Last blog on non resectible Lung cancer

With the Yahoo blog coming to the close.
I would like to write my last blog on target drug therapy for non small cell lung cancer which turn out to be unresectable.

The treatment of lung cancer always falls into a trap of discovering the tumour late.
For small tumour in young patient, the impact on breathing and systemic upset is minimal.
Only large tumour is symptomatic
But it is not necessarily that small tumour need to grow big to disseminate to other part of body.

Quite a lot of patient present with serious or widespread metastases when diagnosed lung cancer.

Today tissue biopsy is mandatory as genetic study is important to guide target drug therapy.

Usually the EGFR is tested first followed by EMLA- ALK and some time Kras study.

The latter is mainly for prognosis purpose.

Is testing for EGFR mutation and ALK-FISH testing mutually exclusive each other?
Since if EGFR is +ve, oral tyrosine kinase inhibitor is used with good efficacy.

If EGFR is -ve, traditional chemotherapy with cisplatinum + permetrexed is the norm.

With failure of response to chemotherapy, the use of monotherapy with crizotinib is considered after ALK testing,
response is usually remarkable.

The concern of cost makes crizotinib not popular. As in every new drug without competition, usually the cost or charge is arbitary.
with oral TKI, now Iressa and erotinib( Tarceva) has good and patient- benefited competition. Not long later, a new oral TKI known as Icotinib will be entering the market, this would further bring down the charges.

Also the percentage of alk FISH mutation +ve is only 6 - 8 % wihich is growing as more patient are tested routinely.

But oral TKI does not eradicate the disease.
It dose shrink the disease but in much longer duration compared to debulking surgery.
Eradication of remaining non dividing tumour cells remain either the chemotherapy drug or self immunity.

Non cessation or long term oral drug therapy with TKI is compulsory.

So after Complete remission by all radiological or chemical criteria and clinical assessment, chemotherapy may be worthwhile.
Post down-staging debulking surgery may also be considered.

Rechallange with oral TKI after stopping is also reported sometimes to be useful.

So practically all lung cancer can be successfully palliated either with oral TKI drug or iv chemotherapy. But to improve survival, early detection is much more effective.
Cessation of smoking helps but genetic factor predisposing adenocarcinoma is  best fought with screening low dose CT scan of thorax.

Surgery is still the gold standard for curative treatment of lung cancer.

Dr Chung Shiu Shek   Phone 3160 88 65 or HK side 3543 1814

Advanced Lung Cancer

After long interval, I want to discuss a topic not unfamiliar in health post or public education material. The topic on ADVANCED Lung cancer. (晚期肺癌)

The diagnosis of cancer is very important to patient's life.  There is no permission of any degree of error whatsoever.  In addition to the verdict of malignant disease, the

type and stage of the cancer and the approach of staging or treatment must be communicated in skilful and easy to understand manner.  The avoidance of pessimism

(悲观主义) must be balanced with honest and candid approach.

For lung cancer, it is quite common to find out that patient with this disease falls into late stage group.  The handling of such patients demand skill and empathy.

More crucial, it is the time for physician to spend with the patient indirecly convey the sense of "captain ordering vessel abandonment" in its worst scenario.

Patients, especially the young and working group, would seldom recieve the message in positive way.


Nowadays, as spoken by one eminent local oncologist, the development of orally administered target enzyme blocker drug  for anti- lung cancer treatment

(Tyrosin kinase inhibitor, or TKI in short)  is a miles stone in the treatment of all cancers.  Compared to the invention of penicillin (Fleming in nineteenth century)

discovery of insulin synthesis, the invention of exogenous corticosteroid (Cushing in early twentithed century) , the accidental notice of anti-tuberculosis chemotherapy

(Streptomycin, in parenteral form), the use of first TKI gefitonib (Iressa ^R 易瑞沙) in advanced lung cancer brought hope to only small group of patients with lung cancer.

But the concept of personalised treatment of all cancer has revolutionized the entire medical community,

It is rather a change of personal treatment concept that has significant impact on entire medical community that the pursuit of genetic marker for most diseases has the

implication of treatment.

