How to treat the "king of gynecological cancer"? Is it better to have minimally invasive surgery? What if I have a family history?

Pineapple said

In this pineapple parlor, Zou Dongling, director of the Gynecology Cancer Center of the Affiliated Cancer Hospital of Chongqing University, told everyone a lot of relevant knowledge about ovarian cancer of the "king of gynecological cancer", the following is a selection of live Q&A:

Zou Dongling

Affiliated Cancer Hospital of Chongqing University

Director of the Gynecologic Oncology Center

Standing Committee Member of Gynecologic Oncology Committee of Chinese Anti-Cancer Association

Member of the Ovarian Cancer Quality Control Expert Group of the National Cancer Center

Pineapple: Can you please introduce some basic knowledge to you first?

Director Zou: First of all, let's understand what kind of organ the ovaries are in our body.

The image comes from the internet

The middle part is our female uterus, don't think that the uterus should be particularly large, in fact, it is about the same size as our fist when it is normal. In the white next to it is the ovary, and the ovary in the female reproductive system, in fact, holds the position of general, which directs some endocrine functions of the uterus, and there is a tube attached to one of the ovaries, that is, the fallopian tubes, if the fallopian tubes are not smooth, it may lead to infertility.

Don't look at the ovaries so small, it is about the same size as a quail egg, but it is an organ in our human body that may suffer from the most tumor pathological types, it may be an ovarian tumor of the epithelium, it may be an ovarian germ cell tumor, or it may be an ovarian cord stromal tumor.

Through the side view of the ovaries and uterus, we can see that the front of the uterus is the bladder, and the back is the rectum, so sometimes when we women have tumors, she will feel as if the number of urination will increase, and may also feel that there is always a sense of defecation, which may be caused by tumor compression of the uterus or ovaries.

Pineapple: In China, what is the current situation of ovarian cancer, and what are some of the characteristics?

Director Zou: The ovaries are very small, so the tumor may be asymptomatic without compression to other organs, resulting in patients with ovarian cancer having no way to detect it in time at an early stage.

There are three 70% in our medical community: 70% of ovarian cancers are found to be advanced, which is a very unfortunate thing, and so far there is no very good screening method. The second is that 70% of people will relapse within two or three years. The third is 70% of people, who are still sensitive to chemotherapy.

Therefore, although the number of new cases of ovarian cancer in China is about 50,000 a year, there are hundreds of thousands of cases that may recur every year and cases that are being maintained, and the patient population is very large.

This disease is known in our gynecological community as the king of gynecological cancer, also known as the invisible killer. It is a disease that we find very difficult, and it is also a disease that we are very willing to study and overcome with scientists and medical scientists.

Pineapple: Speaking of screening, someone mentioned some of the screening methods that I heard about elsewhere, such as CA125, tumor markers, and vaginal ultrasound, can these screen for ovarian cancer?

Director Zou: In 2018, JAMA magazine published a study of the world's largest ovarian cancer screening, and the results showed that vaginal ultrasound combined with CA125 screening could not increase the early detection rate of ovarian cancer, and it was likely to increase the probability of overdiagnosis.

We highly recommend prevention, but ovarian cancer does not have an early screening indicator due to its insidious pathogenesis, and so far it is not particularly suitable for large-scale population screening.

Of course, if there are corresponding symptoms, come back to the hospital, it is called examination, not screening. However, when many female friends have uterine fibroids or some benign diseases, the ovaries and fallopian tubes will also be seen when the color ultrasound checks the uterus, so some problems may be found in such cases.

Pineapple: As I mentioned earlier, ovarian cancer may have symptoms of frequent urination, urgency or wanting to defecate, but what are some other symptoms?

Director Zou: Many patients with ovarian cancer, at the time of initial treatment, do not come to see the gynecology, the vast majority of symptoms are symptoms of the digestive tract, it may be bloating, abdominal pain, constipation, increased frequency of stools or enlarged abdominal circumference, and even feel that they are not fat, in fact, they may have grown ascites.

So this point must be vigilant, if we female friends have the above symptoms, please go to the gastroenterology department at the same time, do not forget to look at the gynecology.

Pineapple: What age do women need to pay more attention to these symptoms?

Director Zou: Tumors of the ovaries may look for women of all ages.

For women without genetic mutations, the high incidence of people is still after menopause, so many women feel that they have reached this age and are blessed and gain weight, but in fact, the examination is already a long abdominal mass, or a long ascites.

