Chemotherapy and blood clot

Patients with cancer is known to have increase of developing blood clot.  Usually, the blood clot starts in the leg (called Deep Venous Thrombosis) and may travel to the lung (Pulmonary Emboli).   We think cancer causes blood to thicken.  Other factors such as surgery, being immobilized, and obesity are risk factors that exacerbate the blood to thicken further and may increase risks of blood clot development.   New studies now suggest that chemotherapy may also increase this blood clot risk further.
 
Khorana extracted data from health insurance database of commercially insured patients in the United States between 2004 and 2009.  17,284 patients were evaluated for blood clot with age/sex-matched, noncancer control.   The blood clot incidence was recorded during a 3-month to 12-month follow-up period after the initiation of chemotherapy.  The study found blood clot occurred in 12.6% of the cancer cohort (n = 2170) over 12 months after the initiation of chemotherapy versus 1.4% of controls (n = 237; P < .0001).  Another study by Seng indicated that patient taking Cisplatin is more prone to blood clot than other chemo.

What do we do?  One common way to treat blood clot is to use blood thinner medications (Coumadin, heparin, etc).  However, these are risky drugs that could cause blood to thin too much causing bleeding or stroke, even death.   Just like in anything in medicine, there is no free lunch.   Do discuss these risks and benefits with your doctor and health care providers.   But there are things that you could do such as being active, losing weight (you heard this before from me…) to reduce the risk.  Also call your doctor or go to Emergency Room if your leg suddenly swell up or you get short of breath.

Reference:

-Khorana AA, et al.  Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States. Cancer. 2012 Aug 14. doi: 10.1002/cncr.27772. [Epub ahead of print]

-Seng S, et al. Risk of Venous Thromboembolism in Patients With Cancer Treated With Cisplatin: A Systematic Review and Meta-Analysis. J Clin Oncol. 2012 Nov 13. [Epub ahead of print]

Aspirin and colon cancer

About 6% of Americans will develop colon cancer in their life time.   Several randomized trials showed that taking aspirin once a day reduced in patient taking aspirin for many years period.  The risk reduction seemed to improve as we take aspirin longer.   

1121 patients with a history of adenomas were randomized into aspirin (81 or 325 mg daily) or placebo. A follow-up colonoscopy was performed at least one year after study entry in 1084 patients (97 percent). The risk of recurrent adenomas was significantly lower in the 81 mg group compared with placebo (38 versus 47 percent, RR 0.81, 95% CI 0.69-0.96). The risk reduction was even greater for the development of advanced neoplasms (RR 0.59, 95% CI 0.38-0.92). For unclear reasons, the 325 mg dose was not associated with a significantly reduced risk of adenoma recurrence

Another study was on 517 patients with a history of colorectal cancer who were randomly assigned to aspirin (325 mg/day) or placebo.  Recurrent adenomas were observed significantly less often in the aspirin group (17 versus 25 percent, RR 0.65, 95% CI 0.46-0.91) during a colonoscopy performed at a median of 13 months after randomization.

Another  trial (945 patients with a history of an adenoma)  were randomly assigned to aspirin (300 mg daily), folic acid supplementation (0.5 mg daily), or placebo.  Aspirin supplementation but not folic acid was associated with a significantly reduced risk of recurrent adenomas

There are controversies of the dose of aspirin.   In light of aspirin could cause other complications (stomach/bowel bleeding, bleeding in the brain, stomach pain, etc), I recommend taking 81mg (baby aspirin) aspirin a day.  Be extra careful if you take any blood thinners (Plavix, coumadin, etc) because the combinations of aspirin and other blood thinners may cause excess bleeding.   Do talk to your doctor before you start this.  Buy the generic aspirin - cheaper and equally effective.

Reference:

-Baron JA, Cole BF, Sandler RS, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003; 348:891.

-Sandler RS, Halabi S, Baron JA, et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 2003; 348:883.

-Benamouzig R, Deyra J, Martin A, et al. Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial. Gastroenterology 2003; 125:328.

