Cadmore media player playing video SCORE School Colon Cancer
Video Player
Accessibility
Using forms mode, you can utilize keyboard shortcuts to make usability more efficient.
Space bar will play and pause the video. Pressing escape will close all displays and pressing it again will jump to the end of the player.
You can press A to open the Keyboard Shortcut Dialog which also provides an audio description of the player and all of its features.
Language
1x
Play Speed
Adjust Volume
Transcript
Search
Result Count
of
Click to jump to result
Search
Re-center
Segments
Result Count
of
Click to jump to result
Search
Name:
SCORE School Colon Cancer
Description:
SCORE School Colon Cancer
Thumbnail URL:
https://cadmoremediastorage.blob.core.windows.net/41870224-b412-4d34-ac2d-5a4665fb056b/thumbnails/41870224-b412-4d34-ac2d-5a4665fb056b.png?sv=2019-02-02&sr=c&sig=IAQHUYKFtIyl3Sy0GQ1Am5fABosxQ%2BI5b5jET0INunE%3D&st=2025-01-02T23%3A12%3A20Z&se=2025-01-03T03%3A17%3A20Z&sp=r
Duration:
T00H48M45S
Embed URL:
https://stream.cadmore.media/player/41870224-b412-4d34-ac2d-5a4665fb056b
Content URL:
https://cadmoreoriginalmedia.blob.core.windows.net/41870224-b412-4d34-ac2d-5a4665fb056b/SCORE School Colon Cancer.mp4?sv=2019-02-02&sr=c&sig=F%2BkS4OSvqdkSyhesWe4ZuExNsK4WW1xZ%2BaRzi%2FP9%2FUw%3D&st=2025-01-02T23%3A12%3A22Z&se=2025-01-03T01%3A17%3A22Z&sp=r
Upload Date:
2023-10-19T00:00:00.0000000
Transcript:
Language: EN.
Segment:0 .
AMIT JOSHI: Hello, everyone. Welcome to SCORE School. I'm delighted to introduce our speaker today, Dr. Christina Bailey, who's at Vanderbilt University in Nashville, Tennessee. Dr. Bailey received her bachelor's of science from Louisiana Tech University, followed by her medical degree from Louisiana State in 2005. After that, she went to Vanderbilt for her general surgery residency in combination with a master's of science and clinical investigation from Vanderbilt. After that, she did a surgical oncology fellowship at MD Anderson.
AMIT JOSHI: After that she came back to Vanderbilt as a faculty there. Her primary clinical interests are in GI malignancies, including gastric cancer, small bowel cancer, colorectal cancer, GIST tumors, retroperitoneal sarcomas, neuroendocrine tumors. She received the Lotzova Research Award and MD Anderson Training Excellence Award during her fellowship. She is particularly interested now as a faculty member in disparities in cancer diagnosis, treatment, and outcomes in regards to age, socioeconomic status, and race as well as quality of life after cancer treatment.
AMIT JOSHI: She's been widely published including JAMA Surgery, and the Journal of Gastrointestinal Surgery. And she is the program director now at Vanderbilt. Dr. Bailey, it's a true pleasure to have you. Thanks for lending your expertise to SCORE School.
CHRISTINA BAILEY: Oh, thank you Dr. Joshi for that introduction. So today I will be discussing colon cancer and polyposis syndrome. I have no disclosures. So I was going to start off by discussing colon cancer for the first half of this presentation, and then we'll go into the polyposis syndrome. So colorectal cancer is the third most common cancer among men and women in the United States.
CHRISTINA BAILEY: From 2006 to 2015, the incidence of colorectal cancer has decreased 2.9% per year in men and 2.4% per year in women. The observed decrease in incidence is largely attributed to an increase in screening, specifically colonoscopy, which is currently recommended for all adults 50 years or older. Colon cancer can develop along three oncogenic pathways, which include chromosomal instability, microsatellite instability, and cytosine-guanine island methylator phenotype or CIMP.
CHRISTINA BAILEY: The most common pathway is chromosomal instability, which accounts for approximately 75% of all colorectal cancers. This is due to alterations in the number or structure of chromosomes and can lead to gene function loss. Here, you could see a model illustrating the classic model of colorectal carcinom genesis, which starts with normal epithelium, enter a series of mutations, progresses to carcinoma.
CHRISTINA BAILEY: The three most common mutations associated with progression from normal epithelium to adenocarcinoma are mutations in adenomatous polyposis coli gene or APC, K-Ras, and p53. APC is a tumor suppressor gene. And mutations lead to increased cell signaling proliferation and cell-to-cell adhesion. K-Ras is an oncogene and mutations in K-Ras actually turn on the K-Ras signaling, leading to uncontrolled cell growth.
CHRISTINA BAILEY: And P53 is a tumor suppression gene. And mutations leads to inability cells to arrest cell growth or induce apoptosis. The second most common pathway leading to colon cancer is microsatellite instability, and this accounts for 15% to 20% of colorectal cancers. This results from mutations and mismatch repair genes which include MLH1, MSH2, MSH6, and PMS2.
CHRISTINA BAILEY: And deficiencies in dMMR leads to accumulation of unrepaired errors. And the third oncogene pathway is the CIMP pathway. This accounts for approximately 5% of colon cancers, and this is due to repetitive sequences of CpG in the DNA promoter region of tumor suppressor genes, leading to loss of BRAF, p16, and MLH1. The one thing that differentiates this pathway from the chromosomal microsatellite instability is that these patients will present with serrated polyps instead of adenomas polyps.
CHRISTINA BAILEY: Sorry. So colon cancer screening, why is it important? So, as briefly hinted to, colon cancer develops along a spectrum. We usually start with hyperproliferative cells and they progress to cancer. So really, the goal of screening is to capture patients when they have these benign polyps, before they even progress to cancer.
CHRISTINA BAILEY: There are several modalities available for colon cancer screening. They include colonoscopy, flexible sigmoidoscopy, fecal occult blood testing, CT colonography, and fecal DNA testing. Of course, the gold standard is colonoscopy. Flexible sigmoidoscopy is very limited because you're only able to visualize the rectum and the sigmoid colon.
CHRISTINA BAILEY: But if a polyp is visualized, colonoscopy is recommended. Fecal occult blood testing requires three stool samples. And of course, if positive, colonoscopy is also recommended. CT colonography and fecal DNA testing are options, but these are currently not supported by the US Preventive Services Task Force. So as far as screening recommendations, according to the NCCN guidelines, average risk patients should undergo their first screening colonoscopy at 50 years of age.
CHRISTINA BAILEY: So what constitutes average risk? So patients who have no history of colorectal polyps, no history of inflammatory bowel disease, and no family history of colorectal cancer or advanced adenomas. And advanced adenomas exhibit high-grade dysplasia, bigger than 1 centimeter, or villous or tuvulovillous histology. So of course, if patients have risk factors for colon cancer, it definitely changes the recommendations for screening.
CHRISTINA BAILEY: And I think the easiest way to think about this is according to medical history and family history. So if you have a personal history of adenomas, colorectal cancers, or inflammatory bowel disease, that definitely increases your risk for the development of subsequent colon cancer. In regards to family history, any first degree relative with colon cancer or with an advanced adenoma increases your risk for the development of colon cancer.
CHRISTINA BAILEY: And then also, if you have a hereditary colorectal cancer syndrome. The two most common are HNPCC, or Hereditary Non-Polyposis Colorectal Cancer, and FAP, Familial Adenomatous Polyposis. Some of your less common colorectal cancer syndromes include Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, Li-Fraumeni syndrome. So when it comes to screening and you high risk patients, so specifically looking at medical history.
CHRISTINA BAILEY: If you have a history of a low risk adenoma, which is less than-- fewer than two polyps smaller than 1 centimeter, the recommendation is for a repeat colonoscopy in five to 10 years, and 10 years is negative. Low risk sessile serrated polyps means there's no dysplasia, they're are also small, you want to get a to get a repeat colonoscopy in five years, and 10 years is negative.
CHRISTINA BAILEY: For patients with high risk polyps, including polyps that are bigger than a centimeter, have high grade dysplasia, are villous or tubulovillous histology or multiple polyps, want to get a repeat colonoscopy in three years, and five years is negative. And in patients who have a history of the inflammatory bowel disease, they recommend that you begin their colonoscopy surveillance eight years after the onset of symptoms.
CHRISTINA BAILEY: And patients with a family history of a first degree relative with colorectal cancer at any age it is recommended that these individuals begin undergoing screening colonoscopies at 40 years of age, or 10 years before the earliest colorectal cancer diagnosis in their family. And any first degree relative with a confirmed advanced adenoma is recommended the same intervals begin 40 years of age.
CHRISTINA BAILEY: And when we look at our patients with hereditary colorectal cancers, and I just listed the two most common ones, in patients with HNPCC it's recommended that they have a colonoscopy every two years, beginning at the age of 20, and annually after the age of 35. And in patients with FAP, they begin their screening at 10 to 20 years of age and then annually thereafter.
