Our mission is to increase endometriosis awareness, fund landmark research, provide advocacy and support for patients, and educate the public and medical community.
Founders: Padma Lakshmi, Tamer Seckin, MD
×
Donate Now

Marc Possover, MD, PhD - Endometriosis and Pelvic Nerve Dysfunctions in the Pelvis

Marc Possover, MD, PhD - Endometriosis and Pelvic Nerve Dysfunctions in the Pelvis

Marc Possover, MD, PhD - Endometriosis and Pelvic Nerve Dysfunctions in the Pelvis

Endometriosis Foundation of America
Medical Conference 2019
Targeting Inflammation:
From Biomarkers to Precision Surgery
March 8-9, 2019 - Lenox Hill Hospital, NYC
https://www.endofound.org/medicalconference/2019

Dr. Seckin, thank you very, very much for the invitation. It's a really beautiful city. Over the last 10 years, 15 years, I've spent more time with my family. I didn't want to miss my children, my family. And now, it's time for me to come back to the meeting. I feel home. I feel home because I see some big star. For 20 years, I was a small doctor, and I saw ... I remember the big star of endometriosis, a small ... I'm part of you. I'm very, very proud to be here. Thank you so much for the invitation.

And I need the last 10 years not just to spend my time with my family but to perform all those surgeries. And maybe I'm a little bit like Harry. I perform more surgeries. I am writing a paper. I made some paper, but I spend my time to develop the neuropelveology. And the topic today is Endometriosis and the Pelvic Nerves.

And this morning, we had a question, how to do the diagnosis of the endometriosis. And you need surgery. In my opinion, if you have a patient with endometriosis, with infiltration of the vagina, you don't need surgery to make the diagnosis. You see the diagnosis in the sacral Douglas. The second situation where, in my opinion, you don't need under a laparoscopy to make a diagnosis is when you have endometriosis of the pelvic nerves because the diagnosis is a clinical one, and you have to confirm your diagnosis with a laparoscopy.

So in the pelvis, we have a lot of nerves. We have a somatic nerve, we have an afferent nerve, we have an efferent nerve, we have a visceral nerve. An afferent nerve is all the fibers that bring information up to the nerves. So when speaking about inflammation, and I'm sorry because inflammation is not painful. Endometriosis is not painful either. What is painful are the nerves. If your patient feels pain, it's not because she is affected by endometriosis, but because endometriosis affects the pelvic nerves, and the pelvic nerves bring information of pain to the brain, and that is a pain.

You have the efferent fibers, fibers going down. When you have endometriosis or another pathology of the pelvic nerve, you have always had pain and dysfunction because there's a nerve going down. And you have in the pelvis two kinds of nerves, the sympathetic and the parasympathetic nerves or autonomic nerve are always affected by endometriosis. So that's the reason why endometriosis is painful. And sometimes you have an effect, you have endometriosis to the somatic nerves.

The inferior hypogastric plexus are the small nerves, autonomic nerve everywhere in the body. And we were speaking about the different location of endometriosis in the pelvis. It's very interesting. If you check the anatomy of the sympathetic nerves and the pelvis or in the entire abdomen, you will found exactly the endometriosis as the same place you will find the sympathetic nerve. And maybe not all sympathetic nerve in the pelvis. Only in a woman, you have the neural peptide epsilon sympathetic nerve located in the pelvis. And this nerve is involved in the most powerful vascular grow factor in the pelvis and probably are involved in the pregnancy and in the growth of the endometriosis.

So all patients affected by endometriosis have because of the inflammation of the sympathetic nerve that called the inferior hypogastric plexus. And when this nerve is affected by endometriosis, the patient will have pain, visceral pain in the entire pelvis. The patient is not able to say I've just pain on the right side or on the left side. She will say, "I have pain on the entire lower abdomen," maybe a little bit more on the left, on the right, and very, very important. And that is key to the diagnosis.

When you have an affection of the sympathetic nerve, or parasympathetic nerve, or autonomic nerve, you will always have vegetative symptom because the pelvic plexus is a vegetative nerve system. So the patient will have all these vegetative symptoms. And when you ask the question, how to make the diagnosis, you're like a criminalist. You have to check, to look at your patient. You have to look at your patient in the thighs, and you will make the diagnosis before you start with the examination of the patient.

