Good morning, everyone. We're gonna get started in just a few minutes. Thank you all for joining us. Good morning, everyone. We're going to get started in just a minute or two. Okay, welcome everyone. My name is Vance Broach and I'm a gynecologic oncologist at Memorial Sloan Kettering Cancer Center in the United States and I'd like to welcome everyone to today's surgical education webinar on the management of cancers in pregnancy. We are absolutely thrilled to have you with us today. I want to mention a few housekeeping notes relevant to the Zoom platform we're using for this festival. First please, for best viewing, adjust your screen to the full screen mode in the top right corner of your screen and adjust your settings to fit to window so that the entirety of the presentation is visible to you. Second, the quality and clarity of the video presentations and speakers today are directly linked to the speed of your internet connection. High speed and wired connections are best for viewing these presentations and if the quality of your video is poor during the presentations, this webinar will also be available on the IGCS education portal in a timely manner following the presentation. We have an absolutely incredible panel today who will be sharing their expertise on the management of cancers in pregnancy. There will be ample time for discussion today so we encourage you to submit questions via the Q&A feature at the bottom of your screen and we'll do our best to address as many of your questions as possible. I'd like to thank Dr. Rathusilani who is our ghost panelist today and he'll be helping to monitor and field your questions and I'd also like to thank the IGCS staff and particularly Mandy Hansen and Susan Ralph who make this possible. As you can imagine, an enormous amount of behind-the-scenes work goes into allowing things like this to run so smoothly and we are so lucky to benefit from the expertise and work of the IGCS staff. Now it is my honor to introduce today's speaker. Joining us are Michael McHale who's the division chief of gynecologic oncology services at UC San Diego Health in California. Emily Vanderhaar is the assistant professor of obstetrics and gynecology at Weill Cornell Medical College of the Cornell University in New York and Dr. Al Covins is the chair of gynecologic oncology at the University of Toronto Sunnybrook Health Sciences Center in Canada. And without further delay, we'll begin our session with Dr. McHale presenting on the management of placenta accreta. Dr. McHale. Thanks, Vance. I'll try to share my screen here. Okay, good morning everybody from San Diego. First and foremost, I'd like to thank Vance and Ritu and Mandy and the entire IGSC team for inviting me to participate in this morning's webinar. I was asked to review with you and give you kind of a 30,000 foot overview with respect to placenta accreta spectrum, specifically highlighting updates, demographics, some of the more common morbidities that are associated with this spectrum and then lastly to focus on evolving management strategies and at that time I'll review with you a more I think novel approach that we adopted at our institution in 2018 with respect to interoperative management for patients with suspected placenta accreta spectrum. The placenta accreta spectrum is inclusive of placenta accreta, increta, and percreta and this term really has supplanted the more traditional term of morbidly adherent placenta or abnormally invasive placenta. Of course, placenta accreta continues to be the most common followed by placenta percreta and then increta. There is clearly a direct association with the invasiveness of the placenta and morbidity. In fact, some reports have suggested significant morbidity with placenta percreta to be as high as 80 plus percent and clearly this is a problem that is continuing to evolve and become more significant in multiple institutions and even community-based practices. A recent meta-analysis of a pool of prevalence had demonstrated a rate of 0.17 percent, clearly much higher than what had been initially reported the first time we looked at prevalence back in the 50s at 0.003 percent. The obvious question is why and I think most of us understand there's a direct association between the increased rates of cesarean sections and the incidence of placenta accreta spectrum. In the 1980s, placenta accretas occurred about 1 in 1,200 or so pregnancies. In 2016, this rate had increased to 1 in 333 and in fact in 2020, some recent statistics had demonstrated this rate was as high as 1 in 285. There are clearly well-recognized morbidities that are associated with placenta accreta spectrum, the most common of course of which include hysterectomy and hemorrhage requiring red blood cell transfusions, but when we really kind of dial down and look specifically at placenta accretas, we could see that the rate of large volume red blood cell transfusions, i.e. greater than 10 units, is approximately 10 percent, ureteral injuries 10 percent, and infection as high as 30 percent. And there are clearly risk factors that are associated with the spectrum. A recent meta-analysis of 46 studies identified the following risk factors, all of which had odd ratios greater than 2. The highest odd ratios were associated with placenta previa in combination of a prior cesarean section or with a greater than one cesarean section. Additionally, in women that have placenta previa and a prior C-section, the number of prior C- sections have a significant impact on the risk of placenta accreta spectrum within that current pregnancy. So for instance, in a patient who presents with a placenta previa with two prior cesarean sections, the risk estimate for a placenta accreta spectrum, and more commonly, a placenta procreta, is as high as 40 percent. So with respect to strategies and management, diagnosis obviously is essential, and early diagnosis is important for appropriate counseling, and so that management can be dictated or directed very early in the course of pregnancy, especially if one was to expect an untoward outcome. Transvaginal ultrasonography and transabdominal ultrasonography and pelvic MRI continue to be the hallmark diagnostic strategies that are employed worldwide. There are now recognizable, clear sonographic appearances that are suggestive of a placenta accreta spectrum, specifically low implantation within the first trimester, placental lakes, myometrial thinning. This is an example of transvaginal ultrasonography, and if we look at the image here on the far right, clearly this looks like a normal implantation. SAC is high in the fundus, well away from the cervix. In contrast to this image of a patient that we actually managed that I'll highlight a little bit more for you later in the presentation, this ultrasound was obtained at approximately six weeks, and you