Cancer-Etiology

Another Story-Breast Cancer

Few days back did a second opinion consultation. The husband and son had come with some reports.

The history started from May 2009. The lady had a lump in the right breast which was confirmed as malignant by Fine Needle Aspiration cytology (FNAC). The next report they had was a discharge summary from (HCG) Health Care Global Hospital, Bangalore which was dated October 2009. The discharge summary indicated a metastatic disease with metastasis in mediastinal lymph nodes, hilar lymph nodes and lung.

They did not mention what they did from May to October! My guess is that they would have taken either ayurvedic or homeopathic medicine and are now shy to tell about it.

She received 6 cycles of docetaxel+adriamycin+cyclophosphamide at HCG with partial response. Her ejection fraction had also dropped to 40. Possible a side effect of adriamycin. During the work up, they mention that, HCG missed getting estrogen, progesterone and Her 2 marker. After few chemotherapy the tests were done and she was found to be Her 2 positive and negative for hormonal receptors. But they did not add any trastuzumab or lapatinib.

As she had lump in her breast they consulted Dr.Raghavan. He started her on Lapatinib (Tykerb), Letrozole and Zoledronic acid (Zometa). Zometa was added prophylactically as she did not have bone metastases at that time, February 2010. According to their narration, Dr.Raghavan wanted them to take medicines directly from him and also get admitted for zoledronic acid administration. Zoledronic acid can be administered on an OPD (out patient) basis.

The good part was that PET scan done in September 2010 showed complete resolution of disease. There was no evidence of disease anywhere in the body.

The story gets murkier here. They did not have any reports post this and did not divulge any information regarding what medical decision was taken at that time. They mentioned that they took Tykerb for one more year but did not have any prescription for that period. It would have been a challenge to advice on the appropriate course of action in September 2010.

Fast forward to August 2013.

She has visited HCG again. She has local recurrence and now the disease has also spread to hilar lymph node, mediastinal lypmh node, lung, brain (right parietal and left temporal region), and also metastases in dorsal and lumbar spine. She is symptomatic for spinal metastases (she has pain). She is asymptomatic for brain metastases.

A new set of doctors have advised her gemcitabine+paclitaxel chemotherapy with pegfilgrastim support! They have mentioned that, if required, they will treat the brain metastases with Cyberknife!!

What did i counsel or suggest them?


Priority wise

1. Whole Brain Radiation 30Gy in ten fractions and RT to spine (involved areas)
2. Restart Tykerb, as it was taken 2 years back.
3. Consider Capectiabine oral chemotherapy.

I referred them to Dr.Vadiraj at Manipal or to Dr.Siddanna at Kidwai.

I am yet to hear from them...

Dumb Stuff People Say To People With Metastatic Breast Cancer

Exercise And The Benefits For Cancer Patients

The following article describes in detail the benefits of exercise.

http://www.onclive.com/#

Read and deploy.

International Clinical Trial Day-May 20

Scottish physician James Lind pioneered the field of clinical research. On May 20th, 1747, Lind began the first-ever clinical trial. The trial produced the then-revolutionary finding that citrus fruits prevented scurvy.

Ask questions. know your rights, know your responsibilities but participate to improve health care, improve science. 

Breast Cancer Risk-BRCA and Angelina Jolie

Thanks to Angelina Jolie, the awareness about Breast Cancer has hit the roof. Any kind of publicity is good! Those interested in reading her op-ed and comments can click here, here, here.

You can read some interesting views and points worth considering here and here.

If you are a person with BRCA 1 or 2 mutation what should you do?

What are the questions you should be asking?

Here the list goes.....

1. What is the sensitivity and specificity of BRCA testing? To put it more crudely how many times does the testing give a positive report when the person does not have BRCA and how many times does it miss the positive ones!
Will not complicate it with introduction of positive predictive value.

2. What do you mean by 60-80% risk of developing breast cancer when i am BRCA positive?

Normal woman have 2-10% risk. That is out of 100 woman 2 to 10 women can develop cancer. But at what age?

Ok. In BRCA positive ladies, the chance of developing cancer is more. That is out of 100 ladies with BRCA positivity 56 to 84 of them will develop breast cancer. They are also at increased risk for ovarian cancer.

3.Important question to ask, at what age does my risk peak? If at all i have to get mastectomy done, what is the optimum age?

In one study the mean age of people who underwent surgery and showed to have benefit had median age of 40 years.

4. What other modalities are there? Tamoxifen, oophorectomy? that is removal of ovary. How good are these options?

5. What are the risks of various treatments?

When you visit your doctor or genetic counselor, please ask these and any other question which you want to.

Crizotinib-A Patient's Story Of Lung Cancer

Beta Blocker-Old Drug, New Uses-Ask Your Oncologist

Recent retrospective study published in Annals Of Oncology made me sit up and notice beta blockers closely.
Beta blockers are predominantly used as anti-hypertensive and anti-arrhythmic drug. They are also used to control tremors in Parkinson's disease. But here i am talking about its role in improving survival of lung cancer and breast cancer patients.

The article in Annals of Oncology from M D Anderson Cancer Center estimates a 22% improvement in median overall survival for those who took beta blockers.This was in a cohort of patients who had received definitive radiotherapy. The molecular mechanism being hypothesized for the benefit from beta blocker should improve survival for all kinds of lung cancer patients. There is a need to do a prospective study but practitioners and patients should explore the use of beta blockers considering the data available for its safety.
Improvement in overall survival is not a small thing when most new costly agents struggle to show meaningful difference in progression free survival!

Reach out today to your doctor and if you are a doctor read more and start thinking!!

The benefit of beta blocker is also there for patients having breast cancer and melanoma.

References:
1. http://www.medscape.com/viewarticle/777342
2. http://annonc.oxfordjournals.org/content/early/2013/01/01/annonc.mds616.full
3. http://jco.ascopubs.org/content/29/19/2635.abstract?ijkey=dc966043b03d255244605330d386a363baad8d7a&keytype2=tf_ipsecsha
4. http://www.nature.com/nrclinonc/journal/v8/n9/full/nrclinonc.2011.123.html


Conflict of Interest None.

