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Summary

This on-demand teaching session is relevant to medical professionals and would entice them to attend by offering an overview of the Impact of New Adjuvant Chemotherapy Interval on Tumor Grade, Tumor Regression Grading for Rectal Cancer. This study was written by fellows in the Department of Colorectal Surgery and presented in the International Journal of Surgery Research and Practice. The session will give medical professionals a comprehensive but easy to understand overview of rectal cancer and its various treatments. Additionally, the session discusses established treatment guidelines from the annals of oncology and the European Society for Medical Oncology to help medical professionals provide the best possible care.
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Learning objectives

Learning Objectives: 1. Explain the differences between descriptive and analytical scientific studies 2. Identify the most commonly noticed early symptoms of colorectal cancer 3. Demonstrate comprehension of TNM staging for colorectal cancer 4. Describe the typical treatment guidelines for locally advanced rectal cancer according to the Annals of Oncology and the European Society for Medical Oncology 5. Discuss the implications of tumor regression grading on prognosis and individualized care decisions for rectal cancer
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Uh huh. That's there, I think opinion. It's I'm getting ready. I forgot. Um, thank you is just let me know if you're around. I'm just hoping, my friend, just Yeah, it was something. So, you know, uh, Mohammed, I wonder if we should give everyone else and a shoots forward. God, we just gave us. So, guys also, but it's working. And if we wait and five minutes or should we just start? Okay. Mhm. See that? Some people find thing I'm having difficulty find length. Um, give me one second. I'm going to go back on again. It's fine, but everyone five minutes. Um, and if we don't have any more joint is we'll just continue. Okay, there's there's already a chat room. Just feel actually, you guys going on and, uh, because you control the Northern Ireland's have quite right, and they're all connected to a bus. And he did say that he didn't want to strain for years and they were playing. And so he would like to ask for today And the next time you talk to everyone. So you felt well, joining us. So how's the page? No mhm evening. Every one of these with these must have just joined us just like I was saying and wait for another three or four minutes to see how many of us are getting and then just stop it. Okay, Um, fulfilling having a reaction. You get joint today, he will get external club Some things. Uh, nice to see you here, Children. So I don't know, like, you know, uh, I'm sorry, pasta. And does that sound welcome? Prudent. Think, Uh, I Okay, um I didn't know That's a medication issue. Okay? And I think for the same time, um, with maxalt, you know what I'm saying? Just be able to accept. I think I've read. Um I have, uh, event and his three different is now. I think everyone said Hey, it start any deficit. So and you're active. Um, excuse me. So you have to do anything when I was young. Uh, take some subject. A good one to have your paper, but not for calories. Correct. So I guess I'm not a good um hum. Okay. Okay. I think I can take date just like that. Me? Okay. Sensible. Just inside. Thank you. Yeah, just a yes or no. You need both together. Right? All right. Okay. It's just my one. Okay. I think, uh, the answer may be I want you guys have, uh I'm just a presenter. We'll have an idea of what is going on. Let me just see. Uh huh. To So, uh, a, uh, thank you. Uh huh. Uh huh. A look. Four. Um hum, yeah. Thank you. Thank you. Definitely. So they say based on you. Uh huh. It's, uh yeah, General. Uh huh. It's How's that? So it's a uh huh. Okay. No, just so you know, you just a I think she's Yeah. Yeah. Uh huh. Yeah. Thank you. Right. It's like, Yeah. Okay. Okay. Yeah. Please. Uh huh. Mhm. Yeah, he it wasn't pretty. Yeah. Destroyed. Uh huh. He was Yeah. Uh huh. It's all right. Okay. So, business, it's your seen before Push. Okay. Uh huh. Christmas? Yeah. Uh huh. Happens, okay. Piece of Uh huh. Okay. Exactly. Right. So Okay. Okay. Thanks. And but uh huh. Point Texas. Yeah, West Company. He's He's had Well, like okay. Yeah. Pounds. Yeah. Uh huh. What was that? Okay. That's what I'm sorry. I'm that puff weight to a single Thank you way. Yeah, because Definitely. Okay. Yeah. Okay. With I know. It's like, uh right. Be off. Absolutely. No, because it is. It's nice. Thank you. Really? Uh huh. Okay. Okay. Thank you. If uh huh okay. Oh, it's not as long. Uh huh. Oh, Uh huh. Yeah, it's 44. Uh, everyone pressed. Okay. It's a, uh Okay. Good. Okay. Uh huh. Okay. Okay. Yeah. Yeah. Coloma. Hello, Ma. What you see? Um hum. Hello? Ma. Ma, we can't hear you. We can't hear your voice. Your voice is breaking Ma with me. Yeah, uh, Let's see. Income sleep. Yeah, you can. Yeah, yeah, yeah. Um uh huh. Thank you. Okay. Yes. Yes, I did. I think I would do mhm. No, my point, people. That's good. Okay. And yeah. Okay. Okay. Yeah. Okay. Can can everybody hear me now? Am I still audible, or am I still inaudible? Hello? So