When you have an irritation of the nerve, when it's an irritation of the somatic nerve, like sciatic nerve, the patient will develop irradiation pain going down. When the patient has an irritation of the inferior hypogastric plexus, the pain is going up by following superior hypogastric nerve and then the superior hypogastric plexus. And that's the reason why all patients affected by endometriosis always suffer from back pain because the nerve is following the back. The patient will have back pain, cranial irradiation.

And when we have patient today, we see a young patient, 18 years old maybe affected by endometriosis, and every month she's suffering from pain, and sometimes she's falling down in syncope. So it's easy to say, "Yeah, it's a small lady. She's maybe a little bit sorry." But it's what we heard about endometriosis, a little bit crazy. No, she's not. If a boxer is giving you a punch in plexus Solaris, you're knocked out. And it's exactly what endometriosis can do with this patient. When you have really an over-activation of the sympathetic plexus and the solar plexus, the patient will fell down in syncope.

And the patients are affected by anxiety, oppression. It's normal. it's because of the activation of the sympathetic nerve system. It's not a question of here. It's a question of here. When you have overactivity of the sympathetic nerve, you will have your fragment spasm, lot of patients affected by endometriosis even when they don't have endometriosis of the diaphragm or the lung, very, very certain. She will say, during the main bleeding, "I have some difficulty to breathe." Why? Because she has an activity of the sympathetic nerve system. She will have diarrhea, bloating. She will gastric pain, shoulder pain on the write. We all think about endometriosis of the diaphragm. But on the left, it's because of the overactivity of sympathetic nerve system.

And we were speaking about immunity in endometriosis. So sympathetic nerve system control also the immune system. The patient affected by endometriosis has trouble over the immunity. But it's true you can make the diagnosis when the patient is sitting in front of you during the consultation. When you have overactivity of the sympathetic nerve system, I don't say that you can do the diagnosis of endometriosis without examination. I say you can make the diagnosis on overactivity of the sympathetic nerve system. And the most frequent etiology in young woman is endometriosis. So vegetative symptom. You will found a dilation of the pupil. It's typical patient affected by endometriosis, dryness of the lips, on the mouth, you see that. The patient will have flashing like. It's typical. You have patient pallor in the face. She seems to be very tired. She has anxiety. She has depression. You will found flatting. You will found tachycardia, maybe nausea. You will see all this even when the patient is coming with your office. She's pallor in the face. "Good morning lady." And you will feel in the hand.

So you have the diagnosis after one minute. Just look your patient and take your time to do that. So when you have overactivity of the sympathetic nerve, you have sympathetic nerve everywhere in the body, also in the uterus. So you will have trouble of the motion of the uterus that maybe explain the retrograde menstruation. You will have an increased risk for ectopic pregnancy because the sympathetic nerve controls the motion of the tube. The patient will have polymenorrhea, dyspareunia. Apareunia because the upper part of the vagina is controlled by the sympathetic nerve, the lower part by the pudendal nerve as well as the vulva.

When the patient and overactivity of the sympathetic nerve is typical, probably also in the city of New York, when the is going down, you will see that all patient are not able to empty the bladder. That's the reason when the is going down, you will see more bladder infection in people because they are not able to void the bladder properly. And you will see exactly the same patient affected by endometriosis. If you send your patient on the toilet and you check by sonography, you will see a post void residual volume from more or less 40 to 60 percent. And that explains while patient affected by endometriosis during the menstrual have to go quite often on the toilet, imperiosity, pollakisuria, increased risk of bladder infection because they are not able to empty properly the bladder. Over time, they may develop a bladder over-dilation, especially if you perform surgery before and you cut a lot of nerves.

You have the same in the bowel. 60% of the patient affected but endometriosis is suffering from what we call an outlet constipation syndrome. And gynecologists will have to be aware that when we see such a bowel, it's something pathologic. It's an elongation of the bowel with a lot of kicking, and it will use a lot of symptom typical for an outlet constipation syndrome with a lot of bloating, pain in the back, and in 30% of the patient, pain going down in the anterior face of the legs. And that is typical for this pathology, the outlet constipation syndrome.