There may be publication bias but asking questions and searching available data can help us in using old weapons against new targets. Academic institutes can do this kind of study.

Volunteering For Clinical Trials-Story of CML

The link provided below to an article describes beautifully the story of Chronic Myeloid Leukemia (CML). It also captures the treatment options for CML, their risks and benefits. It brings out the advancement and innovation which has happened in CML.

And above all HOPE!!

http://thestar.com.my/health/story.asp?file=/2013/5/5/health/12990835&sec=health

A story worth reading....

Breast Cancer

In the previous post mentioned about the story of a lady suffering from breast cancer. For those who want to delve deep into scientific understanding the following resources should help.

For latest treatment options and any other questions who can mail me.

Breast Cancer from fondas vak

Hormonal treatment of breast cancer from Santam Chakraborty


Tata Memorial Hospital treatment algorithm for metastatic breast cancer https://tmc.gov.in/cancerinfo/breast/Popup/clinical%20staging%20algorithms-MBC.pdf

A Sad Story Of A Doctor's Wife With Breast Cancer

In month of February I met a doctor, a surgeon, who is working for government insurance hospital. As i needed by certificates to be attested, i had approached this hospital and had bumped into him. As he came to know that i am an oncologist he started asking about breast cancer. His questioning made me realize that someone known to him is suffering from breast cancer and has also developed metastases. He mentioned that the lady is post menopausal and has hormone positive breast cancer. I drew the algorithm of breast cancer treatment and recommended him to start letrozole 2.5 mg and a bisphosphanate. I mentioned that letrozole may cause osteoporosis.

The surgeon intermittently kept calling me. Also i had to help him get letrozole as it was not available easily in local pharmacy shops. This non availability was also a result of restriction on its supply because it was being rampantly misused in treatment of infertility. Pharmaceutical companies used to sell letrozole for more than 35 Rs when marketed for infertility but same for breast cancer patients was available for around 2 Rs!!

Yesterday made a house call to the surgeon's home. The patient was none else than his wife. She was using a walker to help her walk and appeared tired. She had pain in thoracic and lumbar spine. It was tender on palpation. From what she mentioned made the clinical judgement that the left ischium, left side of pelvis are also involved. Went through her reports.

She was diagnosed of breast cancer in December 2010. She had undergone surgery in early 2011. Was advised adjuvant chemotherapy and radiation. She had declined to take them both. This fear of chemotherapy and radiotherapy was from what she had read and seen. Her mother had suffered from carcinoma cervix and had some side effects from radiation therapy.
This lady is well read, runs a trust and a school. Takes pride in social activities and is respected and consulted in local area. She surfs the internet for answers.
What she had gathered she has refused to take main stream medicine. She takes HOMEOPATHIC medicines. She is reluctant to stop taking homeopathic medicine.

When i asked the surgeon whether she is taking letrozole for last 3 months, he sheepishly mentioned that he had brought the tablets but she has not taken them because i had mentioned that it may cause osteoporosis. Ah! I regretted!

I gave them assurance, explained about observational bias. Somebody else had recommended MRI but since she is claustrophobic they did not want to get it done.

I strongly recommended that they should get 8 gray single fraction radiation to the painful bone areas. It should hardly take 60-90 minutes inside the hospital-from registration, X-ray to getting radiation done.   Start letrozole immediately.

I did feel sorry for the doctor. Being a relative and a doctor is never an easy task. His decision making was hampered because of his emotions.He was concerned and also feeling guilty. But he was not making the right decisions.

I am hurt and angry. This is because there is no need for the lady to suffer in pain. She deserves a good palliative treatment.

What do we learn?

1. The scientific community fails to educate its own members about the risks and benefits of present and emerging evidence based treatment.

2. Fear handicaps and paralyses us. It also makes us take wrong decision.

3. Allowing homeopathic treatment to be available, accepted and taken by patients? Why do we not demand the same scientific rigor from homeopaths? The scientific community by being quite about it, is also equally responsible for nurturing unscientific treatments. I would love to be proved wrong about homeopathic medicine by good scientific research. See the reference section to what i could assess.

4. Anecdotal experience can wrongly influence doctors and patients decisions.

I know it is not easy to take decisions. I do not suggest that you should blindly accept experts. But please make an informed decision. Consult different doctors, take second opinion, speak to survivors.

This is only one of the stories which i have narrated. I have had multiple patients, educated and uneducated who have taken ayurvedic, herbal, homeopathic only to come back for palliative treatment.

References:

1. Bannerji protocol-Homeopathy http://www.homeopathyeurope.org/media/news/beneficial-effect-of-homeopathic-medicines-on-breast-cancer-cells

2.Homeopathy in general: http://rationalwiki.org/wiki/Evidence_for_homeopathy, http://www.guardian.co.uk/notesandqueries/query/0,,-9542,00.html

3. Treatment of metastatic breast cancer: http://www.cancer.gov/cancertopics/pdq/treatment/breast/healthprofessional/page7

4. Treatment algorithm: https://tmc.gov.in/cancerinfo/breast/Popup/clinical%20staging%20algorithms-MBC.pdf

Drugs Targeting Epigenetics

In a previous post have talked about the fascinating concept of epigenetics. You can read it here.

There are four drugs approved which target the epigenetic mechanism. Two drugs are in, MDS, myelodysplastic syndrome named 5-azacitidine and decitabine. They marginally improve the survival and do have myelosuppression as toxicity but have scope for further refinement and improvement.

The other two drugs are Vorinostat and Romidepsin, HDAC inhibitors (histone deacetylase) approved in Cutaneous T Cell Lymphoma (CTCL).

Better understanding of acetylation, methylation in cancer. Better targeting by newer drugs. Possible combination therapies limiting toxicity but improving efficacy are much needed in the use of these new drugs.

For those interested to know in detail..