is this Is this clearer, or is it still? Yeah, I can hear you audibly. Okay. Well, now and then you're not You're not. You're not hearing any feedback, are you? Yes. Yes, yes, it's clear. Okay, that's fine. Um, so apologies for that, everyone, um, that was really super unfortunate. um, So you know what? Let's just start from the beginning. I see we have more people in the chat now. Welcome everybody to see gobs. First journal, club meeting. Apologies for the issues with audio. Had to log into my phone. Um, as I said earlier, we do expect these sessions to be very interactive. Okay. And from the pole we took early, I can see that most of us haven't read the paper, but that's okay. But we just hope that in the coming in the coming, uh, sessions that we may be able to have some sort of a clue as to what's what's really going on because it really helps to make it more fun. So the paper we will be addressing today is titled Impact of New Adjuvant Chemotherapy Interval on Tumor Grade. Tumor Regression Grading for Rectal Cancer. It was written by Thomas Tang and close to Do David Williams and Andrew, who are all fellows in the Department of Colorectal surgery across Austin. Health and Northern Health to hospitals in Australia was first presented in the International Journal of Surgery Research and Practice. Volume nine in 2022. This must have been at least a month or two ago. I apologize for not getting the exact month. Um, now, just as a background to the study, Okay, I'm not sure what level all of us are, but I will assume that we're all sort of, you know, not not. You know, research fellows or anything were organizing that we're all on the same level. Um, so just by way of introduction, this is a descriptive retrospective study, okay? And just just to have, like, a background on study designs, studies or scientific studies are basically have two types there. Either descriptive or they are analytical. Okay. Purely descriptive studies are things like case studies, case reports and cross sectional studies. Um, in these types of studies, the researcher that does nothing, they're basically just observing and naturally a phenomenon that is occurring in nature without any intervention. And they're basically commenting and writing on what they see. They do not seek to measure anything or any sort of relationship there just purely observational. The other type of study is the analytical study, which is what this is. And now analytical studies are of two types. There's observational or they are experimental. Now the difference between an Observational Analytics study and an experimental analytic analytical study is that in an observation, analytical study, uh, the the the causal factors already taking place. So for in this paper, the cost factor is rectal cancer. Everybody already has rectal cancer. In this study, we didn't give anybody rectal cancer. Um, and we're just basically observing and looking for a cause of relationship. So this is an observational descriptive study. Um, and experimental analytical studies. These are purely the pure research topics, as many people have come to know them. These are your, um, your randomized controlled trials. Okay, add locally advanced rectal carcinoma. Now, all of the patients had biopsy given rectal identical carcinoma. And this is just a significant a bit later when we explain the type of rectal. Okay. Now, if you're anything like me, you didn't really know anything about colorectal cancers till maybe final year for, like, lecture. Um, and then suddenly it's always all the time. Every time. So rectal cancers are known as Yeah. People think maybe this is probably due to the western. Um, developing countries had more stringent data keeping these cases. No youngest I've seen is in an individual that was less than 30 years old. It's actually quite scaling. Just look at this schematic. It's very simple. I do like pictures and put them everywhere. I can. Uh this is just basically a picture of the large colon, the colon ascending, transverse descending, sigmoid and right. Um, okay. And if you look to the left, you can see where it's divided. The most common colorectal cancers by percentage common, followed by most individuals with early disease will be a symptomatic. But when they do symptomatic one of the first training on the toilet, um, also become very thin. Um, I'm seeing a bit of blood in my stools. And months later, when you become, you know, very tired without explanation, most individuals won't even really notice these changes. All these surgical changes in the toilet habits, they're important to the waist. A very, very, Uh, yeah, wh classifies rectal cancers based on histological types. And as you can Are you an A Yeah. Again, we said that this study is looking at locally advanced rectal See a. Okay, So what do you mean by because tnm staging okay to tumour node metastasis. Okay, now it's very nice day of the tumor and the T four b, which is basically when the tumor has penetrated all the way down through the surgery. So and and basically does what or it's not. We talked about locally advanced. We're basically looking from re stage three a 23 c, maybe four depends. That's quite according to do this classification, which is also really simple. Easy