Transcript

TRANSCRIPT PODCAST: Mediastinal cryobiopsy

TRANSCRIPT PODCAST: D225343, 2021-12

TRANSCRIPT PODCAST: Welcome to this Erbe group podcast produced by our Medical Insights studio. In today’s episode our Clinical Application Manager Dr. Niklas Froemmel is talking with Prof. Venerino Poletti from Italy and Dr. Hari Kishan Gonuguntla from India about an approach for which initial clinical feasibility data is now available. Various publications have reported on transbronchial cryobiopsy of mediastinal lymph nodes.

TRANSCRIPT PODCAST: Prof. Poletti is head of the Department of Respiratory and Chest Diseases at the Ospedale G.B. Morgagni in Forli. He is also a member of the European Respiratory Society and often called to moderate international congresses. Dr. Kishan is lead consultant Interventional Pulmonologist at the Yashoda Hospital in Secunderabad. He was the organizing chairperson for the BRONCHUS 2021 Congress.

TRANSCRIPT PODCAST: In this episode our guests are talking about their experiences with practical implementation of this biopsy technique. They go into what to watch out for, and discuss what the current position is in addition to the established EBUS-TBNA could be in terms of the therapeutic algorithm.

Dr. Froemmel: So may I start with you, Dr Hari. Your data and your experience on mediastinal cryobiopsy.

Dr. Froemmel: What's the implication of that for your daily practice or for which subset of patients are you using this biopsy technique frequently?

Dr. Hari: I thank you for including me in the podcast. So my implication on this procedure, like often trying to look at the feasibility of letting the lymph node biopsy to the miniature cryoprobe and then we were successful in the first four cases with the definitive diagnosis. So this procedure was followed after an initial EBUS-TBNA was done in the normal way using a 19 or 21 G needle and then followed by a small cryoprobe. So late we started to include more and more patients to this procedure. And as an institutional protocol, we are trying to look at the initial negative EBUS and then proceed those patients with cryobiopsies. Maybe in future, it can be a first procedure of choice after a lot of data gets evolved in the current and in the future.

Dr. Froemmel: It's quite a new technique now, and there are some technical issues still. So, Professor Poletti, what would you say? Which level of experience does a bronchoscopist need to have to attempt a cryo TBNA. What would you say?

Prof. Poletti: Good morning to you all and thank you for including me in this podcast. I think that you need to be expert in TBNA and in ultrasound guided TBNA first, and you need to be expert also in the approach using intubation or rigid bronchoscope, because you need to extract all the bronchoscope en-bloc including the cryoprobe. So you need to be expert in all these elements of the procedures.

Dr. Froemmel: In case I deem myself sufficient according to the characteristics that you have just mentioned, which lymph node stations would be rather good for beginners and which ones would rather be something for more advanced bronchoscopists? What do you think, Dr Hari?

Dr. Hari: I think to begin with station 7 would be more ideal and are choosing very large lymph nodes in the initial aspect would prevent complications as this is a very new technology. And also, I suggest a station 11L is more easy for doing a cryobiopsy and also 4R a few lymph node stations like 4L because it is close to vessels and you sometimes you may not have control over the cryo and even 11R superior in that way. It is far more advanced bronchoscopy level. So for the beginning, go on for the 7, 11L. And the 11R inferior.

Dr. Froemmel: This leads me to the next point in which conditions would you deem a cryo TBNA contraindicated and I mean, we have very few data at this point. So of course, whatever you deem contraindicated may evolve still an indication in the future. But based on the current experiences and data, what are the contraindications in your eyes? Maybe Professor Poletti.

Prof. Poletti: We don't have, I think, so far enough data to be sure about contraindication, but we follow the general contraindication of ultrasound guided TBNA. So when you have a large lesion with necrosis or you have some cysts, these are a kind of contraindications for using EBUS guided TBNA. So I think this should be a prudent approach so far. Yeah.

Dr. Froemmel: Dr. Hari, you have told me about the condition that you can have two larger vessels surrounding a lymph node and that a needle offers the benefit that it can bend more and therefore still puncture the node, but not injure the vessels. How's that with a cryoprobe?

