Farr Nezhat, MD - Endometriosis and cancer

Farr Nezhat, MD - Endometriosis and cancer

Farr Nezhat, MD

Endometriosis and cancer

Scientific Symposium
Advancing the Science and Surgery of Endometriosis

Monday and Tuesday, April 19, 2016
The Union Club, New York

It is a pleasure to be here and I admire Tamer and Ms. Lakshmi for their vision to put this society together to increase our awareness of the physician and patients of endometriosis. Harry was mentioned last night at dinner. I know him exactly 30 years since I met him in Atlanta, Georgia when he came to give a lecture during post-graduate courses. Tamer and I know each other at least 15 to 20 years. These people have been great friends and I thank them for giving me this honor and inviting me to these sessions.

I do not have anything to disclose except that some of the information that I will discuss with you comes from the 4th edition of our textbook and I get a small royalty from this book.

Before I start I would like to show you this video tape of a patient referred to me by Dr. Radha Syed. She is a patient with a history of endometriosis. She is post-menopausal and Dr. Syed found she has ascites, so ovarian cancer and she referred her to me. I do ovarian cancer laparoscopically and you see metastasized disease all over. That is her pelvis and her uterus on the right side. When we resected this right ovary and sent for the frozen section it came back clear carcinoma of the ovary arising from endometriosis. I will talk about this case later.

A little bit of background of why I became interested in the subject of cancer arising from endometriosis. Before my fellowship, actually in New York, I had extensive experience in endometriosis. When I started in my fellowship I saw a lot of similarities surgically between endometriosis and ovarian cancer. Endometriosis is an invasive disease like ovarian cancer, could metastasize to the diaphragm exactly like endometriosis sometimes goes to the diaphragm and even the lung. So I did my thesis which was published in Cancer looking at the immunohistochemical standing between endometriosis and cancer. Since that time I have probably several papers and the last one was published in the Grey Journal looking at endometriosis, cancer and where we could use this information in our practice.

This morning I want to share with you some of those thoughts, to briefly discuss about the overview of the cancer and endometriosis. Dr. Dennis Chi, I think he will talk later about the pathogenesis of this transformation but I will mention it briefly. I will spend most of my time in clinical applications of these things, for example, what Tamer has shown in that movie about how should we use this information. Again, I would like to open the podium to get your thoughts.

If you look carefully there are a lot of similarities between ovarian endometriosis and ovarian cancer. We know early menarche is a higher risk for endometriosis, more menstruation, more possibility of endometriosis, I think cancer, infertility is a risk factor for endometriosis and cancer. Tubal ligation is protective, hysterectomy is protective and you will see during my lecture you will find it explains all of these similarities between these two diseases.

As Dr. Seckin mentioned Sampson, who was originally from upstate New York and was a general practitioner, developed retrograde menstruation. He was also the first to suggest the transformation of the endometrioma to cancer. Since his suggestions we now have a lot of evidence, epidemiologically, histologically and molecular biology testing that shows this transformation exists. For example, cases that have endometriosis and cancer next to it if you look at those normal looking tissues next to the cancer 50 percent of them have atypical endometriosis. But what does it mean? It means these cells are abnormal. They are not cancerous but they are abnormal like hyperplasia which is one stage before cancer. However the incidence of atypical endometriosis in patients that do not have cancer is only 1.7 percent.

This is an example. This is an endometrioma. It is removed and there is a nodule inside of it and if you cut this under the microscope you can see here this is atypical endometrial lining and next to it is endometrioid adenocarcinoma. So histologically we have proven that this transition occurs.

This is an example of the clear cell carcinoma. You can see this is the cancer and endometriosis next to it. We have probably some other people who ____ when you do molecular testing and then you can see the transition between this benign tissue next to the cancer, and the cancer there are several markers that have been shown between these two earlier. Histologically we have evidence.

How about epidemiologically? There are a lot of papers published and I just discussed two of them. The largest one was from the Ovarian Cancer Association Consortium. It was published by Pearce a couple of years ago and that was an international collaboration of several countries. They looked at 13 case control studies and compared patients that had endometriosis compared to patients that had cancer and they looked at the histology, subtype, grade and stage. They looked at more than 23,000 cases; of those cases 10,000 of them were a controlled group. They had a history of endometriosis and almost 8,000 ovarian cancer cases. They found that the incidence of the endometriosis there was 9.3 percent compared to 6.2 percent in this group.