thing to remember a B, C or D bowel wall, lymph nodes not involved, lymph nodes involved and widespread metastasis. There's also a slight color classification, but this is just something to put in your back pocket and something for you to remember now. This is very large, Um, intimidating looking table is from the annals of oncology, and it's just basically once again grades tumors into very early or good and advanced and ugly tumors. And once again we're going to the intermediate, intermediate or locally advanced and where we sea Possible therapeutic options for these individuals here, our surgery alone or chemo radiotherapy followed by surgery or chemo radiotherapy alone. Um, why I'm putting this in is because it's important to know why the researchers are doing what they're doing. So every single disease, there is established treatment guidelines. Now, the thing with the medicine is that everybody has their opinion guidelines. Things should be done. So just for ease of understanding, we're just going to take two, which are the annals of oncology and the asthma classification. Okay, diagram or schematic from the annals of oncology. And it basically just showing for locally advanced rectal see is what you should do. And they all advocate for chemo radiotherapy, Um, after which you you have an MRI to assess for tumor regression after which will either watch and wait, or you will proceed to surgery. Now, what determines what you will do after the chemo? Radiotherapy is, um it's on an individual basis. How fit they are. Um, what the tumor looks like so on and so forth. And how likely are you to ensure, um, good, um, tumor clearance if you went into surgery? So we've established that locally advanced that the established treatment guidelines, According to the another, oncology for locally advanced rectal see a is chemo radiotherapy plus or minus surgery depending. Now, this is just another breakdown from the asthma. Asthma means European Society for Medical Oncology typically what you flock to if you can't. If you're in doubt, you're not sure what the hospital is doing. You're not sure what anyone else is doing? Just the best way to the biggest guideline you can find. Either nine sports my guidelines. We talked about adjuvant chemotherapy. Who knows what they're doing? Chemotherapy is anything. Who? In the box? Oh, we're having audio problems. Can you still hear me? Or is it is it? Still? Is it becoming an issue again? Okay, Okay. Thank you. But for me, that's perfect. Absolutely perfect. Chemo. Keep know. Adjuvant chemoradiotherapy is basically any chemo or radiotherapy that you use to downstage. The tumor basically means to decrease the bulk of the tumour in order for you to go in and do what you primarily want to do, which is cut it out. Okay, that is it. Now, the agents in which we typically advocate for are a combination of any of the, uh, six or seven listed on the left. The most common is your fall, folks, which is a combination of five fluorouracil and leucovorin. Oxaliplatin is a combination of three drugs. Okay, now, radiotherapy, um, is basically given as either a long course or a short course. Um, and a long course. You typically give around 50 grazer radiation, um, around 1.8 daily in over. Like a course of 20 plus days and short course. You deliver a higher dose in a few a lesser amount of days and followed by surgery. A week or so later, we'll see that most of the individuals in this study have under undergone a long course. Chemo, chemo, radio, Long course, chemo, radiotherapy. Now why This is important. It's just so you can understand, um, exactly how, um, the treatment goes. So the aim of this paper is not really to say a long course versus short course or surgery versus no surgery is really to say if we give individuals chemoradiotherapy, whether long or short, how likely is it that after nine weeks or before nine weeks, that the tumor would have significantly gone down in bulk? That's essentially what we're assessing here now, going on two methods. All these 114 patients were enrolled, and the inclusion criteria is basically everyone above the age of 18, with biopsy confirmed rectal adenocarcinoma that is locally advanced on imaging um, individuals that were excluded are individuals with number one early disease. So I don't know carcinoma in situ Know any other individuals with any other type of histological type of rectal? See, A was excluded, and also they decided to exclude individuals that were not for surgery. I eat individuals that after chemo, radiotherapy were on the watching and waiting. And you remember when I said earlier that, um, watching and waiting was for individuals that may be a bit too frail to undergo debulking surgery now results, um, so just going through the results tables that were published, um, in the in the in the paper, I think, personally, I think there was a bit to be desired so we can see. Obviously, as usual, there's always more males and females. Um, we can have the age and it's typically individuals over 50 which is understandable. But then again, we now see that the only that this data just came from two hospitals in Australia, Australia's a very large place. I felt like maybe, um would results have been better if they had included