Browse Month: October 2007

Cancer Prevention, Detection, and Chemotherapy 6

As far as the cervical cancer screening recommendations, any woman having intercourse, initial smear normal, repeat once a year. First two smears normal, every three years to age 35 and every five years to 65. There’s some people that don’t agree with this. Low risk women over 65 with prior normal smears or in high risk such as with age, continue to do yearly.
One of my colleagues who is a gynecologic surgeon is very upset with this type of approach to how often you should do your pap smears. He says his problem is, “Okay, you can do this and you only do it every three or five years.” He says, “But that’s where all my cancers are and you can go out there and you’ll see a couple of my patients who are now dying of cervical cancer.” So he particularly feels you should do it continuously much more often. But these are the recommendations at the present time.
In Denmark, they were having a terrible time because they didn’t seem to be able to control this at all so they decided every woman is going to get a pap smear. As you can see, the incidence went up and then plummeted as the screening became effective and the mortality in these patients went up a little bit but then it was going steadily down again related to the fact that we’re doing adequate and good pap smears.
I had to put lung cancer screening in here as to effects on mortality rate and if they get a chest x-ray three times a year there’s no effect at all. If they have sputum cytology three times a year, there’s no effect at all. So in other words, our screening is of no value. It’s not effective in patients with lung cancer.
Prostate cancer is a bigger problem and you’re going to see more and more of that as time goes on. New cases now, 334,000, deaths 42,000. A significant problem that’s getting bigger all the time because we ignored a lot of people who said the screening for prostate cancer, PSA, is of no value and that’s obviously not true. It’s been proven now that it’s been a very significant improvement in our ability to pick up prostate cancer.
The PSA is a glycoprotein. It’s a serine protease lysosomal coagulation and it’s positive in 98% of prostate cancer. There’s very few things that are positive at such a high incidence and so you can see why this has been very helpful as we check on our patients.
PSA elevations are found in benign prostatic hypertrophy and inflammation and these can really cause a problem for the practicing physician. With inflammation, the PSA goes up to like 8 or 10, maybe even 20. Now you think the patient’s got the cancer and it’s actually only inflammation or BPH. So we have to be careful about that as time goes on.
Prostate cancer screening. First of all, you should be aware that the African American has a much higher incidence of these cancers than does the regular Caucasian and that goes through all these various groups. Digital rectal exam being age 50 and yearly. High risk groups, the African American age 40-45. Asymptomatic men, if the tumor is found more favorable with its stage. Digital rectal exam, DRE, less effective than PSA and I think we all know that.
Now when we’re talking about prostate cancer detection, same sort of problem as we saw in the polyposis deal and here you can see the initial screening 60 plus percent had detection of prostate and then as time went on, year 3, year 4 it went down further and further.
Adjuvant therapy of proven value with breast cancer in the premenopausal and postmenopausal and also Dukes’ C colon cancer.
The adjuvant chemotherapy of proven value in this group include Dukes’ C colon cancer treated with fluorouracil and levamisole and rectal cancers with radiation and fluorouracil.
New chemotherapy agents that you’ll be starting to work with with the oncologists include irinotecan. Cancer uses are fluorouracil resistant colon cancer. Side effect of note is diarrhea. Cladribine is used to treat hairy cell leukemia, beta cell lymphoma and is associated with fever and sepsis. Topotecan is relapsed ovarian cancer where it can be quite effective and it causes diarrhea and dyspnea in some cases.
Now we talk about new chemotherapy agents again, if we look at Taxol or paclitaxel, it works on the microtubules. Its cancer use is ovary, bladder, lung and breast. Side effects are myelosuppression, neurologic symptoms and fatigue. Vinorelbine or Navelbine, microtubule assembly. Lung, breast, myelosuppression and some neuropathy. Gemcitabine is one we’re quite excited about. It causes DNA inhibition but it’s active, although it’s not a lot, it’s definitely active in pancreas. It can cause fever and lethargy and myelosuppression.
I’ll just sum up to point out that gemcitabine, as I mentioned, doesn’t have a very high incidence of helping in these diseases. As you can see, the patients with response rate are usually in the rather low areas but nevertheless when you get a pancreas that goes two years, that’s pretty impressive.
Here’s another group which you can see ovary 22% response rate. Down here at pancreas 11%. But then they do last for a long time.
Non-small cell lung cancer. Paclitaxel and carboplatin are the best agents we feel. 62% objective response which is twice as high as it used to be and duration of response, it used to be about 20 weeks. Now it’s 53 weeks. So we’re doing better.
Here, again, we’re talking about treatment of resistant tumors and that works better with the use of these agents and this particular one is paclitaxel.
Cancer Prevention, Detection, and Chemotherapy at Cancer Treatment