Ref:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615839/

Efficacy of epigenetic therapy as cancer treatment from janelle_leggere

HDACI from Vahid Nikouei

Apoptosis-Why We Get Cancer?

As I have mentioned in my previous post there are multiple reasons for getting cancer. We can add diet, smoking, alcohol, viruses, ageing, hormones, polyphenols, benzene, toxins, radiation etc to the list which can contribute in causing cancer.

But to change the perspective let me introduce the concept of apoptosis.

Apoptosis is programmed cell death. To give an example the skin which you have today is not the same as 21 days back. Skin gets new cells every 21 days. Similarly the mucosa in our mouth and intestine changes every day. The old cells die and new ones take their place. The old ones die a planned, programmed death known as apoptosis.

If the cell refuses to die for any reason it becomes a problem. We need a healthy balance between death and birth of new cells in the body.

Apoptosis also plays very important role in our growth. Growth of the baby from single cell to a new born. From new born to infant and from infancy to teenager. At all this growth periods apoptosis plays a very crucial role of controlled, structured, beneficial growth.

Cancer cells become immortal by avoiding apoptosis. Many genes play a role in this apoptosis game. p53, BCL, TRAIL pathway etc. There are many drugs being developed to promote apoptosis of cancer cells.

To just give a philosophical touch...........cells which become too selfish and forget that they have to reside inside an organism become malignant, cancerous. They evade apoptosis but unfortunately kill the body in which they reside. They forget that their selfishness has to be balanced with the survival of the whole organism/body..

Does it strike a chord?

19 Year Old With Chronic Myeloid Leukemia And Kidney Failure

Last year 3 new drugs got approved for Chronic Myeloid Leukemia. They are Bosutinib, Ponatinib and Omacetaxine. Chronic Myeloid Leukemia (CML) has been the poster child for development of new targeted therapy. The hype started with Imatininb (Gleevec) which targeted the BCR-ABL translocation, one responsible for driving CML. Apart from above mentioned drugs we also have Nilotinib and Dasatinib.

Ponatinib is a second generation tyrosine kinase inhibitor while as rest all are first generation. Omacetaxine is an inject-able agent against protein synthesis. Ponatinib and Omacetaxine are also effective against the tough acquired mutation called T315I.

As I read about the progress being made I am reminded of a case which i had encountered few years back. 

A 15 year old boy in Jan 2005 presented with weakness, etc.

Feb 2005 Hb-12.5 gm%, WBC 52,000. ( No comment on blast cells etc.)
              Serum Creatinine 2.1. He was evaluated by physicians and nephrologist.
              He was diagnosed to have Ig A Nephropathy with Chronic renal insufficiency.
              Biopsy report reads -Mesangioproliferative glomerulonephritis.

               For one year he was managed as Nephrotic patient only.

March 2006 He was suspected for CML and investigated for same. He visited Tata Memorial hospital and was found to have Philadelphia chromosome positive. He was started on Imatinib. As he  had his renal derangement also , he was often had to move between KEM  hospital Mumbai and Tata Memorial Hospital. 

The patient was on Imatinib till August 2007, along with dialysis, thrice weekly. In July/August 2007 he started developing resistance to Imatinib. 

The resistance to Imatinib was proven by mutation studies. E 4536 mutation.

He was offered Dastanib for 2 months. The support for Dastanib could not be extended because of financial constraints. He was a beneficiary of Railways.
 
The nephrologist state that it is Chronic Renal disease stage V at present. 

He  tested positive for anti-Hbsag antibodies in June 2006.

He was on Hydroxyurea with stable disease and was undergoing dialysis when I had written this summary in  June 2008.

I happened to meet his father while on a journey. Decided to facilitate the best I could. They were reluctant to go to Tata Hospital again. 

I discussed the case with Dr.Lalit from AIIMS at a conference in 2008. He suggested that both Bone Marrow Transplant and Kidney transplant can be done for this boy at a single setting. Encouraged by this I gave some hope to the boy's father. He was willing to do anything and go any where to get his son cured.

They also got HLA test done and the report was sent to HLA scientist at AIIMS. I copy the reply below 

"Prof Lalit Kr from Medical Oncology requested me to reply to you regarding HLA reports of your patient Mr X. 
 
As per the HLA reports the sister seems to be a match and can be considered as a donor for BMT and the mother for the renal transplant.
 
 
In this case it seems the testing has been done by serology and we have only one HLA-A antigen identified for both patient and his sister ( HLA-A2, A-). It is possible that the second antigen is also HLA-A2 ( i.e. A2 inherited from both mother and father ) but unless the father's report is available and that shows presence of HLA-A2 we would not be sure that the children have inherited HLA-A2 from both parents. Its also possible that the second HLA-A antigen is something else and not A2.

Alternatively, if the test is done by molecular technique, and that too shows the same results as serolgy test, we would be sure. 
 
For all transplants patients at AIIMS, initial screening of family is done by serology to pick a potential donor.  However, as a policy we normally confirm the matching status by a molecular test before the patient undergoes BMT. 
 
I do hope the above information is helpful.
 
Once the molecular tests are done, I will be happy to review the reports again if you feel the need."

We sent the blood to Delhi and also the boy traveled to AIIMS.

The next reply was, 

"We have tested the patient and his donor for HLA class I genes and we shall proceed with the Class II gene testing tomorrow. 
I just need to find out if the patients father has been tested or not. As was mentioned in previous reports, we also notice only one HLA-A allele in both patient and donor.  The purpose of testing again was to check what are the HLA genes inherited from father. We are presuming on the basis of previous and current reports that itis HLA-A2 but having fathers' reports will be very helpful. 
 
As soon as we have completed the tests we shall send the reports and receipts. In the meantime if the father is not tested, can we suggest that he be tested and report sent to us."

The next reply

"X's test was done and reports were complete by last week of may. Yesterday we have received the reports of X's father and we are now very sure of the HLA tests done for X and his sister . They are a perfect match and the BMT can be planned for the patient.

