Intro
Thanks for listening to the GOSH podcast. GOSH stands for the Gynecologic Oncology Sharing Hub, an open space for real and evidence-based discussions on gynecologic cancers. We'll share the stories of gyne-cancer patients and survivors and hear from researchers and clinicians who are working behind the scenes to improve the lives of people with gynecologic cancers. Our podcast is produced and recorded on traditional unceded territories of the Musqueam, Squamish, and Tsleil-Waututh Nations. It is produced by the Gynecologic Cancer Initiative, a province-wide initiative in British Columbia with a mission to accelerate transformative research and translational practice on the prevention, detection, treatment, and survivorship of gynecologic cancers.
Hi, I'm Nicole Keay, and I'm Stephanie Lam and you're listening to the GOSH podcast.
Hi, I'm Almira Zhantuyakova. I do behind the scenes work for the GOSH podcast. Today I'll take over Stephanie and Nicole's place as a host. And you are listening to the GOSH podcast.
00:00:00 Almira
Dr. Paul Yong (MD, PhD, FRCSC) is a distinguished Gynecologist, directing the Research Program at the BC Women’s Centre for Pelvic Pain & Endometriosis. Dr. Young’s clinical focus lies in pelvic pain, with a particular expertise in endometriosis, painful periods, sexual pain, and associated bladder, bowel, and musculoskeletal issues. Dr. Yong's commitment extends to the academic realm, where he serves as an Assistant Professor in the UBC Department of Obstetrics & Gynecology.
His translational research endeavors include spearheading bio-banking initiatives for endometriosis, conducting gene sequencing studies to unravel underlying mechanisms, and investigating nerve formation in the pelvis as a potential source of pain. Beyond his clinical and research roles, Dr. Yong actively contributes to medical education, imparting his knowledge and experience to the next generation of healthcare professionals. His multifaceted approach underscores a holistic commitment to advancing the understanding and treatment of pelvic pain and endometriosis.
Welcome Doctor Yang. Thanks for joining us today.
00:01:35 Dr. Young
Thank you for having me.
00:01:37 Almira
I wanted to start with couple of sorts of clinical questions that we came up with our previous guest Anna, Anna and Leonova about sort of clinical presentations and some symptoms about endometriosis. So, first question, how do you diagnose endometriosis?
00:02:01 Dr. Young
Well, historically that largely dependent on was largely dependent on having surgery. So laparoscopic surgery and then seeing endometriosis tissue at the time of surgery and then sending that tissue to the pathologist for histopathological confirmation. But now it's recognized that there is actually a myriad of other ways that endometriosis can be diagnosed, so there can be a clinical diagnosis based on history and examination. There are certain findings and examination that are actually quite predictive and there's also been a lot of advances with imaging, so ultrasound and MRI that could actually some types of endometrioses can be diagnosed quite accurately as well. And so, these different ways of diagnosing endometriosis. And I think ultimately, it's up to the individual patients and the care provider to decide what means of diagnosis is most valuable or most useful to that person at that point in their life. So, for one person it might be a clinical diagnosis on history and examination is all that's needed and has its advantages and disadvantages. And then for another person's surgical diagnosis with pathology confirmation might be very important. So, we just try to personalize it to each situation.
00:03:23 Almira
Mm-hmm. I see it's good to hear that there are options like the more invasive and less invasive ones. Yeah, that's good. And you mentioned history. I was wondering if there is a family like relationship between family history and the endometriosis at all.
00:03:39 Dr. Young
So, I think it's like other multifactorial conditions where there's a partial genetic component, but it's not like a single gene disorder. But it's like, currently, there's several dozen snips in the genome that have been reproducibly associated with inherited risk of endometriosis. So, there is some inherited component. But there's other factors as well.
00:04:02 Almira
Hmm, I see. And does endometriosis affect fertility?
00:04:08 Dr. Young
So, in some individuals have more difficulty conceiving, others don't, and sometimes it's more evident why. So, the more anatomically severe and electrolysis which can it correlates to the staging of surgery. So, it captures things like the amount of endometriosis, adhesions, stuff like that. Those patients tend to have more, more likely to have difficulty conceiving. So, that I think it's more obvious why, but in other cases other cases of endometriosis, you can have the exact same endometriosis lesions and one person is able to concede quite easily and the other person is not. And there is, you know, there's still a lot of work remains to be done(?). The exact same thing with pain you the exact same endometriosis lesions in two different patients. One patient might have no pain and endometriosis is just noted incidentally, at the time of another surgery, while another patient has severe pain and again the research question is why is that the case?
00:05:15 Almira
Mm-hmm.