can see here clearly the implantation is very close to the cervix. There's a little bit of hemorrhage. This was a patient who ultimately was diagnosed with a cesarean scar pregnancy that eventually evolved into a placenta accreta and unfortunately led to a maternal death. This is an example of myometrial thinning. You could clearly see here that there's the normal loss of the normal myometrium between the bladder and the uterus. Again, here, a loss of myometrium between the bladder and the uterus in comparison to what looks like your normal hypoechoic myometrium or this clear space that's usually indicative of a normal implanted placenta. Additionally, we'd like to see these nice bright lines that clearly delineate the differentiation between the uterine sclerosa and the bladder. However, in contrast, you can occasionally get this interruption in the sclerosa, and here you see normal sclerosa, and then there's a loss of sclerosa here, suggestive of a placenta accreta spectrum, or more specifically, a procreta. Then to complete this series of images, this was the same patient where clearly it was suggestion here of a loss of myometrium. When we look down at the bladder, there was loss of sclerosa and suggestive of bladder invasion. Then to the right, I apologize, to the right, this is the final path specimen after the hysterectomy with histopathology confirming a procreta. There was, however, no invasion into the bladder. Similarly, MRI appearances have evolved, and there are now a particular pattern that is sought by our radiologists that would suggest placenta accreta spectrum, the most common of which include uterine contour bulging, T2 dark bands, which I'll highlight for you later on, bladder tenting, and then direct invasion. Here's a series of T1 and T2 weighted images, and I'm bringing your attention to the far right. If you look at the far right, clearly here's placenta here, and if you look between these two arrows, this represents normal myometrium indicative of a normal placentation. In contrast, what you're seeing in this series of images is that there is a loss of that myometrium in bulging within the lower segment and laterally suggestive of a potential placenta accreta spectrum. Again, what we're looking at here on the far left, you could see a loss of myometrium and a suggestion that this placenta is abutting the bladder. Fortunately, on this T2 fat diffusion image, you could see the fat plane is maintained, and so not suggestive of a bladder invasion. In fact, this patient did also have a procreta as one of our original cases, but again, no invasion of the bladder. I show these series of images because this was a patient that led to a modification in our interoperative management protocol, and this was a woman who the original ultrasound I had demonstrated to you that had shown a very low implantation around six weeks. She was scanned multiple times, again, very suggestive of a cesarean scar pregnancy, which again evolved into a procreta, but some suggestion that maybe this pregnancy actually had evolved the cervical, the cervix. There was a great deal of concern regarding the imaging findings very early in her pregnancy and a suggestion to move forward with a termination based on these imaging findings. This is a highlighted view of what was most concerning for us. This represents the cervix. Clearly, you see this very disordered pattern of placenta. Here are those T2 dark bands that are usually hallmark signs of a placenta accreta spectrum, or in fact, a procreta. This woman actually had involvement of the cervix and the parametria. I bring your attention to this image very early in her pregnancy, and what you notice very clearly is the fundus is empty. We shouldn't see an empty fundus as someone reaches their second and, of course, their early third trimester. Everything is really distorted and pushed inferiorly within the uterus, again, suggestive of a pregnancy that initiated at the cesarean scar and potentially even at the cervix. Interoperatively, this is what we identified and what should be most noticeable for all of you is that the fundus is empty. There are no fetal parts in the fundus clearly. This is her large placenta that had invaded to the parametria and the cervix. Despite two gene oncologists, cardiothoracic surgeon participated in this woman's care. Unfortunately, her outcome was unexpected, and there was a maternal death. This made us pause and began to think about the cases that we were seeing in our institution that were being referred from multiple different sites throughout the county. It made us rethink what some of our management strategies actually should be and should we modify what we currently were performing as part of our routine interoperative structure for patients with presumed placenta accreta spectrum. Before I launch into that, oh, I don't know what happened. Hang on, people. Dr. McHale, I have your slides. I'll start sharing the screen, okay? Are we still there? I'm actually just getting it up again. That'd be great. Thank you very much. Dr. McHale, I'm going to send you a text if you can check your phone in a second. We'll come back to you. We'll move on to the next presentation and come back to you in a second. Sorry about that, everyone. We'll make sure that we get the second half of that talk presented. Our next speaker is Emily Vanderhaar, who is a maternal fetal medicine specialist from Cornell University. Dr. Vanderhaar, unfortunately, is not able to join us live today, but her talk has been recorded and we're very happy to present it for you. We'll go ahead and present that and then come back to Dr. McHale. Again, apologies for the technical difficulties. It is my absolute pleasure to introduce our next speaker, who is Emily Vanderhaar. She is an assistant professor of obstetrics and gynecology in the Division of Maternal Fetal Medicine at Weill Cornell School of Medicine of Cornell University. She'll be discussing the management of adnexal masses and ovarian cancer in pregnancy. Dr. Vanderhaar. Thanks so much for having me. As you mentioned, I'm going to be discussing adnexal masses in pregnancy. As many of you may know, it's rare. It's probably seen in about 0.1% to 2.4% of all patients. Malignancy is diagnosed in about 1% to 6% of those, so even less commonly, and often identified incidentally, either at the time of a routine ultrasound or during cesarean section. It's actually one of ovarian cancer's, one of the most common cancers in pregnancy, behind breast, thyroid, cervical, Hutchins lymphoma, and then ovarian cancer, so it's number five. And we tend to think of them either as these adnexal masses as either benign or malignant, and then complex or simple in appearance. When you think of benign neoplasms, kind of the first thing you want to look at when you're looking at an adnexal mass, when