Duration of Tamoxifen for breast cancer

Women diagnosed with Estrogen-receptor positive breast cancer benefit from taking additional pill called Tamoxifen.  The usual duration is usually 5 years therapy.    The Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial randomized 12,894 women for 5 versus 10 years of Tamoxifen therapy.   The study found that women who took tamoxifen for ten years had a significantly lower risk of breast cancer recurrence and lower death rate compared to women who took tamoxifen for five years.   However, taking Tamoxifen for 10 years also resulted in a significantly higher incidence of adverse events including endometrial (uterine) cancer, blood clot in the lung, and ischemic heart disease.

Overall, this study recommends the use of tamoxifen for ten years, instead of five years. Patients with a relatively higher risk of recurrence based on their tumor characteristics (ie, pathological node involvement, large tumor size, or high tumor grade) seem to benefit even more.  The study concluded: "For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis"

Reference:
- Dizon DS, et al.  Uptodate. Accessed 5-26-13
- Davies C, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2012

 

Obesity seems to increase the risk of uterine cancer recurrence

Obesity is well known to be associated with uterine cancer.   However, how obesity affects the prognosis of patients with uterine cancer is unknown.   Arem et al studied 1400 women with uterine cancer as part of the National Institutes of Health-AARP Diet and Health Study.  She evaluated the relationship of BMI (obesity) with overall uterine cancer cure rate.    

Compared with women with a BMI in the range of 18.5 to less than 25kg/m(2), the hazard ratios for 5-year all-cause mortality were 1.74 (95% CI = 1.13 to 2.66) for BMI in the range of 25 to less than 30kg/m(2), 1.84 (95% CI = 1.17 to 2.88) for BMI in the range of 30 to less than 35kg/m(2), and 2.35 (95% CI = 1.48 to 3.73) for BMI greater than or equal to 35kg/m(2) (P trend < .001).   In other words, for a patient with uterine cancer and obesity (BMI > 35), she has more than 200% increase risk of dying from the cancer recurrent than the patients with normal weight.  Higher BMI was also statistically significantly associated with poorer endometrial cancer-specific 5-year mortality.

The study concluded that higher prediagnosis BMI (or obesity) increases risk of overall and disease-specific mortality among women diagnosed with endometrial cancer, whereas physical activity lowers risk.

Obesity and physical activity may affect endometrial cancer survival through various pathways. Obesity may cause tumorigenesis and tumor progression through insulin resistance and hyperinsulinemia, increased bioavailability of steroid hormones, and localized inflammation.  My own intake is even after you have completed your uterine cancer treatment, you should continue to lose weight and to increase exercise.

Reference:

Arem H, et al. Prediagnosis body mass index, physical activity, and mortality in endometrial cancer patients.  J Natl Cancer Inst. 2013. 6;105(5):342-9.

High recurrent rates of patient with uterine cancer who has tumor in lymph vascular space

Uterine (the womb) cancer is the most common gynecologic cancer in the United States.  Approximately 49,000 new uterine cancer cases will occur annually.   The treatment usually consists of hysterectomy and lymph node removals.   We then get more information after surgery whether to add radiation or chemotherapy.   

A recent study evaluated131 patients with stage IB – IIA whose pathology showed negative nodes but there was invasion of lymphatic and vascular space by tumor (LVSI).  Median age was 67 years.   After surgery, 45 patients were observed (Obs), and 86 patients received adjuvant radiation. The study reported 30 total relapses 30/131 (23%): 11/45 (24%) in the Obs group and 19/86 (22%) in the adjuvant radiation group. Recurrence rates were similar between staged and unstaged patients: 24% (20/84) and 21% (10/47), respectively. Among Obs patients, 82% of relapses were local, whereas in patients treated with adjuvant radiation, 84% were distant. Both cancer-related survival and overall survival (OS) were not significantly impacted by adjuvant radiation, because of distant failure rates. Adjuvant radiation significantly improved pelvic control (P = 0.007). 

The conclusion of the study was overall recurrence rates for stage IB-IIA patients with LVSI are high (23%). Although adjuvant radiation therapy improved pelvic control, it did not impact recurrence rates, cancer-related survival, likely secondary to distant failures.  Chemotherapy may have important role in the future study.  The role of systemic therapy with or without radiotherapy for early-stage uterine cancer with LVSI should be evaluated, particularly in patients with high-grade tumors or involvement of the LVSI

Reference:

Simpkins F, et al. Patterns of recurrence in stage I endometrioid endometrial adenocarcinoma with lymphovascular space invasion. Int J Gynecol Cancer. 2013 ;23(1):98-104

Exercise may prolong your life

Despite of the ups and downs of life, most of us enjoy our life.  I don't know anybody, in the right mind, who wants to die right away.   Some patients have ask if there is anything we could eat or do to increase our life expectancy.   Surely you have seen my previous blogs about maintaining ideal body weight, eat less meat, salt, sugar, fat (I know these are taste goods…).   One more aspect of what we could do to improve our chance of long healthy living is EXERCISE.