Yeah, great. And now that you mentioned that the pain as a symptom and we talked about fertility, there are some questions regarding about like if pregnancy will affect endometriosis, especially endometriosis. Like alleviate the pain symptoms. Is it true at all?
00:05:39 Dr. Young
Well, I think perhaps historically there was maybe generalizations made that and we chose this will perhaps always get better during pregnancy or be better afterwards. But I think it's recognized now that that's not the case and there's a lot of variability. So, you might very well have an individual whose endometriosis symptoms are better during pregnancy because they're not having menstrual periods. If their pain is very dependent on that factor and then postpartum, they notice their symptoms are better all the way to another individual who might have symptoms. Actually, even during pregnancy. And I've seen that in two branches. The first branches patients that have endometriosis that has developed into chronic pain and that chronic pain can be exacerbated during pregnancy. And also, patients who have the anatomically severe types of endometrioses, like deep endometriosis, those sometimes can still cause symptoms during pregnancy so that there's those two scenarios, and then similarly, postpartum studies now show it's about 5050, it's about 50%. Might report being better still, while another 50% will report this just recurrence of symptoms again, so a lot of heterogeneity for sure.
00:06:58 Almira
Yeah. Yeah, a lot of variation, it seems like.
And continuing about the pain that's endometriosis stage affects the pain symptoms.
00:07:10 Dr. Young
So, I think most people recognize that there is a marginal correlation between surgical stage or the amount of endometriosis and the pain symptoms. And that seems to be because endometriosis may predispose an individual to develop other causes of pain. And then those other causes of pain, then confound the association between stage and the pain symptoms. But I think if you do really well controlled studies and adjusts for these other pain confounders, there are probably some elements of stage that are still important like one study was done of 1000 patients of animatronics and found that with a big enough sample size, you and they, they tried to remove individuals that had other pain causes they were able to detect an association.
Between deep Endometriosis, which is an invasive subtype in a particular location of the pelvis at the near the top of the vagina, that being associated with deep pain during sexual activity, and so that anatomically completely makes sense. But you wouldn't detect those type of associations if you're don’t not have a big enough sample size. And you're not controlling for other factors.
00:08:24 Almira
Yeah. And we're going to talk about the sample size, how sometimes it can be hard to get the necessary materials for the research. But going on about the clinical sort of management of endometriosis, but as a common treatment strategy on endometriosis
00:08:45 Dr. Young
So, it can be divided, I guess into medical, surgical or interdisciplinary and medical treatments involve anti-inflammatory which are not just empirical. There seems to be probably has some of the physiological effect, because there's a relationship between the Cox enzyme and estrogen metabolism in the endometriosis lesions and endometriosis being an estrogen dependent disease, so if you use an anti-inflammatory to inhibit the Cox enzyme, you in theory at least, are going to be affecting estrogen metabolism and reducing it. So, in theory it is a treatment. But I think in research these and also clinically find many patients it does it only offers a partial response. And then the other treatments are various hormonal treatments that essentially aim to reduce estrogen level in the lesions themselves. So, they have local effects in the lesions themselves and also systemically, because any mitosis lesions not only produce their own estrogen. But by kind of grabbing metabolites from the system systemically and then using them to produce estrogen, but they also utilize estrogen produced from the ovaries, essentially, and to survive. So, if your hormonal therapy aims to address both the sources of estrogen, and there's a variety of ways and then surgically there most surgeries are done laparoscopically and then you visualize it and you choose these lesions and then you attempt to excise lesions as much as possible, ideally to a complete, but seems visually at least to be a complete excision of the disease. And then it's been working again as I mentioned in the metros, this seems that predisposed to other pain comorbidities, and that's where an interdisciplinary approach to pain is important. And at our center, that includes things like physical therapy, counseling, psychological type therapies and not saying the pain is in someone's mind, but we know from a biopsychosocial understanding of pain that really the best approach to treat pain is a holistic approach and then also a foundational element of what we offer at our centers pain neuroscience education. So just education about how pain is generated in the human body and how this brain and the spinal cord are involved. And that there's some plasticity there. So, you can kind of remodel the nervous system to help reduce pain as well.
00:11:32 Almira
Mm-hmm. So, there is. There are options. And there are holistic approaches usually necessary and couple more last questions about like a clinical presentation. Will endometriosis lead to ovarian cancer?
00:11:51 Dr. Young
Well, in most cases no. But there is a small, slightly increased risk of endometriosis associated ovarian cancer. So, for example, endometrioid and clear cell, but there, there, there is a statistically a slightly elevated risk, but the vast majority of patients within metros, this will not develop ovarian cancer. But of course, the important research question is for those. Minority individuals that do develop ovarian cancer, how do you find those individuals? I know which form a small number of a disease that has a prevalence of 1 and 10. So how do you find that small number that are at risk to develop these endometrioses, associated ovarian cancers? And then how can you intervene?