Unfortunately I do not know the end of the story. The boy did not undergo the transplant at AIIMS for various reasons. He was taking his treatment at St.Johns Hopsital, Bangalore when I knew last.

Very eager to know how he is doing now.

Lessons for me:

1. Should have followed up with the father. I felt guilty of not being able to do much for him and stopped communication. The father also had got tired of me !

2. The need for well planned research in India. Information about the same made available to all doctors.

3. Unique cases need extra perseverance and innovative action plan. In routine practice when clinicians are overburdened they triage their time and effort towards curable and simple cases. Need for special units to take care of complex cases. 

4.Making care affordable and available. 

Learning never ends........

Vaccines In Cancer

We all are aiming and waiting for the day when one can get vaccinated against cancer!

Vaccines can be of two types prophylactic and therapeutic. Prophylactic ones have been developed for few cancers.
Hepatitis B vaccine is predominantly encouraged to prevent oneself from Hepatocellular cancer. This has helped in keeping the rate of liver cancer in check. Liver cancer is a leading problem in China, Taiwan, India etc. In US, hepatitis C infection is expected to create a huge burden of liver cancer in baby boomers. Efforts are on to bring better therapy for hepatitis c.
Another vaccine which has the potential to make an impact is HPV vaccine. HPV vaccines from GSK and Merck are expected to decrease the incidence of cervical carcinoma. There are many types of HPV virus and these vaccines take care of HPV 16, 18. The immunity against these is expected to help fight against other HPV's also. Vaccinated or not, it is highly recommended to get oneself screened for cervical carcinoma.

Provenge, sipuleucel-T, for prostate cancer is a successful therapeutic vaccine for prostate cancer used in metastatic setting.

There are plenty of therapeutic vaccines in clinical trials for lung cancer, head and neck cancer, brain cancer, melanoma.

Next few years are interesting but none of the vaccines are any near to cure.

Reference: http://www.cancer.gov/cancertopics/factsheet/Therapy/cancer-vaccines

Colon Cancer With Solitary Liver And Solitary Lung Metastases

One of my colon cancer patient, a 55 year old lady, is undergoing treatment for metastatic colon cancer.
Brief history:
In summer of 2008 she came to me post surgery. The tumor was extending to the serosa but the 9 nodes analyzed by the pathologist were negative for metastasis. In mofussil towns, the extent of surgery and pathology reporting are a suspect but i decided to give the benefit of doubt to the patient. For multiple reasons, which i intend to discuss some day, i treated her with 5 FU and Leucovorin which benefits 3.5% of people receiving it. FOLFOX 4 the competing regimen benefits 7.2% of people when the node is positive!

The lady tolerated the chemotherapy well and returned back to her normal life. Around 1 year 8 months later in December 2010 she presented with metastasis to liver and lung confirmed by biopsy and PET-CT. PET-CT was done in Mumbai. At the same time I move out of this mofussil town to a cosmopolitan city.

As the lady,  her husband and the referring surgeon wanted me to giver her treatment eventhough i was leaving the town and was going to be available only once a month, I was compelled to give her CAPOX, that is, capecitabine and oxaliplatin. After 6 cycles, with partial response, i switched to metronomic capectiabine therapy-flat 1000 mg per day. She tolerated this dose of capecitabine very well. With periodic Chest X ray and sonography of the abdomen, she continued her treatment. Her symptoms disappeared and she was/is like any other lady of her age.

On July 2012 it was reported on Chest X ray that the chest lesion had mildly increased in size.The liver lesion had reduced considerably in size. The lady and her husband were not willing for injectible medicines. For some reasons i did not push for Bevacizumab but hinted to them that they can visit their daughter in Mumbai and seek treatment there. They reiterated their trust in me and asked me to do the best i can. The lady was being monitored by telephonic calls and once in 2/3 month physical check up now.

At this juncture i added Thalidomide (phase 2 trial evidence) and Aspirin. She continued to take Capecitabine. Radiological investigation done in September 2012 indicated some objective response. I asked them to continue the same tablets. All this lead to excellent quality of life, good appetite, no symptoms or signs, and  the lady wished to know when she will be stopped of medication. Tough call! I kept pushing it.

Last week i reviewed her again. The liver lesion is not to be seen on USG (sonography). The lung lesion has increased in size. She is finishing her capecetabine this week and thalidomide in another few days.

I have said i will let them know about further treatment. My question/thoughts are

1. Advice them Bevacizumab therapy? {Cost, reluctance of patient?}

2.  Get PET-CT done and decide further treatment?

Surgery of both lung and liver metastases? {Emerging evidence, morbidity and also chance of surgical mortality. Why rock the boat?}

3. Enroll her in any trial? {Logistics, no study in India using new molecules like Regorafenib, most studies are with capecitabine}

4. Continue Aspirin and add Topotecan.

5. Hand her case to my partner and let him decide what is best for her. Make it very clear to the relative that I have done the best and that she will benefit more from dedicated care. {Question the role of mind, placebo etc effect of me!}

Will take some decision next week.

What is that i am aiming for this lady? Objective of treating her?

Aim for Quality of life or increasing her survival?  Both.

With metastases she has lived 27 months. I wish that she crosses 60 months milestone. The best will be that she wins this battle.

Cancer-Is It Increasing?

One of the most often asked question to me is whether the incidence of cancer has increased in last 100 years. Is cancer a disease of 21st century? Is it the price we pay for pollution, toxins, plastic, radiation etc.

Cancer statistics can indicate that incidence of some cancer has increased and for some has decreased. My view on the subject is slightly different. I personally believe that "Observational bias", if that is the right term, always misinforms us.

You may hear many elders or even middle age people mentioning that diseases have increased and that they are seeing more number of people with cancer nowadays.

Some of my views:

1.Cancer has been there since time immemorial. It is mentioned from the time of 1500-1600 BC and also by Hippocrates  (460–370 B.C).

2. The average life expectancy has steadily increased in the last century. Cancer being predominantly a disease of old age you have potential more number of people at risk as well as suffering from cancer.