more, more individuals from a wider geographical location. There's no really any info about the ethnicity of these individuals, so we don't know if the ethnicity was significant in the results or if it had anything to do with it. They decided to put the location of the tumor, which is also important somehow, um, and then MRI staging before and after chemo neoadjuvant chemo, radiotherapy. And this just basically continues. It gives you the list of operations that each individual underwent if they had any operations over 61 individual's, um, and basically the list of operations you can have for colorectal cancers are. It's very long and very variable. And again it's a case by case basis. It can either just go. It can be either be as simple as an as an endoscopic, uh, local excision or as as destructive as a total pelvic exaggeration. Which means, basically, everything in your pelvis is cleared out. If you're a woman, it means that your part of your vagina is also cleared out as well, and this is what we're really concerned about now. So if you look at the two tables it showed, the first on top is a table showing the complete pathological response. According to the surgical interval. Now you see the table says on the first or second row or second column before nine weeks and then after nine weeks, and you can see next to it that the P value is for both the Ky squared and fishes exact. Um, we're, um so both the ky squared. We're not significant fishers exact. Also not significant as well. If we look down, we can also see the short and long term radiotherapy responses again. Not many significant responses now. In this study, we they classify the patients into two groups before less than nine weeks and having surgical intervention and greater than nine weeks after chemo, radiotherapy and having an intervention. Now, after nine weeks, there was no real, um, cut off as to what time after that they had the intervention. As you know, that there's lots of factors that can influence that basically spaces on surgical lists and so on and so forth. They really didn't give us any explanation. And I guess you guys must also be asking why nine weeks, why it's nine weeks so significant. This is based on several randomized controlled trials have been that have taken place in the past. Um, and following this, they've They've basically advocated that anything around, um, eight weeks on is valid. So I think these researchers have chosen nine weeks, is what they want to go on now. This is possibly the most important table in the study. This is a multi variable logistic regression analysis. Now what this means is basically, it's taken every single factor that could be measured in this study giving age gender interventional in surgery in weeks, whether they had long course or short course, um, and what type of reception? Um, they had. Now, if you know anything about, um, logistic regression analysis, it's not something that's done by hand. Um, it's basically you have to run it in the computer because it's very complicated. Same with fish is exactly what kind of squared You can basically do that by hand. And what you will notice is that the only place, um, where the Pee values had any sort of significance, um, was in the age and gender. Okay, What this means is that they had a non hypothesis to test, and there's no hypothesis. Meaning. Basically, what we want to assess in this study is, um, that tumor tumor um, tumor resection grade is not affected by the length of the interval following chemo Radiotherapy? That's denial hypothesis. Okay, So, typically, when we're testing the know hypothesis, we we asked our P value to be greater than 0.5 for it to be significant. Now, this took me a very long time to understand, um, and sometimes it still does, like sometimes I start to, like, sit down and really think about it before I go off on an angle. Typically, what it's telling us is that for any of these values, it is only significant if the P value is less than 0.5. What they're typically trying to say is that if it is less than 0.5% at that confidence interval, that's 5% confidence interval that there is a less than 5% probability that the hypothesis is due is correct or it's due to chance. So where we have, um, P values that are less than 0.5% we reject the non hypothesis, and we say right, this is a significant factor. It can't be due to chance, but when everything is greater than 0.5%. You have to accept the the know hypothesis and you say, Well, it's not significant. It's probably not due to chance. And these are how things are on the next table. On the next slide, it's just a box chart just basically showing tumor response grade versus before and after nine weeks. And as you can see, a box box box spots are really good for comparing two sets of data, values and agency. It's it's really it's really not Not interesting at all. There's no difference. Um, so in conclusion there were 114 patients, only 61 of which were analyzed. Okay, and there were more males than females in terms of a complete pathological response, There was no significant difference observed in individuals who have undergone surgery within nine weeks or after nine weeks, following long or short course chemoradiotherapy. Okay, there's no