we diagnose them on our ultrasounds, we want to see, do they have complex features or do they not have complex features? And so simple adnexal masses, or sort of masses without complex features, are typically round or oval in shape, have anechoic fluid, thin walls, and no real internal flow with color doppler. Those tend to be functional cysts, either follicular or the corpus luteum, serous or mucinous cystadenomas, or can be a hydrosalping, so those can also look complex in appearance as well. And the good news about those is, a large majority of those actually resolve spontaneously during the early part of the second trimester, so those are cases where you really can watch to see what happens. Those masses that have complex features tend to have solid components, can have these floating globules, although that is rare, but it's kind of diagnostic for a teratoma, can have hyperechoic foci within the cyst, thickened walls, septations, fluid-to-fluid levels. And then the types of masses that these typically are associated with are things like a mature cystic teratoma, a hydrosalping, so that maybe has septations, the gluten cyst, endometriomas, multilocular cystadenomas, extrauterine or ectopic pregnancies can sort of look like an anexal mass, luteomas, or even pedunculated leiomyomas. So these all have complex features but are still typically benign. And then you have the malignant neoplasms. There's kind of three major groupings, epithelial, ovarian tumors, which really make up about half, germ cell tumors, which take up another about 33%, and then stromal and kind of other rarer things tend to fall, are a little less frequent, and they're around 17% of the time. Here's just an image of what sort of an epithelial ovarian tumor looks like. You can see that it's got some anechoic fluid but there's these little excrescences kind of within the cyst itself that look a little bit concerning. Half of the time, these epithelial ovarian tumors are sort of a borderline or low malignant potential, and the rest of the time, they're really a true invasive epithelial cancer. There are tumor markers associated with these, the ones that people probably most commonly think of, CA-125 and CA-199. Germ cell tumors can also be seen, this is an example of a dysgermanoma, which is kind of the vast majority of the germ cell tumors that we typically see, but there are other germ cell tumors such as endodermal sinus tumors, immature teratomas, or mixed germ cell tumors. Tumor markers for those tend to be LDH, AFP, and HCG. And lastly, the sex cord stromal tumors, which are the kind of more rare tumors that we tend to see. Granulosa cell tumors, which make up about half, or sirtolylactic cell tumors, and then other unclassified kind of rarer stromal tumors can also be part of this grouping of cancers. Tumor markers for these tend to be inhibin A, inhibin B, estrogen, and testosterone. So as you can see, from all of those things, we really don't recommend routinely drawing tumor markers preoperatively when you find an agnesal mass in pregnant patients, because a lot of them, the AFP, beta-HCG, CEA, CA-125, are actually involved in fetal development and maturation and can be abnormal or elevated kind of normally for patients, and so they're not gonna give you a lot of information preoperatively. However, if you do make a diagnosis kind of post-dissection or post-resection, I should say, you can send them to kind of follow for patients and kind of continue their management. So how do you manage patients with an anexal mass? There are definitely patients that you can manage expectantly, and I think we discussed a little bit previously. It's really those anexal masses that don't have any of those complex features or concerning features, and as long as the sonographer is reasonably certain, and also the doctor reading the sonogram, that the neoplasm is either a follicular cyst, some kind of corpus luteum, an endometrium, or a mature teratoma, you can watch those closely, follow with ultrasound, and not kind of take those patients to the OR more urgently during pregnancy. But which patients should undergo surgery? Those tend to be patients who are out of their first trimester and have really large masses, greater than 10 centimeters, or if they have characteristics that we are possibly concerned for, or suspicious for, malignancy. So solid, can maybe have solid and cystic areas, papillary areas, or those expressances, or have multiple septae. You may be more concerned, and we may discuss whether or not surgery during pregnancy is kind of the best option. Timing of surgery is really important. So typically we'll try to recommend for these patients that they undergo surgery kind of more early in the second trimester, as most of the functional cysts will typically have resolved by this time. Organogenesis is really mostly complete. And the hormonal function, importantly, of the corpus luteum has really been replaced by the placenta. So you don't need to think about doing progenitor surgery or doing progesterone supplementation or replacement at that time. And lastly, spontaneous pregnancy loss, like an early miscarriage, is much less likely during this time period. So you can be less concerned about a patient erroneously attributing their loss of pregnancy to the surgery itself. General principles of surgery. Typically we do think overall laparoscopy is preferred, at least in one meta-analysis of four studies. When they looked at laparotomy versus laparoscopy for anexal masses in the second trimester, they found that laparoscopy led to better surgical outcomes, although it was also associated with sort of smaller masses and a slightly longer operative time. And then you do also need to think about, in general for pregnant patients, and it's always good to just kind of put on your list, that pregnancy is a thrombogenic state. And so you do need to think about thrombocryphalaxis. There are different recommendations from different societies. The Society of American Gastrointestinal and Endoscopic Surgeons recommends mechanical alone, whereas the American College of Chest Physicians discuss either mechanical or pharmacologic prophylaxis. And I think you could do either, depending on the length of surgery and kind of how significantly concerned for cancer you are, but you should be thinking about some kind of, you know, thrombocryphalaxis during surgery for these patients. The other really important things to think about are sort of more specific to the gravid uterus. So you wanna make sure that your positioning is appropriate, especially after 16 weeks. You wanna make sure there's a leftward tilt. You wanna avoid that significant compression of the aorta and vena cava. You can even do a left lateral rotation of the operating table to try to help displace the uterus. If you're doing laparoscopic