With colon cancer increasingly found in younger patients as well as a leading cause of cancer-related death, Aparajita Singh, MD, MPH, director of the UCSF GI Cancer Prevention Program, offers an important update. She presents the pros and cons of various tests – including Cologuard and advanced options such as CT and capsule colonoscopies – and helps providers assess risk, know when to start (and stop) screening, and be prepared to answer patients’ questions.
it's my privilege to be here today and talk to you something I'm really passionate about. That's colon cancers breathing. So I have no disclosures. All right, so my objectives for next 40 45 minutes are we will talk a little bit about epidemiology of colorectal cancer and then I'll focus on existing and emerging screening modalities for colorectal cancer screening. In my talk. When I say C. R. C. I refer to colorectal cancer. Uh and then we would talk about when to start and stop cancer screening for uh these patients. And also I would briefly mention new colon polyps surveillance guidelines based on how your patients would be seeing a newer interval for polyps that didn't have the past. So let's get started. Epidemiology for colorectal cancer. We all know colon cancer is common and lifetime risk of colorectal cancer is about five in this country. It's the second leading cause of cancer related debt in the U. S. And it's the third most common cause of cancer in this country as well. Based on some estimates. Uh four year. About 147,000 new cases are diagnosed just in this country. And out of these 147,000 roughly, 50,000 of these patients die from colorectal cancer. So here you can see it's a significant public health problem, incidents of colorectal cancer is rising in younger patients. So all the colon cancer screening modalities that have been out there. We have noticed that risk of colon cancer and death from colon cancer is actually going down in patients 50 and above because those are the patients we have targeted in the past. However, for many unknown reasons In the age group of 20-49 years, um the rates are rising up both for cancer incidence and mortality. Despite these alarming numbers, screening rates are below target. So based on one estimate in 2016 in this country, 1/4 of eligible adults had never had any type of colon cancer screening, neither by stool testing or colonoscopy. And these are very alarming numbers because unlike many cancers, colon cancer has a pre cancer stage for the most part. And cancer is not just early detection, which we target for several cancers like breast cancer, Where the screening is targeted for early detection in in in colon cancer ward cancers are actually preventable with timely screening. Uh still, we have significant proportion of patients who are not getting screened. So what causes colon cancer there? If you Look at this pie chart here, you can see that about 65-85 of colon cancer is sporadic and these are considered average risk patients, patients, about 10-30 would have some type of family history of colon cancer. A smaller fraction, which is about 3-5 of these patients here in this chart, the colon cancer is due to Lynch Syndrome, which is a kind of mutation in mismatch repair genes. A smaller fraction is about less than one are due to some other various syndromes like F. A. p. um and there are newer polly poses syndromes that make further smaller fraction here. So here you can see majority of colon cancer is sporadic. So there are several known risk factors for colon cancer and many of these are obvious. But I have a slide here just to show which are the known risk factors. So age, family history are the two most important risk factors that we know. Other risk factors are raised gender. So it's more common in men compared to women smoking, obesity, different genetic cancers in Rome's inflammatory bowel disease history of abdominal radiation, prostate radiation, HIV acromegaly, any transplant history like kidney transplant, diabetes are other risk factors. So here we can see that there's certain defined risk factors. But other than age and family history and and raise for some part, we do not necessarily have stratified risk, uh, screening modalities, like, for example, we do not screen men differently than women. So we do hope that in future these risk factors may be utilized to stratify there and modalities for screening, but as of now, they do not exist. So family history, it's an important risk factors for colon cancer. And in the slide here, we can see that patients who do not have family history for colon cancer compared to those those with first degree relative of colon cancer. Their lifetime relative risk is about 2.25 and those diagnosis of colon cancer in a younger Family member, like those with less than 45 years, the risk goes up by 3.87. And if your patient has multiple family members with colon cancer, the risk is further higher. So therefore when you see a patient having a family history of colon cancer is extremely important to have that discussion and make the right referral for patients who have fostered very relative with colon cancer. If I'm counseling those, I would discuss colonoscopy as the preferred modality over school based testing based on the elevated risk. All right. So what are the screening modalities uh that exists and recommended by our different societies? So there are multiple societies. U. S. B. S. D. F S E G E G A S. G. Asco american Society of Clinical Oncology and CCN. They all have different