There are also some relatively few pathological types, such as germ cell tumors, which have a very high incidence in children and adolescents, so if children have sudden pain in the lower abdomen after physical education classes, this situation must be paid attention to.

In addition to the symptoms of the digestive tract and urinary system, because the ovaries are very small, even if it grows a tumor as large as the uterus, its activity space in the pelvis is also very large, so it is easy to rotate, and after rotation, symptoms of abdominal pain may occur, including symptoms of dysmenorrhea in the physiological cycle.

For epithelial ovarian cancer, which is known as the king of gynecological cancer, the age of incidence is after menopause, and when there is a BRCA gene mutation, the age of onset will move forward by about 10 years, if the mutation type is BRCA2, the age of onset may be slightly later than BRCA1 and about 5 years.

Therefore, for people with genetic mutations, it is recommended that you come to a special genetic counseling clinic to understand how to do screening.

Pineapple: The genetic counseling you just mentioned, is it that you have already done genetic testing and found that you have a mutation to consult, or do you suspect that I have this family history and should go?

Director Zou: Both of these points you mentioned are very necessary to do genetic counseling.

After finding a genetic mutation to do genetic counseling, for her relatives within two to three levels, that is, mother, grandmother or grandmother, down to the daughter and then to the grandson, we will draw a very detailed family tree to understand the probability and order of inheritance in this family, and then do some recommendations, in the end what relatives in the family should come to do genetic testing, this is very accurate.

Another point that you just mentioned is that if I have a lot of cancer patients in my family, I feel very scared, and it is also very necessary to do a genetic consultation in this case, because different genetic mutations may cause different tumors.

Of course, there are some who say that there are many tumor patients in the family, but they are not necessarily related to genetic mutations, they may be sporadic, and they may be related to some living habits of the family, etc., so if they come to genetic counseling, they can help them solve such confusion.

Pineapple: If a BRCA mutation is detected, is it necessary to remove the ovaries preventively?

Director Zou: Don't think there is a genetic mutation, so you put a label that is prone to cancer. In fact, there are many kinds of genetic mutations in our human body, which have not been fully understood.

If it is a BRCA gene mutation, it is actually very lucky, because we know how to prevent and deal with it. For this type of patient, it is important to understand whether it is a germline mutation or a system mutation.

Germline mutations are also innate to us, every cell in the body is filled with the site of genetic mutations, and the system mutation may be that there is exactly one such mutation on the tissue sent for examination, but other parts of the body do not.

If it was just a system mutation, there was no need for us to do such surgery. However, if there is a germline mutation, and a family member or yourself also has such a medical history, the guidelines recommend that the resection be done, but at the appropriate age.

Pineapple: Which hospitals have genetic counseling clinics, and what doctors will visit?

Director Zou: In addition to our hospitals, there are Peking Union Medical College, Beijing Cancer, The Third Hospital of Beijing Medical College, Fudan Tumor, Fudan Obstetrics and Gynecology, Zhongshan Tumor, Zhongshan Sun Yat-sen Hospital, etc. in the North, Liaoning Tumor and Harbin Cancer in the northeast region, Yunnan Provincial Cancer Hospital in the southwest region, and Xijing Hospital in the western region.

Our hospital's genetic counseling clinic may be slightly different from other hospitals' genetic counseling clinics, our genetic counseling clinic has 6 specialists, 1 gynecological tumor, 1 urinary tumor, 1 breast tumor, 1 laboratory specialist, 1 molecular pathologist, and 1 professional geneticist, 6 professional specialists come together to consult a patient, so she can get very comprehensive information.

Pineapple: Some people say that menopause finds a lump in the ovaries, how likely is this situation malignant? What should I do?

Director Zou: I can't give the probability explicitly, but I will give you some professional advice. We need to understand that menopause is very long, it may occur before menopause, it may be after menopause and still continue menopause.

Usually after menopause, the ovaries will continue to shrink with endocrine changes. Basically, it is not visible from ordinary images, and it is good to not see, and it is not a good thing to see.

But some of these lumps may also be cystic, which is colloquially a blister. In this case, it is possible to combine the examination of some tumor markers and the follow-up of patients, and it is very important to have a doctor's hand consultation.

Many times when we touch our hands, we can understand whether the problem is pathological or physiological, and if it is physiological, in fact, we do not need to care too much. However, after menopause, some of these lumps still persist, so we must be vigilant.