significant association with observed. No significant association was observed, except, um for a female gender, which is saying, basically, if you're female, you're you're According to the study, you're likely to be better off after chemo Radiotherapy. You're more likely to have a bit of tremor regression um, afterwards. So this is just some very complicated tables of the randomized controlled trials that were referenced in this study. The first, uh, given table there is by the, uh, by a Swedish group. And it was just basically showing the fact that you could Actually, it was better for rectal cancer patients to have chemo radiotherapy. That's what that first one shows. But then afterwards, people started to notice, like, really high recurrence rate. So they did another study with the Dutch, and then it shows that you know what? Actually, chemoradiotherapy is good for these patients, but it's also really good for them to have surgery afterwards. And that's how that treatment guideline was established. As to the nine we the whole duration of, um what what time After, um, after chemo. Radiotherapy. You should have surgery that was established by the French studies. They're quite complicated, and you can go up and read about them in your spare time. But basically, that's really it for this For this study, I picked really short, um, to the point paper. Um, I think if you if you have, you know, if you you have the chance to go back and read the paper after this, You you sort of see that, Really? I I picked something that has a lot of holes that we could talk about. So I guess my takeaway from this first journal club meeting concerning this paper is it was a fair attempt as a research study, but obviously there was a lot to be desired. Um, where the results are consistent with the hypothesis being tested, we can't really say. And I would say, You can't really say because I just feel like 61 patients is not enough for you to establish a causal relationship in a disease that has such a high burden. Again, I didn't see any ethnicity in the demographics. And I think most of the times ethnicity is an important factor in these diseases based on based on whether you're looking at treatment or even whether you're looking at just, uh, outcomes after treatment. My biggest issue was the geographical spread of the data. These 61 patients were literally just from two hospitals in Australia. I just feel it wasn't conclusive enough, and that probably is the reason why we didn't have enough patients enrolled into the study either. There was no indication as to whether these patients presenting with this rectal cancer we're presenting as, um, first time rectal see a or they're presenting as recurrence. So what you will find out is that if you go ahead and re sect erectile, see a and you've not cleared those margins out, you will just have cancer again within, like, a year or two again. Very small sample size. I mean, that is so. The thing with mostly probably noticed that they used Ky squared as well as fish fissures. Exact test Both of these tests statistical test tests and all hypothesis. Um, and you're probably asking why we need to, um, and I think that they did that because of the sample size. Whereas High Square is good for really large samples, it's very difficult for you to have an accurate result with a very small sample size. Um, and that's where fish is exact test comes in. It's sort of came in, in my opinion, to corroborate whatever we saw on the high square test, because 61 is just not enough to push an all hypothesis. True, if your data set should be larger or significantly larger than what it was, Um, but we got to see that Even with the fissure's exact test, there was really nothing significant. The only significant thing there, as we say again, is gender. Um, no. Other. Um, no other significant associations were found Fishers. Tests can be really calculated by hand. It has to be run in the computer. It's very complicated, very difficult to calculate. So don't try and wrap your head around it. That is a question that it asked really frequently on the M R M R C E P exams. And sometimes MRCs is what what really is the difference between the fissures and chi square, and it's basically it's good to remember that fish is exact is exact, and that's just just remember that and go ahead with that. Um, as always, a randomized controlled trial would have been more accurate. But obviously not everyone has the manpower. Not everyone has the funds to push. A randomized controlled trial didn't see any major outliers in the data. I think to improve on this study, um, definitely. We need to more enrollees. I feel we should include other different types of cancers because I would like to see if, um, Mucinex or Signet Ring had better tumor regression rates than adenocarcinomas. We don't know. This is something that we should look at. Uh, I think this study should be performed again. That's probably something that you got to look at. Maybe in the in the distant future. Um, and yes, there's my takeaway points. Um, please, as you're kind of leaving the chat room, please do not forget to fill in the feedback for me because there's a certificate at the end. Certificates are very, very important because every time you do