When you have cut, you've performed surgery and you have a resection of the rectum, you have to keep in mind that the voiding nerve of the bladder, what we call the parasympathetic nerve is located deep in the pelvis. The parasympathetic nerve from the left bowel up to the last structure is coming from the sacral nerve 2, so sacral nerve route 2. That means when you perform a bowel resection and you cut all this nerve and use paraplegia of the entire left big bowel, the right is controlled by the nervus vagus. That means supposed you had performed nice surgery, you cut all the nerve, your patient nerve to void the bladder with a catheter, and she is suffering from chronic constipation, you send the patient to the general surgery, and he said, "Let's cut a part of the bowel. It will help." No. It will not help.

If you want to do surgery, and you want to help your patient, you have to perform a hemicolectomy. You have to remove all the left side because the parasympathetic nerve is controlled ... the left big bowel is controlled from the pelvis. For more or less 10 years, I make a study. I got a patient. I'm a neuropelveologist today. That means I was dealing with pacemaker and electrode. I put the device on the nerve and the pelvis in order to have a recovery of bladder function in the patient after surgery. And I make a study in order just to check why patient after bowel surgery or after endometriosis surgery have such difficulty with the bladder. And over the last 10, 15 years, I always hear, "Okay, when you do surgery, you cut all parasympathetic nerve, so the patient will develop atonia of the bladder and the rectum."But the first reason for bladder atonia is not the motor atonia of the bladder by cutting the parasympathetic nerve, but the cutting of the sympathetic nerve, the nerve of the feeling.

And if you see this publication, all the data, if you perform bowel shaving, rectum shaving, discoid resection or segmental resection, you don't make any difference. The difference between after and before the surgery in term of bladder function is if you perform parametric resection because the nerve are in the parametrium, not in the bowel. And the first reason for bladder atonia is the over-dilation of the bladder over time. When you perform nice surgery, you resect the sacrouterine ligament, that means you will resect part or the big part of the sympathetic nerve, the feeling nerve of the bladder. That means your patient will not fill properly, so time when she had to go on the toilet. So instead to go every three, four hours on the toilet. It will be easy if she has walked in life, she has kids. So if she can go maybe every six hours on the toilet, it makes her easy, but it will disrupt her bladder because of a six, seven, eight years because of over-dilation of the bladder, so bladder function will decrease, and the patient will be not able to void the bladder anymore.

That means when you're performing radical surgery in the pelvis, surgery of the sacrouterine ligament, you have to control the post void after emptying the bladder, and you have to advise your patient to go at least every three, four hours on the toilet. And not just three times per day. So now, let go to the sacral plexus and the sciatic nerve. I perform the first surgery of the sciatic nerve 2004, for a long time. And that time, the comment was marked its nice surgery. But maybe you will see one or two cases in your life of endometriosis of sciatic nerve. I make another choice. I didn't go further to the meeting of gynecologists to present my data. I went to a meeting of orthopedics, neurosurgeons, and neurologists. And I said, "Hi guy, if you have a young woman 30, something like that, suffering from a sciatic, we all read cyclical sciatic pain. The patient will suffer from sciatic pain every month during the mens bleeding. It's not true.

When your patient is affected by endometriosis of the sciatic nerve, she will have permanent pain all the time, maybe with increased during the mens bleeding, but she will have terrible pain, neuropathic pain, somewhere between 8 and 10. And I say to guy, if you see such a patient, think about endometriosis. And at that time, I see from year to year, I got more and more and more patients affected by endometriosis. Here, you see a patient affected by endometriosis of the femoral nerve. And the diagnosis, you can do before the surgery. Pain have pain, a lot of pain. She has lots of patella reflex. You will see a neurodeatrophia of the quadriceps muscle. And she will not able to walk properly. We heard before if you have endometriosis of the sciatic nerve, the patient have to come in your office in a wheelchair. No. So sciatic nerve, it just involves in the control of the buttock and the toe and the ankle. But the main nerve for the walking function is the femoral nerve.

And so far, you don't cut completely your nerve. Even if you resect 70, 80 percent of the nerve, and you have to do that, if you resect, if you have endometriosis of the bladder, you will resect this part of the bladder, the bowel is the same. And you have exactly to do the same with the nerve if you want or not. I know that we have only femoral nerve on the left and one on the right. But when 80% of the femoral nerve was destroyed by the endometriosis, you have to resect. Otherwise, you will have to do the next surgery six months later. And here you will see the far you don't resect all the sides of the nerve, and you'll here that is the right femoral nerve, and we remove the endometriosis.

