General Anesthesia cause Angiogenesis?

[jml]

Hi All~
Just wondering if anyone out there has heard about this?
One of my close friends is an anesthesiologist & is attending a big conference this week in San Francisco.
He left me a message saying he'd attended a session discussing new research exploring BC metastatic activity post surgery & the possibility that General Anesthesia (some component of the drugs) may encourage angiogenesis.

I've had 5 surgeries in the past 2 years & after each surgery, I've discovered new disease.
8 weeks after my liver resection, 1cm disease in breast
12 weeks after mastectomy, 1cm supraclavicular node
4 weeks after reconstruction, supraclavicular node larger +1 new one.

I'm so relieved to be wrestling w/neck nodes vs. liver mets again. Regardless, it's all very suspect!
This is going to be very imporatant news to follow.
I'm interested in any additional info that may come forward @SABC.

Any thoughts?

[Sheila]

I find this interesting also as my mets to the supraclavicular nodes, appeared during reconstruction surgery (within a month)!

[molpus53]

my recurrence was found after all my reconstructive surgeries were done. my husband and i wonder if the surgery 'woke things up and got them moving again'. i dont' know if what i found on the interent makes sense.
I was also having lymphatic massage and wonder if that got the bad cells moving around. my docs say no way.....


The growth of blood vessels into tumors is only half of the story. It was postulated as long ago as 1971 by Dr. Judah Folkman that prevention of angiogenesis could inhibit tumor growth by starving them of vital nutrients. The existence of natural inhibitors of angiogenesis was hinted at by an intriguing observation made by surgeons. They found that the surgical removal of a large primary tumor often lead to the rapid development of metastatic growths. This observation suggested that the primary tumor was producing something that kept small metastatic growths from progressing. When the large tumor was removed, the smaller tumors were free to grow.

[Becky]

There are many theories on this concept.

Firstly - there are many schools of thought that the primary tumor does produce chemicals that say "I am king here! No other tumors can grow so I can get all the nutrients and energy!".

Secondly, at least with Her2+ tumors, the Her2 protein is greatly needed for healing. That said, when you have surgery for any reason, that protein is needed and if there are micromets, it can fuel their growth. This is one of the reasons that I had my ovaries removed while still on adjuvant Herceptin and got a colonscopy during that time too (just in case some polyps had to be snipped out). This is also why the clock starts ticking as soon as one has their bc surgery (and why many oncs want you to start chemo within 3-6 weeks).

I am not sure about the other subtypes of bc (although most triple negatives are more like Her2+ women in that they may be Her1+ or Her3+ which are also healing growth factors). It may not be quite the same for women who are only highly hormone positive but not Her2+ as well.

[Soccermom]

Becky, interesting...your comment that "her2 protein is needed for healing". I am 7 weeks out from stage 1 of DIEP reconstruction and have had numerous healing issues. I still have 2 good size wounds and two smaller ones that require a home health nurse and dressing 2X day. I NEVER had healing issues prior to BC,chemo etc.
I wonder IF I am now to consider myself "healing challenged"? I wonder too if I have stirred the beast within? Scary... Good thing my 6 mo scans are only 3 weeks away.

Marcia

[Lani]

general anaesthesia causes angiogenesis, then wouldn't the control arm be the same procedure not done under general anaesthesia?

We know surgery produces angiogenic responses (if it did not, surgeries and injuries and inflammatory conditions would never heal). It is theorized that the bigger the surgery the greater the angiogenic response, although I don't know that this has been proven, hence the trend to needle biopsies and the trend away from mastectomies.

I guess the question is how much more angiogenic response is there if you add general anaesthesia to the trauma of surgery...and then there is the fact that the angiogenic response differs according to the phase of the menstrual cycle the surgery is performed in and certainly other variables as well.

Let's hope they can sort this out well enough to give informed recommendations.

[Mary Jo]

After reading this post and Becky saying she even opted for her colonoscopy during her herceptin in case a polyp "needed to be snipped" off makes me wonder if I should cancel my Wed., colonoscopy procedure. Of course I'm praying that there will be nothing of significance inside my colon and nothing needs to be snipped BUT what if there is a polyp or two. Makes me wonder if mets will follow shortly after reading this post.

What to do?

Mary Jo

[Mary Jo]

After thinking about my above post I realized later on what a stupid question it really was. Of course I need to have my colonoscopy. Of course I need polyps removed if I have them. Those develop into cancer. Colon cancer - breast cancer mets - neither one what we want, of course not, but following through with my exam is what I need to do.

Guess I was a little scared by the post and reacted without thinking.

Thanks for reading my rambling.