Then when they looked at the histology it is very important that they found that the incidence of clear cell carcinoma was three times higher compared to the patient that did not have endometriosis and also endometrioid adenocarcinoma the risk was twice as high and for the first time this group reported low grade serous carcinoma also was higher.

Let me talk about the high grade serous carcinoma and low grade carcinoma and what it means. This is a ____ you can see that again the menstrua___ low grade and clear cell carcinoma the odds ratio was higher and the most interesting part was when I look at all these different countries you can see all of them, unanimously. It does not matter which country, in all of them this was significant that there is epidemiology a correlation between endometriosis and cancer.

This is another study of a meta-analysis that was published by Kim two years ago and they looked at the studies between 1990 and 2012. They looked at 20 case control and 15 cohort studies of more than 400,000 cases. They looked at the risk ratio or a standard incidence ratio. When they looked at the case control or two-arm cohort study they found there is again increased risk. For those of you who are like me who are not very good with statistics, anything above one is significant and the higher it goes – the significance goes higher. So it is more than one ____ significant, for example five or six, it is more than one it is significant and again single arm cohort studies showed the incidence is 1.797, almost two.

Interestingly enough you can see the exact confirmation of the other study when they looked at endometrioid and clear cell carcinoma you can see again the relative risk is 1.79 and 2.6. So there is more with clear cell carcinoma than endometrioid. And serous carcinoma again high grade risk carcinoma there is no correlation. Keep this in mind when we later on discuss about what is ___ have to use in your practice. Again the most important thing was when you at this stage, grade and nulliparity you could see again the relative risk is 1.9 stage one or two, 1.3 is grade one and nulliparity. This means that fortunately the majority of these patients are at stage one or two, early stage, not advanced stage.

I do not want to go to the pathogenesis Tomer, he is going to explain but essentially keep in mind three things; there is some genetic alteration of these patients with endometriosis, inflammation and hormonal milieu. These three cause this transformation.

As I mentioned, endometriosis itself when compared to normal cells there is some aberration of the cells. But those cases either have become malignant or those cells have some alteration in certain genes. We published a paper on bcl-2 and p53, other people have published on p10 and also ARIDIA1. That is one issue. Two more important things are, and this is a study published that I mentioned about the alteration of bcl-2 and p53, the second most important thing is inflammation. The hallmark of endometriosis is inflammation. Through two mechanisms is inflammation could help this transition. Again, I just mentioned this and later on we will discuss about how to use this data. One is to the cytokines, persistent exposure to cytokines causes disruption of the homeostasis and of the cells and causes the proliferation of the cells and also in the environment of the endometrial cyst and even the lesion on the peritoneum causes free iron and increases inflammation to oxidative stress. It helps the proliferation of the abnormal cells.

The other important thing is estrogen. We know the ovary has highly ___ estrogens. The endometrial implants have been shown the level of the estrogen and those implants are actually higher than the level of the serum estrogen. These implants produce estrogen, causes more proliferation of the cells, bleeds, creates inflammation and the vicious cycle continues. Keep this in mind as later on we will discuss the treatment. Again, the combination of the gene alteration, inflammation and estrogen are the triangle that causes this transformation.

What do we do with this information? First of all the majority of this transformation is on the ovary. However on the peritoneum there is also a transformation that could happen and we will talk about it later if anybody has any questions. If you look at the ovary and if you look at the general population of risk by age of seventy with no family history of any cancer, the risk is 1.4 percent. Patients who have BRCA1 mutation or BRC2 mutation the risk is higher. In this group of people our recommendation is to follow them in a certain way to a certain age and take the tubes and the ovaries out. Hereditary nonpolyposis colon cancer or Lynch syndrome as you may have heard it the risk of ovarian cancer is 10 percent. Again, this group of people know that we do very good genetic testing. If we find it and they are past child bearing we take the ovaries out.

How about endometriosis? As I showed you compared to the general population the risk may be two or three times higher than the general population. About one out of ten women have endometriosis. You cannot take all the ovaries out, right? It does not always make sense. What should we do?

We looked at a series of data and I would like to present this case that is a real case. She is 29-years-old and she presented to her fertility specialist for infertility. In his office he did ultrasound and he found she has a 2.6 x 3.6cm cyst. He thinks this could be a dermoid cyst or endometrioma. She is 29, para 0, regular menstrual cycle, not obese, she has mild dysmenorrhea and no significant past history. He took her to the operating room and found some peritoneal endometriosis and that the left ovarian cyst that he thought by the ultrasound could be an endometrioma or could be a dermoid cyst he removed it. It is well differentiated as endometrioid carcinoma.