And there's a lot of training, physiotherapy. And you see, here, it's not a lot of rest of the femoral nerve. Just few millimeters here, resect this part too. The nerve will recover. Never cut completely a nerve. But when you resect a nerve, the fiber you cut will use the rest of the nerve to pass over the lesion you did. So the sciatic nerve. The sciatic nerve, I know that is becoming more and more modern to speak about endometriosis of sciatic nerve, where different kind of endometriosis of the sciatic nerve. And at that point, I want to really say you have to learn how to make the diagnosis. It's not just the patient of sciatic pain, and now, I have to do the surgery. We are not technicians. We have to make first a diagnosis. If you have a suspicion of endometriosis of sciatic nerve and you don't know where you have to look for the endometriosis of the sciatic nerve, maybe you will make a nice dissection of the sciatic nerve, but you will not remove the disease.

So the first kind of endometriosis is endometriosis of the lower part of the sacral plexus close to the sacral bone. It's a typical endometriosis of the parametrium, deep infiltration endometriosis probably with a filtration of the ureter because the ureter and the sacral nerve route is a few millimeters each from the other just a few millimeters. And when you have an endometriosis at this place, you will have involvement of the sacral nerve route S2, S3, and S4. S2, that means the patient will develop a sciatic pain in the inner border, dorsal aspect, inner board of the thigh, down to the 2s because of S3, S4, she will develop vulvodynia, perineal pain, perineal pain mean, a pudendal pain on the same side. And because nerve involve in the bladder function are located in the sacral nerve route S2, S3, S4, the patient will develop an hypersensitivity of the bladder. If the endometriosis only irritated the nerve, that means the patient have to go every hours on the toilet to pee.

But if the endometriosis destroys the nerve, she will have also pollakiuria but not because of hypersensitivity of the bladder, but because she's not able to pee. So she has high volume after voiding of the bladder, and she will develop the pollakiuria. That means when you have a patient with deep endometriosis, parametric infiltration, mostly on the left side, you see maybe that the patient present dilation of the ureter, you have to ask the patient, "Do you feel pain in the legs? Do you have burning pain in the vulva, in the perineal or in the perineal rear? Do you have to go every hours on the toilet?" When they answer, "Yes," you have high suspicion of an infiltration of the sacral plexus.

And we are lucky because this kind of endometriosis usually ties to nerve but it don't grows inside the nerve. So usually, it's not need to resect the sacral nerve route. But if you have to go there and remove the endometriosis, of course, you will cut all the splanchnic nerve on this side. That mean the patient will be able to void the bladder from the other side. You have maybe to use a suprapubic bladder catheter. And please, don't go on the other side. Otherwise, the patient will have to void the bladder using a bladder catheter.

Now, we are coming to the true sciatic nerve endometriosis, the super cardinal portion of the sacral plexus, that means, we are above the uterine vessels and antennal vessel. And then the patient will develop the typical sciatic pain. L5 is involved in the dorsiflexion of the toe and of the foot. S1 is typical. The plantar flexion of the toe and the Achilles reflex. The patient affected by this endometriosis, when you have a destruction of the nerve will be not able either to have a plantar or dorsal flexion of the toes. So when you have a lesion of S2, from S2 you have one very, very important nerve, is the inferior gluteal nerve. This nerve control all the gluteal muscles, the main gluteal muscle. That mean the patient has a lesion, destruction of S2, she will have a destruction of the inferior gluteal nerve, and while walking, she will develop the typical Trendelenburg sign. That mean, normally, when you are walking, you will keep up the hip. This patient will be not able to keep up the hip. So hip will be down while walking.

And when you have the patient of your consultation of the stool, just look. Here she had endometriosis on the left side. What do you see? Typical neurotrophy from the gluteal muscle. And it's exactly what I said before. Neuropelveology is clinical observation. You have to make the diagnosis by open your eyes. Here, the pudendal nerve, the pudendal nerve, we have two, one on the left, one on the right. It's involved in the control of the sphincter. But look this patient. If I'm looking once again, I ask the patient to contract. And what do you see? The anus is going in this direction. Normally the clitoris, the vulva, and the anus are on one line. So that means when asking the patient, "Can you contract the anus," the anus will go up following the midline. When the anus is going on the left side, that means you have a destruction of the pudendal nerve on the right side.