For example, the association of chromosomal abnormality  with retinoblastoma, the use of target therapy in iv form for Gastrointestinal Stromal cancer (GIST), the use of

propanolol for the treatment of facial or other childhood haemangioma, the screening for congenital hypothyroidism and familial polyposis. All these discoveries are not

applicable to all form of diseases but the spirit has strong repercussion on medical knowledge advancement. It is in fact a change of paradigm. (though a cliche陳詞濫調)

but very true)


The diagnosis of advanced lung cancer is usually based on PET scan (正電子斷層掃描) or advanced symptoms such as pleural effusion, hoarseness of voice

or palpable lymphadenopathy or multiple lesions in X ray/CT scan.   With the need for tissue for genetic study, the requirement for tissue confirmation and

genetic marker study is mandatory irrespective what stage of disease or patients' status are.

Using efficient DNA extraction  and/or amplification technique, even a small amount of tissue or cells are sufficient for EGFR receptor study.   Sometimes, the shredded

cells in pleural effusion specimen or TBNA (transbronchial needle aspiration biopsy) is enough for marker study.  Another study for the ALK- receptor study is more

expansive and less easily available (in both Universities' lab.).  Radiological guided biopsy can generate core of tissue (with 20 G or 18 G needle) which is even better.

For TBNA , if performed by endobronchial ultrasound, the accuracy is very acceptable and risk-free.  The endobronchial ultrasound is now widely available in all HA

hospitals and most private hospitals.

However, the aspirated cells are still less abundant than mediastinoscopic biopsy and both procedures should be complementary and not mutually exclusive

to lung cancer patients.


Finally, the handling of message to patients and their familes must be careful and consistent. It is best dealt with by patient 's primary care physicians.  So the consulting

Oncologist can spare the effort of bad news breaking.  Clinical oncologists can concentrate on various form of treatment and pros and cons of chemotherapy.

With oral TKI, target drug therapy is main stay for advanced lung cancer treatment.

For the rest of patients who did not have EGFR +ve addenocarcinoma, induction and maintenance of chemotherapy with Premetrexed or other drugs are well

tolerated and beneficial to young and fit patient.


I welcome all question on advanced lung cancer diagnostic procedure, such as CT guided Fine needle biopsy or core needle biopsy, Video assisted thoracoscopic,

Pleural effusion biopsy and eradication, Endobronchial ultrasound TBNA, Endoscopic Ultrasound FNAC and mediastinoscopy and Ultrasound guided neck or chest wall

biopsy.  My clinic no is 3160 8865.

My clinic in Mongkok (3160 8847) and in Central (3543 1814).

Lack of manpower in Cardiothoracic Surgery Divison in Prince of Wales Hospital

Doctors manpower supply is always a sensitive question to politician and general public.There is no point of satisfaction. More doctors mean more comprehensive service and shift the balance of power to patient's side. For all types of treatment approach, patient will have no choice or no say if there is an insurmountable statement of lack of man power.

In Cardiothoracic Surgery, this is creme de la creme of all surgical specialties. Competition for training post is difficult and learning of skill is tedious and demanding.The talent of the trainee will in some form or the other affect the maturity of the surgeon. The character of the surgeon in this field must be perfectionist in surgical skill, diplomat in dealing with relatives and colleagues and decision maker for difficult situation.  Training usually span for more than 6 - 8 years.

Also, the higher the professional ladder , the higher demand of time ane energy in this field.

Not long ago, this specialty has suffered a manpower loss with shift of senior surgeons to private market.

However, there is no lack of new comers and young budding surgeon to take up the challange.

There is no complaint of lack of surgeon then.

In fact, there is complaint of lack of cases and referral from their medical colleagues.

So, why is there a sudden outcry of lack of resources? Lack of doctors? Lack of trainees and expert surgeon?

This boils down to the surgeons desire of easy life and competition for resources.

For all 3 centres in Hong Kong, to speak the truth, I would say it is never the Prince of Wales Hospital that is lacking resources.

Indeed, the climbing of number of heart cases is evident to that.

The reason of demanding more manpower is just a gesture to demand for reward for the volume of cases.

In Cardiothroacic field, usually one doctor is shouldering responsibility that the mean number of works hours is among the highest in all field.
We cannot judge the number of expert surgeon needed in a large centre. Only that there is pros and cons of more expert surgeon. First the experience is diluted. Second the competition and challange of the team to meet different surgeons demand is high. The surgeons may be in standby time more than actual service. The number of operations delegated to experienced trainees are much less.

Overall, more supporting doctors are needed instead of mature surgeon in a busy unit.
Maybe it is Prince of Wales Hospital CT Surgery Division wish to recruit more basic or higher surgical trainee instead of saying there is failure of retention of experienced staff.

Who would like to see their surgery postponed or waiting list lengthened from patients perspective.
But it is still an unknown black hole of crying for more resources.