CHRISTINA BAILEY: I did want to mention some modifiable risk factors, which includes diet, obesity, lack of physical activity, alcohol and tobacco, all of which are associated with an increased risk of colon cancer. Specifically in regards to diet, patients who consume what is referred to as the Western diet which consists of foods-- or I should say, a diet with high levels of red meat, processed meat, fast food, refined grains and sugar are all associate with an increased risk of colon cancer.
CHRISTINA BAILEY: Whereas a diet high in fiber, including vegetablas and fruits, decrease the risk of colon cancer. So the easiest way to look at it, fiber, exercise are good. Red meat, processed meat, candy, tobacco, alcohol, and obesity are all bad.
SPEAKER 1: Just in time for Halloween, I see.
CHRISTINA BAILEY: Of course.
AMIT JOSHI: Dr. Bailey, I think your microphone is a little bit touchy. Maybe if you tried just talking directly into the computer, would that be easier?
CHRISTINA BAILEY: OK. Is that better?
AMIT JOSHI: Yeah. I think so.
CHRISTINA BAILEY: OK.
AMIT JOSHI: I do have a couple of questions for you. So I wonder, in this time of postponing a lot of elective screening for COVID for the last, well, six months, and maybe even going forward, how much of an impact do you think that will have on development of colon cancer? And I guess one question a lot of patients ask us is, Doc, you diagnosed with colon cancer-- how long has it been there? And so give us some sense, particular for trainees when they're trying to give that answer, how long does it really take for these things to progress?
CHRISTINA BAILEY: Yeah. So the answer to your second question, as I mentioned earlier, these definitely progressed along a spectrum. And it can take anywhere from five to 10 years to progress from just kind of hyperproliferative epithelium to an invasive carcinoma. And to answer your first question in regards to the impact of, as you say, lack of screening because of COVID, it's hard to determine.
CHRISTINA BAILEY: The fortunate thing, at least for us here in Nashville, are actually starting-- I shouldn't say started, we've actually resumed-- more elective procedures, and so I have not seen a change thus far. But the one thing that concerns me, of course, is the potential for seeing patients present with more later stage disease, just due to the delay in screening and subsequent staging studies.
AMIT JOSHI: And one more question for you. You had a nice slide there for the different options for screening and the ones that are sort of sanctioned, or reimbursed, and those that are not. So in a patient who is adamantly against the screening colonoscopy, what advice do you give them in terms of the next best option?
CHRISTINA BAILEY: Yeah. So the next best option would be CT colonography or even a barium enema. But my advice to them would be, if we get this study and we see something, we can't biopsy it and you would still need a colonoscopy.
AMIT JOSHI: OK. Great. Thank you.
CHRISTINA BAILEY: All right. So you get your colonoscopy, what do you see? So in gross endoscopic findings, there are essentially two gross polyp types. You have your pedunculated polyps, which are polyps which have a stalk. Then you have your sessile polyps, or your flat polyps, without the stalk. In regards gone to the histologic subtypes, you have tubular adenomas, which are by far the most common.
CHRISTINA BAILEY: They represent 65 to 80% of polyps. These are most often pedunculated and have less cellular atypia. Your villous adenomas represent 5 to 10% of polyps. These are usually sessile, and you can't see some atypia or dysplasia at these polyps. And then you have your tubulovillous polyps, which represent about 10 to 25% of polyps. In regards to malignant polyps, I did want to spend some time with you on Haggit's classification.
CHRISTINA BAILEY: Which essentially, you have four levels and it is based on the depth of invasion. Your Level 0, these are your carcinomas in situ. There is no invasion to the muscularis mucosa. Your Level 1, the carcinoma invades through your muscularis mucosa, but is limited to the head of the polyp. In regards to Level 2, you get invasion into the neck of the polyp.
CHRISTINA BAILEY: Level 3 is into the stalk. And in Level 4, you see carcinoma invaded into the submucosa of the bowel wall below the stock of the polyp, but above the muscularis propria. And all sessile polyps by definition are level 4 by your Haggit's Classif criteria. So what are the signs and symptoms of colon cancer?
CHRISTINA BAILEY: Most patients are actually asymptomatic. But in patients who do develop symptoms, they can present with iron deficiency anemia, abdominal pain. You can sometimes see changes in bowel habits and changes in stool caliber. In patients what changes in stool caliber, these are usually patients with left-sided lesions. They can also present with bright red blood from the rectum and melena.
CHRISTINA BAILEY: And patients with sizable lesions, they can present with obstructive symptoms, which include constipation, abdominal distension, nausea and vomiting. And patients with more advanced disease can present with unexplained weight loss and fatigue. So how do we diagnose colon cancer? I briefly mentioned this, but you have the options of doing a barium enema or CT colonography.
CHRISTINA BAILEY: But the gold standard is colonoscopy because colonoscopy allows you to not only identify the polyp, but you can also remove the polyp so that it can be evaluated in pathology. In regards to staging, so who needs additional staging work-up? So in a patient who has an endoscopically resectable polyp, my approach to these patients is that it's cancer until proven otherwise.
CHRISTINA BAILEY: Patients who have a resected polyp that contains invasive cancer and has one of the features listed below-- if the polyp was removed in a piecemeal fashion, if the margins cannot be assessed by pathologists, or if the polyp has unfavorable histology which includes poorly or undifferentiated presence of lymphovascular invasion or positive resection margin. These are all patients who need additional staging.
CHRISTINA BAILEY: And as far as what that entails, labs-- the CBC, CMP, and CEA-- imaging-- a CT of the chest, abdomen and pelvis to rule out the presence of distant metastasis. And the two most common signs of metastasis from colon cancer include the lung and the liver. There is no indication for PET CT during the initial workup for patients with colon cancer. And just as a side note, if there is a possibility for an ostomy at the time of surgery, it's prudent that you refer these patients for an ostomy consultation not just for marking, but also for teaching as well.
CHRISTINA BAILEY: In regards to colon cancer staging, staging is based on a AJCC TNM staging. And I think the easiest way to remember staging for colon cancer is that Stage I is T1 to T2 node negative disease. Stage II is T3 to T4, also node negative disease. Stage III is any T stage, but node positive.
CHRISTINA BAILEY: And of course Stage 4 is anyone with distant metastasis.
AMIT JOSHI: Dr. Bailey, one question. One question for you.
CHRISTINA BAILEY: Yes, sir?
AMIT JOSHI: So when you put up that Haggit's classification, we've certainly seen that before. My question clinically is that, is that something that your pathologist reports to you, or is that something that you, as the endoscopist, will kind of synthesize based on your interoperative or interendoscopy finding and then meld that with what comes back in the pathology report? Or is it just kind of a, sort of basic science classification that's not clinically relevant?
CHRISTINA BAILEY: So, definitely clinically relevant, and it is reported by the pathologists. I actually, just Tuesday, at my clinic, had a patient with a Level 4 Haggit's classification tumor in a polyp that was removed. It's very interesting because I had to specifically call my pathology colleague to get a sense of the depth of invasion into the submucosa, because it does matter in regards to who needs resection versus who you can just follow.
AMIT JOSHI: And so I guess if that's not being reported-- because I'm pretty sure at my institution that is not reported-- that's certainly an area of improvement, I think, then, right?
CHRISTINA BAILEY: Yeah. Particularly for the pedunculated polyps with invasive cancer.
AMIT JOSHI: OK. Thank you.
CHRISTINA BAILEY: No. You're welcome. So as far as treatment. So now patient had colonoscopy, carcinoma, no evidence of metastasis. The recommended treatment is a segmental colectomy with a regional lymphadenectomy. You want at least a 5 centimeter margin on either side of the tumor and you want to remove a minimum of 12 lymph nodes.
CHRISTINA BAILEY: So the key for surgery for colon cancer is not just removing the colon itself, but you want to ensure that you are removing all of those draining lymph nodes of that segment of the colon. And the lymph nodes travel with the vessels, so it's prudent when you're ligating those vessels to ligate them at their origin. And I'll go into this in a little bit more detail in the next couple of slides.
CHRISTINA BAILEY: In regards to minimally invasive versus open surgery, there is no recurrence or survival difference. But one, or I should say two of the noted benefits of minimally invasive surgery is that it is associated with less pain and a shorter hospital stay. But like I said, the oncologic results are equivocal. So in regards to what segment of the colon you remove, that 100% depends on where the tumor is.
CHRISTINA BAILEY: So if you have a lesion in the cecum, you're going to do a formal right colectomy which entails migration of the ileocolic vessels, your right colic vessels, and the right branch of your middle colic artery. And if you have a lesion that's in your proximal transverse colon, these patients typically need an extended right colectomy which of course entails division of your terminal ileum and slightly more of your transverse colon compared to what you usually remove as a right colectomy.