Mary Jo

[Lani]

when I get time I will read the original article, but just be aware, that there are different types of anaesthesias and even different types of general anaesthesia. One of the anesthetic agents, propofol (sp?) has even been found to have anti-bc effects.

A recent article seems to make virtual colonoscopy the new gold standard, so maybe you might look into whether you might want that first (and whether your insurance company is paying for it) as it quoted something like only 8% of those who get a virtual colonoscopy as needing a biopsy thereafter. It was not only as accurate in finding lesions, but more so than optical colonoscopy.

I will try to post link to it.

It sounds like a great way to skip a general anesthesia, but still involves a prep and gives you more radiation exposure.

Hope this helped more than confused. Hope I get some time soon.

[Lani]

Virtual Colonoscopy May Be Used First in Screening for Colorectal Cancer
News Author: Roxanne Nelson
CME Author: Charles Vega, MD


Release Date: October 10, 2007
October 10, 2007 — Computed tomographic colonography (CTC), also known as virtual colonoscopy, produced similar rates of detection for advanced neoplasia vs optical colonoscopy (OC), researchers report. The results of this large comparative study, which appears in the October 4 issue of the New England Journal of Medicine, suggest that primary CTC along with selective OC should be considered as a preferred screening strategy.

"Virtual colonoscopy is an effective method of colorectal screening, with less risk of complications as compared to optical colonoscopy," said lead author David H. Kim, MD, from the Department of Radiology at the University of Wisconsin, Madison. Seven colonic perforations were observed in the optical colonoscopy group, and 4 patients required surgery to repair the injury. However, there were no perforations or any other serious procedure-related complications observed in the CTC group. "CTC is less invasive and some patients prefer to go this route," he told Medscape Oncology in an interview. "The screening population is a very heterogenous group and some patients prefer one method over another."

"A common question from the referring physicians is why would patients want to have a virtual colonoscopy if they are going to eventually need both," said Dr. Kim. "It seems to be a common misconception."

In reality, most patients undergoing a primary screening CTC would not need to have an OC. "About 87% of test results are negative," he said, "And only 13% are positive, of which only 8% have undergone therapeutic colonoscopy. Thus, only about 8 out of 100 patients would need to undergo both tests."

However, despite the fact that colorectal cancer can be prevented in many cases by removing advanced adenomas before they progress to cancer, screening compliance remains less than optimal. "There are probably 40 million people over the age of 50 that are not screened," said Dr. Kim. "Both methods are going to be needed in order to make a positive impact."

Dr. Kim and colleagues compared the diagnostic yield from parallel studies of CTC and OC by comparing primary CTC screening in 3120 consecutive patients with primary OC screening in 3163 consecutive patients. The main outcome measures were to compare the rates of detection for advanced adenomas and adenocarcinomas, as well as the overall rates for polypectomy.

At the University of Wisconsin, there are 2 clinically established programs for colorectal cancer screening. "We have screening based on CTC which operates independent of screening by traditional optical colonoscopy," Dr. Kim explained. "That's what allowed this study to be done. We have the results of 2 programs that are operating and drawing from the same geographical group of patients, the same referring physicians, and a choice of procedure that was made by the patient in consultation with their physician."

Patients were referred for polypectomy if CTC detected a polyp that was at least 6 mm in size. Those with smaller polyps, in the range of 6 to 9 mm, were also offered the option of continued CTC surveillance as an alternative to polypectomy. Patients who underwent a primary OC had nearly all detected polyps removed during the procedure, regardless of the size of the polyps, in accordance with established guidelines.

A total of 123 advanced neoplasms were detected during CTC, including 14 invasive carcinomas. During OC, 121 advanced neoplasms were detected, with 4 invasive carcinomas. Among patients who received CTC screening, 246 (7.9%) were referred for colonoscopy.

Confirmation of advanced neoplasia was similar between the 2 groups: 100 (3.2%) patients who received primary CTC, and 107 (3.4%) who received primary OC. These numbers did not include 158 individuals with 193 unresected small polyps that were detected on CTC who had chosen to undergo surveillance.

"There is more data than people realize suggesting that surveillance can be done safely," explained Dr. Kim. "If our patients have polyps that are 6 to 9 millimeters, they are given an option — they can have them removed or we offer them imaging surveillance as part of an IRB [Institutional Review Board]-approved research protocol."

The number of polypectomies performed differed significantly between the 2 groups, although the overall outcomes were similar. In the CTC group, a total of 561 polyps were removed vs 2434 among patients who underwent OC.