Dr. Hari: See, comparing the needle and the cryoprobe, the advantage of the cryoprobe is flexibility of the EBUS scope. So some needles like, you know, the flexibility of the EBUS probe comes down and then we are not able to access, especially the 4L and 10R lymph nodes. In that aspect EBUS cryoprobe and also EBUS needle. But when it comes to puncturing, yeah, sometimes the probe can slip. When you're doing the EBUS cryo TBNB, those things can be addressed in the research by producing a bit more stiffer cryoprobes maybe in the current, in the evolving time.

Dr. Froemmel: Speaking of slipping, that you just said, I would like to move on to procedural questions and the peri-procedural patient management. Has it happened to you that you've been slipping around the lymph node and maybe sampled the capsule instead? That's something we have heard so far? And how could this maybe be prevented, Professor Poletti?

Prof. Poletti: This can be a problem, because with this, the kind of problem it tends to be more tangential to the lymph node you want to biopsy. But anyway, I think that you can overcome this approach in two ways. You can help your access using electrosurgery cutting the mucosa. This is the first point and the second point is just to move a little bit the bronchoscope in order to avoid this approach. But I think it is not so important because it's very unusual to have such kind of fibrosis in the capsula of the lymph nodes. So yeah, you need just to know that with the cryoprobe you attempt to be more tangential compared to the normal needle you use.

Dr. Froemmel: As a pathologist, let me ask you this question, which area actually do we need to have from a lymph node we puncture? Do we need the subcapsular area or do we need the hilar region?

Prof. Poletti: This is a good point, because we know that metastasis usually start in the subcapsular sinusoids of the lymph node. So to stay just subcapsular, it's quite good from the pathological point of view, mainly when you are dealing with epithelial tumors. Also, if you are dealing with lymphomas to be subcapsula, usually is quite useful because the lymphomas infiltrate tend to go through the capsular. So yes, I think that is not so important to be central in the lymph node when you want to capture the lesion.

Dr. Froemmel: You have mentioned it a bit earlier, Dr. Hari, for the necrotic lymph nodes. You see a bit of a contraindication also in cystic conditions. Can you elaborate on this a bit more why we should avoid cryobiopsy in such conditions?

Dr. Hari: It's not just with the cryobiopsy. Even for EBUS TBNA needles, if you look at puncturing a simple cyst is not really indicated it is a quite surgical resection is the diagnostic choice. As you know, there is a lot of necrosis and if you do EBUS the chances of mediastinal abscess formations are more with the previous experience from EBUS TBNA. But overall, if you look at the complications that are mentioned in the actually history, they are less than 1% conventional EBUS TBNA. As the literature evolves, I think the same should apply for EBUS cryo TBCNB. At this moment, since this is a new technology, I think it’s aggressive on doing on this necrotic nodes. Maybe the coming days we try to and see what complications can arise.

Dr. Froemmel: Professor Poletti, you have managed a bit earlier that you need to be advanced when it comes to airway management and that you are doing it in rigid intubation. So what are the anesthesialogical requirements from your side? Why are you doing it in a rigid way? Can you please give us an insight about that?

Prof. Poletti: Yeah. We use rigid intubation also with normal EBUS TBNA, because we have this kind of facilities. But the needs for general anesthesia are not so complicated. You need to use propofol and remifentanyl, the patient maintains spontaneous breathing and so you can intubate the patient after local anesthesia of the vocal cords and then they are already sedated with propofol. We don’t use jet ventilation, for example, because the patient maintains his spontaneous breathing. So I think you need, of course, very equipped endoscopic room. But we took this approach quite frequently. Even when we use EBUS TBNA. Not cryo, EBUS TBNA. So I think this is a normal approach we use already.

Dr. Froemmel: Dr Hari, what's your approach to that and can you elaborate on this a bit more, please?