-Benamouzig R, Uzzan B, Deyra J, et al. Prevention by daily soluble aspirin of colorectal adenoma recurrence: 4-year results of the APACC randomised trial. Gut 2012; 61:255.

-Logan RF, Grainge MJ, Shepherd VC, et al. Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology 2008; 134:29.

- Uptodate.  Accessed 12-2-12

Red meat and cancer

Eating a lot of red meat (beef, pork, veal, and lamb), is associated with an elevated risk of colorectal cancer in both men and women. One large study (n = 148,610) concluded that the risk of colon cancer was increased about 50%  in people who eat processed meat for many years. 

Eating red meat also increases dying from cancer.   In one large population study (n = 617,119), an association between cancer-specific mortality and eating red meat especially in individuals aged 50 to 71 years. Findings were similar in another study of over 121,000 men and women where red meat consumption was also associated with an increased risk of cancer mortality (HR 1.16, 95% CI 1.09-1.23).

The mechanisms for this increased risk have not been determined.  Several risk factors have been postulated including heme (red cell) content in the meat, animal fat, and carcinogens produced when the meat is cooked at high temperatures. It isn’t known if risk varies with different animal raising strategies (eg, grass-fed beef).

Reference:

-Giovannucci E, Goldin B. The role of fat, fatty acids, and total energy intake in the etiology of human colon cancer. Am J Clin Nutr 1997; 66:1564S.

-Giovannucci E, Rimm EB, Stampfer MJ, et al. Intake of fat, meat, and fiber in relation to risk of colon cancer in men. Cancer Res 1994; 54:2390.

-Willett WC, Stampfer MJ, Colditz GA, et al. Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. N Engl J Med 1990; 323:1664.

-Norat T, Bingham S, Ferrari P, et al. Meat, fish, and colorectal cancer risk: the European Prospective Investigation into cancer and nutrition. J Natl Cancer Inst 2005; 97:906.

-Chao A, Thun MJ, Connell CJ, et al. Meat consumption and risk of colorectal cancer. JAMA 2005; 293:172.

-Sinha R, Cross AJ, Graubard BI, et al. Meat intake and mortality: a prospective study of over half a million people. Arch Intern Med 2009; 169:562.

-Pan A, Sun Q, Bernstein AM, et al. Red meat consumption and mortality: results from 2 prospective cohort studies. Arch Intern Med 2012; 172:555

- Uptodate.  Cancer prevention.  Accessed 12-2-12

Nipple discharge

Nipple discharge is common after childbearing.  Usually a mother may still have milky discharge a few months after cessation of breast feeding, but sometime longer.  Milky discharge may also be caused by hypothyroidsm or prolactin-producing pituitary tumors, and certain medications (antipsychotics and tricyclic antidepressants).

You should call your doctor or health care providers if you have spontaneous, clear, colored, sticky or bloody unilateral nipple discharge. Leis reported that in 503 patients operated on for one of these types of discharge, 67 (13.3%) had cancer, and 36 (7.2%) had a precancerous lesion. Among the 67 patients with cancer, eight (11.9%) had no palpable mass, 11 (16.4%) had negative cytology ("pap smear of the breast discharge"), and seven (10.4%) had a negative mammogram.

You could also get breast discharge when you stimulate your breast.  It is usually less worrisome if the discharge stops when you stop the breast stimulation.  However, do talk to your health care providers with any of your concern or finding.

Reference:
- Leis HP Jr, et al. Nipple discharge: surgical significance. South Med J. 1988;81(1):20.
- Sabel MS.  Breast mass and other common problems.  Uptodate November 2012. 

I found a breast mass - what do I do now?

Most breast masses are benign such as fibroadenoma.   But most patients and physicians are concerned for possible of breast cancer. There are certain characteristics that are concerning mass for cancer such as single hard, immovable lesion with irregular borders. 

If you found any breast mass, I recommend that you see a physician who will obtain your history and do breast examination. The next steps may include ultrasound, mammography and/or biopsy, depending upon the findings from the history and physical examination, patient age and other clinical factors.  If your age is less than 30 years old, your breast probably more dense.  Thus, your physician may start with ultrasound first.  If you are 30 years or older, your breast usually less dense.  Then your doctor may order mamogram first.

