So the follow up at one month, there were 52 out of 57 patients who had normalized calcium levels. Uh but when you look to six months that's dropped significantly. So only 43 out of 57 patients had follow up at, at six months and this, this definitely uh is a bit of an issue because these results can't really be taken anymore. Uh You know, you, you, you, you'd have to take these re re these results of the serious pinch of salt. Um uh be be because there are a lot of patients that we have lost. And like I said, it's much more important to have the six month value rather than the one month value. Um Again, so they also looked at the reporter agreement and uh this is, and, and they used the Cohen S Kappa test which uh I was saying for the first time. And again, it's just a statistical measure that quantifies how well two or more ator agree with classifying items into categories. Uh So they, they received a, a level of 0.81 which is almost uh perfect agreement. So both, both the, both the um uh nuclear medicine physicians who reported the scans were quite in agreement with each other regarding um the test. Uh you usually don't get too many questions based on, on, on these kind of, um, um, more unusual statistical questions. Um, but, but, and, and, and, and many times the paper will give you a lot of clues towards it. Um So just moving on to the discussion quickly, uh, you know, this study said that pet CT is fairly safe because in both, both groups, there was no adverse uh events from the scan itself. Uh They do suggest that they of you, you, you know, if you do a pet CT, you can offer the patient um a higher rate of a successful focused parathyroidectomy, which leads to normal calcemia one month after the surgery and a higher sensitivity as well. Um This study is unique because it actually looked into first line pet city uh flooring uh pet city compared to most other studies. Again, the strength that this was a multicenter randomized phase detail. And again, this is strengths stated by the authors uh outcome, the patients were cured of primary APAS rather than a diagnostic accuracy. Again, this is, it's, it's, it's, it's it's good that they have done that. But uh it's an the cure is kind of directed from the diagnostic accuracy. Uh if that makes sense, um they use the clinical parameter of calcium in one month as a surrogate for cure. Uh whereas most of the studies would use histology and mo mo most of the studies would not look at calcium. Um and that, that's something definitely uh admirable that they have done. But, uh, if they had done it six months after surgery, that would, this would make the, the paper a lot more stronger and their message would be definitely a lot more uh louder. So, um, they also included all primary hyper palliative patients with the surgical indication who are fit enough and willing to undergo surgery. Again, this is more of a real world use um that they're talking about. So, um um the, the, the, the, the, the disadvantage is if you see it was a small sample size and again, like we come back to the sample size calculation 90 versus 60%. Um If not for that, sorry, that then it, it would, would, we would be looking at different uh a much larger sample needed. Um There was absence of follow up after six months, they didn't use P TH normalization, which uh many people would use again. That's, that's, that's debatable. Um Many centers would, would look at calcium because calcium is what affects the patient and not P th. Uh But then P th gives you a big clue that there's disease left behind. Um corrected calcium levels were not used. And it's standard practice in the UK to use corrected calcium levels because you know, calcium binds to albumin uh and albumin levels can affect um the calcium levels. Uh The, the, the, the primary endpoint was assessed after the second line imaging was used. So patients who had a pet CT which was negative had a maybe later on. Uh but rightly, so it's unethical to just, you know, submit patients to a new scan and uh submit more patients to an unnecessary surgery, which could, could have more morbidity than, than needed. Uh Importantly, the raters were not blinded to the ultrasound result before randomization. And uh the authors defense of this is this is just their standard protocol that they follow in their hospitals. Uh There was no comparison to ultrasonography interestingly, uh or other scans, in fact, but that's not possible, but they did not really publish their ultrasound results, which is, which was a bit strange if you ask me, um they did use an interop frozen section but they didn't use intraoperative P th. Um which is, which is, which is a, you know, it, it require considerable investment. It can't be, it's not there in most centers in the UK, for example. And even in the centers in the UK, it might not be used routinely because a nice does not recommend it for first line surgery. Um So, so, so, so, so far we've just talked about what the authors have, have talked about their own paper. Um For the exam, of course, you'll, you'll, you'll be asked to do a critical appraisal. Um And um this is, you have half enough with the examiners for the Fr CS and they can ask you a lot of questions. So uh when you apply for the exam, I think most of you guys who have applied will know this. They will actually send you all this document, the JCI E sends you out this document um on how to actually critically appraise the paper. Um And uh this is actually a very good document because it tells you what you can do. You know a all that's mentioned here can actually be done within half an hour. There are a lot of tools to critically appraise paper. There's ac a sp tool. Uh I think the Oxford website has it Cambridge website has a tool. Um Those can be quite long. Some of them are very long and some of them are very short. Um So I think, I think it's important to find the balance and that's something in a, in a way that you can actually