Cancer Prevention, Detection, and Chemotherapy 5

One of the things I wanted to discuss with you because you probably have not heard about this and a lot of us haven’t either, classic familial adenomatous polyposis, the number of adenomas are usually thousands. The attenuated familial adenomatous polyposis or the FAP, only 1 to 50 cases of polyps, are never more than 100 as you can see. The morphology of the classic FAP is polyploid and the attenuated is flat and the fact that it’s flat makes it hard to realize that you’re dealing with a genetic type of disease. The location of the FAP is through the colon and proximal to the splenic flexure in the attenuated variety. The location is through the colon for the classic and proximal to the splenic flexure for the attenuated. Colorectal cancer is through the colon and proximal splenic flexure for the attenuated.

Here’s where you again can see the difficulties in making sure you’ve got the right diagnosis. Classic FAP age of onset is 39, pretty early. It makes you think about cancer. The attenuated familial adenomatous polyposis is at age 55. So it’s a little bit later and it looks a little bit more like classic but it’s not.

Fundic gland polyps is a constant feature in the classic and in the attenuated. Extracolonic cancers are preampullary, thyroid sarcomas, brain tumors and small bowel are in the classic and periampullary in the nonclassic.

Desmoid tumors are common in the classic and not identified in the attenuated. Hypertrophy of the retina is found in 70% of these patients and absent to almost gone. When we’re looking at these patients with the flat polyps, when we look for the incidence, you’ll notice that percent of the total is over 50,000 in the cecal area and it slowly goes down to the rectum where it’s less than 10%. So this is a group of patients that you should be looking for and I think you can really do some good in taking care of these people.

Guidelines for screening and surveillance then for the early detection of colorectal polyps and cancer. Repeat FOB every year. Flexible sigmoidoscopy every five years. Colonoscopy every ten years. A double contrast barium enema can be used every five to ten years.

Screening costs are really something else with this disease. As you can see, 50-70_year_olds screen every five years and the cost is over $1 billion. So we’ve got to do a little bit more conservatively than what we’re doing at the present time.

We’re talking here about breasts and breast self examination should be started at 20 and over every month. Breast physical 20-40 and over 40 every year and every three years from 20-40. Mammography 35-39 baseline and 40-49 every one to two years. As you probably know, it’s now been established that 40-49 is the way we should do this and we don’t need to do it every year for 35-39, just the baseline. But 40-49 is going to be every year now and 50 and over, of course, we’ve already talked about that being every year. So we should have an annual mammography beginning at age 40. Guidelines for women age 50 and over remain unchanged and then we just discussed the 40-49.

Mammography screening. 30% reduction of breast cancer mortality and 20% false negative are found. It’s very important to keep this in mind because I have seen a number of patients that were in litigation because they had decided that it was a false negative and nothing to worry about but it wasn’t nothing to worry about.

The typical breast has normal fat tissue. Everybody can see this one has carcinoma here. It’s spiculated and irregular in shape and a classic cancer of the breast.

The other thing that you all now know is the study on using tamoxifen in breast attenuation and decreasing of breast cancer has now been easily picked up as being very important. It does increase the likelihood of us being able to cure these patients and this has been a very significant improvement in our care of these particular patients.

Now, when we talk of cancer of the cervix, we all know that that pap smear is the best type of study that we can do – better than anything else. Here’s an area in 1994 with the number of cases being 15,000, the number of deaths being 46,000. Cancer of the cervix risk factors include early sex, parity over five, multiple partners, papilloma virus, DES in utero and non-Jewish.