recommendations at certain level. But I I'm going to summarize multi society Task force screening recommendations that came out a few years ago because they give a nice year of different testing options that exist so appear when testing includes fit testing which should be done every year or colonoscopy. And Tier two testing options are fit physical DNA also known as follow guard and and the other name you may hear for that is uh stool DNA testing that's multi uh targeted to DNA testing. Empty S. D. N. A. Is the other name you may see around. Other options are city kahlan ah graffiti also known as virtual colonoscopy or flexible Sigmoidoscopy Dear three testing is a capsule colonoscopy. Um as as the last option. Other emerging modalities are to um sorry blood testing for certain and here you can see that multi Society Task force did not include that testing as a preferred modality. So some of the new latest guidelines, american College of Gastroenterology just a few weeks ago published their updated screening guidelines. That may be a good resource for you. U. S. P. S. D. F. Is also actively undergoing revision for their screening recommendations. The draft came out a few months ago and the final version is about to come out very very soon this year. So from the e. c. d s 2021 latest guidelines uh primary screening modalities. They recommend fit and colonoscopy and here is a screenshot. You can see that they recommend colonoscopy and fit testing as a primary screening options. And this is a strong recommendation for other screening modalities. They say we suggest consideration of following screening test for individuals unable or unwilling to undergo colonoscopy or fit testing. So how I'm going to take home Uh these guidelines is when I see a patient, the discussion should start with the 5th test or a colonoscopy And uh if they are unwilling or unable to do, then go to tier two testing. Which party listed here and here is against some info from ACDC latest guidelines about fit testing, sensitivity and specificity. It's important to have this discussion with the patient. That sensitivity of fit test is about 80 and specificity is 94 for colorectal cancer. So, fit is more of a diagnostic test and you are mainly trying to diagnose a colon cancer. If your patient has a preference for detection of polyps, uh, then fit is not necessarily the best test. So as you can see, fit is detecting the blood that's being released from the large polyps or cancer. So any small polyps is not going to have any any bleeding. Uh, small flag polyps, especially societal serrated polyps are not hyper vascular and they are less likely to have bleeding. And those polyps are also more likely to be missed by fit testing. So the numbers shown here are for cancer detection, not for polyp detection. And that is an important discussions to have with your patient. What is their goal for detection when they undergo the testing and fit testing is non invasive, no risk to the patient. And many times patients when they are offered fit testing, they should be considered that a positive result would require a colonoscopy and they must agree to annual fit testing as well. Now, moving on to the second roll, multi targeted to DNA testing, also known as Hildegard. So color guard combines both fit and DNA testing. So because of this nature, it's more sensitive and the way it's designed to be more sensitive, it lowers the specificity. So cola guard is more likely to generate false positive results and long term reduction in political cancer incidence and mortality is unknown with boulevard. Therefore you can see multi society task force does not that list follow guard str one test and also in their latest guidelines. They do not list color guard as the preferred screening modality. And I'll talk a little bit more about that in my slides coming up. Uh 79 is the blood test which has much lower sensitivity and very high specificity, but again it's not a preferred modality for testing. And HCG does not list this as an option to discuss as well. So a little bit more about fit testing. Fit testing is fickle immuno history. Chemical testing, also known as I. F. O. B. T. So it's kind of a fecal occult blood testing which uses antibodies to detect lobbying protein from human hemoglobin. So unlike old fashioned wire based testing, which would you know, generate lots of false positives because there was detecting more him with a peroxide it reaction and that would detect nonhuman him as well. And uh that requires multiple dietary restrictions. Fit test is much cleaner and patients do not need to have any any any restriction of their diet like holding aspirin, Coumadin or any dietary restrictions as well. And unlike GFO Bt, which was the old fashioned again, wire testing that would detect blood loss coming from upper Gi tract as well. Uh fit does not detect upper gi blood loss because uh hemoglobin released from upper Gi tract is partially digested and would not be detected by this new based um antibody based uh testing. And so therefore it's more specific. Your chronic blood loss And only one sample for you There is needed in this country, but some other countries actually do fit every 2-3 years as well. All right. So now a little bit more about color guard, also known as fit D. N. A. Testing. And the other name again is multi targets to D. N. A. Test empty S. D. N. A. Testing. So, uh, this is the sensitivity is about 92 for color guard compared to fit, which is 80 sensitive for detection of