They are are small details, really small details, but open your eyes, and you will see. And point. Here S2, you have the sacral nerve route, S2. S2 is involved in the flexion of the big toe, S3 of all toes. Here, you see. It's during a procedure. I'm putting electricity on S2 and S3, and I have a contraction. That means, if you want just your patient, are you able to go on the top. She will say yes. Yes. That means she had preservation of the Achilles reflex. But if the patient has some trouble of the equilibrium because she loses the function of the big toes, so big toes is very, very important to control the pronation of the toes. So that means the patient will have some difficulty.

Make the diagnosis with the right question and just see your patient. And now, I will show you sciatic nerve because, over the last few months, I get some video from a colleague that perform very, very nice dissection of the sciatic nerve and asked me, "Marc, I have a problem. I know that the patient has endometriosis. The radiologist told me. Yes, there is probably endometriosis of the sciatic nerve. I made a dissection, but I didn't found the endometriosis of the sciatic nerve." And that is the point. You have to know before the surgery where you are to look for the endometriosis of the sciatic nerve. You cannot through with your and you open everything just to look, where is my endometriosis? You have to know that before the surgery.

And let me show just two cases. Here patient, typical sciatic pain, L5, though we are here in this area is the cranial part of the sciatic nerve, L5 and S1. Though you will see patient have a loss of the Achilles reflex, you see here and neurotrophy from the calf on the left side. You will see. You will make the diagnosis by looking the shoe of the patient because the patient have a steppage gate. She have no dorsiflexion of the ankles. That mean she will destroy the tip of the shoe. So you will make the diagnosis by looking the shoe. And then when you make your examination, you will found reduction of the Achilles reflex, no front plantar and dorsal flexion of the ankle. You will find the typical. But you will never found, in endometriosis of sciatic nerve, vulvodynia, pudendal pain because we are in this area, not in this area.

And then you will confirm the diagnosis by doing the laparoscopy, and today, we have performed more than 300 cases of endometriosis of sciatic nerve. So when I remember the college 2004, Mr. Possover, you will see one or two cases on endometriosis of the sciatic nerve in your life, no. I'm seeing more and more every day. And for several months, I send some letter to collect, please, help me. We have a big, big, big problem because there are still college giving hormone to treat endometriosis of sciatic nerve, and that is a big mistake. If you give hormone to treat endometriosis of the bladder and the rectum and you have to resect two centimeters instead of one centimeters, okay, it's not a big deal. But if you're missing an endometriosis of the sciatic nerve and you have to resect five millimeters from the sciatic nerve, instead one millimeter, because you try with hormone for the six months, then you made a big, big mistake.

Here, you see, it's not a video. And it's like the endometriosis of the pelvis. Sometimes you found a lot of fibrotic tissue, sometimes. Sometimes you found endometrioma. And here, that was a patient I found an endometrioma in the middle of the sciatic nerve. And when I made my paper here, very interesting, I had 178 of endometriosis. I sent more or less all patients to MRI before. The radiologist made the diagnosis of suspicion of endometriosis of sciatic nerve in only 21 patient from 178. So if you go the radiologist after and said, "I found endometriosis," or show, then they will see. But before the surgery, most of them will not see. And here, you see, I have to resect part of the sciatic nerve. I found chocolate fluid within the sciatic nerve. You have to do your job. But you have to be aware when you go to this field of surgery, and in my opinion, it's not gynecology anymore, it neuropelveology, you have to completely control the situation.

You can kill the patient there, and you have to finish the procedure because if you try and in the middle of the procedure, you stop, for the next surgeon, it will be awful because he will not just found endometriosis, the scar tissue from endometriosis, but also your scar tissue. So you have only one shot if you want to do this. And here, you see a patient, I resect more or less 50% of the sciatic nerve. This is part of the sciatic nerve is destroyed by the endometriosis. You have to resect this part.

Now, I show you another endometriosis of the sciatic nerve. The same name. Patients have the same pain, sciatic nerve, but she have a Trendelenburg sign. She have a deviation of the anal. She have difficulty to sit, difficulty to sit, of course, it's an Alcock's canal. It's a pathology of the pudendal nerve. No. No, no. You can also such difficulty when you have pathology of the pudendal fibers within the sciatic nerve or the sacral nerve route. And you have this neurotrophy. So it's a typical endometriosis of sciatic nerve.