Interestingly enough he did a D&C and the D&C showed proliferative endometrioma next to it and complex endometrial hyperplasia with marked atypia. She is 29 years old, she has regular menstrual cycles and her endometrium shows some atypia. She was referred to us. We did a metastatic work up. It was negative. I staged her and removed that ovary but we saved the other side, gave her chemotherapy and since that time she got pregnant twice with two successful pregnancies.

After this case I want to look at this data. We published this paper several years ago. We looked at 76 patients that had early ovarian cancer and all of them were completely staged. We looked to see characteristics of these patients. These are all stage one ovarian cancer and we had two of them they were serous carcinoma, 40 of them were endometrioid carcinoma, ten of them were clear cell carcinoma and four of them were mixed clear cell/endometrioid. The number one thing we found was the majority of the stage one ovarian cancers were not serous carcinoma. Gyn-oncology overall when we looked we see serous carcinoma are the most common histology. When we looked we found out that stage one the majority of them are not high-grade serous carcinoma. They are endometrioid clear cell carcinoma. The other thing we found that these patients with serous carcinoma are almost ten years older than those with endometrioid carcinoma. Endometrioid are a younger patient.

How do these patients present? The serous carcinoma a lot of them presented asymptomatic and they were found during the pelvic ultrasound, pelvic examination or some of them they had a history of the BRC mutation or breast cancer. They were followed very carefully and they found them to have serous carcinoma. However, the patients that had endometrioid clear cell carcinoma most of them had symptoms. They had pelvic pain or some of them had abnormal vaginal bleeding. During the evaluation for these two they found them to have ovarian masses and they were operated on.

The other interesting point was when we look at the association of other pathology with this cancer you could see the patient had endometrioid clear cell or mixed. The majority of them had ovarian endometrioma or pelvic endometriosis. This is very important for us and the way you operate. For endometriosis do not drain the endometrioma or not taking the biopsies or peritoneal lesion ___ we showed you exactly looked like endometriosis but if you take the biopsy you could not miss cancer. I had a very similar experience.

The other important thing that we found was that you could see that a large number of these patients, especially the endometrioid adenocarcinoma, they had some sort of endometrial abnormality. Either they had hyperplasia or they had cancer – 36 percent of them. We call them synchronize 2. If you have any gyn-oncologist here or some of you may have seen either the patient has two cancers, endometrium and the ovary, it is synchronize 2. Very similar to our case that she is 29, a skinny woman, endometrioid cancer; the average age of the patient is 60 but this patient was 29 and she had complex atypia hyperplasia. You can see these types of patients. If we do endometriosis cancer surgery always have sample endometrium to make sure you are not missing a pathology.

That was a summary of all papers that non-serous ovarian carcinomas most of them at stage one are non-serous, clear cell carcinoma or endometrioid. Most of the time those patients present with pelvic pain or endometrioma and also about 36 percent of them have abnormal endometrioma.

Now let us go back to ovarian cancer. In the United States each year we have about 24,000 ovarian cancers. You all know most ovarian cancers at the time of the diagnosis are advanced stages and bad prognosis. The average age is 63.

We know stage one and stage two ovarian cancer has good prognosis. Now we know a little bit further what have been our mistakes. We have always tried to find early stage ovarian cancer and we have been trying to do all kinds of screening tests but we have been looking in the wrong directions. CL125 and ____ these are the two tests that so far we have been using and have not got anywhere. Why? The majority of the earliest stage that I showed you are endometrioid and clear cell carcinoma ____ endometriosis are a lot of times CL125 is elevated because of the inflammatory process. The high grade serous carcinomas are not advanced stages and I will discuss the outcome for the fallopian tubes.

We had been looking so far and until now only by histology. You have to go one step further you have to find out genetic structural each tool to help us. If you look briefly at ovarian cancer the majority of them are epithelial types of tumor. A small section of them are sex cord or germ cell tumor – these are the minorities. These have a specific characteristic, they have their own markers. It is not difficult to make the diagnosis of these two groups. And even if you make the diagnosis this group responds to chemotherapy very well. This group does not need too much tumor therapy so we do not talk about this group.