3. Please note, if we use the numerator denominator concept, the incidence might not have really changed much. Let me explain, the population was less, less people used to live beyond 60 and therefore you had less number of people having cancer.

4. Our diagnostic modalities have significantly improved.  This picks up more cancers. Previously we did not even know, who suffered, when they suffered and how they died. 

5. We are also picking up cancers which would not have manifested at all! Example prostate cancer.

6. More number of people are seen in the society living with cancer or having been cured of it.

So the way i look at this is, we are living long enough to be afflicted by cancer. But this optimism is of no help unless we find ways and means to evade it, eliminate it. What is the progress we have made against cancer? 

Has survival improved in the last 30 years?

Has mortality rate declined?

We will look at these questions in next few posts.

The same is true for some neurological conditions like Parkinson, Alzheimer's.  They are at the other spectrum. Old age risks us to degenerative disease or a disease like cancer. A fine balance between these two kinds of diseases is "life".

References:

1. History of Cancer

2. New Yorker,  Cancer World

3. Cancer Statistics

4. Inverse relationship between cancer and Alzheimer's:
     a. http://www.bmj.com/content/344/bmj.e1442
     b. http://roma.cshl.edu/pdfs/Sebat%20et%20al%20Science%202004.pdf
     c. http://www.captura.uchile.cl/bitstream/handle/2250/10598/BEHRENS_Inverse_Association.pdf?sequence=1

Deep Vein Thrombosis & Cancer

Deep Vein Thrombosis (DVT) is a serious complication in many diseases. It is a common post-surgical complication which with the righ prophylaxis is taken care of.

Deep vein thrombosis is clot in the deep vein and when this gets dislodged and move can cause stroke, pulmonary embolism and also damage to heart.

DVT is seen in upto 50% of cancer patients but unfortunately is underdiagnosed. DVT in cancer patients can be because of various reasons. Some cancers like lung, colon, ovary, pancreas, stomach and endometrium have greater risk of DVT because of increased viscoity of blood. Few treatments can increase rik of DVT, example tamoxifen.

DVT can present insidiously. At times one can have redness, pain when the veins in the thigh are involved. If pulmonary embolism ha happened there can be dry cough, breathlessness.

Any perosn with cancer needs to be aware of DVT and should ask his treating Oncologist about the same and be on vigil.
Primary and seconadry prophylaxis have their own challenges. One needs to tell the treating phyician about all the medications one is taking as drug interactions are very common.

Take home message is:

1. Be on vigil
2. Drug interactions are common, so ask your doctor about the same when you are taking multiple medications.
3. Be active, exercise helps blood circulation and also in many other ways.
4. Be hydrated always.
5. Take extra precautions on long haul flights.

Be aware and ask right questions!

References:

1. http://www.cancerresearchuk.org/cancer-help/about-cancer/cancer-questions/cancer-and-the-risk-of-blood-clots

2. http://annonc.oxfordjournals.org/content/16/5/696.long

3. http://www.telegraph.co.uk/health/healthnews/9357487/Blood-clot-patients-to-receive-routine-cancer-checks.html

4. http://www.cancer.gov/ncicancerbulletin/062910/page5

5. http://www.webmd.com/cancer/features/exercise-for-cancer-patients

Pancreatic Cancer, Open Source, 15 year old's perseverance and brilliance

Steve Jobs, Patrick Swayze (Dirty dancing), Randy Pausch (The Last Lecture), Luciano Pavarotti (Italian Opera Singer) have all had a battle with Pancreatic cancer.

Pancreatic cancer is one of the toughest cancer to diagnose and treat. The survival rates are dismal, 5% at 5 years and there are no easy ways to diagnose or screen early. There can be variations  in survival based on the histology like neuroendocrine tumors doing well. CA 19.9 is a biomarker available for pancreatic cancer but with not that great sensitivity or specificity. It can raised in benign conditions like biliary tract obstruction, cholangitis, inflammatory bowel disease, acute and chronic pancreatitis, liver cirrhosis, cystic fibrosis, thyroid disease!!

There is light at the end of the tunnel. A 15 year old took up this challenege, went through open source articles and has created a cheaper and more effective way to diagnose pancreatic cancer early!

Watch this video

http://www.youtube.com/watch?v=Nq4x8C6Dcf8

This finding is yet to be peer reviewed. It is not indexed in pubmed but he does get a mention...http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392557/

We have a long way to go but progress is being made.......

Epigenetics

Among the many topics which i like to debate about, Nature versus Nurture holds a special place. It can also be called as debate of free will verus determinism. Will ponder more about that in some other post.
Today would like to bring attention to "Epigenetics". A very interesting field which kind of favors nurture theory or on second thoughts does it!!.
Let me get this by posing few questions.

1. Does our diet have an influence on our children?

2. Can I blame my health condition on my mother for what she ate or did not eat during pregnancy?

3. How do our genes learn from our experiences? How is the information incorporated into the DNA?

4. How does from a single cell embryo we become complex human beings? How does the stem cell know to become eye or ear or cardiac cell?

5. How does my nutrition and my environment influence the expression of my genes?

6. Why are identical twins different in terms of characteristics, behavior preferences?

7. Can anxiety or calmness be related to the amount of cuddling and care you received during infancy?

The answer to above question partly lies in epigenetics.

Excellent site to learn is http://learn.genetics.utah.edu/content/epigenetics/

But answers with my bias and understanding are:

1. Yes, our diet has an influence. If your paternal grandfather had food abundance you may have a shortened lifespan!!

2. During early embryonic period it is very crucial for mothers to have balanced nutritious diet (vitmin B complex, folic acid etc.). Lack of key nutrients can increase risk of obesity, cancer and diabetes.

:) Boys, men eat less and feed the women properly!

3. Our experiences can be tagged to DNA by processed called as methylation and acetylation. They are prone to change. Toxins have detrimental effect by acting on these processes.