surgery, you wanna make sure you're doing an open entry technique versus the varus in the left upper quadrant, because if you do an entry into the umbilicus, you may actually perforate the uterus, which would be catastrophic and you could have significant hemorrhage and also damage to the pregnancy. You don't wanna use a uterine manipulator, which obviously I'm sure no one would do, but you wanna just, you can use a sponge stick if needed to help kind of maneuver the uterus. You wanna make sure that your intra-abdominal pressure is maybe a little bit less than what you would typically use in a laparoscopic case. So between eight to 12 millimeters mercury, you really don't wanna go above 15. And then for anesthesia, you wanna make sure that they're monitoring the end tidal carbon dioxide, just to make sure that they're avoiding respiratory acidosis because that can really affect the fetus. So if you do suspect maternal acidosis, you can do some immediate hyperventilation and decrease intra-abdominal pressure to try to improve placental perfusion and kind of improve fetal outcomes. So I have just a really quick case that was recent that we saw of a patient who presented kind of early in her pregnancy for her nuchal translucency, which is typically around 11 to 12 weeks and was found to have this incidental six centimeter left adnexal mass. She hadn't noticed any discomfort, no symptoms. The overall, the mass appeared like this. This is, can you see my pointer here? Let's see. This is actually the uterus. This is the gestational sac. There is a fetus in there. You just can't see it in this image. And this is that left adnexa with sort of two smallish cysts that kind of all together look around six centimeters. You can see they're mostly anechoic fluid, maybe slight thickening on the small, but overall relatively without major complex features. Suspected to probably be an endometrioma based on appearance and some of the kind of layering here. But given the size and given her gestational age, the decision was made to kind of continue to monitor and see how things went moving forward. So she had her followup anatomy ultrasound around 20 weeks. And unfortunately at that time, the mass really was noted to have enlarged. There was increased thickening, some vascularity. You can see on this image, it's actually quite a bit bigger and you can really see the color flow here. It's starting to look like there's some mass kind of effect being like, there's some feeding vessels that look like maybe they're actually within the cyst itself. So given these findings, kind of after discussion with the patient about kind of the risks and benefits of anesthesia and surgery, the decision was made to take the patient to the OR for diagnostic laparoscopy. She actually underwent a leptovarian cystectomy and they sent a frozen sample. And unfortunately for her, it returned back likely endometrioma. So they were able to finish the case. They had set washings and everything ahead of time, but they were the finished case. She went home post update zero. And the final path actually just came back as an endometriotic cyst, which was great for her. She's actually still pregnant already 30, I think five or 36 weeks and doing really well. So this just kind of a quick example of, usually these are usually benign when we catch them. That's the majority of these cases, but you wanna make sure that you're being careful because they can find malignancies and we wanna make sure we're doing the right things for patients, regardless of whether they're pregnant or not, like a surgery may be the most important, most appropriate thing for them. Questions? Okay, that was an absolutely spectacular talk. Thank you so much. And I really learned so much just from listening here. One question that I had was about fetal monitoring during the procedure. How do you approach that and sort of what are the principles you apply? It's a great question. It depends a lot on gestational age. So, obviously sometimes, ideally we do these procedures in the second trimester, we think it's the safest. And at under 24 weeks, we really don't recommend continuous monitoring of any kind because there's really no fetal interventions that can be done. So typically we'll do a heart rate check, obviously before the case, and then after the case to kind of reassure patient and everyone that baby did okay during the case. If you discover these masses later in pregnancy, it depends a lot on gestational age, but you may have to do some kind of continuous fetal monitoring depending on the patient's wishes. So it becomes kind of a multidisciplinary discussion about what's possible and what the patient's wishes are for resuscitation depending on the gestational age at the time of the surgery. Okay. And then just one other question I had that's maybe a little bit, kind of the next step after a patient, unfortunately, let's say somebody was diagnosed with a malignancy and would have otherwise required treatment like chemotherapy or some other post-surgical treatment. How do you approach that and in what circumstances would that be appropriate or how does the circumstance of pregnancy affect that? Obviously it's a very rare scenario, thank goodness, but in those rare scenarios, how might you approach that? It's a good question. So actually for most patients, it depends on obviously what the mass looks like. And sometimes if there's a large concern for like an underlying neoplasm, we'll even discuss with patients about whether or not like a neoadjuvant chemotherapy would make sense. But you can do chemotherapy during pregnancy. We recommend not doing it in the first trimester, mainly because of all the organogenesis that's happening. And then you would work with your gynecology, oncology partners and the medical oncology people to discuss kind of what the best regimen for that specific tumor is and kind of how to best tailor it for like safety for baby. But there are a number of chemotherapy regimens that we do use routinely in pregnancy. Typically for those patients who need chemo, then you discuss delivery timing because you wanna make sure that they are not having issues with like leukopenia or other things kind of close to delivery. And so you'll time your delivery kind of at the end of kind of one of their cycles. So a couple of weeks or three weeks out sort of where they're past their nadir. And then you'll also just have to time it with when they think they need like further therapy or even further surgery. You may deliver them a little bit early too. Gotcha. Okay, well, what a spectacular talk. Thank you so so much. We're so appreciative of your time and such a wonderful discussion. Thank you for having me. Okay, so I think what we're going to do at this point is go ahead and switch back to Dr. McHale's presentation, which I believe