Do remember that no test or exam is 100 percent accurate.  Thus, if you have persistent mass or concern, despite negative test, you should get 2nd or more opinion from other doctors or providers.

Reference:
- The palpable breast lump: information and recommendations to assist decision-making when a breast lump is detected. The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. Canadian Association of Radiation Oncologists. CMAJ. 1998;158 Suppl 3:S3
- Sabel MS.  Breast mass and other common problems.  Uptodate November 2012.

HE4 blood test and ovarian cancer prognosis

A study published in December 2012 evaluated the relationship of preoperative HE4 with ovarian cancer survival.  HE4 (Human Epididymis protein) is a blood test that appears to be elevated in patients with ovarian cancer - almost similar to CA125 blood test.

The study found that preoperative (before surgery) levels of HE4 were strongly associated with all ovarian cancer standard prognostic factors. HE4 levels increased significantly with age (p=0.02), cancer stage (p<0.0001), grade (p=0.005), preoperative CA-125 levels (p<0.0001), and residual tumor (p<0.0001). HE4 levels above the median value (394pmol/L) were significantly associated with mortality (HR=2.17; 95% CI: 1.42-3.32) and progression (HR=1.81; 95% CI: 1.21-2.72). After adjustment for the FIGO stage, which was the only factor significantly associated with prognosis in multivariate analyses, the association of HE4 with death remained statistically significant (HR=1.67; 95% CI: 1.08-2.59). However, the association with progression was no longer significant (HR=1.32; 95% CI: 0.87-1.99).

In English, the way I understood it, the high level of HE4 before surgery correlates with aggressiveness of ovarian cancer and the risk of death from this cancer.  Thus, preoperative HE4 level may be used to discuss prognosis of the cancer.  Do be careful since this study is based only on 136 patients.   Usually, we want to see more studies before using this approach clinically.

Reference:

Trudel D, et al. Human epididymis protein 4 (HE4) and ovarian cancer prognosis. Gynecol Oncol. 2012 Dec;127(3):511-5.

 

Painful bones and muscles after Neulasta/Neupogen injection

Patients undergoing chemotherapy usually experience bone marrow suppression.   Our bone marrow is actively dividing, just like cancer cells, thus are prone to be affected by chemotherapy.  As a results, low white blood cells (neutropenia), low red blood cells (anemia) and low platelets (thrombocytopenia) are common in patients on chemo.   When your white blood cells are too low, you may get severe infection.  Your doctor may prescribe you Neulasta (Pegfilgrastim) or Neupogen (Filgrastrim)  injection in between of your chemo sessions.

Neulasta/ Neupogen induces your bone marrow to work harder to produce white blood cells.  Commonly, patients would complain of muscle and bone aches after Neulasta/ Neupogen injection.  One patient complained in her blog "My stomach felt like I did a hundred sit ups, without the flat abs to show for it"  :-).
Bone pain has been reported in approximately 22% of patients.

One of rare complications of Neulasta/ Neupogen is it may cause your spleen to enlarged and can rupture.  A ruptured spleen can cause death. The spleen is located in the upper left section of your stomach area. Call your doctor right away if you have pain in the left upper stomach area or left shoulder tip area. This pain could mean your spleen is enlarged or ruptured.  There are other serious risks that you could review from the website below.  

For the common aches, taking acetominophen (Tylenol) before and after the injection usually help.  Sometimes, your doctor may have to give a stronger pain medication such as hydrocodone or oxycodone.  Reducing the dose of neulasta also may reduce the pain while still giving you the benefit of white blood cell production.  Some patients reported that claritin also help reducing the bone pain.  But I could not find a study confirming it.

Reference:
- http://www.neulasta.com/starting-chemo-with-neulasta/white-blood-cell-counts.html?src=ppc&WT.srch=1&SRC=2

- Kubista E,et al; Pegfilgrastim Study Group.Bone pain associated with once-per-cycle pegfilgrastim is similar to daily filgrastim in patients with breast cancer. Clin Breast Cancer. 2003 Feb;3(6):391-8