4. By epigenetics cells become destined organs! (Language)

5. Even for adults having methyl ric food is beneficial. Food guide.

6. The genes may be same but the expression is different because of epigenetics. Also the genes are not same!!

7. Yup, if we extrapolate data from rats. Pup which is licked for first week is more calm. But we do not want the whole world to be full of Buddhas (Monks).

In another post will try to focus on role of epigentics in cancer and how this is being targeted to fight cancer.

International Childhood Cancer Day-February 15

Cancer is predominantly a disease of old age. But there are a few unfortunate children who have to deal with the ordeal of fighting cancer. The common pediatric cancers are Acute Lymphocytic Leukemia (ALL), brain tumors (medulloblastoma and gliomas), retinoblastoma, neuroblastoma, Wilms tumor, osteosarcoma and ewings sarcoma.
Why children suffer from cancer is not completely known. There are no definitive etiolgical factors associated. Cancer is a genetic disease and few genetic conditions are associated with increased risk of pediatric cancer, they are Li Fraumeni syndrome, Fanconi's anemia, Blooms syndrome, Downs' syndrome, neurofibromatosis etc.
In last 50 years significant advacements have been made in the treatment of childhood cancer bringing the mortality down by half.  Today around 80% of children with cancer can be expected to be cured but for the aim is to find cure for 100% without short term or long term toxicity.
There have been advancements in surgery, radiotherapy and chemotherapy but long term survivors of childhood cancer are at increased risk of second malignancy because of treatment ith radiation and certain types of chemotherapeutic agents. The sword of Damocles is always hanging for them!  Also they can have stunted growth both mental and physical becuase of disease and treatment. The newer targeted therapies considered less toxic need to be used with caution in children and preferably in a clinical trial, according to a paper in Lancet.Lancet.
Better understanding of childhood cancers, better therapeutic agents, better trial design, long term data, mandates greater scientific rigor and research. All fields of science from technology, genetics, clinical trials, data management, growth and development research need special focus and thrust to eliminate cancer.
As i recollect the few pediatric patients i have treated, i recollect two happy stories, one with Nasopharyngeal cancer and other with Craniopharyngioma, but numerous kids in front of whom i was helpless and was defeated. Metastatic retinoblastoma (cute 6 year old girl), metastatic Ewing's sarcoma (young 15 year old boy), a kid with Medulloblastoma. They all remind me to become a better and scientific person.

References:
1. http://www.cancer.gov/cancertopics/factsheet/Sites-Types/childhood
2. http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2812%2970530-2/fulltext
3. http://www.hopau.org/uploads/flash/lessons/lsn38/2010_Boot_Camp_Koontz_Pediatrics_Appendix_2.PDF 

Diabetes and Cancer

Chronic diseases are the scourge of the new age. All over the world people living with diabetes are expected to increase, especially in India.
Epidemiological studies indicate an increased risk of cancer for diabetic people. There is increased risk of hepatocellular cancer, pancreatic cancer, breast cancer, endometrial cancer, colorectal cancer, stomach cancer and bladder cancer. Prostate is the odd guy out as the risk for it is decreased if you have diabetes (possibly because of low testosterone levels).
The causal relationship between diabetes and cancer is not well established. There may be confounding bias, observational bias as the evidence is epidemiological. There are few biological hypothesis. Hyperinsulinemia drives growth and diabetics have hyperinsulinemia. Also cancer cells express IGF-1 (Insulin like growth factor receptors) receptors. Inflammation is more common in diabetics and chronic inflammation is a risk for cancer.
Summary and Actions To Be Taken:

1. Epidemiological evidence is there to say that diabetics are at increased risk for cancer.

2. Causal relationship and biological mechanism still needs further elucidation.

3. Diabetes and cancer share several risk factors, like obesity and physical inactivity. An effort to prevent and control diabetes will have a positive effect on cancer incidence. One need not have to wait for conclusive evidence to implement healthy habits and preventive measures.

4. Researchers and clinicians need to be more aware and collect prospective data. Also design studies to benefit patients.

5. The cancer risk conferred by diabetes may be moderate but considering that 366 million people have diabetes worldwide and it is expected to reach 552 million by 2030 calls for awareness and action.

Reference: Diabetes mellitus and cancer risk: Review of the epidemiological evidence

World Cancer Awareness Day-February 4

Cancer is a dreaded disease. There is lot of stigma, prejudice, lack of information, misinformation, lack of awareness which makes this even more dreaded disease. The media also unknowingly plays role in perpetuating certain biases. Whenever a person dies of cancer it is always mentioned that she/he dies of cancer. Celebrities and laymen both have it mentioned in their obituary that they died of cancer. This creates a perception, observational bias that cancer always results in death. This is aggravated by the fact that those living with cancer are loathe to come out and claim that they are cancer survivors. There are few exceptions but they are exceptions.
On Cancer Day multiple agencies worldwide are trying to dispel myths surrounding cancer. The theme this year is Cancer-Did You Know?

Myth 1: Cancer is just a health issue

Myth 2: Cancer is a disease of the elderly, wealthy and developed countries.

Myth 3: Cancer is death sentence

Myth 4: Cancer is my fate

Tremendous effort is required to dispel these and other myths surrounding cancer.

Around 33 to 35 percent of people who smoke believe smoking's detrimental effects are exaggerated. Developing countries are at an increased risk for burden and death from cancer. Cancer treatment in past few decades has improved survival in many cancers. Early diagnosis and better therapies with multimodality collaboration has made difference to many patients. There is lot of progress still to be made. Foremost is in prevention  awareness, and educating each and everyone.
Let us all work towards a healthy present and future.