is we're back up and running and and then if there are questions related to the previous speaker I think we can try to field them at the end. And, but we'll go ahead and proceed on with with Dr. McHale. Great, thank you. I apologize everybody you think after a year of doing these zoom meetings that we would have seen every glitch that was obviously a first for me so where I left off was with this case and this again was a patient unfortunately had a maternal death, and it really made us pause and rethink our approach with respect to intraoperative management for placenta creative spectrum. So, as I mentioned earlier, the strategies for managing this disease as have been evolving and clearly early diagnosis is important. The primary goal of therapy, obviously is reduced blood loss and morbidity. One of the strategies that has been demonstrated in multiple studies has been the multidisciplinary team approach which we, we typically have been utilizing at our at our institution. Some of the, the studied pre and interoperative management strategies that many of you probably utilize at your particular hospital and they include internal LA balloons that now the percute percutaneous Eric bloom placement and rebella. At our institution we had routinely been utilizing internal LA balloons for over almost two decades, and as many of you are aware these are placed prior to surgery in the interventional radiology suite. After delivery of the of the fetus. The balloons are typically inflated at the discretion of the surgeon, but there are certainly some some issues and some shortcomings with respect to this approach clearly. They will not affect blood flow that's being directed to the placenta in the uterus from collaterals that are originating from say the ovary or the external aliex and our interventional radiologists have long felt that this has been the area that needs to be addressed, and that these balloons, more than likely we're not facilitating some of the outcomes that we are hoping for. This has been studied in multiple retrospective and prospective evaluations the data has been mixed interpreting the data is relatively challenging because that most of the populations have been very heterogeneous. Our experience was first reported in 2018 there's 117 patients 59 of which had balloons place. And there clearly was a reduction in mean blood loss and those with or without balloons as well as there was a decrease in the need for our massive transfusion protocol. Of course this had been what we've been utilizing for for quite some time. As I mentioned, there's evolving data looking at aortic balloons, clearly some of the initial studies have demonstrated are relatively safe and acceptable safety profile, there are still some technical challenges with the utilization of these aortic balloons, recent meta analysis analyze approximately 500 patients. There was a range of of cases within that placenta create a spectrum and there was clearly a reduction in in blood loss and of course, this may be perfectly suited for particular institutions but it might not be reproducible or portable from from center to center and I think more to come with respect to the use of aortic balloons interoperatively or at times preoperatively. So as I mentioned to you. After that case we took a step back and we said what can we do better. And our intervention radiologists have felt that maybe we should be utilizing our hybrid room in the main operating room and we should be performing multi vessel interoperative embolization and what came from this is what we now call our past time protocol which stands for placental creative spectrum treatment with interoperative multi vessel embolization one of our fellows decided this was going to be this is subsequently become the name of the protocol that we currently utilize. It's a busy slide but you can see there's a lot of interaction between multiple different services, again maintaining our multidisciplinary approach early diagnosis is really essential for the manager of these patients and so radiology kind of starts this cascade and if there's any evidence suggest that a placental creative spectrum. These patients are seen by our high risk obstetricians, who then, if they concur with our radiologists. These cases are then referred to do an oncology and they're all presented our multidisciplinary gynecologic oncology team report conference with our maternal fetal medicine specialist and our MRI body imagers, and the decisions made if to move forward And of course, there are a number of other touch points within this this cascade including a console with anesthesia and Nick you. The protocol then utilizes again our hybrid room the main in the main of our patients are prepped for abdominal surgery and angiography intervention radiology will place a sheet for femoral access to complete their, their selected arteriograms and embolization. The baby is delivered by our maternal fetal medicine team the history is closed placenta is left in situ. And then our team takes over and performs multivessel embolization typically using polyvinyl alcohol particles. After completion of their embolization they they perform digital subtraction and geography really to better assess it we get what we really want to get before you proceed with their hysterectomy which is then completed by the gynecologic oncology team to the left you can see a nice arteriogram prior to embolization. Clearly you could see this very apparent crazy kind of appearance to all the vessels that are supporting the placenta. This is a catheter and selectively cannulating the uterine artery and you could clearly see this is the uterine artery but you notice here is a blush and a lot of flow to the placenta that's obviously originating from from collaterals that that would not be controlled by placement of a balloon in the internal iliac artery. This is the MRI. Again, we reviewed this previously but placenta. This was a patient who had evidence on imaging of a procreate a clearly had evidence of procreate intraoperatively. Here's her pre embolization arteriogram, and this is just looking at the, the left anterior side and you could see all of this is gone. All of this is gone after our selective embolization. So in 2018 we move forward with this this protocol and after our first 15 pastime cases, we wanted to objectively compare in a two to one ratio with our match controls our match controls are those patients that had placenta create a spectrum that was diagnosed in 2010 and 2017 treated with our traditional protocol again multidisciplinary and alien balloons. This diagram illustrates the differences between the two protocols and I'm going to highlight for you. One of the things that's probably one of the negatives about this protocol by using interoperative embolization is this time. to complete