colorectal cancer. Uh, the sensitivities and specificity vary for polyps. Uh, and these numbers are for cancer detection. Color guard again detects DNA musicians on top of doing the fit part of the testing and it's protecting carreras and methylation markers as well which are seen in the setting of colon cancer and large polyps. The disadvantage of polo guard is it's expensive. So a typical fit test will cost about 40 to $60. But the color guard can be 606 or $650 depending on the pair. So even if you do annual fit testing, uh it's still much cheaper compared to call of our uh done every three years. Uh And the way it can be patients may like it because it has to be done every three years. And like every year for a fit test, Color guard is now covered by Medicare and it's approved FDA approved for colon cancer screening. So one other criticism of cola guard is because of very high sensitivity. Uh for this test, it's likely going to generate more colonoscopy is downstream. So overall cost, how that compares remains questionable And therefore this was not included in Tier one testing options. All right. So now moving on to city Colonna graffiti. So city Colonna graffiti, also known as virtual colonoscopy. It uses city data to generate two D. And treating display of colon and rectum. It's minimally invasive. Uh But it does need small amount of prep and generally the prep is much smaller. For example, it's just a little bit of help relax and magnesium uh laxatives for this procedure. Unlike a colonoscopy which needs a full politely uh and patients have to be able to lie in a certain position and a small rectal tube is inserted to insulate the colon. And we see the Colonna graffiti. There is no need for ivy sedition and actually no need for I. V. Contrast as well. So patients who have kidney issues can easily undergo because the conscious is is just a reproduction situation. Scan time is very quick and uh you know, it has a quick interpretation. The disadvantages of city Colonna graffiti are of course the amount of radiation and it can miss small polyps. And um it's not designed to detect polyps less than five millimeters. So uh that is one disadvantage and flat polyps. So as you can see, it's designed to look for protuberance polyps and many societal serrated polyps, which are super flat. And sometimes even with optical colonoscopy, very hard to detect would be easily missed by a city Kahlan ah graffiti. So that remains a bigger concern. And radiation risk of it needs to be repeated everything five years. But newer generation scanners are actually the amount of radiation has literally gone down pretty minimal. So not that much of concern. But the cost remains a concern not approved by I think Medicare doesn't pay for it. Uh So uh pear issues are exist, but the bigger concern with city Kahlan ah graffiti is approach for extra colonic finding. So in one study, there was about 15% of patients undergoing cp Colin ah graffiti. And those were average risk patients had some incidental findings of splenic lesions liberalization that needed for their testing. So it remains uncertain how much harm and extra costs is created by those incidental Omar's. All right. So the next option is capsule colonoscopy that patients sometimes read online and asked us. So capsule colonoscopy is FDA accrues only for use in patients who have had an incomplete colonoscopy. An example for that would be a patient has multiple adhesion, scarring and they have extremely tortuous colon and it's not possible to safely reach their see them. So very rarely those scenarios happen. That would be a good patient for this kind of uh capsule study. And also patients who are not candidate for colonoscopy, uh you know, can tolerate prep, they have difficulty swallowing. Uh they have their high risk for sedation like severe heart disease, lung disease patients would be the other category. Capital colonoscopy is not approved for screening. Average risk persons. So that excludes many of the patients that you see. And actually the other issues are it needs more extensive prep. So here you can see a few images. I try to put um you don't have this at UCSF. These are from uh pill cam images showing how extensive uh needs to be to be able to see these images on on the capsule camera. When we are doing colonoscopy. We have the advantage of having a water flush and a small amount of you know, 10 stickies tools we can easily wash off, but with the capsule, that option would not exist. The other issue includes bubbles that happen again. An optical Fillon, Oscar P can wash those off. But we are an option. And the way capsule colonoscopy is designed that patients have to undergo extensive prep for the capsule. And ideally they are supposed to have a colonoscopy the same day if there is a finding but logistic arrangements, it's going to be very complicated. Try to create a program like that. So even for a small fraction of patients who meet the indication, um it's going to be challenging H. B. This. Alright, so another test that is available patients ask about but a CG latest guidelines suggest against using it. I have never ordered it but patients would inquire. So Peppy Proco Poland 20 which is a methylated 79 DNA. What is It's FDA approved but it has limited sensitivity and its role is limited to patients who have refused colonoscopy or any stool based testing like fit or follow guard. It could be considered as an option but not suggested to use by the latest guidelines. Yeah. Other old fashioned tests