Dr. Hari: I think the way you do the procedure depends on the institutional policies, if you look at the west, like Professor Poletti said they do most of the EBUS-TBNA under general anesthesia. But as our institution, we do all using a supraglottic device. But I think by this time with the two papers on EBUS cryo TBCNB, it is already established that this procedure can safely be done even under conscious sedation. So it depends on where you're practicing. But this procedure can be done either in conscious sedation or general anesthesia using a supraglottic device or a rigid bronchoscopic intubation.

Dr. Froemmel: Facing this rather, yeah, let's say heterogeneity that you have just displayed. What is your post procedural protocol? So how do you monitor? Does the patient stay in the Post Anesthesia Care Unit. Do you perform a chest X-ray afterwards, etc.? Professor Poletti, can you tell us how you do this with your patients?

Prof. Poletti: We perform this approach in outpatient settings so that patients remain in our institute for two or three hours after that, and we don't perform chest X-ray just too, but only if clinically needed. So we usually don't perform any assessment. We just observe the patient for two or three hours after the procedure and then we dismiss the patient. I told you, Yeah.

Dr. Froemmel: How about you, Dr. Hari?

Dr. Hari: Yeah, we also do the same protocol like we do observe them in the post-bronchoscopy period for two to three hours like normal EBUS, but in the initial days we were doing just X-rays as this is relatively new technique. And then now we are changing to develop not to do an X-ray as we see that there is no immediate complication as we saw in our patients.

Dr. Froemmel: Professor Poletti has mentioned that the incision to the airway wall using electrosurgery might be one possible approach. We have heard some doctors raising concerns about damages to the ultrasonographical transducer at the distal end of the EBUS bronchoscope when you A) incise with electrosurgery and B) also rapidly extract the scope along with a cryoprobe like we know from the peripheral transbronchial biopsies. How is your experience with that, Dr. Hari?

Dr. Hari: We, to now, have not practiced doing incision and then doing a biopsy. Maybe we need to try that, but I think the incision need not be done using an EBUS scope. It can be done with a flexible scope and then change it to the EBUS scope to prevent damage to the EBUS scope. And also, what we are trying to do is like once we pass with the needle, we try. Once the needle is in, we are trying to extend the the site of perforation by just flexing and extending the EBUS scope so that we can avoid doing an extra electrosurgical knife perforation. So that is one technique we are trying to see the feasibility. And I think that should work like in cases where we are not able to pass. I think electrosurgical options can be tried. But EBUS scope damage with this technique is relatively not very significant, I guess.

Dr. Hari: Yeah.

Dr. Froemmel: When you pass, sorry, please, Dr. Hari.

Dr. Hari: Yeah. And also the probe lies very far from the tip of the EBUS scope when you're freezing and bringing it out. So I think as the procedure itself, it is very safe to the scope also.

Prof. Poletti: Just to add something. When you use elctrosurgery cutting, because when you collect material using the cryoprobe, the size of the sample is quite large. And so in this way, you have enough room not to lose the material. Then you go out when you throw out the bronchoscope.

Dr. Froemmel: The sample size, of course, always is subject to also the probe size and the pressure of the carbon dioxide. So based on your experience, how long would you freeze before extracting the endoscope and the cryoprobe? Professor Poletti?

Prof. Poletti: 3, 4 seconds. This is the freezing time we normally use. Yes.

Dr. Froemmel: And with this freezing time, you are still able to extract the specimen through the puncture hole.

Prof. Poletti: We use this freezing time. It depends also on the pressure you have in the bottle, but of course you need to have at least sixty bar of pressure. But with this freezing time, we obtained good samples so we don't have experience with other freezing times. We use longer freezing time, when we use the 1.1 cryoprobe in the periphery of the lung. But in the mediastinal lesions we use this freezing time. I do not know if Dr. Hari has the same experience.

Dr. Hari: Yeah, professor, we also in the initial cases, what we did, we were using only three to four seconds. On all the cases we were able to demonstrate good sample size with freezing time of three to four seconds. And also I noticed like if you freeze it for a very long time and not incising and going through the same hole, sometimes the shaft of the EBUS probe becomes very cold and then it gets stuck to a bronchial mucosa wall. So that is one thing. For disadvantage if you're using for a longer freezing time.