If it is a cystic tumor, the indications for surgery must reach 4-5 centimeters before it is necessary to go to a corresponding exploratory surgery. But if it is not cystic, but some mixed masses, even if the tumor markers are normal, excluding the physiological corpus luteum or blood body, we must be vigilant about whether it will be a tumor. It doesn't have to be cancerous, but it may be some low-grade malignant tumor that also requires surgery.

Images are from the public image gallery

Pineapple: If you have ovarian cancer, how should you treat it?

Director Zou: Ovarian cancer is in great need of comprehensive treatment. Surgery and chemotherapy are now essential, as well as targeted maintenance therapies.

For the above-grade ovarian cancer, we still hope that there must be a maximum tumor reduction surgery in the lifetime of the disease. Surgical treatment is very important, and the operation of ovarian cancer is usually to "stand up to the sky", that is, how big the stomach is, how big the mouth is.

Because ovarian cancer is like a dandelion, it scatters a lot of seeds into our abdominal cavity. You can touch it yourself, from the chest to the abdomen to the pelvic cavity, so the dandelion seeds will scatter everywhere, and then planted somewhere, and then grow new tumors, and then spread again. Therefore, we often see that ovarian cancer patients will have densely spread tumors in the abdominal cavity. And the more the place, the easier it is to grow there.

For example, ovarian cancer is particularly easy to metastasize to the diaphragm horn lymph nodes, where the metastasis may often be small, and when the imaging technology is not yet developed, ordinary CT can sometimes not be found.

After the emergence of PET-CT, because of the absorption of imaging contrast agents, there is a higher probability of finding tumors, and the IV. patients with ovarian cancer have also risen from about 15% to more than 40%, because of the discovery of diaphragm lymph node metastasis, as well as some lymph node metastases in the inner breast area and the clavicle fossa, which are easy to ignore before the diagnosis and treatment of ovarian cancer.

Pineapple: What is the most important point for surgery for ovarian cancer?

Director Zou: The operation of ovarian cancer is very difficult, we must remove the whole piece, just like making a bun, even the belt filling is taken out, and the filling cannot be scattered and then taken out. Therefore, the technical requirements for doctors are very high, even if they are already gynecologists with considerable experience, if they want to do ovarian cancer surgeons, they must train at least 3-5 years.

Because the operation of ovarian cancer is not only the ovaries, the operation of the pelvis is relatively simple, the difficulty is the upper abdomen, the doctor must understand all the anatomy of the digestive tract, you dare to go to the next knife.

Of course, we also have a lot of doctors, may be looking for a surgical MDT (multidisciplinary consultation) team, if there is a very professional gastroenterology or hepatobiliary doctors, can be willing to cooperate with you to do this operation, it is also very good, the most important idea is to be sure to cut clean.

Pineapple: Is it still appropriate for patients who are already stage IV to undergo complete tumor reduction surgery?

Director Zou: A comprehensive assessment is needed. This is very dependent on the doctor's experience and surgical ability, and if he is confident that he can cut you clean, it is certainly the best choice to cut it clean.

But if the patient's lesions have been spread very widely, in this case, we must "bow down" to the tumor in time, that is, we need to do the early neoadjuvant chemotherapy, shrink the tumor to a certain extent, the tumor markers have declined, and even some of the distant metastases have disappeared, such a control interval to do thorough surgery, is also a very good choice.

And the tumor may be scattered in the place that is usually invisible to the naked eye, there are some places where it is physiologically adhesion, and all the adhesion structures must be opened for a full probing to know whether it is cut clean.

Therefore, ovarian cancer surgery is indeed very difficult, from preoperative evaluation, adequacy of surgery, and then to postoperative recovery, the surgical blow to patients is definitely very large. There are many patients who are likely to go to the ICU for two days after surgery, and then transfer to the general ward after stabilization.

Pineapple: What should I do with chemotherapy?

Director Zou: Chemotherapy must be standardized. The chemotherapy regimens recommended by our existing guidelines have undergone many clinical trials, not that as long as a new drug is released, it can be replicated in ovarian patients.

So our existing front-line solutions are actually not very many, do not use a variety of ways, must be used on the basis of standardization, worth choosing, in order to benefit our patients. In China, bevacizumab and including 4 kinds of PARP preparations, have corresponding approved indications, everyone gets the drug after the first look at the instructions, will definitely be in accordance with the instructions to make recommendations for everyone.