CHRISTINA BAILEY: And as far as vessel ligation, you would ligate your endocolic vessel, your right colic, and your middle colic vessels. And once again, you want to ligate these vessels at their origin because you want to ensure that you are removing all of them with nodes draining that segment of the colon. In regards to lesions within the descending colon, recommended surgical treatment is a left colectomy. And here you would divide your transverse colon proximal to the splenic flexure and division of the distal colon at the junction of your left and sigmoid colon.
CHRISTINA BAILEY: Or depending on margins, it could potentially even entail division at the rectosigmoid junction. And then for your sigmoid lesions, you want to do a sigmoidectomy. So for Stage I disease, once again these are your T1, T2 lesions. Treatment is segmental colon resection with lymphadenectomy and there is no indication for adjuvant chemotherapy. For your Stage II tumors, which are your T3 or T4 node negative tumors, once again you want to do a segmental resection and a lymphoadenectomy.
CHRISTINA BAILEY: And some of these patients do require adjuvant chemotherapy. So who are those patients with Stage II colon cancer who need adjuvant chemotherapy? So based on the NCCN guidelines, patients with high risk features are recommended at least for consideration for adjuvant chemotherapy. And those high risk features are poorly differentiated tumors, the presence of lymphovascular or perineural invasion, obstruction, patients presenting with T4 lesions, if the margins are close, indeterminate, or positive, and if you remove less than 12 lymph nodes.
CHRISTINA BAILEY: Studies have shown that removing more than 12 lymph nodes is associated with improved disease-free survival and overall survival. And the reason for this is that if you remove less than 12 lymph nodes, there is a concern that there could potentially be residual cancer in those lymph nodes that were left behind.
CHRISTINA BAILEY: Stage III cancer, once again these are your node positive cancers. Once again, segmental resection with lymphoadenectomy followed by six months of adjuvant chemotherapy. And the two chemotherapy regimens are FOLFOX which is 5-FU leucovorin and oxaliplatin, or CAPOX, which is capecitabine and oxaliplatin. And for Stage IV disease, chemotherapy is typically the treatment for these patients.
CHRISTINA BAILEY: But some patients who have oligometastatic or low volume metastatic disease actually may be candidates for resection of not just their primary tumor, but also for resection of their metastatic disease. So it really depends on how much metastatic disease they have, the location of their disease, whether or not they are potential candidates for surgery.
AMIT JOSHI: Dr. Bailey, regarding FOLFOX, is it true that the oral and IV versions of 5-FU leucovorin are equivalent in their efficacy?
CHRISTINA BAILEY: Yes. Yes, so it's pretty interchangeable. And really, as far as whether patients get follow FOLFOX or CAPOX, it really depends on the medical oncologist and their preference.
AMIT JOSHI: OK.
CHRISTINA BAILEY: So in regards to prognosis, as one would suspect, patients with Stage I disease have the best survival. They have a five-year survival which is 90%. Stage II, 75%. Stage III, 50%. And Stage IV, particularly if they're not candidates for mass resectomy, their five-year survival rate is less than 5%.
CHRISTINA BAILEY: In regards to surveillance after surgery, so in patients with Stage I colon cancer, after resection it's recommended that they undergo a colonoscopy one year after surgery. And if that colonoscopy is negative, then their subsequent colonoscopy will be at 5 to 10 year mark. And for patients with Stage II, III, or IV disease, these patients need an H&P every three to six months for the first two years, then every six months thereafter for a total of five.
CHRISTINA BAILEY: CEA every three to six months for two years, and then every six months for five years. CT of the chest, abdomen and pelvis every six to 12 months for five years. And they also require colonoscopy one year after surgery. If an advanced adenoma is found on that one-year colonoscopy, it's recommended they undergo a repeat colonoscopy in one year. If there is no advanced adenoma, repeat in three years, then every five years thereafter.
CHRISTINA BAILEY:
AMIT JOSHI: That's a great review. Particularly the staging and the stage by stage breakdown of how to proceed. Could you just review for listeners, what is the actual difference between Stage I, Stage II, Stage III, Stage IV? My understanding is that if it gets recalibrated every couple of years based on the actual survival. So Stage IV is supposed to do worse than Stage III, and Stage II, and Stage I. And the reason why these things change is because with new studies and new data, every now and then it gets out of whack where maybe a Stage II actually-- maybe a Stage III actually does better than a Stage II in a certain circumstance, and that's why the independent TNM classification has to get re-shifted.
AMIT JOSHI: Is that a fair assessment?
CHRISTINA BAILEY: Yeah. Because there are-- I wouldn't constantly, but there are often changes made to the HACC staging. And I think it's more so because we're just learning more about the tumors. Now, I did try to basically simplify the Stage II and the III particularly. Because if you go back and look at that table, actually, Stage II you can kind of break it down into Stage IIa, IIb, IIa, IIIb, IIIc.
CHRISTINA BAILEY: And it all as relate to, or I should say correlates with prognosis. And so that's why it's constantly evolving, because we're just learning more about the tumors.
AMIT JOSHI: OK. And I notice you didn't talk about any of the other sort of old-fashioned, I would say out of date staging system. Those are-- I won't even mention them. They're basically ignored at this point, correct?
CHRISTINA BAILEY: Yeah. And really, because if you look at like Duke's classification, you know, that really only comes up when you're reviewing some of the older literature and older data sets. But outside of old papers, it's really not talked about, and not really applicable to clinical practice, at least now.
AMIT JOSHI: Thank you.
CHRISTINA BAILEY: No. You're welcome. All right. Well, we will shift gears now and go into a discussion of our polyposis syndromes. So sporadic colon cancer is by far the most common, and these patients tend to present with solitary lesions. Approximately 5% of patients have a hereditary colon cancer. And the two most common of those, I mentioned earlier, are your HNPCC, or Lynch syndrome, and FAP.
CHRISTINA BAILEY: And then anywhere from about 10% to 30% of people actually have familial cases with familial risk. So when do you suspect hereditary colorectal cancer? And a lot of this is really based on your history. So you have a patient who's young at age of onset-- it is very important, and I can't emphasize this enough, to take adequate family history.
CHRISTINA BAILEY: Because if you have a patient who has multiple generations or multiple members of the same generation, it definitely increases your suspicion for hereditary syndrome. People who have multiple cancers of the same type or cancers of different type, such as colorectal cancer and endometrial cancer, some of these hereditary cancers are associated with extra colonic features, for example, mucosal pigmentation in patients with Peutz-Jaegers.
CHRISTINA BAILEY: And also patients with uncommon tumors, such as sebaceous skin carcinoma in Lynch syndrome or desmoid tumors in patients with FAP. So the way I've, in my mind, kind of conceptualized these patients is that I basically kind of divide into, or I should say separate them, into patients with polyposis syndromes versus the non-polyposis syndromes.
CHRISTINA BAILEY: Polyposis syndrome are where your adenomas predominate, includes FAP which is caused by a mutation in the APC gene. And this is an autosomal dominant syndrome. You can also have attenuated FAP and MYH polyposis, which is recessive. You have your hamartomas and your hyperplastic, serrated adenoma syndromes. And with your non-polyposis syndrome, by far the most common is Lynch syndrome.
CHRISTINA BAILEY: But there is also a mismatch repair syndrome, familial colorectal cancer type X. So we'll spend a little bit of time talking about FAP, and this is the most well defined and understood of the syndromes. It is an autosomal dominant inheritance. And clinically, these patients who are present with numerous colorectal adenomatous polyps. They typically present during their 30s.
CHRISTINA BAILEY: And it's also associated with intra-abdominal desmoids, jaw osteoma, multiple epidermoid cysts with a family history of FAP. The germline confirmatory testing is APC mutation, and it has a detection rate of about 80%. And when you refer patients for genetic testing for concern of FAP, they do do a full gene sequence analysis of the APC gene.
CHRISTINA BAILEY: There are some associated phenotypes. One is the congenital hypertophy the retinal pigment epithelium. It's actually present in about 60% of families with FAP, and it can be used to screen family members. Gardener's syndrome is associated, of course, with colonic polyps, but you also see epidermoid skin cysts and benign osteoid tumors of the mandible and long bone. Some patients present with hereditary desmoid disease where they actually have an absence of colonic polyps but present with desmoids.
CHRISTINA BAILEY: Then you have your Turcot syndrome, which is characterized by colorectal polyps and hepatoblastomas. In regards to surgical management. So when you look at out the chances of having adenomas based on age, it's about 15% by age 10. That jumps to 75% by the age of 20, and 90% by the age of 30. In patients who receive no treatment, 90% will develop colorectal cancer by the age of 45.
CHRISTINA BAILEY: So surgery on these patients is actually not just for treatment, but it's also for prophylaxis to prevent the development of cancer. So there are essentially three options in regards to surgical management for these patients. You could do a total abdominal colectomy with the ileiorectal anastomosis. Of course this procedure is reserved for patients who do not have a large burden of rectal polyps.