your annual appraisal, you have to pull your certificates on. And it's just really something that you you need. Um yeah. So that's my take away from this paper. I would like at this point to ask for audience opinions about this paper and questions. Please remember to ask me questions about the carrying out the research because I wasn't there. So questions that are the presenter who wasn't involved in research be able to answer, um, any questions or opinions, because while I'm a great and charge my laptop questions or opinions, should I look in the chatter box? There with me. Are there any questions or opinions concerning this paper? Was it a good paper? Was it a bad paper? Is there anything you would have done differently? Please ask questions or state your opinions. If anyone would like to say something, you can just like to try to switch off your microphone and just speak. Yeah. Okay. Was there anything that anybody didn't understand that they would like clarification on? Okay, Then I'll just assume that my presentation was awesome. Unless one of you comes and tells me that it's not, um, thank you very much for being at this journal club presentation. Hopefully, one of you will be presenting the next one. Um okay, so we've got a question. What would the least amount of sample size for a study like this be so there is, um, a method to calculate sample sizes and hold on for something for for the amount of patients that actually you you first of all need to know the amount of patients that have rectal cancer in Australia in general, that our existing So you need to know the the the prevalence. You would need to know the amount of new rectal cancer cancer patients in Australia. That would be the incidents. And with that, there's a very lovely um uh, there's a very lovely, um, formula that you input. I remember from my comment days and that typically generates a sample size for you. Give me a few minutes after this, I'll put it. I'll paste on the group chat, how to calculate a sample size. But I would say that for this kind of study, I would expect nothing less than at least, UM, 1000 patients for you to confidently say you had the amount of data you needed to make a conclusion. I think 61 patients over six years is not significant, and it doesn't hold any water whatsoever. But that's just my opinion. I thank you both for me. Yes, you guys will would benefit from regular journal clubs, and that's why I really want you guys to have a girl presenting. I know it seems really daunting, but when you get used to it, it becomes very easy for you. Um, it's also a good way to practice, and when you're presenting your own original research works and case studies or whatever in international journals. Um, this is good practice for you. Prudent. Said it was fair. Yeah, exactly. A more robust study? Definitely. Definitely. Um, yes, I think so, as well. I think I think there's just so many holes that we're missing. Um, I mean, even if you didn't have 1000 patients, I think a good geographical spread of at least more than two hospitals and within the area would have been nice. Um, or if you're going to say it's only from two hospitals, I would have said maybe at least give it 10 years, um, to have an appropriate appropriate amount of people. I think six years just wasn't wasn't cutting. Mohammed Ali have said it was a good paper. I feel bad now. Yes. Okay. Well, it was it was a fair paper, but there was still a bit more to do. Then again, I don't think there's a perfect paper out there. I've not seen one yet. Um, thank you so much, guys. Um, so we'll let you guys know the next presenter. I've been told that they are interested parties, and I'm super excited about this because I want this to become self sustaining. Um, as I said, it's really good for your CV. What I would say is, um, filling the feedback forms. What I would say you don't always have to present original research like this where you have to, like, wrap your brain about, um, statistics. I think you can also think about really nice case presentations and you can use it as a teaching point. If you find a really nice, complicated case in the BMJ or wherever you can bring it to the journal club and we can discuss it. Yes, of course. Prudence. Yes, there are, um there are opportunities to present. So if you either contact myself or, um, Mr Moses, we will put you on the rotor to present. So as it stands, we're aiming to present maybe once a month, Um and then when we get more confident, we can have more frequent meetings. Um, so I think the next presentation is is next month. Um, on the third week of September, maybe was the fourth week of September, I'll clarify, but yeah, please do get back to either myself or Moses and we will put you down. Um, there is always an opportunity to be active in siga. Thank you for you're careful listening. I please do feel the feedback form. It's useful for me. It's useful for you. Um, it gets your certificate and then it also allows me to see where I need to improve as a presenter. Thank you very much for joining in today. It was lovely to talk to you all. Thank you for suffering through my crappy microphone. Um, and I have to see you guys soon. Good night.

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