that do exist but should not be used. Our variant enema and uh Wyatt based testing on digital rectal exam uh should not be done anymore. Alright so now coming to the important question like when to start screening. So Dr Geller son and I were speaking before we started you know starting screening at age 45. So this recommendation is not new American cancer society actually started recommending starting at 85 in 2018. And this um uh you know everyone paid attention when U. S. B. S. D. F. They published their draft guidelines last year uh to start to recommend starting at 45 that's likely to come up in their final version very soon as well. And a. C. D. S. Latest guidelines say They recommend starting at 50 but they suggest starting screening at 45. So the bottom line is we should offer colon cancer screening to our patients starting age 45. And that does not necessarily have to be a colonoscopy. A fit test is an is an equally acceptable option for average risk patients and generally pairs uh start paying for it. Uh Once you S. T. F. U. S. P. S. T. F uh finalizes it. So I'm looking forward to that. And the criticism for uh starting at 45. Well let me go back here is is if you see in the age range of 45 50 49 we have roughly 2021 million americans. So opening, you know screening let's for example, colonoscopies lodge to those patients. The concern is would that take away slots from older patients who have much higher risk of colon cancer. So that remains to be discussed. And at the same time, 90 of colon cancer occurs in patients, you know, above age 50. And patients less than 50 make up only 10 of colon cancer patients. and the bigger rationale to lower the age to 45 was The incidents of colon cancer at age 45 now matches that at what we were recommending to start at age 50. So that justifies starting at earlier age for these patients. And uh So, so with the latest guidelines, multiple societies are supporting, starting at age 45. All right. So now switching gears to patients with family history of colon cancer or advanced adenoma. When should you start Colon cancer screening for those? So those with one first degree relative less than 60 should start at 40 or 10 years earlier. And if they have to first degree relatives at any age, um they should also start at age 40 and repeat every five years. And patients who have won first degree relative more than age 60, they can start at age 40 but they do not need to repeat every five years. So if they're one colonoscopy is normal at age 40, then they should go back to every 10 years. Unless they have any findings. And the same way if they had to second degree relative at any age, then they could also start at age 40. And if normal repeat every 10 years. They also do not need to go every five years. So that brings to a question that often patients would have like they have one second degree relative at any age. Um They do not need enhanced screening uh protocol. So they can be screened as average risk person. And these patients are often concerned. So for example, a second degree relative is uncle, aunt, nephew, knees, grandparents, grandchildren. So a common scenario is someone with the grandfather who had colon cancer at age 40 and those patients are generally concerned. Uh As of now, the evidence Does not support doing any earlier screening for those patients because they share about only 25 of jeans with the second degree relative. All right, so now moving on to the next part is screaming in elderly. So benefit of quality ectomy is delayed by 7-10 years. And spinning is of limited benefit for those not expected to live For at least 7 to 10 years and elderly patients have competing causes of death. So screening is uh is just one of the options to lower mortality. But uh the overall picture should be considered and U. S. P. S. D. F. Says screening would be of most appropriate use to those who have never been screened. So if I see a patient 80 year olds, they are in good health and never had a screening colonoscopy. Uh and if they are very functionally active, we do offer them like any person either of a test or a colonoscopy. And many would uh except colonoscopy as if if it's normal that would be uh they would not need any further screening afterwards and also before offering any colon cancer screening options to these patients, they should be healthy enough and willing to undergo treatment if colon cancer is detected otherwise the screening is your diet. Um And again those with limited life expectancy, it should not be offered. So bottom line again is to stop screening when life expectancy is less than 10 years. And uh this applies actually to even younger patients. So for for example, sometimes if I get a referral for some someone with advanced breast cancer, you know, they just turned 50. Uh if their life expectancy is not at least 10 years doing a screening colonoscopy or even a fit test at that moment may not be a cost effective option or safe option for them as well given the risk and benefits. So, um for age 75-85 screening should be considered a case by case, and more than 85 screening should not be offered. All right, so quickly talking a little bit about boosting colorectal cancer screening rates in african americans. So, uh lots of disparities exist in colon cancer screening and mortality and outcomes based on race and ethnicity. I just briefly wanted to mention that african americans have among the highest rates of colon cancer of any racial or ethnic groups in this country And rate