CHRISTINA BAILEY: But if you leave the rectum in place, the rectum is at risk for polyp formation and also rectal cancer, so annual surveillance is key in these patients. The second option is a total abdominal proctocolectomy with an ileal pouch-anal anastomosis. Or you can do a total abdominal proctocolectomy with an end ileostomy. So of course, you know, with all things there are pluses and minuses.
CHRISTINA BAILEY: As I mentioned on the last slide, if you do a total abdominal colectomy with an ileorectal anastomosis, there is an approximately a 23% risk of rectal cancer in 20 years. So these patients do require yearly flexible sigmoidoscopies, so this would not be a good option for a patient who you know is noncompliant. Total proctocolectomy with a pouch, there are morbidities associated with a pouch.
CHRISTINA BAILEY: And the pouch is also at risk for adenocarcinoma, so periodic surveillance is also required. And a total proctocolectomy with and end ileostomy is you have to deal with a permanent ileostomy. So because FAP is associated with other types of cancer, extracolonic surveillance is important. These patients can develop desmoids, and they can also develop tumors of the duodenum.
CHRISTINA BAILEY: They can develop ampullary adenocarcinomas, thyroid tumors, and brain tumors. So here is a table listing the screening for these patients. So for colorectal, particularly if they-- specifically if they still have their rectum or they have a pouch, annual endoscopies. For desmoids, do perform a CT scan at the time of diagnosis, just to evaluate for the presence of desmoid tumors, for duodenum and ampillary tumors, and/or EGDs.
CHRISTINA BAILEY: Ultrasound for the thyroid. And as far as the brain, this is based on symptoms. So if someone is totally asymptomatic, it's not recommended that you perform annual CT or MRIs of the brain. It's purely based on symptoms. So now moving to HNPCC, or Lynch syndrome. Clinical features for these patients are early age of onset, that means 45 years of age.
CHRISTINA BAILEY: Right sided colon cancers do predominate. Approximately 70% of patients present with colon cancers proximal to the splenic flexure. They can present with synchronous or metachronous disease. Patients with synchronous disease present with multiple colorectal tumors at initial diagnosis or within six months of surgical resection, whereas patients with metachronous tumors present with recurrent or multiple colorectal cancers more than six months after resection of their initial tumor.
CHRISTINA BAILEY: These patients also have an increased risk of extracolonic cancers which include endometrium, which in women is second to colorectal cancer. They can also develop ovarian, stomach, biliary tract, small bowel, and urothelial cancers. These patients may also present with cutaneous manifestation of their disease, which includes sebaceous adenomas and keratoacanthomas.
CHRISTINA BAILEY: One thing I did want to highlight is the pathologic features of patients who have HNPCC. These patients tend to present with poorly differentiated tumors. On histology, you can see peritumoral lymphatic reaction. There's a high incidence of mucinous tumors in patients with Lynch syndrome, and also the presence of infiltrating lymphocytes within the tumor on histology.
CHRISTINA BAILEY: In regards to genetics, this also is an autosomal dominant inheritance. And once again, it's the cause of five mutations in your mismatch repair genes, which are listed here. Here's a typical pedigree of a family with Lynch syndrome. And as you can see, there are multiple generations that are impacted. The young age of diagnosis-- particularly here, and this patient was 37 at their diagnosis-- and different types of cancer.
CHRISTINA BAILEY: So once again, this just highlights the importance of taking a thorough family history of your patients. So who should we test for Lynch syndrome? So the Amsterdam criteria-- I should say the Amsterdam I-- was introduced in 1991. And what the Amsterdam I criteria stated was that there should be at least three relatives with colorectal cancer, and all of the following criteria had to be present.
CHRISTINA BAILEY: One, the family members or relatives had to be a first degree relative of the other two. At least two successive generations impacted, and at least one colorectal cancer diagnosed before the age of 50. And of course you excluded patients with FAP, and tumors had to be verified, of course, by pathologic examination. The one issue with this was that it's pretty rigorous, and it actually excluded a lot of people with Lynch syndrome.
CHRISTINA BAILEY: This subsequently led to the development of Amsterdam II criteria, and so it was changed to include at least three relatives within an HNPCC associated cancer. Once again, one had a first degree relative of the two, two successive generations, and at least one person diagnosed before the age of 50. But even with the change in the criteria, you know, approximately 68% patients with Lynch syndrome were still being missed.
CHRISTINA BAILEY: So this led to the development of the Bethesda guidelines, and it basically was to help clinicians to identify individuals who should be tested for microsatellites instability given the suspicion for Lynch syndrome. And it basically includes colorectal cancer diagnosed in patients younger than 50 years of age, presence of synchronous metachronous colorectal cancer, or another HNPCC associated tumor regardless of age, colorectal cancers with MSI high histology diagnosed in a patient younger than 60 years of age, and colorectal cancer in one or more first degree relatives with an HNPCC related tumor, with one being diagnosis in a family member younger than 50, and colorectal cancer diagnosis in two or more first or second degree relatives with HNPCC related tumors regardless of age.
CHRISTINA BAILEY: And studies have shown that patients fulfilling the revised Bethesda guidelines have an odds ratio of carrying a germline mutation in MLH1 age or MSH2 are 33.3.
AMIT JOSHI: Dr. Bailey, does that mean that microsatellite instability is only relevant for HNPCC, or does it have something there on the non-Lynch colon cancers?
CHRISTINA BAILEY: So-- yes. So I know a lot of institutions, actually, all patients undergoing resection for colon and rectal cancer, all of the specimens are tested for MSI status. And for patients who are identified as MSI high, you know, then it can trigger the conversations, OK, does this patient-- what's the family history? What's the age? Is this someone I need to refer for genetic testing?
CHRISTINA BAILEY: But the microsatellite status also is useful, particularly in patients with Stage II colon cancer, when you're trying to decide if they need adjuvant chemotherapy or not. Because in patients with a Stage II colon cancer who may have one high risk feature, part of this is MSI high tumor, they actually have a more favorable prognosis so we don't recommend adjuvant chemotherapy.
CHRISTINA BAILEY: So the microsatellite status, yes, it is useful in assisting in the diagnosis of Lynch syndrome, but it also is useful, particularly in patients with Stage II cancer when you're deciding between adjuvant chemotherapy versus no adjuvant chemotherapy.
AMIT JOSHI: Got it. Thank you.
CHRISTINA BAILEY: You're welcome. So as far as surgical management for patients with Lynch syndrome, you have two options. You can do a segmental colectomy, or you can do a total abdominal colectomy with an ileorectal anastomosis. Of course if you do a segmental colectomy, the remaining colon is at risk for metachronous colorectal cancer, so these patients do require yearly colonoscopy.
CHRISTINA BAILEY: And really kind of like, their overall risk for development of cancer after segmental colectomy is about 62% in 30 years. If you do a total abdominal colectomy with ileorectal anastomosis, of course your risk for metachronous cancer is a lot lower, because you no longer have a colon. But you still can develop rectal cancer, and the incidence of that is about 12% in 12 years, and it is associated with a poor bowel function.
CHRISTINA BAILEY: But there is no survival advantage between the two as long as the people who undergo segmental colectomy undergo surveillance. And what that surveillance is, it is an annual colonoscopy. And so it is definitely an individualized decision. In my practice, when I have a patient with Lynch syndrome I definitely have the discussion, the segmental colon resection versus the total abdominal colectomy.
CHRISTINA BAILEY: And really, kind of that conversation is, if we do a segmental colectomy, you have to get annual colonoscopies, but your survival is the same. Whereas if we do a total abdominal colectomy, you still have to get annual flexible sigmoidoscopies, which are not as invasive as colonoscopy. But it's a balance, because there definitely is a difference in regards to quality of life associated with an ileorectal anastomosis versus just a segmental colectomy.
CHRISTINA BAILEY: And in regards to surveillance, yes, you want to survey the colon and the rectum. But as I mentioned earlier, these patients are at risk for other tumors. So you want to ensure that you're not just doing here colonoscopies, but in females it is important to do endometrial sampling due to the risk of endometrial cancer. Some clinicians actually perform trans-vaginal ultrasounds and see them once every five.
CHRISTINA BAILEY: EGD with duodenoscopy for evaluation of the duodenum and the ampulla. Urinalysis due to the increased risk for urothelial tumors. And you want to make sure that these patients are undergoing annual history and physical exams. So that is all I have in regards to slides. Happy to answer any other questions.
AMIT JOSHI: Yeah. What a great review. Thank you so much, Dr. Bailey. Really a masterclass in colon cancer. Loved it. [LAUGHTER] Thank you so much, and we'll see everyone-- [INTERPOSING VOICES]
CHRISTINA BAILEY: You're welcome.
Segment:0 .