the embolization prior to us, stepping in G1 oncology to complete the hysterectomy and I can tell you I've been in in every one of these cases and you're sitting there and you're like God, why are we doing this, but once we get started and the blood loss is minimal, it really demonstrates for me and for my colleagues, how impactful. Novel intervention has been with respect to managing these patients, including some of the more high risk patients. This is our demographics that I only want to highlight the following these are these are really significant cases in that 46% of them almost 50% of them were procreators or procreators with invasion. So this wasn't a low risk patient population that we were investigating or that we typically see within our institution. If you look at EBL and you compare the past time protocol to our standard or control there was a statistically significant reduction in EBL, and although this was not statistically significant, the massive transfusion protocol or use of more than 10 units of PAC cells in 24 hours was zero in the past time protocol so that our new protocol, compared to five within our control population. So I think this is a novel approach that clearly has demonstrated a minimization of hemorrhage and maternal morbidity. It requires multi vessel embolization and that this is has been safe and feasible with no untoward effects from the multi vessel embolization. It clearly is another potential management option it not one size fits all it might not be something that can be performed in all institutions. At this point, the American College of OBGYN and the SM FM have yet to endorse any specific surgical approach and again, it really is clear why and it's because there hasn't really been a clearly suggestive approach that is better for all and maybe very needed to be tailored for each institution. Clearly there are some limitations to our novel approach and that is the time it takes for the embolization, as well as the need for a hybrid room to perform interoperative embolization. With that, I'll close I thank you for your time again I apologize for our little halftime, and certainly welcome any questions or suggestions. Thank you so much. What an incredible talk and thank you for sharing what your experience. We have a couple of questions that happy to ask and we can go over if you have a moment here so one of the questions was about the ideal imaging in in these cases, you know his ultrasound best always get an MRIs or time when MRIs unnecessary. I mean, how do you approach that. MRI is best in the early and very early trimester and that really kind of points to where is this pregnancy and is this really going to evolve into something more significant, we will do an MRI in every case. But that's one of the problems with this placenta creative spectrum you know it's, you may look at an MRI and say this looks okay and then we've all been there we get in the OR and it's not okay or the MRI looks really suggestive of something that is bad it's, it's, it's, it relates to that but we will complete an MRI around 16 to 18 weeks for every one of these patients. And that's typically when they'll be presented at our multidisciplinary tumor board. Gotcha. And another audience member asked about your experience with leaving the placenta behind in cases of procreate for fertility preservation trying to preserve the universe. I just didn't for the sake of time I didn't present our data and we do have a series of patients where we've left it in sight to some of which for preservation, some of which, because the amount of involvement of the pelvic sidewall was so substantial that we felt that her risk for mortality was really high and when your vascular surgeon says, I don't know if I could help you with this based on what I'm seeing. We've been, we've had a great deal of success. And we've also had cases where, you know, one to two weeks post cesarean and leaving the placenta inside to DIC has evolved and unfortunately they've, they've had to. They've had to move forward with an interval hysterectomy which of course is has its own set of challenges because now you've, you know, physiologically change the playing field a bit so it's certainly something to consider, certainly something to consider, especially if you have a morbidly adherent placenta that is clearly clearly involving structures that you don't think that you can manage appropriately and properly without significant morbidity and mortality. And one last question that has come in. Do you have any thoughts or feelings about using a one versus two layered closure at the time of cesarean section for preventing future procreative. You know I my thought I, yes, but I don't know if it's substantiated by any data that would support that there is a reduction in risk I know there's been some retrospective reviews that have suggested maybe two layers would improve that in outcomes and decrease the incidence of placenta creative spectrum, but I could tell you that it's really not well understood at this point. Right. All right. Thank you so much for an absolutely incredible talk. We were so appreciative. I think what we'll do at this point is move on to Dr. Covins presentation of the management of cervical cancer and pre invasive disease and pregnancy, Dr. Covins. So thanks everybody for inviting me to give this talk. Let me bring my presentation up. So I'm not going to really discuss pre invasive disease, as I thought this was really more relevant to what individuals wanted to hear. With respect to pre invasive disease for the most part, if that's definitively what they have then management tends to be delayed till postpartum. It's only when there's a diagnostic question of whether there's invasion or not that that would lead to procedures such as comb biopsy or leap or something. Just some background information here. What I keep on stressing to the trainees and to the patients as well is that in this scenario, our goal number one is to cure the cancer. And I think that's important because it's not necessarily just to preserve the pregnancy or fertility. Because in my mind, and maybe I'm showing a little bit of bias, but I think that's better to have a cured woman with one less child than a motherless baby. And it's important to note that most deaths in cervical cancer and pregnancy come from the node positive patients. And that's important and we're going to come back to that in a couple minutes. In general, the cure rate is no different stage for stages non pregnant patients, as long as there's no excessive delays in therapy. So as you're going to obviously see, there is no large studies in this scenario. For the most part, what we have done is amalgamated case series and case reports and various areas of data to come up with some guidelines. So the important considerations in cervical