We do any treatment, and one of the words I often say is to be conscientious and to do our best for the benefit of patients, which I think is very important.

Pineapple: Now lung cancer has minimally invasive surgery, abdominal tumors also have laparoscopy, why do ovarian cancer surgeries still have such a big opening?

Director Zou: In fact, there are still some controversies about open abdominal surgery and laparoscopic surgery.

Personally, I am actually a doctor who does open abdomen, does laparoscopy, and does robots. For our center, the proportion of minimally invasive surgeries is more than 75%. But I still want to say one thing first: the treatment we bring to the patient is not the way we are best at it, but the way that the patient is most suitable.

This is very important, as a comprehensive and qualified gynecological oncologist, should master the comprehensive technology, this patient is suitable for what technology to solve his problem, what technology to use.

M.D. Anderson, the most well-known cancer center in the world, is now doing open and laparoscopic surgical controls for ovarian cancer, but it may take at least 5-8 years to produce results.

Last year, when I was live streaming with Professor Irina of the United States, she said very intuitively that there are some special parts of the anatomy that cannot be removed with minimal trauma, and even the instruments that are so much better than the laparoscope cannot be removed, and the laparoscope still has some blind spots.

In addition, many of my tumor growth sites need to be opened after the anatomy is opened, and the doctor touches it with his hand, and minimally invasive is unattainable.

Another point, for minimally invasive surgery, because we will fill the stomach with carbon dioxide during the operation, blow the stomach like a balloon and expand it, so that all the organs in the stomach can be separated and the doctor can see clearly. And such a pressure on the abdomen will not lead to the implantation or spread of tumors, there is no corresponding evidence and data, and occasionally we will see some laparoscopic surgery, in the puncture of those holes, there are tumor recurrences.

We have plenty of evidence that open and minimally invasive postoperative recovery is not particularly different in the long run. The most important thing is to live well, and the wounds of the moment are secondary in front of life.

Pineapple: Just now you repeatedly stressed that the operation should be clean, but some people say that after she got ovarian cancer, she only cut one side of the ovaries, so what are the cases where only one side will be cut?

Director Zou: There are some reproductive system tumors that may occur frequently in adolescents or young women, or that need to preserve reproductive function, or some junction tumors, low-grade malignant ovarian tumors, which can actually be done, because there are too many types of ovarian pathology.

Pineapple: It seems that everyone will think that there are many targeted drugs for lung cancer breast cancer, and there are relatively few ovarian cancers.

Director Zou: Do you think that gynecological oncologists are not as diligent as other doctors, and there is only one bevacizumab for so many years. But in fact, I want to explain to you that these drugs have been clinically studied in gynecological tumors, but they are not beneficial in ovarian cancer or other gynecological tumors.

Not other tumors use good drugs, in the ovarian cancer use must be good, really must listen to the professional advice given by professional doctors.

Pineapple: The normative treatment for PARP inhibitors is to eat for two years, some people say that they have now eaten for two years, if you don't take into account the factor of money, do you need to eat longer?

Director Zou: Money is not the main consideration, because they are all enrolled in medical insurance. Now Olapali in the first line of maintenance therapy, that is, the initial treatment of stage III. IV. patients, we recommend eating for two years, but if there are some high-risk patients, he still has some lesions at the end of treatment, can prolong the time of taking the drug, but such patients are very few.

In addition, if the patient is in the platinum-containing regimen of chemotherapy to achieve remission, and then eat olaparib, after the recurrence of maintenance treatment, you must continue to take the drug can not stop, until the toxicity has been intolerable, or relapse again, do not eat.

Pineapple: There are more patients who relapse each year than there are new ones, what should I do after the recurrence?

Director Zou: The treatment after recurrence also needs to comply with the norms, and individualization must not be an individualization that leaves the norms, it must be an individualized choice based on the norms.

After the recurrence, we have two options: one is that we can have surgery, but we must cut it clean to benefit.

For patients who are initially treated, cutting clean means that all places are opened and looked at, and there is no lesion at all, which is called R0. There is also a satisfactory one called R1, that is, the size of a single tumor does not exceed one centimeter. Except for these two cases, it is called dissatisfaction.

For our relapsed patients, there is only one situation of satisfaction, that is, it must not be seen, not at all.