do it within half an hour. You also need to see the levels of evidence. And uh based on, on, on nice, this would be uh level one evidence, probably a one minus I would give because there's still a risk of bias and the risk of bias is because they've done the randomization after the ultrasound um was done. And we don't even have results of the ultrasound. So we don't know whether all the patients in one group have been, uh you know, let's say, um have all been patients who have had negative ultrasounds we can't say that for certain. Um So uh this is the classic way of uh appraisal that, that most of us know, even, you know, from our ST interviews. So it's uh po so it's patients intervention comparison outcomes. This is a very quick way to do um a summary of the paper and uh you know, the and the examiners commonly will ask you as the first question, just summarize the paper. So po is really good for that patients included all adults with primary hyper uh excluded those who had no previous surgery or non familial disease. Uh The intervention was first line imaging. Um uh that was Pet Ct versus the standard which is maybe uh that's the comparison and uh outcome was surgical ex excision of the localized gland just by a focused approach with early biochemical cure at one month. So, so, so, so this is a very easy way to do a 32nd to 1 minute um summary of the paper. But as as you know, the, the the examiners want a bit more. So again, I've just used the tool that they've, they've that they have um listed themselves for this. Um And you know, you, you, you first look at the abstract, did the abstract actually reflect, reflect the content of the actual paper? Yes, it did. Uh introduction was the background stated. Yes. The aim was a clearly stated. Yes. What was the hypothesis that pet Ct can improve rates of um focused parathyr and, and can surgically cure hyperparathyroidism. Ok. So far so good. But when you look at the methodology, was there selection bias with the authors? Yes, there was a bit of selection bias perhaps uh because of the randomization after ultrasound. Um I'm saying yes, but that's a bit harsh. It might be a maybe um what patients were excluded from the study, very few were excluded. And this is very important with R CT S because when we get lost in our CT S, some of the R CT s really look at a very narrow spectrum. So most R CT will not include pediatric patients, not include geriatric patients. Um um And, and if, if your disorder is actually affecting a lot of pediatric or adult patients, for example, then you're in, you know, you can't really apply this R CT to common clinical practice. Um They, this did exclude red and familial but those are treated separately. So, so uh looking at the real world, we are looking at a fairly large group of patients who present with primary. So where these patients representative of patients encountered in general surgical practice? Yes. Uh that was the, that's what we just talked about. Uh are the methods appropriate. Yes. Apart perhaps from the randomization, uh if a randomized study was the power calculation use, yes, it was. And about the power calculation like we said, they, they assumed a 30% difference in sens of the test. Uh this can be debatable, but again, we can't really question it because they've used their own data which has been published previously. Um But to, to, to, to a, to a reader, it, it does appear a bit overestimated. So even the other studies done on Pet City say that it's around um around more than more than 80% let's say. And maybe as well. I told you that some centers can get as high as 75 to 80% cause they usually combine it with act scan as well. Um spect CT. So that's that, that, that, that, you know, that's a bit debatable. Um Was the endpoint valid? Again, that's a bit debatable because they use surgical cure and they specifically use one month calcemia, not six months like we discussed. Um was the different sort in the study of clinical relevance. Yes. Um looking at appraisal of the results again, were the results well set out? Yes. Was statistics. OK. Uh appropriate. Yes. Um Is there, was there a type one or type two error? Um These are very important in, in surgical trials and, and you know, again when you're using drugs and things like that, but in this, um we know that there were, there were no false positives. Uh but we don't know that because we don't know, we, we don't have very long follow up. We just have pretty much one month follow up and it's a biochemical follow up, we have no idea to say that uh patients who had a positive scan, had the gland removed, had normal calcium. We don't know if these patients are gonna develop recurrent disease. Um six months down the line or one year down the line. So, so um but, but overall in, in the calculations we have done, there have been no false positives. Um the type two error which is the false negative. Again, both modalities we know have false negatives. And that's, that's really the reason why we are trying out this new uh C PCT. Um but the, but the, but the false negatives were lower in the intervention arm have the results been present in a biased way. Probably no uh to be fair. Um Is the followup adequate. And again, that's probably a hard, no, I would say because most patients will follow up till one month. Again, you, you're limited by your study and study design and maybe the, the study just couldn't uh follow up patients until six months. But that, that is, that is an important point. If they had done this in six months, this, this study becomes a lot more uh stronger, I would say um and any other potential complications excluded. Um Well, no, but uh they didn't really include uh analysis of other factors such as cost and availability. Uh They have done it in four centers, but I'm not really sure whether all patients came to one center. Um you know, whether patients had to travel a lot, whether that's covered, I'm not, I'm