cancer and pregnancy is, and these are not necessarily in any particular order, but does the patient want this pregnancy? Maybe it's desired, maybe it's not, and that may influence how you're going to manage the pregnancy. How far along is this patient at the time of your diagnosis? What are the patient's future fertility wishes? Is this her last child? Does she want many more? That's going to influence some of your decision making. And obviously the typical factors that are associated with all cervical cancers, that is, what's the clinical stage? What's the pathology? If you've done a biopsy or a cone or a leap, do you have some depth of invasion? Do you have the histological subtype? Whether there's lymphovascular space invasion. Fair to say most of these patients would be staged through MRI. And most of these patients just purely because of their age tend to be 1B or less. So let's talk about some very easy scenarios. The pregnancy's not desired. It's a simple way to manage up until the mid-trimester. And that would be with a radical hysterectomy and no dissection. If you're after the mid-trimester, it's a little more complicated. And at that time you need to consider whether you're going to give some chemotherapy and cesarean section. Obviously this involves a broad range of specialty involvement, including maternal fetal medicine and neonatology. Usually you want to intervene at the earliest, safest gestational age. And as I'm going to indicate a little later, that usually in most places tends to be around the 32 week range, give or take a week or two. No dissection is very important because as I mentioned, the patients with positive nodes do not do well. And you may be a little more aggressive in management if you knew the patient had node positive disease. That's not easy with a big uterus. And so, I've put down here less than 24 weeks. It obviously depends on the kind of uterine size as to whether or not you can do a node dissection or if you wouldn't consider termination of the pregnancy, particularly if chemo rads are planned. Microinvasive cancers, exact same management, not a huge deal. Those patients are universally cured. Another big question is laparoscopy versus laparotomy and sentinel lymph nodes versus lymphadenectomy. So with respect to laparoscopy versus laparotomy, I would say this is predominantly determined by the size of the uterus and other typical factors, which would be identical to non-pregnant patients. So, a patient with huge fibroids and a cervical cancer with respect to patients who maybe have some preexisting lung disease or cardiac disease, those are all factors that you would independently make decisions about with respect to laparoscopy. With respect to sentinel lymph nodes, sentinel lymph nodes are very possible. They've certainly been performed many times. I've certainly performed sentinel lymph nodes in pregnancy several times. However, there is no tracer of ICG, technetium, patent blue that is officially approved or declared safe in pregnancy. So I can tell you that for the most part, the patients I've done tended to be ones that didn't know they were pregnant. And we didn't know they were pregnant until we operated on them. And all of them universally did well. And I've used all of those tracers on pregnant patients. And if you look at the literature, it's pretty hard to find, and I don't think you can find any really adverse effects different from the non-pregnant population. So, just to go through some of the scenarios, and it really amounts to the sort of stage or size of the tumor and the gestational age of the patient. So if we talk about stage 1Bs, and you're in the first trimester, then you've got a lot of options. You could consider a comb biopsy depending on the size or a tricolectomy and lymph nodes. If it's a 1B2, so, and I'm using the new staging system. So that's a two to four centimeter range. Obviously, termination of pregnancy is an option depending on the patient's wishes. Certainly nodes are much easier to do in first trimester. You could follow the cervical cancer if the nodes are negative, or if you're really concerned about it growing, I'm gonna give you some data on chemotherapy to shrink it. And some, despite that size of two to four centimeters would consider a radical tricolectomy. 1B3s surgery becomes less of a reasonable option. And the question becomes termination of pregnancy or nodes followed by chemo to shrink the tumor if the patient wants to continue the pregnancy. I will point out if nodes are positive, you really need to be aggressive. It's unclear whether the mortality rate with node positive pregnant patients is worse than non-pregnant patients. And it may be influenced by the issues of delay of therapy, but survival is not a given in the node positive patients. And just about every guideline you will read will recommend aggressive therapy. And by aggressive therapy, that usually means termination of the pregnancy if it's early or early delivery and getting on with definitive therapy. In second trimester, this is where you really need to involve the maternal fetal medicine people and the neonatology individuals to determine what is the earliest possible delivery date in terms of lung maturation and everything. So that's usually several case conferences discussing with the patient and family. And I'm gonna tell you probably that's gonna center around 32 plus or minus two weeks. And so if you are more than four to six weeks away from that 32 week range, that's a long time. And you may consider doing lymph node dissection pending the uterine size followed by chemotherapy. If you're less than four to six weeks, then you may consider just waiting and doing a cesarean section radical hysterectomy in nodes, again, depending on the size of the tumor and the future fertility wishes of the patient. Stage twos and threes aren't very common. For the most part, they're managed with either termination of the pregnancy followed by chemo rads or nodes and chemotherapy. That's an option, but most people would not recommend that type of therapy. And in second trimester, hysterotomy or cesarean section followed by either radical hysterectomy or chemo radiation. What about fertility preserving surgery? So we've certainly done, I've personally done a number of radical trachelectomies at early pregnancy and a different approach for patients who are later in pregnancy. So you can easily do a cone or trachelectomy. Now I've used the word trachelectomy and I don't mean to say simple trachelectomy versus radical trachelectomy, just trachelectomy as to whatever you think is appropriate given that tumor size. They can certainly be done in first trimester and early second trimester. Once you get past early second trimester, while it's still possible, it's not something I would recommend. You would be shocked