AMIT JOSHI: Hello, everyone. Welcome to SCORE School. I'm delighted to introduce our speaker today, Dr. Christina Bailey, who's at Vanderbilt University in Nashville, Tennessee. Dr. Bailey received her bachelor's of science from Louisiana Tech University, followed by her medical degree from Louisiana State in 2005. After that, she went to Vanderbilt for her general surgery residency in combination with a master's of science and clinical investigation from Vanderbilt. After that, she did a surgical oncology fellowship at MD Anderson.
AMIT JOSHI: After that she came back to Vanderbilt as a faculty there. Her primary clinical interests are in GI malignancies, including gastric cancer, small bowel cancer, colorectal cancer, GIST tumors, retroperitoneal sarcomas, neuroendocrine tumors. She received the Lotzova Research Award and MD Anderson Training Excellence Award during her fellowship. She is particularly interested now as a faculty member in disparities in cancer diagnosis, treatment, and outcomes in regards to age, socioeconomic status, and race as well as quality of life after cancer treatment.
AMIT JOSHI: She's been widely published including JAMA Surgery, and the Journal of Gastrointestinal Surgery. And she is the program director now at Vanderbilt. Dr. Bailey, it's a true pleasure to have you. Thanks for lending your expertise to SCORE School.
CHRISTINA BAILEY: Oh, thank you Dr. Joshi for that introduction. So today I will be discussing colon cancer and polyposis syndrome. I have no disclosures. So I was going to start off by discussing colon cancer for the first half of this presentation, and then we'll go into the polyposis syndrome. So colorectal cancer is the third most common cancer among men and women in the United States.
CHRISTINA BAILEY: From 2006 to 2015, the incidence of colorectal cancer has decreased 2.9% per year in men and 2.4% per year in women. The observed decrease in incidence is largely attributed to an increase in screening, specifically colonoscopy, which is currently recommended for all adults 50 years or older. Colon cancer can develop along three oncogenic pathways, which include chromosomal instability, microsatellite instability, and cytosine-guanine island methylator phenotype or CIMP.
CHRISTINA BAILEY: The most common pathway is chromosomal instability, which accounts for approximately 75% of all colorectal cancers. This is due to alterations in the number or structure of chromosomes and can lead to gene function loss. Here, you could see a model illustrating the classic model of colorectal carcinom genesis, which starts with normal epithelium, enter a series of mutations, progresses to carcinoma.
CHRISTINA BAILEY: The three most common mutations associated with progression from normal epithelium to adenocarcinoma are mutations in adenomatous polyposis coli gene or APC, K-Ras, and p53. APC is a tumor suppressor gene. And mutations lead to increased cell signaling proliferation and cell-to-cell adhesion. K-Ras is an oncogene and mutations in K-Ras actually turn on the K-Ras signaling, leading to uncontrolled cell growth.
CHRISTINA BAILEY: And P53 is a tumor suppression gene. And mutations leads to inability cells to arrest cell growth or induce apoptosis. The second most common pathway leading to colon cancer is microsatellite instability, and this accounts for 15% to 20% of colorectal cancers. This results from mutations and mismatch repair genes which include MLH1, MSH2, MSH6, and PMS2.
CHRISTINA BAILEY: And deficiencies in dMMR leads to accumulation of unrepaired errors. And the third oncogene pathway is the CIMP pathway. This accounts for approximately 5% of colon cancers, and this is due to repetitive sequences of CpG in the DNA promoter region of tumor suppressor genes, leading to loss of BRAF, p16, and MLH1. The one thing that differentiates this pathway from the chromosomal microsatellite instability is that these patients will present with serrated polyps instead of adenomas polyps.
CHRISTINA BAILEY: Sorry. So colon cancer screening, why is it important? So, as briefly hinted to, colon cancer develops along a spectrum. We usually start with hyperproliferative cells and they progress to cancer. So really, the goal of screening is to capture patients when they have these benign polyps, before they even progress to cancer.
CHRISTINA BAILEY: There are several modalities available for colon cancer screening. They include colonoscopy, flexible sigmoidoscopy, fecal occult blood testing, CT colonography, and fecal DNA testing. Of course, the gold standard is colonoscopy. Flexible sigmoidoscopy is very limited because you're only able to visualize the rectum and the sigmoid colon.
CHRISTINA BAILEY: But if a polyp is visualized, colonoscopy is recommended. Fecal occult blood testing requires three stool samples. And of course, if positive, colonoscopy is also recommended. CT colonography and fecal DNA testing are options, but these are currently not supported by the US Preventive Services Task Force. So as far as screening recommendations, according to the NCCN guidelines, average risk patients should undergo their first screening colonoscopy at 50 years of age.
CHRISTINA BAILEY: So what constitutes average risk? So patients who have no history of colorectal polyps, no history of inflammatory bowel disease, and no family history of colorectal cancer or advanced adenomas. And advanced adenomas exhibit high-grade dysplasia, bigger than 1 centimeter, or villous or tuvulovillous histology. So of course, if patients have risk factors for colon cancer, it definitely changes the recommendations for screening.
CHRISTINA BAILEY: And I think the easiest way to think about this is according to medical history and family history. So if you have a personal history of adenomas, colorectal cancers, or inflammatory bowel disease, that definitely increases your risk for the development of subsequent colon cancer. In regards to family history, any first degree relative with colon cancer or with an advanced adenoma increases your risk for the development of colon cancer.
CHRISTINA BAILEY: And then also, if you have a hereditary colorectal cancer syndrome. The two most common are HNPCC, or Hereditary Non-Polyposis Colorectal Cancer, and FAP, Familial Adenomatous Polyposis. Some of your less common colorectal cancer syndromes include Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, Li-Fraumeni syndrome. So when it comes to screening and you high risk patients, so specifically looking at medical history.
CHRISTINA BAILEY: If you have a history of a low risk adenoma, which is less than-- fewer than two polyps smaller than 1 centimeter, the recommendation is for a repeat colonoscopy in five to 10 years, and 10 years is negative. Low risk sessile serrated polyps means there's no dysplasia, they're are also small, you want to get a to get a repeat colonoscopy in five years, and 10 years is negative.
CHRISTINA BAILEY: For patients with high risk polyps, including polyps that are bigger than a centimeter, have high grade dysplasia, are villous or tubulovillous histology or multiple polyps, want to get a repeat colonoscopy in three years, and five years is negative. And in patients who have a history of the inflammatory bowel disease, they recommend that you begin their colonoscopy surveillance eight years after the onset of symptoms.
CHRISTINA BAILEY: And patients with a family history of a first degree relative with colorectal cancer at any age it is recommended that these individuals begin undergoing screening colonoscopies at 40 years of age, or 10 years before the earliest colorectal cancer diagnosis in their family. And any first degree relative with a confirmed advanced adenoma is recommended the same intervals begin 40 years of age.
CHRISTINA BAILEY: And when we look at our patients with hereditary colorectal cancers, and I just listed the two most common ones, in patients with HNPCC it's recommended that they have a colonoscopy every two years, beginning at the age of 20, and annually after the age of 35. And in patients with FAP, they begin their screening at 10 to 20 years of age and then annually thereafter.
CHRISTINA BAILEY: I did want to mention some modifiable risk factors, which includes diet, obesity, lack of physical activity, alcohol and tobacco, all of which are associated with an increased risk of colon cancer. Specifically in regards to diet, patients who consume what is referred to as the Western diet which consists of foods-- or I should say, a diet with high levels of red meat, processed meat, fast food, refined grains and sugar are all associate with an increased risk of colon cancer.
CHRISTINA BAILEY: Whereas a diet high in fiber, including vegetablas and fruits, decrease the risk of colon cancer. So the easiest way to look at it, fiber, exercise are good. Red meat, processed meat, candy, tobacco, alcohol, and obesity are all bad.
SPEAKER 1: Just in time for Halloween, I see.
CHRISTINA BAILEY: Of course.
AMIT JOSHI: Dr. Bailey, I think your microphone is a little bit touchy. Maybe if you tried just talking directly into the computer, would that be easier?
CHRISTINA BAILEY: OK. Is that better?
AMIT JOSHI: Yeah. I think so.
CHRISTINA BAILEY: OK.
AMIT JOSHI: I do have a couple of questions for you. So I wonder, in this time of postponing a lot of elective screening for COVID for the last, well, six months, and maybe even going forward, how much of an impact do you think that will have on development of colon cancer? And I guess one question a lot of patients ask us is, Doc, you diagnosed with colon cancer-- how long has it been there? And so give us some sense, particular for trainees when they're trying to give that answer, how long does it really take for these things to progress?
CHRISTINA BAILEY: Yeah. So the answer to your second question, as I mentioned earlier, these definitely progressed along a spectrum. And it can take anywhere from five to 10 years to progress from just kind of hyperproliferative epithelium to an invasive carcinoma. And to answer your first question in regards to the impact of, as you say, lack of screening because of COVID, it's hard to determine.
CHRISTINA BAILEY: The fortunate thing, at least for us here in Nashville, are actually starting-- I shouldn't say started, we've actually resumed-- more elective procedures, and so I have not seen a change thus far. But the one thing that concerns me, of course, is the potential for seeing patients present with more later stage disease, just due to the delay in screening and subsequent staging studies.