for example is 25 higher in African American meals compared to white meals. And AC. G. has had a recommendation to start colon cancer screening at 45 for African Americans for a long time but now they have lowered it to 45 for any race and ethnicity uh in this country. All right so this slide is just to show you what else is new in the colon polyps surveillance world. Uh So multi society Task force which comprises a CG american College of Gastroenterology, american Cast Technology Association and S. G. American Society of Gastrointestinal Endoscopy. So three main G. I. Societies they got together last year around March and they published updated guidelines That may affect your patients referral patterns for surveillance. And the important one that may be applicable most to uh internees primary cares would be 1-2 tubular adenoma of less than 10. Now they say to to surveillance in 7 to 10 years. This number used to be 5 to 10 years before. So patients with three millimeters, small tubular adenoma, you know the guidelines for 5 to 10 years, many of those who are in every five year cycle, but now they have extended to 7 to 10 years. So many of these patients may get confused with the newer recommendations. Uh And these are based on data that patients with these small polyps, their risk of colon cancer development. In long term, it's not much different from patients who have normal colonoscopy. And uh it remains to be seen whether those small tubular adenoma, you know, two or three millimeters which we see very commonly would have ever turned into cancer. So these patients, we can say with high confidence do not need uh Frequent colonoscopies. So we are very comfortable recommending 7-10 years for those patients. The other big change is for 3-4 tubular adenoma is less than 10. So now the guidelines are 3-5 years. So this used to be three years. So here you can see the interview is lengthening to up to five years for certain patients. Okay, So I just wanted to take a moment to talk about harm of colonoscopy. Uh the numbers are for bleeding risk is about eight in 10,000 colonoscopy is being done and perforation is about four in 10,000 procedures. The other rare injuries are electrolyte injury, splenic injury and missed cancer. So it's important to emphasize when you are having a discussion with your patient that the risk of bleeding and perforation are actually associated with polyp removal. And in a normal colonoscopy, which does not have any polyp, the risk of bleeding. And corporation would be much much smaller. And uh rarer for patients and any patient undergoing fit testing or Polo guard, if they have a polyp and they undergo a politic. To me, they would have these associated risk as well. And the important one is missed cancer. So several studies show that kahlan patients after colonoscopy having interval cancers are associates associated with the quality of the colonoscopy. And their multiple quality indicators have been put forth by several gee societies. And the important ones are adenoma detection rate, uh sickle intubation rate. So who does your colonoscopy is an important, is an important indicator if a patient will get internal cancer or not. So uh endoscopy is with higher adenoma detection. Re their patients are less likely to have interval colon cancer and has been validated in several studies. Uh So for patients to know the Q. I. Measures of their endoscopy practice is also important. So a little bit here about colonoscopy referral checklist that you should think of when talking to a patient is their willingness to drink colonoscopy prep should be discussed. And uh you know, they must have a right to take home after Salvation and if they do not have a right, um you know, you were left are not considered right. Uh you know, acceptable right options after procedure. So it has to be an adult who can take them in a in an Uber or lift, but nurses will not discharge them unless they have a reliable christian. Those without a right can actually book a medical transportation, but that needs to be booked in advance and depending on how long they live. Uh they can cause I've seen up $250 uh as well. At the time of referral, please consider obtaining last colonoscopy report. Because if a patient has normal colonoscopy, when their next one should be depends on their past colonoscopy, politics findings. So it's extremely helpful when you have access to those and pathology as well. Safety for sedation should also be reviewed and mentioned in the referral. A patient who has a past history of excessive alcohol use, ongoing marijuana use. Uh Those are important risk factors for us to know because when we are scheduling uh we need to decide whether a moderate sedation will work. A common scenario that comes up now is a regular use of marijuana with patients at high risk and they may be on the, on the procedure table and and the moderate salivation between blue fentaNYL. All of them are always said even at the maximum amount of nurses allowed to give their fully wide awake. So if we know those risk factors in advance, we can schedule them with general anesthesia and they can get propofol and have a nice and easy procedure. Also consider city collar pornography if patients have high risk for situation. So in my practice, I consider city Colonna graffiti. Actually, commonly when I'm seeing high risk patients, uh if they get referred for clearance colonoscopy before undergoing a heart transplant or a lung transplant. So these patients, you know, city