Dr. Froemmel: Very valid point. Thank you, Dr Hari. Looking at the complications and when I was reading the publication of the Group of the Thorax Clinic in Heidelberg and the Chinese Working Group, I was surprised that the reported bleeding rate was so low. Gentlemen, what's your hypothesis on the rationale behind this low reported bleeding rate? Why is that, Professor Poletti?

Prof. Poletti: I think that cryotechnology is used to avoid bleeding or to control bleeding. We have bleeding when we have biopsy in the peripheral of the lung, because you tear the bronchial artery or the pulmonary veins or the pulmonary artery, but in the mediastinal lesions. First of all, you can control the best colorization by ultrasound and then usually biopsy, not in area where you have large vessels. I think it's very easy to have a very low rate of bleeding in this context.

Dr. Froemmel: How do you think about that, Dr. Hari?

Dr. Hari: If you look at that, registry of conventioanl EBUS-TBNA bleeding complications, that means bleeding requiring intervention is only less than 0.2%. So as Professor said, this is not a TBNA where you have been aware you have bronchial and pulmonary supply and then we are biopsing that area where bleeding can be anticipated, but in a lymph node, if you choose a proper lymph node with low vascularity and avoiding the areas of vessels in the lymph node. I think a bleeding should not be a problem with mediastinal cryobiopsy as well.

Dr. Froemmel: In your eyes is especially when you do the approach with the electrosurgical incision, you're going to have a larger compromise to airway patency than you would have with only the needle puncture to pass the cryoprobe. Is mediastinitis in your eyes, Dr. Hari, an issue when doing the cryobiopsy here.

Dr. Hari: My cases are still evolving, and I need more time to have an answer on this because until now, we had not. We are just following up the patients who are doing this cryobiopsies. So I need more time to have a specific answer on mediastinitis related to cryo TBCNB.

Dr. Froemmel: Are you undertaking prophylactic measures to prevent mediastinitis like antibiotics that you administer before the procedure?

Dr. Hari: In our institutional protocol, we don't routinely administer antibiotics pre- or post EBUS procedure and we continue to follow the same protocol for cryobiopsy as well.

Dr. Froemmel: So we move on to the pathological considerations and I think it's very beneficial to have you here, Professor Poletti, as you are demonstratingly a very good pathologist, as well. So have you met any agreements with your pathology department in Forli on this new sampling technique as opposed to the TBNA.

Prof. Poletti: I think that we had already a very large experience with cryobiopsy in the periphery of the lung, so we have no problems dealing with this kind of samples and they are very normal samples. What I can say about from the pathological point of view that usually when you have an epithelial tumor, you have enough material in the majority of the cases, at least using a traditional approach with EBUS TBNA. This new approach can be very helpful. Then you can have it. You need the diagnosis of lymphoproliferative disease or even benign disorders, maybe granulomas in the context of sarcoidosis versus tuberculosis or a typical mycobacteriosis. So I would say that this approach so far at least is mainly devoted or useful for diagnosis of unusual or complicated lesions starting from the lymphoproliferative. Disorders to other primary tumors in the mediastinum or benign lesions regarding epithelial or metastases. The material you collect with the normal approach is good in the majority of the cases. We don't know in the near future. Now we are using NGS analysis for all tumors in a primary or secondary particularly tumors in the thorax. I don't know exactly what will be the role of this new technique in assessing the molecular profile of tumors, because of course, you have much more material compared to the normal EBUS TBNA.

Dr. Froemmel: Dr. Hari, what was your pathologists first reaction to this new sample?

Dr. Hari: Definitely. My pathologist, especially when it comes to malignant nodes or metastatic disease. They'll be more happy because size is a very big advantage here. We definitely get more samples than the conventional needles, but we have to see being TB endemic country how this technology evolves. Especially, I am more interested in patients with TB lymphadenopathy, where conventioal EBUS-TBNA comes negative and then we have to see the cryo TBCNB can be superior to the conventional TBNB to that aspect.