how vascular that cervix and lower urine segment can become. You're looking at vessels that are two to three times the size of what you have in a non-pregnant patient. So not only is the bleeding increased, but also as you get further along in gestation, abortion or premature delivery becomes a little more likely. So in second trimester, what if the uterus is not terribly big, I consider doing lymph nodes. If they're negative, then deliver again at the earliest possible date and do a trachelectomy four to six weeks postpartum. So just some data on chemotherapy. So in fact, there is quite a fair amount of data of chemotherapy in pregnancy. Most authorities would certainly recommend avoiding chemotherapy in the first trimester due to organogenesis, even though there's no obvious fetal effects. There have been studies evaluating platinum levels in both umbilical cord and maternal levels. And they're in the order of about 25 to 65% of those that you've seen in maternal levels. In one series of over 200 patients with over two centimeter tumors, and these are non-pregnant, you can see what the pathological complete partial and progressive responses rates were. And I stress, this isn't clinical response, this is pathologic. So 33% of patients had no invasive cancer on pathology after chemotherapy, and 50% had a partial response. So chemotherapy is pretty active in stabilizing or shrinking cervical cancers. And it's fair to say that platinum, paclitaxel, doxorubicin, VP16, bleomycin are all, I use quotations, safe in pregnancy, none have been associated with any more adverse effects that we see in the non-pregnant patient. Having said that, it's sometimes very difficult to convince pregnant patients to accept chemotherapy for obvious reasons. So schematically, this may look a little complicated, but I've sort of drawn this up at the top, your clinical evaluation based on staging and pathology, and you can see stage 1A2, 1B12, 1B23, and obviously the bigger tumors that were created were B3s. And it's divided by the gestational age because that helps you determine sort of options for management. And at the bottom, as I say, if nodes are positive, you really need to consider terminating this pregnancy if it's early, or chemotherapy and delivery shortly because those are the patients that die. So these are the references I use for most of this. I thank everybody for listening and happy to entertain some questions. Okay, thank you so much for such a wonderful talk. We are, I'm getting some questions from the audience. One question that I had is, when you're approaching patients who are suspected or on exam, a concerning finding on an exam, just from the perspective of bringing that all up with the patient and the potential effects that might have on the pregnancy and that's a very emotionally charged and difficult conversation to have. What strategies do you have that sort of frame these sorts of conversations for patients so that they can kind of both understand the gravity of the circumstances in addition to the uniqueness of being diagnosed with this in pregnancy? It's a difficult issue. I think you usually need to involve the patient's family or partner or whoever else involved. And it would also depend on the gestational age. So if it was first trimester, then I probably might not necessarily get the maternal fetal medicine people involved or neonatology at that point in the discussion. And it would center around, obviously if you're talking about a frank invasive cancer, it's not a question of a diagnostic issue. They would center around whether the patient wanted to keep this pregnancy or not and what the options were. Usually when you're in second trimester, then things become more complicated in terms of, do you wanna keep this pregnancy? Do you wanna terminate it? And most patients, my experience is most patients wanna keep the pregnancy. And then it becomes a question of the risks of nodal involvement, whether you can assess that in an operation during pregnancy. Most patients are a little reluctant to accept chemotherapy in pregnancy and I can't blame them. And then it becomes a question of delivery as early as possible and definitive management or at least part of it. So it usually involves discussions on several levels over a period of time. It's not a one-stop shopping where you have a conversation and the decision is made. It's usually something that evolves over several weeks, particularly as you gain more information with respect to MR staging. Gotcha. One question from the audience, if you have a preference in chemotype, carboplatin versus cisplatin and taxol when patients are pregnant. So I don't have a lot of experience. I don't think anybody does, but in patients who I was going to give chemotherapy, I would probably just use single agent cisplatin. It will have the least amount of effect on blood counts, myelosuppression, although it will have a little more effect. There is reported fetal autotoxicity, so you just have to be careful. You obviously don't want to give any chemotherapy within the last three weeks before delivery for the whole platelet and neutrophil count, but that's what I would pick. Gotcha. And then one last question is about the type of termination that would be selected in patients for whom that's appropriate, whether a surgical or medical termination is the most appropriate in this setting. Well, I think it would depend on the gestational age and the tumor size. So, you know, a 1B1 or 2 first trimester, I would just do a radical hysterectomy. Obviously, if it was like a stage three in the first trimester, then you're going to either have to do a hysterotomy or a medical termination, depending on how early that pregnancy is. So it would depend on those two factors are the big issues. Gotcha. Okay. Well, I think we're at the time that we allotted for this, and I just want to take a moment to thank all of our speakers again for really outstanding discussions and talks. I'd like to remind all of our participants that this video will be available through the education portal by the middle of next week. You know, we do plan to continue surgical education offerings throughout 2021, and there will be ample surgical education as part of the 2021 annual global meeting, and we'll continue to offer surgical film festivals throughout the duration of the year. We'll keep you updated about the dates and the session details as that becomes available on the IGCS website and through emails. And I just want to thank again to our speakers and to all of you for attending, and I hope you all have continued health and safety in the coming year. Take care. Thank you.

cancer management

pregnancy

gynecologic cancers

cervical cancer

placenta accreta spectrum

management strategies

surgery

chemotherapy

radiation therapy

multidisciplinary approach