AMIT JOSHI: And one more question for you. You had a nice slide there for the different options for screening and the ones that are sort of sanctioned, or reimbursed, and those that are not. So in a patient who is adamantly against the screening colonoscopy, what advice do you give them in terms of the next best option?
CHRISTINA BAILEY: Yeah. So the next best option would be CT colonography or even a barium enema. But my advice to them would be, if we get this study and we see something, we can't biopsy it and you would still need a colonoscopy.
AMIT JOSHI: OK. Great. Thank you.
CHRISTINA BAILEY: All right. So you get your colonoscopy, what do you see? So in gross endoscopic findings, there are essentially two gross polyp types. You have your pedunculated polyps, which are polyps which have a stalk. Then you have your sessile polyps, or your flat polyps, without the stalk. In regards gone to the histologic subtypes, you have tubular adenomas, which are by far the most common.
CHRISTINA BAILEY: They represent 65 to 80% of polyps. These are most often pedunculated and have less cellular atypia. Your villous adenomas represent 5 to 10% of polyps. These are usually sessile, and you can't see some atypia or dysplasia at these polyps. And then you have your tubulovillous polyps, which represent about 10 to 25% of polyps. In regards to malignant polyps, I did want to spend some time with you on Haggit's classification.
CHRISTINA BAILEY: Which essentially, you have four levels and it is based on the depth of invasion. Your Level 0, these are your carcinomas in situ. There is no invasion to the muscularis mucosa. Your Level 1, the carcinoma invades through your muscularis mucosa, but is limited to the head of the polyp. In regards to Level 2, you get invasion into the neck of the polyp.
CHRISTINA BAILEY: Level 3 is into the stalk. And in Level 4, you see carcinoma invaded into the submucosa of the bowel wall below the stock of the polyp, but above the muscularis propria. And all sessile polyps by definition are level 4 by your Haggit's Classif criteria. So what are the signs and symptoms of colon cancer?
CHRISTINA BAILEY: Most patients are actually asymptomatic. But in patients who do develop symptoms, they can present with iron deficiency anemia, abdominal pain. You can sometimes see changes in bowel habits and changes in stool caliber. In patients what changes in stool caliber, these are usually patients with left-sided lesions. They can also present with bright red blood from the rectum and melena.
CHRISTINA BAILEY: And patients with sizable lesions, they can present with obstructive symptoms, which include constipation, abdominal distension, nausea and vomiting. And patients with more advanced disease can present with unexplained weight loss and fatigue. So how do we diagnose colon cancer? I briefly mentioned this, but you have the options of doing a barium enema or CT colonography.
CHRISTINA BAILEY: But the gold standard is colonoscopy because colonoscopy allows you to not only identify the polyp, but you can also remove the polyp so that it can be evaluated in pathology. In regards to staging, so who needs additional staging work-up? So in a patient who has an endoscopically resectable polyp, my approach to these patients is that it's cancer until proven otherwise.
CHRISTINA BAILEY: Patients who have a resected polyp that contains invasive cancer and has one of the features listed below-- if the polyp was removed in a piecemeal fashion, if the margins cannot be assessed by pathologists, or if the polyp has unfavorable histology which includes poorly or undifferentiated presence of lymphovascular invasion or positive resection margin. These are all patients who need additional staging.
CHRISTINA BAILEY: And as far as what that entails, labs-- the CBC, CMP, and CEA-- imaging-- a CT of the chest, abdomen and pelvis to rule out the presence of distant metastasis. And the two most common signs of metastasis from colon cancer include the lung and the liver. There is no indication for PET CT during the initial workup for patients with colon cancer. And just as a side note, if there is a possibility for an ostomy at the time of surgery, it's prudent that you refer these patients for an ostomy consultation not just for marking, but also for teaching as well.
CHRISTINA BAILEY: In regards to colon cancer staging, staging is based on a AJCC TNM staging. And I think the easiest way to remember staging for colon cancer is that Stage I is T1 to T2 node negative disease. Stage II is T3 to T4, also node negative disease. Stage III is any T stage, but node positive.
CHRISTINA BAILEY: And of course Stage 4 is anyone with distant metastasis.
AMIT JOSHI: Dr. Bailey, one question. One question for you.
CHRISTINA BAILEY: Yes, sir?
AMIT JOSHI: So when you put up that Haggit's classification, we've certainly seen that before. My question clinically is that, is that something that your pathologist reports to you, or is that something that you, as the endoscopist, will kind of synthesize based on your interoperative or interendoscopy finding and then meld that with what comes back in the pathology report? Or is it just kind of a, sort of basic science classification that's not clinically relevant?
CHRISTINA BAILEY: So, definitely clinically relevant, and it is reported by the pathologists. I actually, just Tuesday, at my clinic, had a patient with a Level 4 Haggit's classification tumor in a polyp that was removed. It's very interesting because I had to specifically call my pathology colleague to get a sense of the depth of invasion into the submucosa, because it does matter in regards to who needs resection versus who you can just follow.
AMIT JOSHI: And so I guess if that's not being reported-- because I'm pretty sure at my institution that is not reported-- that's certainly an area of improvement, I think, then, right?
CHRISTINA BAILEY: Yeah. Particularly for the pedunculated polyps with invasive cancer.
AMIT JOSHI: OK. Thank you.
CHRISTINA BAILEY: No. You're welcome. So as far as treatment. So now patient had colonoscopy, carcinoma, no evidence of metastasis. The recommended treatment is a segmental colectomy with a regional lymphadenectomy. You want at least a 5 centimeter margin on either side of the tumor and you want to remove a minimum of 12 lymph nodes.
CHRISTINA BAILEY: So the key for surgery for colon cancer is not just removing the colon itself, but you want to ensure that you are removing all of those draining lymph nodes of that segment of the colon. And the lymph nodes travel with the vessels, so it's prudent when you're ligating those vessels to ligate them at their origin. And I'll go into this in a little bit more detail in the next couple of slides.
CHRISTINA BAILEY: In regards to minimally invasive versus open surgery, there is no recurrence or survival difference. But one, or I should say two of the noted benefits of minimally invasive surgery is that it is associated with less pain and a shorter hospital stay. But like I said, the oncologic results are equivocal. So in regards to what segment of the colon you remove, that 100% depends on where the tumor is.
CHRISTINA BAILEY: So if you have a lesion in the cecum, you're going to do a formal right colectomy which entails migration of the ileocolic vessels, your right colic vessels, and the right branch of your middle colic artery. And if you have a lesion that's in your proximal transverse colon, these patients typically need an extended right colectomy which of course entails division of your terminal ileum and slightly more of your transverse colon compared to what you usually remove as a right colectomy.
CHRISTINA BAILEY: And as far as vessel ligation, you would ligate your endocolic vessel, your right colic, and your middle colic vessels. And once again, you want to ligate these vessels at their origin because you want to ensure that you are removing all of them with nodes draining that segment of the colon. In regards to lesions within the descending colon, recommended surgical treatment is a left colectomy. And here you would divide your transverse colon proximal to the splenic flexure and division of the distal colon at the junction of your left and sigmoid colon.
CHRISTINA BAILEY: Or depending on margins, it could potentially even entail division at the rectosigmoid junction. And then for your sigmoid lesions, you want to do a sigmoidectomy. So for Stage I disease, once again these are your T1, T2 lesions. Treatment is segmental colon resection with lymphadenectomy and there is no indication for adjuvant chemotherapy. For your Stage II tumors, which are your T3 or T4 node negative tumors, once again you want to do a segmental resection and a lymphoadenectomy.
CHRISTINA BAILEY: And some of these patients do require adjuvant chemotherapy. So who are those patients with Stage II colon cancer who need adjuvant chemotherapy? So based on the NCCN guidelines, patients with high risk features are recommended at least for consideration for adjuvant chemotherapy. And those high risk features are poorly differentiated tumors, the presence of lymphovascular or perineural invasion, obstruction, patients presenting with T4 lesions, if the margins are close, indeterminate, or positive, and if you remove less than 12 lymph nodes.
CHRISTINA BAILEY: Studies have shown that removing more than 12 lymph nodes is associated with improved disease-free survival and overall survival. And the reason for this is that if you remove less than 12 lymph nodes, there is a concern that there could potentially be residual cancer in those lymph nodes that were left behind.
CHRISTINA BAILEY: Stage III cancer, once again these are your node positive cancers. Once again, segmental resection with lymphoadenectomy followed by six months of adjuvant chemotherapy. And the two chemotherapy regimens are FOLFOX which is 5-FU leucovorin and oxaliplatin, or CAPOX, which is capecitabine and oxaliplatin. And for Stage IV disease, chemotherapy is typically the treatment for these patients.