1. http://download.thelancet.com/pdfs/journals/lanonc/PIIS1470204513700275.pdf?id=4d037fefcb72946c:-1bac8636:13ca10773a7:-15d91359914026138

2.http://www.thelancet.com/journals/lancet/article/PIIS1470204511702984/table?tableid=tbl1&tableidtype=table_id&sectionType=darkBlue

3. http://www.worldcancerday.org/

Aspirin and Colon Cancer

Aspirin is well known drug. In recent years evidence has accumulated to show that aspirin has beneficial effect on colon cancer patient. If you are a colon cancer patient or relative of colon cancer patient it is time you asked your doctor whether you should be taking aspirin.
The potential side effects of aspirin are gastrointestinal ulcers and stomach bleeding. But the risk benefit ratio is definitely tilting towards aspirin being used to prevent as well as treat colon cancer patients.
You may also participate in Aspirin trial as molecular testings are further defining who will benefit from Aspirin.

References:
1. Harvard
2. BJC and Nature
3. NEJM
4. Lancet

Aspirin also has action on other cancers which requires more research before aspirin is routinely recommended.

Second Opinion-A Story Of Cervical Cancer Patient

January is the Cervical Cancer Awareness Month, let me share a story of one of my patient.

One afternoon in 2007 post lunch, I had a knock on the door. It is a common practice for patients, patients relatives to seek consultation at doctor's residence. They normally would be from nearby village and the need to catch bus/train back home compels them to disturb doctor during his personal/private time.

This time it was a bunch of people with MRI scan and other reports in hand. The MRI showed mass in the cervical region extending into the bladder. MRI is not a part of FIGO staging but widely done scan. There is a learning curve to interpret MRI's and I had to rely on the report given by Radiologist to get more out of the MRI report. The description mentioned cervical mass invading the bladder. The histopathology report had confirmed it as squamous cell carcinoma. They had consulted a gynecologist who based on the reports had counselled them that it was Stage 4 cervical cancer and the best treatment would be symptomatic care. Looking at the reports, I also opined that it is Stage 4, Surgery and Radiation both would cause more harm. Benefit from chemotherapy is doubtful. One of the relative insisted on getting the patient examined by me. I reluctantly agreed. 

The same day evening I examined the patient. On pelvic examination, to my surprise, found the anterior fornix completely free. You cannot have the bladder invaded with the tumor without the anterior fornix being involved. The physical examination did not match the MRI report. The clinical diagnosis was Cervical cancer stage II B. This was potentially treatable and curable. But what was that in the bladder? 

CT scan and Urology opinion made us realize that it was a big stone in the urinary bladder.

The patient had surgery for the removal of the stone. When the wound had healed she received Radiation both external and brachytherapy. During external radiation she also received weekly Cisplatin chemotherapy. 

It is five years now since she got treated.  She has occasional urinary tract infection has subcutaneous fibrosis. Probably she can be considered cured of her cancer. Last year her third son got married and he was quite emotional.

The patient and her family hail from the rice growing region in Karnataka. They have constantly shown their gratitude by supplying me with free rice. I call her lucky and i am even more lucky!

Learning:

1. Clinical examination is a must. Scans cannot substitute clinical examination.

2. It is a good idea to get second opinion.

3. PAP Smear screening will reduce/eliminate diagnosis at late stage. Early stage diagnosis or pre malignant lesions are completely curable.

"Cancer is curable, if treated early".

Godspeed!

Lance Armstrong-What do we learn?

The community at large but cancer community specifically feels let down by the confessions made by Lance Armstrong. He was a poster boy for cancer survivors. An inspirational figure providing hope. Yuvraj Singh, Indian cricket player provides the same kind of hope and inspiration.
Everybody has heard the story but what is that we learn from this.

1. Human behavior is dictated by environment as well as self. Peer pressure affects at every stage of our life. Few have the self-confidence and a sense of self worth to be not affected by peer pressure.

Few examples of people succumbing to trends....

a)  Everybody smokes, so let me also smoke! Occasional rationalizing.

b)  Drinking is socially acceptable and is part of marketing, networking!!

c) Ragging is harmless when done inn limit. No one knows when it goes beyond limit.

One can further this theory to good things also.

Let us promote healthy living at all fronts.

Stumbled about something on peer pressure, http://books.wwnorton.com/books/Join-the-Club/

Inequality in Cancer Clinical Trials

In past few weeks multiple instances have prompted me to ponder over inequalities in life. Those interested in them can read here and here.
A recent article published in JCO talks about inequality in recruitment of patients for clinical trials. It is well know that older patients are underrepresented in clinical trials. This get compounded further if they are economically poor. In short poor, elderly patients do not get to participate much in clinical trials. Also if you are less educated chances are you will not participate in a clinical tril.

Musings:
1. Older population needs to be adequately represented in clinical trials to ensure that in "real life" they do not suffer. This is essential for many reasons like, their cardiac, renal reserves are different from young patients. So the effect of drugs need to be know in older patients. Also they are on multiple medications and drug interactions are a common problem.

2. Why income is a barrier to participate in clinical trials? This needs deeper thought. Referring physicians need to be made more aware to ensure patients participation in clinical trials.

A long way to go................

Cervical Cancer Awareness Month-January

January is the Cervical Cancer Awareness Month. Half the month has gone by and I have not heard much about this from hospitals, doctors or media. Probably my observational bias!
Without the support of the doctors, patients, media, pharmaceutical companies, awareness campaigns are a failure. The fact that Cervical cancer does not get the same kind of attention as breast cancer is because there is not much money in Cervical cancer. We all are aware of pink ribbon, October as Breast Cancer Awareness month and lot of celebrities endorse the campaign in October and throughout the year. Let me stop ranting and devote few lines towards Cervical cancer. You can also visit this http://www.nccc-online.org/index.php/january.
Cervical cancer is preventable. Without dwelling on risk factors and other things it is recommended that every female gets PAP smear  screening test done. If you are above 30 years of age please get a PAP smear done. This has the potential to save your life. Consult your doctor/hospital today.
If you are post menopausal lady get your annual checkup done. Post menopausal bleeding is an ominous sign and should lead to gynecological consultation.

Cervical cancer is preventable, prevent it!

Cervical cancer is curable if diagnosed early!

Are you at high risk for Breast Cancer?