Most of them are this epithelial type of tumor. They have high grade, they have low grade, mucinous, clear cell and endometrioid. You can see the genetic structure of this group is completely different. We know that the high grade tumor most of the time comes from the fimbriated end of the fallopian tubes. The genetic alteration of this is mostly BRCA1/2 or TP53 and endometrioid ______ low grade the genetic alterations is different, the background is endometriosis. All these epidemiological studies I have shown you support these two phenomena. To make it simple in your mind: high-grade bad prognosis coming from the fimbriated end. That is the reason that the old _____ does not help. Why? Because the old ____ does not show a small lesion on the fimbria, does it? No. CL125 is not helpful because CL125 is elevated on a lot of benign conditions including endometriosis. That is the reason that a lot of big, big studies from the United States and the United Kingdom did not show that screening at the present time helps. Why, because we have to find a specific screening test for a specific cancer. As I showed you, if you want to find out for example for clear cell carcinoma you have to find one of those markers here. Want to find for the high-grade serous carcinoma? You have to find specific markers. That is right now around the world. Different people, different laboratories and different groups are working to find specific markers for ovarian cancers. Unfortunately at the present time we do not have any screening tests, any blood tests, anything to find these ovarian cancers. That is number one on the list to do. You have to wait, as I said other people are working on it.

What else do we have to do? Again, I do not want to concentrate on the ovary. Right now endometrioma is a very common condition. A lot of infertility specialists do not want to operate on endometrioma because they are afraid they may damage the ovary and decrease the fertility of the ovary.

This is a patient that had this endometrioma and her physician was following her. A few years later she developed this characteristic. This is very homogeneous characteristic old blood and all of a sudden you could see this characteristic has changed. When you operate there is a nodule inside of it and it is adenocarcinoma. If you want to follow endometrioma there are two characteristics that we are aware of; one, all of a sudden the endometrioma becomes big or the characteristic changes from this one to this one and this sometimes could be blood clots. When you operate on them it is blood clots. Those of you who have operated on endometrioma you have seen this characteristic. If you have something like this and you are suspicious about cancer sometimes you do an MRI. They call it mural nodule. A study was published by Tanaka where they looked at ten patients who had endometrioid adenocarcinoma and in all of them mural nodules were there. Not every patient with a mural nodule is cancer but if you have mural nodule that by the MRI looks like this, this is a characteristic of the endometrioma by MRI and you will see something like this. My recommendation is to operate on them. That could be, especially if all of a sudden the endometrioma has increased in size. I have seen at least for the past three years four or five endometrioma – it was followed and actually one of them had five IVFs from that ovary and finally was referred to me to remove it and there was cancer.

What else can we do? Endometrioma – we published this paper several years ago and we classified the endometrioma to two groups. We called them type one endometrioma and type two. I would like those of you who operate a lot with endometriosis, especially by laparoscopy, to pay attention to this classification. Type one is a small endometrioma on the ovary that are not very big and when you want to remove them they do not come out very easily. These are the real endometrioma. Large endometrioma are not real endometrioma. If you look everywhere in the pelvic cavity you have fibrotic nodules. The ovaries are the only place, almost only place that you have a big cyst like this. Why is that? Because we think that large endometrioma starts that is a functional cyst on the ovary and there is endometriosis either on the cortex or the pelvic sidewall. That endometriosis interferes with the function of this cyst and does not allow the cyst to supposedly go away by the end of the month. Gradually this lesion penetrates in two directions, to the wall of the ovary to your cortex and to the pelvic sidewall and gradually becomes like this. A lot of times when the endometrioma is old and is attached to the pelvic sidewall when you put by laparotomy your hand or by laparoscopy you lift it up it ruptures. You think you ruptured it but it is not you. This is a disease and the process of the disease caused this phenomenon. I would like to you pay attention to it.

Type one – you never could take it out in one piece. It is fibrotic lesions exactly like peritoneum on the posterior cul-de-sac or the anterior cul-de-sac. You have to remove it in pieces. However the other ones they come from a large cyst with endometriosis on the surface. All you have to do is excise this area here, and the rest, originally a functional cyst, peels off.

Here is a movie to show you. This is a bilateral endometrioma, typical. You can see the right side and that is the left side. You see the ovaries. There is a uterus down here. You lift up the ovary and you see the endometriosis right here. You lift up, lift up, lift up and you see the ruptures. This is not you rupturing this it is the way the lesion has penetrated to the cyst wall. Now you can see you excise this area because this is the area where endometriosis was. You excise this area that hole and you excise it. Now you put your two grasping forceps and you find the planes. Here, this is the area that you have to remove. If you do not remove that area you have left the disease behind. We published the paper with all kinds of histological study. You see that? Now, this is the cortex here and that cyst wall. Corpus luteum you all know corpus luteum is the easiest cyst to remove. This was a corpus luteum at one point. Now if you can find the right plane you have saved the entire ovary and you have removed the cyst in this part.