And look, here we have the sciatic nerve. We make a nice dissection, but we didn't find endometriosis. And it's exactly what happened the two colleagues. They perform nice dissection of the sciatic nerve didn't the endometriosis and said, "Where is the endometriosis?" They didn't make the diagnosis. The patient has a problem. She has a lesion of the pudendal nerve. She was not able to sit. She has a problem with the liver too. She has a problem with the dorsal cutaneous femoral nerve. That's the reason why she had pain here and in this area, and she had the gluteal neurotrophy.

So I know that when I have this constellation of this four nerve, my problem will be not within the sciatic nerve but below the sciatic nerve. And here, it's a typical endometriosis of the sacrospinous ligament. We have to resect all and part of the obturator muscle. We will have to resect the sacrospinous ligament, and sometime you will see some black fluid coming out. And then we will have to dissect. Here, you see, that is the pudendal nerve. Here, you have the dorsal femoral cutaneous nerve. And that is the reason why this patient has this patient. So you have to make the diagnosis, what you have to do before the surgery.

And in this situation, we had to resect very large nodule from the obturator muscles, the sacrospinous ligament. Here, we have the ischiorectal fossa. It's true. That is more difficult, that oncological surgery. I was oncologist for 15, 20 years, and it was easy, my job. Oncologist, you have just to cut. In endometriosis, you cannot just cut. You have to spare whatever you can spare during the procedure. And sometimes, we have measure endometriosis. And we make a paper with 46 patients where we perform resections at more than 30 to 70 person of the sciatic nerve. And here, you'll see that the patient will have just a small lesion, a really small lesion of the peritoneum, and at least we found here huge endometriosis. We had to resect part of the obturator muscle. Here it's the psoas muscle we're to resect.

You have to know where you are when you do this kind of surgery because we are dealing with the gluteal vessel, the pudendal vessel, all these big vessels below the obturator nerve. If you don't know properly the anatomy there, you can simply kill your patient. So in my opinion, and it was one of our talk in the meeting in before Christmas about this kind of surgery. Who has to do this kind of surgery. And your answer was probably not the normal gynecologist. That is surgery from neuropelveologist at least because you have to able to do the diagnosis, the proper diagnosis before you start with this surgery.

When I'm in the step, I cannot say, "Oh, here's the sciatic nerve. I'm afraid. I cannot cut. Please call Mr. Possover." Mr. Possover is in Zurich. He cannot call me in two minutes to New York. So you're alone when you do this surgery. And if you stop the surgery at this point, you will not help the patient, and you will have a problem with me if I'm the next surgeon. And here, you see, we resect all the pelvic muscle, pelvic floor muscle, and that is exactly what you have to expect. When you deal with such kind of endometriosis, you have to know that maybe you will have to do something on the bowel. You will have to do something to the ureter. You will have to do something, whatever. You have the be able to do that by your own or you have a good team able to walk with you.

And with this huge resection of endometriosis, it's exactly the same that I said before. If you don't cut the nerve. If you give the patient the day after the surgery, pregabalin, and you send the patient to the physiotherapist, and the best is to advise the patient to use high heels. That is really the best training, post operative training. The patient will recover. She will recover, but it takes three to five years. You see, we have a significant improvement in pain. But the patient will recover the motor function after three to five years.

It's not I do the surgery. At the six months, the patient is happy. The pain on ongoing up to six, eight months, and then the pain will start to decrease. It takes really a lot of time to repair after sessions kind of ... So that means, when you have a suspicion of endometriosis of sciatic nerve, you cannot give hormone, you have to the patient to somebody who is able to do this kind of surgery. Don't wait. Otherwise, we will have a problem. And for me, I'm the founding president of the International Society of Neuropelveology. And if I have a message today is learn at least how to do the diagnosis. How to recognize a condition of the pelvic nerve in order to not miss such kind of thing. And you can make the diagnosis with your eyes.

And we make an e-learning program online. You go just on our homepage, and you will learn how to make the diagnosis. There is an exam in the end. But believe me, the exam is very difficult. To become a neuropelveology, mean to learn the neurology. And not just the sciatic nerve or obturator nerve. You have also to know of a condition like spinal cord injury and all these things. And I thank you very, very much once again for the invitation and your patience.