Defining people at risk for cancer will become more refined and defined in days to come. To know the risk for breast cancer there are multiple tools. Once we know we are at high risk, what to do? Those who are at high risk for breast cancer are now officially being recommended tamoxifen. Most newspapers have covered this news of NICE's recommendation-Guardian, BBC, Telegraph.  As our attention span is getting shorter and shorter, let me highlight the safety and precaution. Nice is recommending that pre-menopausal women at high risk should be offered tamoxifen unless they have a history of thromboembolic disease or endometrial cancer,

So if you have thromboembolic disease or endometrial cancer, or history of same, or at risk for these, please ask question to your doctor before you take tamoxifen.

Markets, Prosperity Determine Research-Cervical carcinoma

Pharmaceutical companies focus their research on the most lucrative markets. This is nothing wrong but leaves a huge disparity in the kind of diseases suffered by the rich and the poor. I am tempted to say that some agencies or government should focus on health issues suffered by poor. I am referring to a recent report which mentions that the number of molecules in pipeline for cervical cancer is the least. Lung, leukemia and lymphoma are the top three. Cervical carcinoma is the second common cancer in females but the burden is in Asia and Africa. They are not lucrative markets!It can be argued that GSK and MSD have come up with HPV vaccine which should take care of cervical carcinoma in coming years. But the fine print is that the vaccine is effective against few variants of HPV, especially HPV 16, 18, 31 and 45. They are the risky ones but there is a possibility that other HPV strains can become more virulent when they do not have competition from the regular aggressive ones.
Let me change the direction of thought towards what can be done to decrease the diseases of the poor. The rich benefited  better health  because of various reasons. Cervical carcinoma, tuberculosis, malaria, dysentery etc decreased in the affluent much before effective treatment for the same emerged. Bill and Melinda Gates foundation is doing a great job by focusing on these diseases but at times I have my doubt. Improvements in sanitation, hygiene, living standards, housing, diet have helped the affordable to conquer these diseases. The rise in household income also brings in better female literacy, optimum marriage age!, lower fertility rate, better nutrition. I guess i have stressed my point. Better socio-economic conditions will help the cause of health.

So growth is what is urgently required in Asia and Africa. But how should one deal with the issue. They tend to go hand in hand. How does one allocate resources? What percentage should go towards building infrastructure, improving income of the people versus investing in the research of the diseases suffered by them. Much of this also related to governance and political will/systems, but that will be digressing too far!!

Chemotherapy-Patients' Expectations

We have made lot of progress in the last 40 years in treatment of cancer. The survival has improved for most stages in most cancers. We still have a long way to go as nothing short of cure from cancer is what we all are aiming at. It will be even better to nip it in the bed and do not allow cancer to happen in the first place.

Let us get back to present. Each person dreads the word cancer. When one is diagnosed of it, all one wants/hopes is that he gets cured of it. We go to great lengths to get this cure. Hope is good and it is documented that hopeful people respond better to treatment and live longer.
But at the same time is it justifiable to promise cure in metastatic cases?  Many metastatic patients receiving chemotherapy may take it under the false belief that it may be curative, when all that may be giving is few weeks to few months to live and in anecdotal cases few years!
An article published in NEJM, New England Journal of Medicine talks about the same. They report that 69% of patients with lung cancer and 81% of those with colorectal cancer did not report understanding that chemotherapy was not at all likely to cure their cancer.

Bubbles in Education, Healthcare & Research?

Few years back we witnessed the housing bubble coming to an end. Its effects are still being felt. The internet bubble in 2000-2001 led to the creation of infrastructure.Japanese are still to recover from the bubble which ended in 1989.  There have been numerous bubbles and busts in history documented. Also considered as business cycle this is considered by some as inevitable and also beneficial. The governments try their best to avoid this as it brings the survival of the fittest to a very crude form! We are yet to learn the art of growing without creating bubbles. Trade, economics and financial market have made their contribution and we need to be thankful to them. In the new era we will have to learn the art of creating mini bubbles from which survival is easier and the pain is short lived.
The latest making the rounds is education bubble and healthcare bubble  in US. It will be interesting to see if there is a bubble, and when it will burst. Can we anticipate the consequences of this bubble burst?
There are lot of countries in the world which would aspire to have a bubble in their education and healthcare sector!
Similarly can scientific research suffer from bubbles? The link is to an article which predicted something like that in 2010 http://chronicle.com/article/Will-the-Biomedical-Research/124981/ Bubbles predicted too early have limited impact on the behavior of people. 
It is happening with respect to NIH funds. What will be the impact and when the impact will happen are questions which require more analysis and some speculative work. Does the nature of certain research demand that they have bubbles. Without the failures we would not have had our successes? How do i calculate the return on investment of Human Genome Project? What time frame should one be looking at?
Researchers do have fiscal responsibility. But how does one define it?

Similar thoughts can be expressed about healthcare. Solutions can be varied but difficult to implement as they require behavioral changes. Most behavioral changes happen because of pain or right incentives provided at the inflection point. What incentives can be provided to hospitals, doctors, pharmaceutical industry and patients to contain the so called emerging bubble?

The bubble in education will create bonded laborers new era. There are efforts to prevent this.

Why is it so difficult to learn from bubbles in other sectors? Why is it difficult to contain bubbles after having recognized their formation?
Does nature operate through bubbles?

"Unbridled growth in any sector acts as cancer to the ecosystem called life" Pruning either by nature or by humans, if they can, reduce malignant insults.

Head and Neck Cancer and HPV

As mentioned in the previous post there are multiple viruses responsible for malignancy. In recent years the role of HPV virus in head and neck cancer has become more clear. Patients having HPV positive cancer tend to be 10 years younger, non-smokers, non-alcoholics. They present in stage 3 or stage 4 but have better prognosis compared to non-HPV positive head and neck cancer. Treatments are getting better defined for this subgroup of patients.Trials will determine dose and other details of chemotherapy and radiotherapy for this patients.
It does appear that having HPV positive cancer has better prognosis but the real challenge will be in its prevention. Vaccines are being touted to do this but the pros and cons will have to be weighed.