CHRISTINA BAILEY: But some patients who have oligometastatic or low volume metastatic disease actually may be candidates for resection of not just their primary tumor, but also for resection of their metastatic disease. So it really depends on how much metastatic disease they have, the location of their disease, whether or not they are potential candidates for surgery.
AMIT JOSHI: Dr. Bailey, regarding FOLFOX, is it true that the oral and IV versions of 5-FU leucovorin are equivalent in their efficacy?
CHRISTINA BAILEY: Yes. Yes, so it's pretty interchangeable. And really, as far as whether patients get follow FOLFOX or CAPOX, it really depends on the medical oncologist and their preference.
AMIT JOSHI: OK.
CHRISTINA BAILEY: So in regards to prognosis, as one would suspect, patients with Stage I disease have the best survival. They have a five-year survival which is 90%. Stage II, 75%. Stage III, 50%. And Stage IV, particularly if they're not candidates for mass resectomy, their five-year survival rate is less than 5%.
CHRISTINA BAILEY: In regards to surveillance after surgery, so in patients with Stage I colon cancer, after resection it's recommended that they undergo a colonoscopy one year after surgery. And if that colonoscopy is negative, then their subsequent colonoscopy will be at 5 to 10 year mark. And for patients with Stage II, III, or IV disease, these patients need an H&P every three to six months for the first two years, then every six months thereafter for a total of five.
CHRISTINA BAILEY: CEA every three to six months for two years, and then every six months for five years. CT of the chest, abdomen and pelvis every six to 12 months for five years. And they also require colonoscopy one year after surgery. If an advanced adenoma is found on that one-year colonoscopy, it's recommended they undergo a repeat colonoscopy in one year. If there is no advanced adenoma, repeat in three years, then every five years thereafter.
CHRISTINA BAILEY:
AMIT JOSHI: That's a great review. Particularly the staging and the stage by stage breakdown of how to proceed. Could you just review for listeners, what is the actual difference between Stage I, Stage II, Stage III, Stage IV? My understanding is that if it gets recalibrated every couple of years based on the actual survival. So Stage IV is supposed to do worse than Stage III, and Stage II, and Stage I. And the reason why these things change is because with new studies and new data, every now and then it gets out of whack where maybe a Stage II actually-- maybe a Stage III actually does better than a Stage II in a certain circumstance, and that's why the independent TNM classification has to get re-shifted.
AMIT JOSHI: Is that a fair assessment?
CHRISTINA BAILEY: Yeah. Because there are-- I wouldn't constantly, but there are often changes made to the HACC staging. And I think it's more so because we're just learning more about the tumors. Now, I did try to basically simplify the Stage II and the III particularly. Because if you go back and look at that table, actually, Stage II you can kind of break it down into Stage IIa, IIb, IIa, IIIb, IIIc.
CHRISTINA BAILEY: And it all as relate to, or I should say correlates with prognosis. And so that's why it's constantly evolving, because we're just learning more about the tumors.
AMIT JOSHI: OK. And I notice you didn't talk about any of the other sort of old-fashioned, I would say out of date staging system. Those are-- I won't even mention them. They're basically ignored at this point, correct?
CHRISTINA BAILEY: Yeah. And really, because if you look at like Duke's classification, you know, that really only comes up when you're reviewing some of the older literature and older data sets. But outside of old papers, it's really not talked about, and not really applicable to clinical practice, at least now.
AMIT JOSHI: Thank you.
CHRISTINA BAILEY: No. You're welcome. All right. Well, we will shift gears now and go into a discussion of our polyposis syndromes. So sporadic colon cancer is by far the most common, and these patients tend to present with solitary lesions. Approximately 5% of patients have a hereditary colon cancer. And the two most common of those, I mentioned earlier, are your HNPCC, or Lynch syndrome, and FAP.
CHRISTINA BAILEY: And then anywhere from about 10% to 30% of people actually have familial cases with familial risk. So when do you suspect hereditary colorectal cancer? And a lot of this is really based on your history. So you have a patient who's young at age of onset-- it is very important, and I can't emphasize this enough, to take adequate family history.
CHRISTINA BAILEY: Because if you have a patient who has multiple generations or multiple members of the same generation, it definitely increases your suspicion for hereditary syndrome. People who have multiple cancers of the same type or cancers of different type, such as colorectal cancer and endometrial cancer, some of these hereditary cancers are associated with extra colonic features, for example, mucosal pigmentation in patients with Peutz-Jaegers.
CHRISTINA BAILEY: And also patients with uncommon tumors, such as sebaceous skin carcinoma in Lynch syndrome or desmoid tumors in patients with FAP. So the way I've, in my mind, kind of conceptualized these patients is that I basically kind of divide into, or I should say separate them, into patients with polyposis syndromes versus the non-polyposis syndromes.
CHRISTINA BAILEY: Polyposis syndrome are where your adenomas predominate, includes FAP which is caused by a mutation in the APC gene. And this is an autosomal dominant syndrome. You can also have attenuated FAP and MYH polyposis, which is recessive. You have your hamartomas and your hyperplastic, serrated adenoma syndromes. And with your non-polyposis syndrome, by far the most common is Lynch syndrome.
CHRISTINA BAILEY: But there is also a mismatch repair syndrome, familial colorectal cancer type X. So we'll spend a little bit of time talking about FAP, and this is the most well defined and understood of the syndromes. It is an autosomal dominant inheritance. And clinically, these patients who are present with numerous colorectal adenomatous polyps. They typically present during their 30s.
CHRISTINA BAILEY: And it's also associated with intra-abdominal desmoids, jaw osteoma, multiple epidermoid cysts with a family history of FAP. The germline confirmatory testing is APC mutation, and it has a detection rate of about 80%. And when you refer patients for genetic testing for concern of FAP, they do do a full gene sequence analysis of the APC gene.
CHRISTINA BAILEY: There are some associated phenotypes. One is the congenital hypertophy the retinal pigment epithelium. It's actually present in about 60% of families with FAP, and it can be used to screen family members. Gardener's syndrome is associated, of course, with colonic polyps, but you also see epidermoid skin cysts and benign osteoid tumors of the mandible and long bone. Some patients present with hereditary desmoid disease where they actually have an absence of colonic polyps but present with desmoids.
CHRISTINA BAILEY: Then you have your Turcot syndrome, which is characterized by colorectal polyps and hepatoblastomas. In regards to surgical management. So when you look at out the chances of having adenomas based on age, it's about 15% by age 10. That jumps to 75% by the age of 20, and 90% by the age of 30. In patients who receive no treatment, 90% will develop colorectal cancer by the age of 45.
CHRISTINA BAILEY: So surgery on these patients is actually not just for treatment, but it's also for prophylaxis to prevent the development of cancer. So there are essentially three options in regards to surgical management for these patients. You could do a total abdominal colectomy with the ileiorectal anastomosis. Of course this procedure is reserved for patients who do not have a large burden of rectal polyps.
CHRISTINA BAILEY: But if you leave the rectum in place, the rectum is at risk for polyp formation and also rectal cancer, so annual surveillance is key in these patients. The second option is a total abdominal proctocolectomy with an ileal pouch-anal anastomosis. Or you can do a total abdominal proctocolectomy with an end ileostomy. So of course, you know, with all things there are pluses and minuses.
CHRISTINA BAILEY: As I mentioned on the last slide, if you do a total abdominal colectomy with an ileorectal anastomosis, there is an approximately a 23% risk of rectal cancer in 20 years. So these patients do require yearly flexible sigmoidoscopies, so this would not be a good option for a patient who you know is noncompliant. Total proctocolectomy with a pouch, there are morbidities associated with a pouch.
CHRISTINA BAILEY: And the pouch is also at risk for adenocarcinoma, so periodic surveillance is also required. And a total proctocolectomy with and end ileostomy is you have to deal with a permanent ileostomy. So because FAP is associated with other types of cancer, extracolonic surveillance is important. These patients can develop desmoids, and they can also develop tumors of the duodenum.
CHRISTINA BAILEY: They can develop ampullary adenocarcinomas, thyroid tumors, and brain tumors. So here is a table listing the screening for these patients. So for colorectal, particularly if they-- specifically if they still have their rectum or they have a pouch, annual endoscopies. For desmoids, do perform a CT scan at the time of diagnosis, just to evaluate for the presence of desmoid tumors, for duodenum and ampillary tumors, and/or EGDs.
CHRISTINA BAILEY: Ultrasound for the thyroid. And as far as the brain, this is based on symptoms. So if someone is totally asymptomatic, it's not recommended that you perform annual CT or MRIs of the brain. It's purely based on symptoms. So now moving to HNPCC, or Lynch syndrome. Clinical features for these patients are early age of onset, that means 45 years of age.
CHRISTINA BAILEY: Right sided colon cancers do predominate. Approximately 70% of patients present with colon cancers proximal to the splenic flexure. They can present with synchronous or metachronous disease. Patients with synchronous disease present with multiple colorectal tumors at initial diagnosis or within six months of surgical resection, whereas patients with metachronous tumors present with recurrent or multiple colorectal cancers more than six months after resection of their initial tumor.