One study by Leitzmann involving 252,925 men and women aged 50-71 years showed that vigorous exercise (at least 20 minutes three times a week) combined with regular exercise (at least 30 minutes of moderate activity most days of the week) was associated with a 50 percent decreased death rate.  It appears to be dose dependent.  That means, the more you exercise the more you will benefit.

So, I don’t have a fountain of youth or pills to prolong your life.  But exercise seems to be a strong predictor of healthy living.  Of course, you need to talk to your doctor first if you are fit for exercise.  Yes, some exercises are boring.  Consider make it like a game that is fun to exercise.  I often play basket ball with my neighbor’s children.  These 8-10 years old easily beat me in cardiac performance but I have fun with them.   When they beat me too often, then I would do my “vigorous” gardening: pulling out lots of weeds or cutting up dead trees…

Reference:

Leitzmann MF, et al. Physical activity recommendations and decreased risk of mortality. Arch Intern Med. 2007;167(22):2453.

Excess weight, liver failure and cancer

Liver is one of our most important organs with various function including detoxification, protein synthesis, production of biochemicals for digestions.  We cannot live without a liver.  Many causes can lead to liver failure such as too much alcohol, infection (hepatitis), autoimmune, etc. 

 

Now we learn that overweight/ obesity may also leads to some liver disease as well as liver failure.   When we eat too much, much of the excess calories are deposited in the liver as fatty liver.  These fatty liver destroy the liver gradually.  In some cases, cirrhosis due to fatty liver deposition leads to liver cancer  (hepatocellular carcinoma). 

The diagnosis is usually started with symptoms of liver disease such as weakness, nausea, jaundice (yellow skin/ sclera).   Your doctor may start the work up with blood tests to check liver enzymes and hepatitis virus screening tests.   Ultrasound and xray may then be used next.  The ultimate diagnosis is by liver biopsy.

Unfortunately, the prevalence of fatty liver disease is increasing from 5.5% (in 1999) to 9.8% (2004), 11% (between 2005-8).   Fatty liver is accounting up to 75% of chronic liver disease.

The main treatment is to lose weight and avoidance of alcohol as well as any other foods/medicines that could hurt the liver.    In some cases, liver transplant may be needed.

It is very hard to lose weight.  But this fatty liver disease increases my concern of people not knowingly hurting themselves by excess calorie.  Those extra donuts, mints, candies, cookies, etc actually could hurt us!  Please look at my past blogs about losing weight.  It is so important to get to a healthy weight.  It is worth it to lose weight and becoming healthier because each one of you is so worth it.

Reference

Sheth SG, et al.  Epidemiology, clinical features and diagnosis of nonalcoholic fatty liver disease in adults.  Uptodate  accessed 5-18-13

Stool/fecal transplant?

Yes, you heard it correctly.   A prestigious journal of New England Journal published a study using stool transplant to cure an intractable bowel infection.  Clostridium Difficile bacteria is one of the most common hospital acquired infection in the US.  Many of of these patients received antibiotics for medical reason.   The antibiotics kill bad as well as good bacteria.   The population of good bacteria in the colon becomes unstable and decreasing.  This is when the C. Difficile bacteria becomes dominant and causing symptoms such as severe diarrhea, nausea and vomiting.

The standard treatment usually is using Metronidazole or Vancomycin antibiotics.  However, the C Difficile infection sometime becomes difficult to treat conventionally.   There are even cases require colon resection to cure the bowel infection.

The most recent publication is using donor stool (from other healthy persons) which is infused into your stomach/duodenum thru a tube.  The investigators randomly assigned patients to receive one of three therapies: an initial vancomycin regimen (500 mg orally four times per day for 4 days), followed by bowel lavage and subsequent infusion of a solution of donor feces through a nasoduodenal tube; a standard vancomycin regimen (500 mg orally four times per day for 14 days); or a standard vancomycin regimen with bowel lavage. The primary end point was the resolution of diarrhea associated with C. difficile infection without relapse after 10 weeks.