Cancer Prevention, Detection, and Chemotherapy 4

Now, some of you are aware of the Lynch Syndrome I and there’s a Lynch Syndrome II. It’s a very interesting type of illness. The mean age of onset is 45. It’s found in the proximal colon so when you’re trying to get it and find it and reverse the deaths due to the colon cancer, you have to think about the proximal colon. It has an unusually good prognosis which is usually found in all these types of syndromes and it’s an autosomally dominant type of inheritance.
Lynch Syndrome II is the same as I except multiple tumors, high frequency of colon, endometrium and ovary and less frequent breast, stomach and lymphoma. I have to bring this up because there’s a lot of fights and discussions over in Europe particularly about these two entities and the people felt that this really didn’t jive – that there wasn’t an increased incidence in these Lynch syndrome II. However, they found a number of families with this kind of a syndrome and it pretty well cleared this up. Indeed, this is a cause by the high incidence of the various types of cancers that are listed there.
Here’s a family that’s pretty prolific and as you can see there are seven cases with cancer and five without and you can see the various ages that they had this. Here’s one at 46 years of age. Here’s another one at 55, 42 and certainly a real problem and some of these patients get to the point they just don’t want to talk about it anymore and don’t get the proper studies that they should be getting.
The hereditary aspects of colorectal, again, in familial adenomatous polyposis, percent of colon cancers is less than 1% interestingly enough and that’s one that gets a lot of publicity. Chromosome 5Q21 and gene APC are found. In hereditary nonpolyposis you can see the incidence goes up from 1% to 9%. Chromosome is 2Q3P and then it’s chromosome COCA-1 which you probably know about as well as I do. Now when we’re screening for colorectal cancer, you want to do a digital rectal every year starting age 40. Fecal occult blood test every year age 50. Sigmoidoscopy every 3 to 5 years at age 50. Colonoscopy, first degree relatives of cancer patients at age 50 or less. Age 35 to 40, 2, 3 to 5 years for this test. You will find different groups will do this in a little bit different manner and you may not find the exact type of suggestions as is listed here.
Hemoccult testing. As you know, if the test is positive, 10% of these patients will have cancer and 23% will have polyps. So it’s not a very good test in terms of getting all the cancer patients involved with this. The Hemoccult II only screening test if we use it only like that for asymptomatic colorectal cancer, 50-60% will remain undetected. So not the best test.So if you look at what we’re doing with colorectal cancer, occult blood is a poor marker for colorectal cancer. Most cancers are missed and most bleeding is due to other causes. The HemoQuant is a specific test for blood and some groups are using these too in their studies but there’s really no improvement in picking up the cancers by using this newer test. Both are equally insensitive and we need better screening markers in order to do better in detecting this.

Cancer Prevention, Detection, and Chemotherapy 3

Primary liver cancer is associated with hepatitis, aflatoxin exposure and malnutrition. As you know, this is the most common cancer throughout the world.

Of course, AIDS is associated with a huge number of cases. That’s going up all the time and that is associated primarily with Kaposi’s sarcoma and lymphoma.

There will 186,000 new female breast cancers in the U.S. in 2006 and 46,000 deaths. There’s been no change over the last two or three years and as you know this is very hopeful and gratifying that maybe we’re finally going to start getting a handle on this and decrease this. At the present time, there are 20,000 less deaths than from lung in women. As we discussed, breast cancer, 186,000 and 45,000 deaths, no change.

High risk factors include family history, nulliparity, early menarche, infertility, first pregnancy after age 35. Negative risk factors include negative family history, first birth before age 20, surgical menopause before 40, pituitary insufficiency, early menopause and normal weight and low fat diet.

Now, caffeine, as you know, is associated with painful breasts and we seem to have an awful lot in this country of that and it’s associated with caffeine. If we use danazol, we can cut down the pain and discomfort by about 60% and the tenderness also. There’s no evidence that it does anything in terms of hyperplasia. However, if the patient has atypical hyperplasia, the incidence of cancer goes up about 4-fold.

The other thing we can mention is what about women who have osteoporosis. I’m sure you get this as a real problem all the time. What should we do about these? If we give them estrogens is that bad? Well, I think most of us who are in this business feel that that’s okay and if you use estrogen and progesterone at the same time, the incidence of developing the cancer is going to be so low that I don’t think it’s anything to worry about.

Now, the next thing as we come to a close in this area, if I came around and I said, “Hey, I can cut down the cancers that you’re seeing in your patients by 50%, would you like to do that?” Well, of course, everybody would just be enthralled if you could do that. If we look for lifestyle cancer control, you see in one group, the Mormons, all cancers are down one-third to one-half, lower save prostate. So in other words, we can cut it down by one-third to one-half and the diet is the same except no tea, coffee, tobacco or alcohol. That’s the only difference between the way these people eat and the difference with the cancers being reduced to one-half is really quite remarkable.