Currently, screening colonoscopy removes all detected polyps, regardless of the size of the polyps, but with a screening CTC, the patient needs to have a second procedure if a sizeable polyp or multiple polyps are detected, Dr. Kim emphasizes. "If we are able to filter out the patients with high-risk polyps for referral to colonoscopy, we can save on cost, complications, and resource utilization," he continues. "Selection polypectomy strategies at CTC allow removal of high-risk polyps and surveillance for low-risk subgroups. In our study, these strategies allow similar detection yields of advanced neoplasias yet with a marked savings in terms of polypectomies."

Limited follow-up data are currently available for the patients opting for surveillance screening. The majority of patients are awaiting interval CTC examination, and among those with 1 or 2 polyps of 6 to 9 mm, 54 have returned for follow-up CTC with findings of 70 small polyps. Within this cohort, the majority of polyps (96%) were found to have either remained stable or have decreased in size. Only 3 polyps increased in size and were removed, although they did not reach the 10-mm threshold, and on histologic examination, none displayed a high-grade dysplasia.

At the present time, Medicare does not cover CTC for screening purposes, only for diagnostics. However, 1 advantage to not having national reimbursement is that individuals doing research with CTC have been able to really maintain quality, Dr. Kim pointed out.

"As this rolls out, I think that there will be guidelines that make sure physicians are adequately trained, and quality metrics for programs are in place, so that each facility will be held to a certain standard," he said.

Three of the study authors have disclosed various financial relationships with C.B. Fleet, Viatronix, Medicsight, Philips Medical Systems, and AstraZeneca. The remaining study authors have disclosed no relevant financial relationships.

N Engl J Med. 2007;357:1403-1412.

Clinical Context

Colorectal cancer is an attractive target for screening because of the presence of defined benign precursor lesions and a relatively long interval in the progression from adenoma to cancer. Advanced adenomas are at particularly high risk for progression to cancer, and the current study defines such lesions as those that are 10 mm or greater in size, those with a villous component, or those with the presence of high-grade dysplasia.

CTC has emerged as a potential screening tool to detect the precursor lesions of colorectal cancer. The current study compares the use of CTC and OC in the primary detection of advanced adenomas and carcinomas in a screening population.

Study Highlights

Researchers compared results from 3120 patients referred for CTC during a 25-month period, with 3163 patients evaluated with OC during a 17-month period. Patients referred for polyp surveillance were excluded from study analysis, as were those with a history of bowel disorders or a family history of hereditary nonpolyposis colorectal cancer syndrome.
CTC was performed in accordance with a defined protocol, and patients with evidence of polyps at least 6 mm in size were offered same-day OC for polypectomy. Patients with 1 or 2 polyps between 6 and 9 mm in size per CTC were given the option of CTC surveillance.
Polyps discovered during primary OC were generally excised.
The primary outcome was the prevalence of advanced neoplasia and invasive adenocarcinoma in the CTC and OC groups.
The mean ages of the participants in the CTC and OC groups were 57 and 58.1 years, respectively, and the respective rates of a positive family history of colorectal cancer were 5.1% and 8.4%. There was a preponderance of women in both groups.
The total numbers of polyps removed in the CTC and OC groups were 561 and 2434, respectively. 7.9% of participants in the CTC group were referred for therapeutic OC.
The respective numbers of advanced neoplasias were 123 and 121, a nonsignificant difference. Rates of advanced adenomas were also similar between groups, with no difference between groups with respect to the size of the detected adenomas.
The numbers of invasive carcinomas detected were 14 and 4 in the CTC and OC groups, respectively. This difference was statistically significant.
158 participants in the CTC group had polyps between 6 and 9 mm in size and decided to undergo CTC surveillance. The study authors calculated that if these polyps were eventually diagnosed as advanced adenomas, CTC would still be as effective as OC in screening for colorectal cancer.
Most adenomas were classified as advanced based on size alone, and advanced adenomas were spread throughout the entire colon. All proved adenocarcinomas were large, with a mean size of 34.9 mm. High-grade dysplasia without carcinoma was found in only 0.2% of subjects.
Extracolonic cancers were found in 0.3% of the CTC cohort. Colonic perforation occurred in 0.2% of subjects in the OC group and in no patients in the CTC group.
Pearls for Practice

Advanced adenomas are defined by a size of at least 10 mm, the presence of villous elements, or features of high-grade dysplasia.
The current study by Kim and colleagues finds that CTC and OC are similarly effective in detecting advanced neoplasia in primary screening for colorectal cancer.