colonoscopy is the best test for them. Uh It answers the question whether they have a cancer or a large polyp or not, and no solution needed. No contrast needed. Uh So that's a good place for this procedure. All right, sorry to show you the slide. I try to not show this and I give lunchtime thoughts. Uh This is just a reminder that, you know, having a discussion with your patient uh about the importance of reading the instructions. And a good prep is extremely important. And that's the peace stability is very dependent on how clean the colon is And in its not uncommon, like 10-15 of patients do not have optimal prep. So uh reading the instructions in advance. And most common reasons are that patients start reading the instructions the night before the procedure when they're about to drink the prep and they may have eaten regular diet the day before. So uh if I get to see them in prison before doing procedure and I do take a moment to emphasize. Please read in advance, but I do not have that opportunity in many times because of being open endoscopy access. Uh Sometimes the first time you see a patient is at the time of the procedure. Yeah. Other questions patients ask. Colonoscopy is a quick 20 to 30 plus minus few minutes procedure depending on the palate. And prep patients usually spend about three hours and the endoscopy suite and they cannot drive for 24 hours post procedure. And uh we talked about the need for a ride, an unprecedented colonoscopy. So occasionally patients will inquire and I do do that once every few weeks. Um uh You know that has to be done by uh patients who are highly motivated and uh you know they do not have sensitive abdomen to begin with and they need to be on board that if there is some cramping uh they would be able to tolerate. And uh interestingly if I think of last few patients I have done a week. They are all physicians for some reason. But this is an option but it's not for uh every single patient. So case by case. Alright, colonoscopy prep A lot has happened. That's new. Is we have a tablet uh Base perhaps as well. Here is a suitable that's 24 tablets to be swallowed. There's a plan you that's a smaller volume prep movie prep politely of course. Are there um issues with a smaller volume and tablet based perhaps? Are they are often not covered by insurance? So it may cost 100 $250 for patients uh if they can't afford so. All right. So I'm almost nearing the end of my talk. Uh one slide on aspirin for colorectal cancer prevention that we get asked. And generally we end up referring to us psD of guidelines that suggests low dose aspirin for patients in the age range of 50 to 69 years old. Those with cardiovascular risk of more than 10/10 years. Uh they are not an increased risk of bleeding. So that's very important. Uh and patients should be willing to take aspirin for at least 10 years. And um here, I would say that, you know, aspirin does not have quick and immediate risk reduction for colon cancer or polyps. So it's a long term use that results in lower risk. And uh there was a recent Asprey trial that patients were older. Uh the risk of bleeding was higher aspirin than cancer prevention for them. So, I would be cautious here in older patients, you know, even at around 69 year old putting them. Uh so usually younger and healthier patients. This could be considered. And this is a conditional recommendation based on low quality evidence is important to them. Just a quick few slights about showing different kinds of polyps and our tools, severe forceps. We have snare for polyps. Society polyps and these are pretty populated polyps and some polyps are very hard to see even uh with a good prep so can be missed. And here to show this is a society rated adenoma. These are easily missed and cause for internal cancer. And here you can see it better with some die enhancement. Our tools of doing in this topic. A reception for polyps. So EMR and this topic mucosal resection. Here we inject some mucosal die, dissect the polyp with the snare and the rotten it. We can grab and remove them and patients sometimes need polyp ectomy clip placements these clips fall off on their own and do not need any special remover or looking from the patient. All right. So just to summarize in conclusion fit and colonoscopy are primary colorectal cancer screening, modalities and screening is recommended for all patients in 45 to 75 year age group and consider case based screening in 75 to 85 year old group of patients. And latest guidelines recommend 7 to 10 year interval which is different from previous ones for 1 to 2 small adenomas which are less than 10 millimeters in size and a few quick uh slides on my practice. So I'm a guest urologist at UCSF and um we are at Monza Zion and Parnassus for routine endoscopy. We have three advanced endoscopy pissed food do M. R. S. D. And they are based at Mission Bay. We have put together this website to improve our prep and instructions and without UCSF dot E. D. u. That our patients have access to. Uh we have put together some uh uh as my other hat as quality improvement uh director. We have, I'm proud of my fellows for putting together this uh enhanced instructions for bubble prep. Hopefully this is going to help our patients were studying our data and uh talked about our locations. Um and our clinics are at the visitor uh location as well. And this is all I had for today in the given time limit. And I thank you again for giving me this opportunity and I'm more than happy to take any questions.