Some in terms of cancer control, asbestos and lung are associated, as you know, with being exposed to asbestos in the lung increases the likelihood. I know chloride, which is found in the chemical factories down in the south part of our country cause an increase in hemangiocarcinomas of the liver, dyes such as aniline dyes used by the Germans are associated with an increase in bladder cancer and you already discussed pesticides which are associated with an increase in lymphomas and leukemias.

Now viruses, again, you did discuss this a bit. Epstein-Barr is associated with lymphomas as you know. Papilloma viruses in the cervix cancer. Hepatitis B with hematoma, again, the most common cancer in the world, HIV, lymphomas and Kaposi’s sarcoma as we’ve already discussed.

The family physician is in a unique position to detect cancer based upon the evaluation of the family history, particularly as regards to breast, colon, endometrium and ovary. In the colon, we have approximately three types. As you know, familial polyposis in 100% of these patients eventually, ulcerative colitis in 25% over 25 years and this has to be a constant exposure. It can’t be just sporadic in order for it to be a real factor in this problem. The family cancer syndrome in 50%.

Cancer Prevention, Detection, and Chemotherapy 2

So in cancer control then, what we want to have is a 30% fat diet or less, daily fruits and vegetables, a high fiber grain, low cured, smoked or pickled food and moderate alcohol. Alcoholism as you know is a cocarcinogen with head and neck cancer, esophageal and rectal cancers. So we have to worry about that a little bit also.
This is an area that I was quite surprised at and that is that cholecystectomy raises the incidence of proximal colon cancer by a factor of two, as you can see. Two times greater in females. So we have to watch out for that and try to avoid it and treat conservatively with the things we have available.
Ultraviolet damage is another area we want to look at and as you know the ultraviolet rays will lead to skin problems, lower lip problems and melanomas. In melanomas, as you know, if we take it in 1950, there’s 1:500, in 1980 1:250, in 1985 1:150 and in 2000 1:90 so you can see why melanoma is a real concern because it’s winding up as a tumor that’s occurring at a much more rapid rate than we have seen in the past. Melanoma cases per year constitute 40,300 and 7300 deaths and it’s getting worse, as you know, all the time.
The ultraviolet damage we look for is we want to stop. The necessity of protective clothing. We want to use that to the maximum. Sunscreen. We need to start with the children. I don’t know about you folks but when I was a kid as soon as the period of the year about this time occurred, my family would send us out to get a nice tan so we’d be all protected. As you know, you don’t want to do that at all. But I’m sure that a lot of you have the same problems.
Causes of melanoma are genetic 11%, first degree relatives 1.7 time risk and, of course, sunlight. I don’t know if you’ve had many familial cases of melanoma in your group but I can remember when I was a resident at Minnesota, I was taking care of a lady, she was in her 30s, and there were 12 members of her family, all of them had died from melanoma except her and she was going to die very shortly thereafter. So this is a real problem for us and it’s going to get bigger. As you know, right now, they don’t recommend having studies of your patients. In other words, having breast cancer programs and having a melanoma program. So far most of the groups still don’t feel that that’s necessary. I’m not sure that’s true…

Cancer Prevention, Detection, and Chemotherapy

In the United States, there are some 1.25 million new cancer cases expected in 2006 and 550,000 deaths. Six million Americans have, or have had, a cancer. The types are lung, tongue, pharynx, larynx, esophagus, pancreas, bladder and cervix. Passive smoking in our area constitutes 53,000 deaths per year and 4000 lung cancer cases. So this is a real problem, this passive smoking and, as you know, there’s been a little bit of discussion of it in the papers recently. Not only do you have the passive smoking causing problems in terms of cancers but it also affects esophageal and patients who are having problems with shortness of breath as you are well aware.
When we talk about cancer control we want to tell them to stop and that’s very important. You know, most of us say, “Well, what’s the use of talking to them about it? They’re not going to do anything anyhow.” That’s not true. They really do pay attention to you folks and they will modify things. They can try Nicorette gum. Some of them like the patches. Either one of them we’ll find often they’ll tell you, “Well, it works the best if I just quit.” Then we have to educate children as to this. Get them out of cigarettes and all the problems related to that.
As far as most important areas to look at, diet is the most important and education of patients and families into prudent dietary habits is probably the second most cancer preventive activity. When we talk about this, we talk about a high fat diet. As you know that’s bad. That increases breast and colorectal. There are some recent studies that suggested adequate calcium and vitamin D reduce the incidence of cancer of the colon and of the rectum and this occurs throughout life.
Beta-carotene foods decrease the lung cancers and there’s a couple of studies that don’t really believe that, particularly from over in Sweden and those countries – Finland where the data they have suggests that it really doesn’t help much. In fact, it might make it worse.
The beta-carotene foods, of course, are being studied in lung cancer and head and neck cancers but as you know beta-carotene foods are toxic. They cause dryness, cheilosis, liver dysfunction and a rise in our lipids. All the kind of things we don’t want our people to have…