[Mary Jo]

Hi Lani,

As always, thank you for such wonderful information. I did hear of this virtual colonoscopy as well and did think about asking about it, but didn't.
I will go a head with my regular colonoscopy and if any polyps are found (NOPE - there aren't going to be any) they can snip them out.

Wish me luck,

Mary Jo

[jml]

"...general anaesthesia causes angiogenesis, then wouldn't the control arm be the same procedure not done under general anaesthesia?"

It's my understanding that the other group in the study underwent some type of Nerve Block to isolate & locally anesthetize the surgical area during their surgeries.

The study discussing the correlation between General Anesthesia & BC met activity suggests that it is some component in the drug combination used to anesthetize that may encourage angiogenesis.

We already know what the body must do in order to heal - from surgery or any other trauma or injury - increased Her2 production & all other growth factors & angiogenic activity.
But, how can we avoid or minimize these effects, specifically relative to "dormant" micromets, if surgery can't be avoided?
That is the real question.

We also already understand how significant ANTI-angiogenics, like Avastin & Thalidomide, are in cancer treatment.
This study reveals new information about a potentially PRO-angiogenic drug combo in General Anesthesia.

I'll search for more info on the study, maybe even find an abstract on the ASA website - or here's the web address if anyone else is so inclined:
http://www2.asahq.org/web/index.asp.

ps-general anesthesia is rarely used in a diagnostic colonoscopy.

[Hopeful]

Lani,

The large radiology center where I get my mammo's has been offering virtual colonoscopy for two or three years. A big advantage appears to be the fact that anesthesia is not used, so you can go right from the test to work. The cost, although not covered by insurance, is about 1/3 the cost of invasive colonoscopy (the center near me charges $700). I have been considering it, but don't like the thought of additional, unnecessary radiation. It is just that I WAY over-funded my medical flex account this year, and think I might as well use the money than lose it. I still have 9 months to get it done.

My onc told me one of his partners had invasive colonoscopy last year, and a polyp "snip" perforated his colon, as a result of which he lost 6 weeks work. I certainly could not afford that!

Hopeful

[Lani]

is that it showed that virtual colonoscopy, should it become the gold standard, would save insurance companies a lot of money without risking missing questionable lesions needing biopsy in patients.

Once the bean counters get a hold of the results of this article I doubt they wil want to wait until larger numbers of patients are studied before agreeing to pay for virtual colonoscopy (it could take years, during which they will be paying out a lot of claims with extra expenses for surgicenter fees, anaesthesiologist fees, fees for anaesthetic agents, with fees set to cover salaries of recovery room nurses, monitoring, etc.as well as the requisite preop stuides, IVs etc.which will no longer be needed)

Hopefully this will push things along.

Let's hope, Hopeful!

[Mary Jo]

Thanks jml you put my mind at ease when you said "general anesthia is not used for a diagnostic colonoscopy" I was told I'd be receiving "moderate sedation" through in IV.

Thanks again. Geez, always something or so it seems.

Mary Jo

[chrisy]

First on the colonoscopy issue, most of the time they do not use general anesthesia and put you all the way out, it's more of an "I know what you're doing but I don't care" type.

Second, and do not have the studies to back this up, I have read somewhere, and it seems more likely to me, that the inflammation and especially the REPAIR of tissue that would call growth factors (including those which promote angiogenesis) and possibly stem cells into the picture. Rather than the anesthesia. You'd think I'd know how to spell that word by now, but I don't.

[TSund]

I'm a bit confused here. It seems to me I remember discussion on the "clock ticking" after surgery and the inflammation component. (i.e. inflammation possibly contributing somehow to spread of the cancer). Is this new theory re:angiogenesis replacing that one or adding to it?

[jml]

Addingto it...unfortunately.
NEW RESEARCH indicates some component of the narcotics in general anesthesia may cause angiogenesis, in addition to all the other theories, such as post surgical inflammatory response, etc.

[TSund]

Anyone know which of these theories is carries more weight? Should we (post surgery) be pouring on the supplements which are said to help inflammation (tumeric, fish oil, etc. I think?? Any others?

I wonder if a course of anti-inflammatories (motrin or the like) is a good idea, but these of course are bad for the digestive system which brings on its own issues...

[MagnoliaforJenny]

I am learning something new every day it seems! I am wondering if this situation somehow coincides with the term "inoperable".

I know I've heard it said before that the cancer was at such a precarious place/stage etc. that to operate would cause further spread of the disease.

My friend is a good example of that, the Doc's told her she is "inoperable" and I wonder about the correlation between that term and the conditions talked about here. Maybe it is not so much the anesthesia medication itself; but, the issue of tampering with any diseased tissues that cause it to spread.

Interesting! Thanks for the info.