We have been practicing and following this philosophy for many years and more and more we are convinced that this is the phenomenon.

What does it mean? If you put the patient on some kind of suppressive therapy that prevents ovulation she will not form this large endometrioma. The endometriosis unfortunately could come back on the peritoneum but would not come back as large endometrioma. The data from Vercellini and other people who have published is that when you put the patient on suppressive therapy the incidence of the endometrioma is significantly less than if they are not on suppressive therapy.

Now also you look at the literature the best controlled periods has shown to decrease the risk of the ovarian cancer. We all know we obviously put the patient on oral contraception pills. Why? Because maybe there is control with ___ progesterones, anti-estrogen and also decreases the flow of menstruation because of inflammation. That is the reason the birth control pills decreases the risk of ovarian cancer.

What else can we do? This study from Nurses’ Health Study looked at the tubal ligation, hysterectomy, unilateral oophorectomy and risk of ovarian cancer. There are two prospective cohort studies; number one was more than 120,000 cases and the second one was more than 116,000 cases. They looked to see what kind of effect tubal ligation, hysterectomy, oophorectomy had on decreasing the ovarian cancer. Look at the data. You could see tubal ligation decreases the risk of ovarian cancer by 24 percent. Interestingly enough it decreases the risk of non-serous carcinoma more than serous carcinoma. Hysterectomy also decreases the risk of ovarian cancer, hysterectomy by itself, again non-serous more than serous. Unilateral oophorectomy also decreases risk of ovarian cancer.

Here is data looking at the type of histology and decrease of the risk of ovarian cancer after tubal ligation. Tubal ligation cuts off the retrograde menstruation and the inflammatory process from the vagina to the peritoneal cavity and that decreases cancer. This is exactly what I showed you earlier, the phenomenon that the endometriosis becomes malignant.

In summary tubal ligation decreases the endometrioid adenocarcinoma by 38 percent, clear cell by 52 percent and high grade serous carcinoma by 19 percent. You all know now that when ACOG and SGO have recommended the use of salpingectomy instead of tubal ligation or removal of the fallopian tube at the time of the hysterectomy. If you keep this one in mind and I like to really keep the study in mind when you are operating on a patient with endometriosis, or if you are operating for something else, my opinion is that at one point we will have to teach all of our general surgeons that when they are operating on women and they are doing an appendectomy or cholecystectomy to take the fallopian tubes out. You take the fallopian tubes out you have to remove the fimbria so it decreases the high-grade serous carcinoma and also you remove the fallopian tube to decrease the clear cell and also endometrioid adenocarcinoma. If you are operating on a patient with bad endometriosis and you do not want to remove her ovaries and these tubes are bad, especially because IVF is so good these days, you should take the fallopian tubes out. If you have a question about this I could answer it. If you remove the tubes properly you will not compromise ovarian function.

This is the recommendation that came out of the SGO, Society of Gynecologic Oncology, they recommended that at the time of the hysterectomy we should take the fallopian tubes out. We all know about it. Tubal ligation if you remove the tube is ___ tubal ligation and other pelvic surgeries. You should take the fallopian tubes out. The same recommendation, you are all familiar with it, ACOG that shows at the time of hysterectomy and tubal ligation you should take the fallopian tubes out.

I will just try to finish with the last few slides. Endometriosis is a very common disease. You are all here for the past two days and know about it more and more. I am a gyn-oncologist and we follow these patients with endometrioid cancer for years every three to four months. Cervical cancer with a pap test every two or three months, followed with CT scan and all those things. But we leave all these endometriosis patients alone. Endometriosis could persist on the ovaries, could cause pain, destruction of the ureter and bowel. In my opinion an endometriosis patient has to be followed exactly like cancer cases. Certain people are interested they have to follow these people.

This is another study that showed Melin from Sweden, these people have published a lot, looked at the registry of the patients that had cancer and endometriosis. They found that in multivariate analysis when one ovary was removed all endometriosis was completely excised at the time of the treatment the risk of ovarian cancer decreased by 70 percent when endometriosis was completely removed or one ovary was removed. This one again I showed you. When you remove the lesions you remove those lesions that are producing estrogen and inflammation that could contribute to the malignancy. Of course when you remove one ovary you decrease the risk by 50 percent and maybe we are decreasing the level of the estrogen on that particular person. These are the things that you should keep in mind when you are operating and you are following the patient.