Dr. Froemmel: Do you provide your pathologists additional information when he gets a cryo TBNA sample?

Dr. Hari: Yeah, we specifically tell them like we are going to do a cryo or TBCNB in these patients and then keep them informed. With our samples, what we have processed as professor was discussing. We were able to demonstrate monitor markers in all our samples when we performed EBUS-TBCNB.

Dr. Froemmel: Professor Poletti, when you think of the rapid on site evaluation, do you think that we need to go for a heterologous approach, meaning performing needle biopsy and cryobiopsy in the same patient?

Prof. Poletti: The question is that if you still use a ROSE analysis of the material even during the cryo medistinal lymph node. The answer is yes. We tend to reuse those approach in all cases. And we have some experience now, not in the mediastinal biopsy, but in the biopsy of the peripheral lesions of the lung using 1.1 cryoprobe. And we have some experience with the ROSE. Using this material if you wait a little bit, and you can just smear one of the biopsy in a slide. You can have those analysis of the material. We don't have this experience with the cryobiopsy in the mediastinum, but in the periphery we have already this kind of experience. But I suggest to use ROSE always because first of all, you know, if you are in the right position, if you collect lymphocytes or other specific material, but you also need this information to address further investigation. If you need cytofluorometric analysis or you need some kind of specific immunohistochemistry or molecular analysis, yes.

Dr. Froemmel: When you say we can use samples from cryobiopsy for ROSE, is it the other way round possible to increase the yield of needle biopsy when you, for example, increase the number of back and forth movements of the needle inside the lymph node? Dr. Hari, what do you think?

Dr. Hari: I think this is very interesting to look at like a ROSE maybe not far looking at the diagnostic differences, but definitely shortening the procedure time we use but with evolving technologies like imprint cytology. And also, as Professor was mentioning, doing ROSE from the samples they are getting from the peripheral TBNA. And I think that technology when it applies to EBUS-TBCNB as well, it might be useful at this moment. We also tend to do ROSE and then followed by EBUS cryobiopsy for histopathological analysis. I think in future more data is needed on how many number of cryobiopsies are needed for diagnosis. On that, one thing has to be standardized with time and more cases, case numbers. And again, should this procedure be followed by EBUS TBNA or not, that question again needs specific answers in the coming future.

Prof. Poletti: I agree with Dr. Hari we need, of course, more information and competition between regular EBUS TBNA and cryo TBNA. And we need to assess exactly what is the best approach and to differentiate utility of the two different approaches. Yeah, but we need much more information, a larger experience, you know, to have this and we need prospective studies.

Dr. Froemmel: So with that being said, thank you very much, Dr. Hari Kishan and also Professor Poletti for this interesting discussion. It was great to hear you as two of the innovators of this technique discuss the advantages and disadvantages, and we look forward to further evolvement of the technique, to further data and to see where it finds its niche in the diagnostic algorithm. Thank you very much, gentlemen. And we hope to hear from you.

Dr. Froemmel: Prof. Poletti and Dr. Hari Kishan currently recommend transbronchial mediastinal cryobiopsy to any bronchoscopist who has experience and confidence in performing the EBUS-TBNA. In cases of granulomatous and lymphoproliferative diseases, the features of biopsy specimens procured using this technique can prove to have advantages over those provided by needle biopsy. Further standardization in regard to accessing lymph nodes, airway management, and anesthesia protocols, as well as patient selection is yet to move forward. Crucial additional data will potentially bring answers regarding such issues in the future.

Dr. Froemmel: Thank you, Prof. Poletti and Dr. Kishan, for sharing your experience, which will be beneficial for other bronchoscopists as well and Niklas for being here today. Have a look at their latest study in Respirology Case Reports 2021. Stay tuned for our upcoming episodes.

Dr. Froemmel: Thank you for listening to our Medical Insights podcast, a podcast by the Erbe group. To get further information and view our terms and conditions, please visit our website at www.erbe-med.com.