(Back in the old days, when I was the only cardiothroacic first call surgeon, I and one experienced cardiothoracic surgeon manage the whole services with annual number of open heart surgery 60 - 80 per year and 300 throacic operations and average 2 - 3 major trauma consultations in the same setting of the teaching hosptial. I have not expressed of lacking manpower in year before the turn of millenium)

Need of Histological confirmation of Advanced staged Cancer

Cancer is a lethal disease. However, cancer seldom lead to immediate death.
For patient in acute care setting, infectious disease, trauma and vascular events account for nearly all emergency collapse or demise of previously healthy patient.

Nowadays, we talk about personalised treatment of cancer, we need to know the type and DNA of the cancer cells to formulate a treatment plan for the patient.
In patient when cancer presented with advanced stage of disease, should the medcial personnel insist of obtaining histological or pathological confirmation before proceeding for treatment.

There is usually a dilemma. To obtain biospy of tumour. If deep seating tumour, the risk is considerable. And if the tumour has spread to important oragnas such as brain or heart, to touch this area means major suffering.
So the chance of cure, if absent, should not warrant aggressive biopsy.
However some lesser invasive means if done under good techniques will help obtaining tissue for lung cancer.

They are:

Video assisted pleural biopsy of effusion drainage- targeted pleural biospy and effusion drainage

Bronchosocpic biopsy or transbronchial biopsy under sedation and locan anaesthetics

Endobronchial ultrasound transbronchial fine needle aspiration of paratracheal and carinal lymph nodes

Percutaneous fine needle imaging guided biospy of lung

By obtaining biopsy sample , the nature of cancer can be defined. The genetic and DNA studies of cancer cells can be pursued.

Personalised treatment and palliation of cancer can be achieved.

Yet, those method are however expensive.

Judicious choice of investigation will determine the success rate. Do need to seek specialist advise. For lung cancer, a cardiothoracic surgical specialist is essential.

To excise nodules directly or take in biopsy first - an issue of taking chance

In private sectors, not all patients come for treatment. They are just coming for second opinion. This is a hypothetical scenario to seek help from two soucess. If different, they would not jump on the treatment plan. If more or less the same or the reason given is the same, they can then opt for the original treatment plan. Rarely, they may accept the suggestion of treatment plan of the second doctor. And switch to the new care giver.

For me, as an experienced surgeon, the line of thinking of pursuing one investigation or other is more or less natural to me. Some nodules in the lung, I wound quickly advise surgery. Whether it is open or minimally invasive is not a major issue. The chance of missing lethal lung cancer is the main concern.
For some nodules with background of lot of disease, with chance of multiple metastases or just more likely a reactive change, I wound suggest observation or biopsy. Not always matter with the size. But to balance the chance of morbidity free surgery versus over - positive thinking.

Indeed, as advocated in my earlier blog, size if more than 9 mm should be annually re CT and excised once the possibility of benign lesion cannot be fully established.
Size less than 6 mm can be safely watched. Above 6 mm, can be watched for 3 or 4 years and left alone.
But there is always some exception. Sometime for over cautious patient, needle biopsy is essential though clinically likely Ca Lung is well suggested.

And the way to deal with negative biopsy has to be evaluated. If patient or doctors are totally insecure of leaving the nodule alone. Needle biopsy can be omitted.
For patients where non operative option is highly favorable, like bleeding tendency, very elderly, bread winner of family, needle biopsy at least clear some uncertainty in this occasion.

If patient  otherwise fit and healthy, Video assisted wedge biopsy is always justifiable if the lesion is regarded as suspicious.
For highly likely non malignant case, say with normal CEA, non smoker and calcified mass or very low PET SUV, needle biopsy is safe to document the non malignant nature in a way better than sitting on X ray comment alone.

Milk powder issue - A medcial or marketing issue

Milk product is essential in every part of human life.  There is no doubt that the best choice for infant feeding being breast milk.  For practicality, in every modern society, milk formula is popular as alternative.

From 2010, there is widely known fact or news that milk formula is the target of every Mainland visitors.  Especially in northern district, the dispensary retail outlets run out of infant milk formular in days and weeks.  Actually, it also occurs from time to time in urban Kowloon. The situation in Hong Kong island may be better.  But the cost of inflation, salary and shop rental push the price of milk product to sky high. Therefore the search for cheap milk products in some selected retail is much keener.  In big retail chains, they transfer all cost of high rental to customer. The price of milk formula is higher in such chains. But in individual shop, the demand of milk formula is much more intense if they do not raise price tremenduouly.