We could follow this patient although the risk is low but this patient that I showed you earlier this patient had endometriosis and a few surgeries before and she went to menopause. This particular patient unfortunately had clear cell carcinoma and by the time she got to us it was too late. In a few months she was dead. If we find this group of patients and we find some sort of marker, or if you are operating on them at the end of their reproductive age and they have symptoms, take everything out. At least take the ovaries out, take the fallopian tubes out. My oldest patient who had endometriosis and cancer is 78 years old. Endometriosis is a risk factor. I think if we follow these patients with endometriosis properly, and if they are not ready to get pregnant we put them on hormonal suppressive therapy to prevent endometrioma. Definitely I believe that all ovaries – if the patient can tolerate suppressive therapy we put them on hormonal suppressive therapy. If you are concerned about not operating on this endometrioma you should not leave them alone. You have to follow them with imaging studies to be sure that they will not form a nodule. If they develop a nodule operate on them. I encourage young patients to have egg and embryo freezing.

When you do surgery I believe even if the patient does not have any symptoms of endometriosis those lesions have to be removed. Peritoneal endometriosis I believe it has to be removed. Regarding oophorectomy and salpingectomy it has to be individualized and if the tubes are not good, even if the patient has had PID and you are operating, if this tube is not good I always get a consent form from my patient to remove the fallopian tubes. Regarding oophorectomy again you have to use your judgement. I do not see any benefit to leaving a piece of the ovary on the left side next to the rectosigmoid colon. It does not produce any hormones to leave that ovary. If the patient is in her late 40s and you are operating for endometriosis a bad ovary take it out.

The last study is about the future. And that is what we have to look into. This is the pattern of a cancer. There are so many pathways. As I showed you although under the microscope this looks like a high grade serous carcinoma but there are so many pathways that this cancer has been developed and this cancer is going to respond to chemotherapy or target therapy. That is the reason that one chemotherapy to one patient works and it does not work with another patient. Why, because they have different pathways. And now, all of our efforts in cancer for all kinds of cancer you see every day we have new biological agents coming out. The same way we have to develop different markers for making the diagnosis and also hopefully for endometriosis to find out what kind of molecular structures these patients have and find the right test to make a diagnosis for them and the right treatment.

Thank you very much.

Tamer Seckin, MD: We do not interrupt and cut off our keynote speaker. This was a beautiful presentation. This is an important topic so one has to really note that many endometriosis patients from the get go, from menarche on have heavy periods, irregular and heavy periods with clots at either end. What he says I am underlining there is reverse cell trafficking. Now what he said to you 90 percent of the ovarian cancers are presumed to originate from reverse cell trafficking, most of them from tubes and from endometrium. And also with endometriomas when you do surgery for endometrioma I have not seen a single, well maybe one or two in my life that I remember, that there was no peritoneal implant. There is always peritoneal implant. The third, or fourth, is most ovarian cancer in early stages there is more if you look implant style elements on the peritoneum than you see probably in the ovary. Are there any questions to this topic before, I think you should have, Dr. Wertheim?

Ray Wertheim, MD: I will make this quick. It is very compelling. I am just kind of interested with open powder morcellation _____ fibroids. The literature suggests that 60 percent of these women have co-existing adenomyosis. I have seen case reports of malignant transformation afterwards but I have not seen any studies to show a significant increase in ovarian cancer after open power morcellation.

Farr Nezhat, MD: The power morcellation and the examination of these sarcoma is a different story. But actually that Melin study, that study that I showed you that oophorectomy and excision of the endometriosis should decrease ovarian cancer. They look at the adenomyosis too actually. Adenomyosis was not a risk factor to increase the risk of ovarian cancer. I did not show you that study.

Audience Member: I have a question. In ultrasound diagnosis of complex ovarian cyst you often mention ___ not a nodule but a cyst is that of concern to you? Should we follow that up to make sure it does not develop into anything? One of the patients I am following has increasing density, hyper-density inside the ___ cyst. Now they call it a hemorrhaging cyst within a cystic nodule – a cyst inside the ovary. I do not know if that is something I should worry about? She is peri-menopausal patient.

Farr Nezhat, MD: The ovarian cyst, as we all know, it is a very common finding in women and it has different characteristics. If it is completely cystic the chance of the malignancy is extremely low. It is more complex, the more complex with solid component the higher a chance of malignancy. But when it comes to the endometrioma and when the sonographer says it is endometrioma those ones you have to be very cautious about a mural nodule. That could be a malignant nodule. An MRI could help you to differentiate between the blood clot that could be endometrioma some times and a solid nodule.

Thank you very much again. I will be here if you have another question.