not, I'm not sure how, if that's covered in the French system, for example, um radiation is roughly similar, but they've not done any direct comparison of that. Um Again, lastly, in the discussion, have the, have the authors discussed the results fairly probably. Yes. Uh co comparison with other, with literature. Yes. The novel observations was this was a validation of a new imaging technique in an RCT. Um And um the que the examiners will ask you aware whether this topic is, is is present in any of the guidelines. Uh And uh well, the answer is yes, but uh it's, it's in, in, in most other guidelines, there's no national guideline which would um state a pet city to be done as a first line investigation. Um Although that's today and that might change uh uh in, you know, in the coming years um are the conclusions are put by data. Yes. And we talked about the other healthcare issues such as cost availability access to all. So, so I think uh that's the end of this uh paper. Uh Of course, we can discuss this a lot more. Um The reason that the rhinoceros is there is because the parathyroid gland was the last organ to be discovered um in the human, in, in, in, in animals and in humans. So, and it was discussed, discovered in this rhinoceros, uh the specimens kept in, in London. Um I think in the Royal Society Museum. But anyway, coming back to the, the, the presentation. So, um any questions guys, um so far, I hope most of you all have read the, read the paper. Um And uh any any questions currently can I just say thank you so much, Mr Raja. That was very, very, very interesting, uh very educational. Um I think we have all learned a lot. I haven't seen any messages uh about the topic may be worth giving it a few more seconds to see if anyone has any question in particular. But um me, everything was very well explained. The questions were very interesting as well. That's good to you. II think I just focused. Uh I hope I'm not, I'm not trying to scare anyone. Uh But I did, I did get a bit of a root shock when I started preparing for the exam and you, you usually tend to prepare, start preparing for the exam, what like six months before the exam. Uh you know, um um they do tend to ask a lot of oddities really in uh endocrine surgery in, in, in, in all of the smaller subspecialties, let's say, even in breast for that matter and even in transplant, they do tend to focus a lot on oddities that even if you ask an experience consultant and say yes, you know, we, we only deal with this, uh, once or twice, uh, every 10 years or so. Uh, um, but, but a lot of the questions I usually get around 1015 questions I would say in the Frcs party and they're usually straightforward ones. They're mostly, uh, thyroid based. Um, and, you know, the, the split would be maybe 10 thyroid, five parathyroid and maybe five from the adrenal as well. Uh They usually tend to be a lot more simpler than these, but these are the ones that, uh, you know, they, they, they, they almost will ask a question, one of these questions in the exam, they just really like it. Um, uh, it, it's good that, uh, some of you all are interested in endocrine surgery. Uh, if you guys want to talk about that, we can talk about that as well. Uh, within our dry as, you know, the training opportunities are a bit limited, uh, as I've come to know as well. Um, um, if you're in a hospital that is doing endocrine surgery that will, you know, that I think you, you, you're clearly in a good advantage of that. Um, yeah, so I'm happy to take any questions. Any, anything else you guys wanna ask? I think, I think one question I have, I'm just a bit surprised as you said that they only, uh, stick to one month, follow up rather than the whole six months. Do you think there is any particular reason that they may have done that. Uh It might just be logistics, uh especially in France, II think, uh you know, the, their network of hospitals, it's more centralized, usually, especially the endocrine services. Um I actually went there for a couple of weeks. Um, and, and it's heavily centralized so you would have patients and a fairly large country as well. So you will have patients actually traveling long distances. So maybe it's just that maybe it's just logistics and not getting the patient and they, they're fairly insistent. They don't follow that much. You know, it's not like GP to follow up bloods, uh rather they actually ask the patient to come back, uh, or you do a tele follow up but you, you do it, you know, the, the, the treating center usually does it. So that could be a reason. Maybe that's why they've lost a lot of patients. Uh, maybe, and, you know, the, the study wasn't designed for that. So they stay that in their primary aims that they did six months as well. But, uh, that, that probably wasn't their primary aim. Uh Yeah, but, but that, but that, that, that, that is very important because we do see many patients, they have a normal calcium level after the surgery and it usually starts rising up a lot later actually. Yeah. Yeah. Thank you for that. Um, I don't see any other question, um, in the chart. Yeah. Um, well, one second. Thank you so much. Mr Roja, for your excellent presentation and for sharing all your expertise with us tonight tonight. Uh That was very, very, very insightful and uh very, very interesting. Uh I would like to also thank everyone who has attended uh this uh event with us tonight. Um Again, this session is being recorded so hopefully you can come back and uh and watch it and that should be certificate as well. Thank you very much. Thank you much. I'm just putting my uh email. If anybody wants to ask me about anything, I'll just put that in the, in the right uh in the box. Yeah, thank you. Thank you all. Thanks Marita. Thanks guys. It's, it's, it's, it's a uh thank thank, thank you for giving me this option too. Appreciate it. Thank you so much. You are more than welcome to come and have any other cha in the future. Thank you.