So the problem is there for 2008, 2009 , 2010 then 2011 - 13.  Local birth rises and climaxes at year of 2012.  Therefore the voice of milk powder control is higher and stronger.  For same reason, the privilege of choice exists for mainland mother too. If not all Hong Kong mothers give breast milk to their kids, why can't mainland mothers give better quality milk formula to their off springs.  So there is no wrong or right for them to search milk formula in Hong Kong or through their agents.. Even if mainlanders buy milk formula in Hong Kong and resell for profit. They are not morally right or wrong.

To curb the high competition for milk formula in local stores, immigration control of milk formula is instituted.
This is drastic measure. Back in 2008 or 2009, the competition of milk products is left to the market force that the place where demand is high push up the price. When the price is high the customers drift to other region. Then the supply is back and price is adjusted down and the customer flog back and push up the price once again.
The market control is successful but slow.

Urgency for securing supply of milk formula is there.  So rules set in.
Some scholars advise the baby to switch to whatever brand the mother can get hold of. Theorectically it is sound. But we can do better by sticking to one brand.
Actually, on can observe the same strategy exist for mainland visitors too. They are not just buying on brand only. They prefer one brand. Then if it is out of stock, they don't mind and purchase other brands and transfer up to mainland.


Milk formula are no different from one and other. The only difference is the confidence in the brand.
So that lies on the marketing strategy of each brand.
For milk formula sold solely in HK without distributors in mainland, they can obviously attract more customer.
But of course, no firm or company will look down on the vastness of mainland market.
For some reason, they cannot enter to mainland market directly, then they promote itself more intense in HK so that mainland customers prefer to ship large amout ot it to China.

For local mothers, I would suggest that most infants are capable of tolerating adult milk formula once they reach the age of 8 to 9 months. There body system develop stronger adaptability. In fact the difference between adult and infant milk formula is only minute. As in dfference of different brand, the adult milk may contain more sodium or other substance. So long as trial of milk by infant is successful, they can tolerate adult formula. Then the competition for infant formula can be left to neonate under age of 8 months.

Lastly, I wound point out that milk powder demand fluctuate widely. Maybe in next 5 or 10 years, no one would buy infant formula from Hong Kong. They may buy it direct from supplier. Then, for Hong Kong government, they will limit their own business by insituting so called proctecting local mother rules.

Pneumothorax - a life threatening disease

 

Recently I came across a news peculiar to pneumothorax.  An adolescent aged 18 of a single parent family committed suicide becasue of health trouble of recurrent pneumothorax.  Even working in the field specialising for pneumothorax surgery, I am not aware of similar case.





Although there is high chance that this patient may have psychiatric illness, it is shocking such a treatable disease lead to this tragedy.  The adolescent with pneumothorax must be dissatisfied with the treatment. The recurrence must be frequent causing disruption of school and social life.  With the introduction of minimally invasive thoracic surgery (also named VATS for Video assisted Thoracic Surgery), pleural disease like pneumothorax is easily treated.  However, the popularity of using VATS do induce non -expert surgeons to operate more.  Recurrent pneumothorax (if recur after the first attempt of surgery) do need referral to specialised experienced thoracic surgeons with keen interest in VATS.

Operations maneuvers for treating recurrence must include:

1. Proper identification of lung bleb (weakness of lung causing air leak)

2. Consideration of additional procedure like: pleurectomy, limited deocortication and adhesiolysis esp for lung adhering to medial part of diaphragm
and pleural tenting or transient phrenic nerve paralysis

3. Adding chemical agents like talc insufflation and chemical agents silver nitrate, fibrin glue and oxytetracycline , concentrated glucose

4. Position of suitable drain or drains (2 drains)

5. If patient allow and prefer early discharge, use of ambulatory draiange device or drainage bag with valve.

Proper procedure can reduce the recurrence to less than 3 %.

With patient aging beyond 35, the possiblity is low by nature. But with good surgery, if there is no recurrence in the post operative 3 - 4 years, the chance of recurremce is much less though not unheard of.

Sometime, pneumothorax cause problem of immobilisation. In old days, a young patient has open pleurodesis operation and subsequent deep vein thrombosis. He was put on anticoagulant but unfortunately develop hemothorax in recent operated chest. A redo thoracotomy is needed and patient has prolonged hospital stay.

In patient with Marfan's syndrome, recurrent hemopneumothorax may be troublesome.


By Dr Chung Shiu Shek