Therefore, the guidelines now also recommend that for patients with relapse, first look at it with a laparoscopic probe. Because there is no imaging test to locate all the small tumors, and when you explore, you may find that the tumors in the entire abdominal cavity are densely packed like a handful of sesame seeds.

If you should not do it, the doctor must stop in time, and I also want to appeal to the patient and the patient's family to understand the doctor's choice, so that you can benefit more.

For patients with platinum-sensitive recurrence, compared with clean and not clean, the survival time is three years apart, for patients, let alone three years, three months is also precious. So such a choice must be very precise, we do it.

The other tumor load is too large, and patients who cannot be operated on will undergo chemotherapy or chemotherapy combined with targeted therapy. There are also many chemotherapy regimens to choose from, and we have more than 20 kinds of chemotherapy drugs, which can be imagined how many chemotherapy regimens can be arranged and combined.

In the future direction of treatment, there will definitely be more accurate medical means, including a tumor organoid that I am currently studying, and I think it is also a very cutting-edge model in the world.

Pineapple: Can you tell us about what tumor organoids are?

Director Zou: Tumor organoids are a 3D structure that is cultured in a specific and serum-free culture environment after the tumor cells are digested. Its size is actually only a few tens of μ, and the size may vary depending on the pathological type of tumor. To put it in layman's terms, it is a slightly larger sphere of cells.

There are many ways to do drug screening now, either to do a genetic test for our patients and see what chemotherapy-sensitive genes it has. However, the heterogeneity of the tumor is very large, and it is possible that good results may not be obtained.

There is also a way to plant the tumor on mice to see what drugs are used to shrink the tumor. But the blood and genes are rat-friendly and change the type of tumor, so the final results are not necessarily very satisfactory.

Until the emergence of organoids, first, it can meet the culture of meta-generation cells, that is, from patients, what it looks like.

Second, there is no serum in the entire environmental process of culture, and the serum is peripheral, which may change some biological behavior. At the same time, it is a 3D matrix gum structure, which will give organoids more three-dimensional growth space.

We can use some of these organoids to do immunohistochemistry, the result is to achieve close to 100% anastomosis, and then such a cell sphere and the tissue in our body to do a whole genome sequencing, to meet the international standard is more than 85%, and our team's result has reached 95%.

In this case, some of these cell balls can be built in a similar in vivo microenvironment, do a drug screening, add different drugs to it to the organoid, and see the final result of its response to the drug.

At present, a lot of clinical research is still being done, so far worldwide, clinical trails registration should be 6 teams in the ovarian cancer related clinical efficacy verification, China I am the first and only one.

As the only cancer hospital in Chongqing, we have opened the first and should be the only tumor organoid transformation research laboratory in Chongqing, and we also want to do something with feelings, to achieve the ultimate in standardized treatment and personalized treatment of tumors, at least to give western patients a home that can be relied on.

Pineapple: What should I do with a review?

Director Zou: Whether it is a patient who is taking medicine or following up, we must review it regularly, and the review must be done when necessary, within two years we recommend to do an image within three months, then between 2 and 5 years, it is recommended to do at least once in half a year.

Because if the problem is found early, it is possible to do surgery, if the opportunity to operate is lost, the survival time will be shorter, so it must be standardized follow-up, ct and magnetic resonance must be done, can not simply look at the color ultrasound, may not be able to find some small problems or deep problems.

Everyone must not be afraid, the dose of imaging radiation is very low now, and the magnetic resonance is also radiation-free.

Pineapple: What can we do to reduce some of the ovarian cancer risk?

Director Zou: If there is a genetic mutation, first of all, I think genetic testing and family genetic counseling are very important. If you have a lot of ovarian cancer patients, breast cancer patients in your family, or men with breast cancer, prostate cancer, pancreatic cancer, etc., I hope you can come to do a genetic consultation.

At the same time, if you have a patient with a BRCA mutation, there is already evidence that oral short-acting contraceptives can reduce the risk of death from ovarian cancer. So for women with this type of mutation and who are relatively younger, we would recommend that she take this medication, but at the same time we need to rule out diseases such as fibroids or breast hyperplasia or benign tumors of the breast.

And we can do preventive surgery, and I'm sure everyone has heard Julie's story. Cut when it is time to cut, do not regret, wait until it is cancer, the loss may be more.

*Due to space limitations, only a selection of Q&A has been featured in this article. Remember to book the next live broadcast, do not miss a point of dry goods ~ ~

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