CHRISTINA BAILEY: These patients also have an increased risk of extracolonic cancers which include endometrium, which in women is second to colorectal cancer. They can also develop ovarian, stomach, biliary tract, small bowel, and urothelial cancers. These patients may also present with cutaneous manifestation of their disease, which includes sebaceous adenomas and keratoacanthomas.
CHRISTINA BAILEY: One thing I did want to highlight is the pathologic features of patients who have HNPCC. These patients tend to present with poorly differentiated tumors. On histology, you can see peritumoral lymphatic reaction. There's a high incidence of mucinous tumors in patients with Lynch syndrome, and also the presence of infiltrating lymphocytes within the tumor on histology.
CHRISTINA BAILEY: In regards to genetics, this also is an autosomal dominant inheritance. And once again, it's the cause of five mutations in your mismatch repair genes, which are listed here. Here's a typical pedigree of a family with Lynch syndrome. And as you can see, there are multiple generations that are impacted. The young age of diagnosis-- particularly here, and this patient was 37 at their diagnosis-- and different types of cancer.
CHRISTINA BAILEY: So once again, this just highlights the importance of taking a thorough family history of your patients. So who should we test for Lynch syndrome? So the Amsterdam criteria-- I should say the Amsterdam I-- was introduced in 1991. And what the Amsterdam I criteria stated was that there should be at least three relatives with colorectal cancer, and all of the following criteria had to be present.
CHRISTINA BAILEY: One, the family members or relatives had to be a first degree relative of the other two. At least two successive generations impacted, and at least one colorectal cancer diagnosed before the age of 50. And of course you excluded patients with FAP, and tumors had to be verified, of course, by pathologic examination. The one issue with this was that it's pretty rigorous, and it actually excluded a lot of people with Lynch syndrome.
CHRISTINA BAILEY: This subsequently led to the development of Amsterdam II criteria, and so it was changed to include at least three relatives within an HNPCC associated cancer. Once again, one had a first degree relative of the two, two successive generations, and at least one person diagnosed before the age of 50. But even with the change in the criteria, you know, approximately 68% patients with Lynch syndrome were still being missed.
CHRISTINA BAILEY: So this led to the development of the Bethesda guidelines, and it basically was to help clinicians to identify individuals who should be tested for microsatellites instability given the suspicion for Lynch syndrome. And it basically includes colorectal cancer diagnosed in patients younger than 50 years of age, presence of synchronous metachronous colorectal cancer, or another HNPCC associated tumor regardless of age, colorectal cancers with MSI high histology diagnosed in a patient younger than 60 years of age, and colorectal cancer in one or more first degree relatives with an HNPCC related tumor, with one being diagnosis in a family member younger than 50, and colorectal cancer diagnosis in two or more first or second degree relatives with HNPCC related tumors regardless of age.
CHRISTINA BAILEY: And studies have shown that patients fulfilling the revised Bethesda guidelines have an odds ratio of carrying a germline mutation in MLH1 age or MSH2 are 33.3.
AMIT JOSHI: Dr. Bailey, does that mean that microsatellite instability is only relevant for HNPCC, or does it have something there on the non-Lynch colon cancers?
CHRISTINA BAILEY: So-- yes. So I know a lot of institutions, actually, all patients undergoing resection for colon and rectal cancer, all of the specimens are tested for MSI status. And for patients who are identified as MSI high, you know, then it can trigger the conversations, OK, does this patient-- what's the family history? What's the age? Is this someone I need to refer for genetic testing?
CHRISTINA BAILEY: But the microsatellite status also is useful, particularly in patients with Stage II colon cancer, when you're trying to decide if they need adjuvant chemotherapy or not. Because in patients with a Stage II colon cancer who may have one high risk feature, part of this is MSI high tumor, they actually have a more favorable prognosis so we don't recommend adjuvant chemotherapy.
CHRISTINA BAILEY: So the microsatellite status, yes, it is useful in assisting in the diagnosis of Lynch syndrome, but it also is useful, particularly in patients with Stage II cancer when you're deciding between adjuvant chemotherapy versus no adjuvant chemotherapy.
AMIT JOSHI: Got it. Thank you.
CHRISTINA BAILEY: You're welcome. So as far as surgical management for patients with Lynch syndrome, you have two options. You can do a segmental colectomy, or you can do a total abdominal colectomy with an ileorectal anastomosis. Of course if you do a segmental colectomy, the remaining colon is at risk for metachronous colorectal cancer, so these patients do require yearly colonoscopy.
CHRISTINA BAILEY: And really kind of like, their overall risk for development of cancer after segmental colectomy is about 62% in 30 years. If you do a total abdominal colectomy with ileorectal anastomosis, of course your risk for metachronous cancer is a lot lower, because you no longer have a colon. But you still can develop rectal cancer, and the incidence of that is about 12% in 12 years, and it is associated with a poor bowel function.
CHRISTINA BAILEY: But there is no survival advantage between the two as long as the people who undergo segmental colectomy undergo surveillance. And what that surveillance is, it is an annual colonoscopy. And so it is definitely an individualized decision. In my practice, when I have a patient with Lynch syndrome I definitely have the discussion, the segmental colon resection versus the total abdominal colectomy.
CHRISTINA BAILEY: And really, kind of that conversation is, if we do a segmental colectomy, you have to get annual colonoscopies, but your survival is the same. Whereas if we do a total abdominal colectomy, you still have to get annual flexible sigmoidoscopies, which are not as invasive as colonoscopy. But it's a balance, because there definitely is a difference in regards to quality of life associated with an ileorectal anastomosis versus just a segmental colectomy.
CHRISTINA BAILEY: And in regards to surveillance, yes, you want to survey the colon and the rectum. But as I mentioned earlier, these patients are at risk for other tumors. So you want to ensure that you're not just doing here colonoscopies, but in females it is important to do endometrial sampling due to the risk of endometrial cancer. Some clinicians actually perform trans-vaginal ultrasounds and see them once every five.
CHRISTINA BAILEY: EGD with duodenoscopy for evaluation of the duodenum and the ampulla. Urinalysis due to the increased risk for urothelial tumors. And you want to make sure that these patients are undergoing annual history and physical exams. So that is all I have in regards to slides. Happy to answer any other questions.
AMIT JOSHI: Yeah. What a great review. Thank you so much, Dr. Bailey. Really a masterclass in colon cancer. Loved it. [LAUGHTER] Thank you so much, and we'll see everyone-- [INTERPOSING VOICES]
CHRISTINA BAILEY: You're welcome.
Form Title Download
Transcript
Form Title Bookmark
Entire Media
Segment(s)
Custom Clip
Start At:
End At:
Form Title Share
Entire Media
Segment(s)
Custom Clip
Start At:
End At:
Form Title Accessibility and Keyboard Shortcuts
The cadmore media player is a professional video and audio player experience designed to deliver media as well as relevant transcript, segmentation, and metadata. On the screen is a traditional html video player with buttons such as play, pause, forward, captioning, language and play speed selection and more. Adjacent to the video player are generally tabs, one of which shows a scrolling transcript of the video and the other shows any segmentation of the media, sometimes referred to as chapters. At the top of the video is a menu bar containing an Explore button and Tools button. The Explore button allows you to dig deeper into the video by opening up an explore dialog which contains tabs for a visual navigation of the video using thumbnails, an about tab which contains rich metadata about the media, a segments tab which contains further information about the video, and a related tab which contains links to other media related to this media. The tools button opens a menu with options for sharing the media on social media, creating bookmarking links, creating embed codes for your website, generating citations, and more.
Keyboard Shortcuts
Keyboard shortcuts only work while you are in forms mode. By entering forms mode, you will be able to quickly access portions of the media player with single key commands.
Spacebar: Play/Pause Toggle
I: Info Menu,
O: Tools Menu
T: Transcript Tab,
S: Segments Tab
F: Forward 15,
R: Rewind 15
L: Languages,
P: Playspeed
M: Mute Toggle,
V: Volume Bar
N: Video Only Toggle,
B: Full Screen Toggle
C: Captions Toggle
Escape: Closes dialogs and menus / Exits Player
Z: Next Transcript Chapter
X: Previous Transcript Chapter
Q: Next Transcript Paragraph
W: Previous Transcript Paragraph
Entire Media
Segment(s)
Custom Clip
Start At:
End At:
Embed Size
-
You Size - Responsive
-
We Size - Responsive
-
Picture Overlay Popup
-
400 x 225
-
512 x 288
-
400 x 700
-
768 x 1024
-
1024 x 512
-
1280 x 608
Form Title Cite
No citation provided.
Info
Segments
Related
Thumbnails
Exit Clip Mode
You have requested to see a portion of the video outside of the clip.
Click OK to switch to the full video or click if you would like to stay inside the clip. You can always go back to the clip with Tools and Clip Mode