Diagnosis and Treatment of Breast Cancer 6

What are the short term side effects from chemotherapy? Clearly alopecia in most of the regimens used. Weight gain is very common. This always comes as a shock to patients. Fatigue is the overwhelming most common and problematic problem from adjuvant chemotherapy. Febrile neutropenia is quite rare. Neutropenia is quite common. It usually occurs with every course but febrile neutropenia is quite rare and hemorrhagic complications are even more rare.
Of more concern are the long term side effects from adjuvant chemotherapy particularly if you’re treating young women. It can cause premature menopause and then these women have usually not been thought to be eligible for hormone replacement therapy and are at risk for cardiovascular disease and osteoporosis.
If you look at women treated with adjuvant chemotherapy and compare them to women who have not had breast cancer and not been treated, their incidence of leukemia is actually fairly comparable. Now, there are some investigational arms who escalated doses of cytoxan where leukemia incidence appeared to be increased. But in the general adjuvant therapy we’ve given over the past few years, leukemia doesn’t appear to be increased, nor does cardiomyopathy.
Tamoxifen needs to be used at least more than two years and probably for five years and probably not for more than five years. At more than five years, there may actually be an ability for tumor cells to learn to use tamoxifen to grow and you have increased relapse of breast cancer with more than five years of tamoxifen. You also have an increased risk for other tumors, particularly uterine cancer. It clearly benefits people who are postmenopausal more than premenopausal and usually only those patients who are ER/PR positive will benefit the most. PR positive ER negative benefit also.
Tamoxifen, and you probably have heard so much about tamoxifen in the last few weeks you can’t stand it, probably benefits bone density and blood lipids. In the trial for prevention of breast cancer in normal women, they couldn’t really show that but with only four years followup I don’t think that’s so surprising and I think with longer followup they may be able to demonstrate that. But clearly in breast cancer patients we’ve known for a long time it reduces the risk of contralateral breast cancers by 50%. I think it reduces the risk of new breast cancers in the lumpectomy radiated breast and now we know that in women at risk for breast cancer who have not had breast cancer, tamoxifen reduces the risk of getting breast cancer.
What is the role of adjuvant radiation? I think the thinking about this has changed quite a bit in the past few months. I used to say that local radiation therapy only prevented relapse in the local area and didn’t do anything much for overall survival. There’s two very impressive articles in the New England Journal in October of last year and it showed that patients with any positive nodes receiving radiation therapy had a better survival when that was combined with chemotherapy versus chemotherapy alone. Most of the chemotherapy was with cytoxan methotrexate 5FU. Even in patients who had few nodes, one to three positive nodes, these are the patients who got radiation and chemotherapy versus chemotherapy alone, they seem to have a survival benefit.
In the past I had only applied radiation to patients with four or more positive nodes or large tumors or invasion of the chest wall or something like that. I am now radiating everyone with positive nodes. That may not be standard in all places.
What is the followup for patients who have had breast cancer and then adjuvant therapy or even just breast cancer? See a physician with a good history and physical every four months for the first two years and then every six months to complete five years and then yearly has been my practice and I think is fairly standard. I do a CBC and chemistry profile. You could argue that a CBC is not really necessary. The most important thing is clearly the physician breast exam, the yearly mammograms and other health care maintenance should be followed such as yearly pelvic exam, screening for blood in the stools and sigmoidoscopy after age 50.
Diagnosis and Treatment of Breast Cancer

  • 1
  • 2