Try to prevent it. So, while I say for the vast majority of endometriosis patients, it's not an issue for the smaller number that it does become an issue. It's a really important issue in terms of preventing future cancer.
00:12:53 Almira
Yeah. OK. And of course, yeah. So, as we mentioned endometriosis can be debilitating for patients and some people even, I've heard some questions about the disability for a patients like if people can apply for disability within Demetrios diagnosis in Canada, are you aware of such cases at all?
00:13:22 Dr. Young
I don't know the answer to that question, but for sure you know every patient we see with at our center, we ask about impact on quality of life, day-to-day activity, social activities work. And there I don't think there's any doubt that Metropolis can have a major impact in all those elements. But I can't speak specifically to that question.
00:13:44 Almira
OK, sounds good. I think we are more or less done with our clinical sort of questions, but we still have some more research related questions about your research program. So just maybe we can start by talking about your translational research project in your lab and what kind of projects are ongoing currently in your lab.
00:14:10 Dr. Young
Sure. So, as I mentioned, you know, our research program is closely related to our clinical center and the foundations of the research program are in endometriosis registry and then biobanking of endometriosis tissue samples for those that undergo surgery. So those two elements are the core foundation and then the research is also guided by our patient Research Advisory Board. So, we have patient partners that you know inform the research as well. So, two things on the lab side that we're interested in. So, the first is the role of nerve, I guess hyper innervation around endometriosis lesions. It's been called hyper innovation. It's been called, been called neurogenesis. It's also been called neuroforamen. But you seem to have some patients with endometriosis where they're their lesions of. So, the, the ectopic endometrial epithelium stroma are surrounded by this increased number of nerve endings. And so, we're trying to characterize now why is that the case and what are the clinical implications of that? And then is does that present a potential therapeutic target in terms of endometriosis or the immune system signaling to cause this hyper innervation or neurogenesis or neuroinflammation. So that's one part of it. And the other part where we collaborate with GCI members. So, we've published previously with Doctor Iglesia and Dr. Huntsman. So that's looking at somatic cancer driver mutations in endometriosis, specifically in the epithelium. The reason is that enemy chose this while benign and you know in vast majority of cases, even in those benign situations, it has some subtypes have tumor like qualities. So benign tumor like quality. So that's the deep endometriosis subtype, the ovarian endometrioma subtype. And so that it can be locally invasive elective can grow, and so we hypothesize that these somatic gene mutations that are present in cancers might also be present in endometriosis, and they are actually fairly prevalent. And then we've found so far that these mutations are more likely to be present in those types of endometrioses which are more invasive or like the deep endometriosis or the ovarian endometrioma. So, it's possible that there may be playing a role in this more aggressive type of disease.
00:16:48 Almira
That's great. And what about the current challenges that are faced by researchers in this field and what are your thoughts on how to overcome those challenges?
00:17:03 Dr. Young
Well, I think like many areas specifically in Women's Health research, you know is the needing more funding of course for research. So, I think that's important. Secondly, is more national collaboration between different and mutual centers. So, I think we're slowly getting there. So Chr recently funded a, it was a project grant from McMaster to look at noninvasive diagnosis of endometriosis, or the use of a biomarker and that was a collaboration between multiple sites in Canada. So, hopefully we'll get more of that and we're hoping one day to have like a national registry for endometrioses. This similar to what we've done here provincially. So that's a second thing and then other thing I think is more supportive research infrastructure, I guess. So, we had a guest speaker come here recently from Doctor Andrew Horne from Edinburgh talking about their clinical trial program there for endometriosis and it was really remarkable to see the amount of support they have for clinical trials in this area, both at the federal level but also in terms of a local clinical trial unit. And I think that they are able to leverage that to do a lot of exciting work on innovative non hormonal medical therapies of endometrioses. So, I think that's something I'm hoping the future for Women's Health Research in general to have more of that infrastructure and then I think some areas are further ahead than others. I think gynecological cancers are probably ahead of other groups. And so, we know there's opportunity to learn from those groups as well. In terms of how they become successful in this area.
00:18:53 Almira
So, there is definitely an opportunity to grow and form the international collaborations and the space of endometriosis. Yeah, Thank you.
Thank you for all your insights and answering our questions. And I think that was our last question. So, yeah, thank you again for joining us today and it was Doctor Paul Yang. Thanks.
00:19:18 Dr. Young
Thanks, bye.
00:19:19 Almira
Bye.