The study was stopped after an interim analysis of 16 patients.  In the infusion group, 13 (81%) had resolution of C. difficile-associated diarrhea after the first infusion. The 3 remaining patients received a second infusion with feces from a different donor, with resolution in 2 patients. Resolution of C. difficile infection occurred in 4 of 13 patients (31%) receiving vancomycin alone and in 3 of 13 patients (23%) receiving vancomycin with bowel lavage (P<0.001 for both comparisons with the infusion group). No significant differences in adverse events among the three study groups were observed except for mild diarrhea and abdominal cramping in the infusion group on the infusion day. After donor-feces infusion, patients showed increased fecal bacterial diversity, similar to that in healthy donors, with an increase in Bacteroidetes species and clostridium clusters IV and XIVa and a decrease in Proteobacteria species.

Yes, it is sound like an out of the box idea.  But I praise these investigators who could think out of the box for their patients.   I still think you should only get this treatment after all other conventional treatment have been used - consider it experimental.

Reference:

van Nood E, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile.  N Engl J Med. 2013;368(5):407.

How to reduce pain after surgery

Studies suggests that many patients suffer moderate to severe pain after abdominal surgery.  Most surgeons would use opiates (morphine) as the main pain medication after surgery.  As some of you are aware, morphine (and other opiates) cause your bowel to be inactive and some experience severe nausea and vomiting.  At University Tennessee - West Clinic, we initiated a program to assess and reduce surgical pain.  

Instead of using morphine only, my team started our patients with IV acetominophen (Tylenol) and gabapentin BEFORE surgery.  During surgery, we inject local anesthesia to numb the incision even after patients asleep under general anesthesia.   After surgery, we give patients more acetominophen, gabapentin and ketorolac (intravenous form of drug similar to ibuprofen).  With this regimen, most of my patients reported tremendous pain reduction compared to just morphine alone (data unpublished yet).  Most of my patients experience minimal pain after abdominal surgery with this multimodalities pain control method.   Instead of staying 3-5 days in the hospital after cancer surgery, most of my patients now go home the next day.  Another good thing about using less morphine is they experience less nausea after surgery.

Please note that not all patients have relieved of their surgical pain completely.  But most of them are relieved to the point that most of them can go home one day after surgery.   When you go for surgery, consider asking your surgeon about multimodality pain control.   In the reference below, I included our paper that was published on how to do this.

Reference

Azari L, Santoso JT, Osborne SE.  Optimal Pain Management in Total Abdominal Hysterectomy.  Obstet Gyn Survey. 2013, 68 (3): 215–227

Should I keep my ovary when I about to get hysterectomy (surgery to remove uterus)?

In the case of pelvic cancer, your surgeon usually recommends a complete removal of uterus and ovaries as part of cancer surgery.    However, you may undergo hysterectomy for benign (non cancer) indications.   In this case, your surgeon may recommend preservation of your ovary/ovaries especially when you are young and without menopausal symptoms.

My patients often ask what would be their chances of having future surgery to remove the ovaries if they preserve them during the initial hysterectomy surgery for benign indications (heavy uterine bleeding, painful menstruation, uterine fibroid, etc).   A study published in May 2013 by Casiano evaluated this question.

The study compared the risk of oophorectomy (removal of ovary during hysterectomy) of 4,931 women in Olmsted County, Minnesota, who underwent ovary-sparing hysterectomy for benign indications (case group) between 1965 and 2002, with 4,931 age-matched women who did not undergo hysterectomy (referent group). The incidence of oophorectomy after hysterectomy is only 9.2% at 30-year follow-up and is only 1.9 percentage points higher than the incidence of oophorectomy in referent women with intact reproductive organs.

In other words, as you elect to keep your ovaries during your hysterectomy for benign reasons, you have 9.2% chance of being reoperated again to remove your ovaries in the next 30 years.  This is only 1.9% higher than women who never had hysterectomy needing to have their ovaries remove in the next 30 years.  

Some of you may just want to remove your ovaries during hysterectomy even when you are young and have no cancer for fear of ovarian cancer.  Do keep it in perspective that your ovaries have many benefits reducing risks of heart disease, dementia, osteoperosis, hot flushes, and others.   Thus, do discuss this important decision to remove or preserve your ovaries during hysterectomy with your surgeon.

Reference:

- Casiano ER, et al.  Risk of oophorectomy after hysterectomy. Obstet Gynecol. 2013;121(5):1069-74

- Parker WH, et al. Ovarian conservation at time of hysterectomy - the Nurses' health study.  Obstet Gynecol 2009; 113: 1027-37