Margaret Gray goes to China
Dennis Argall
This is a summary account of travel to Guangzhou (formerly Canton) in South China, 29 August-9 September for treatment. There are, or will be, links from the text to other pages with detail.
Disclaimer
History April-June 2000
Chinese traditional treatment - background
Decision time focus, 24 August
Sun Yat Sen University of Medical Sciences - first meeting
PET Scan
Zhang Bei's review
Gamma Knife
Rest and Return Safely
Seizures and Hospital
The Balance of Stress, Exertion, Risk and Opportunities
Disclaimer: This report is written promptly after return. Although we have high hopes that the treatment undertaken will have real benefits for Margaret, there is no certainty of benefit for any individual. Brain tumors vary greatly and the response of individuals to treatments varies considerably. Nothing in this report should be taken as recommending the use of any treatment by any person, or as representing any claim as to the efficacy of such treatment. Margaret's decision to travel to China was her own; the decisions on treatment were hers, made in consultation with and with regard for the opinions of medical practitioners. I write as husband, not as medical advisor. Also please note that I have attributed remarks and opinions to others in this report, to the best of my recall and recording; responsibility for their accuracy or inaccuracy rests with me. If you are interested in using Chinese herbal remedies or consulting the hospital we visited, click here.
History April-July 2000:
At the beginning of April 2000, Margaret had sinus pain, resolving in several weeks to a persistent and increasing pain behind the left eye, present on waking and exacerbated by movement. She slept more than usual, became weak and muddled children's names. After waiting out a holiday period (during which we visited Accident and Emergency at the hospital; Margaret sent home with Panadeine Forte and a decongestant and advice to 'see her GP if pain persists'), we saw a locum in our family doctor's practice, who, on the advice that Margaret was normally very active and alert and avoided medication and doctors, ordered an MRI. As a General Practitioner was ordering the MRI, no Medicare rebate was available, but there was no time to wait to see a neurologist.
The MRI scan of 27 April precipitated immediate phone call activity between the radiologist, GP and neurosurgeon. On 28 April the neurosurgeon, Nadana Chandran, confirmed the opinion of the radiologist that Margaret appeared to have a glioblastoma multiforme grade IV. In preparation for an operation, Margaret took dexamethosone 4mg three times daily to reduce oedema and thus pressure, ranitidine (Zantac) to deal with stomach-damaging potential of the dexamethosone and 250 mg of phenytoin (Dilantin) twice daily to reduce prospect of seizure. Aspirin and ibuprofin were to be avoided before the operation, as anticoagulants.
Margaret was admitted to Canberra Hospital on 2 May, with no 'neurological signs', and a craniotomy was performed on 3 May, to debulk the tumour, removing perhaps 80% (beyond which it is apparently difficult to distinguish brain tissue from tumour). Margaret's consent form for the operation specified risks of death (5%), infection, seizures, loss of speech, alteration of personality. We made such preparations as we could at home to deal with such contingencies; wills and powers of attorney updated, clue cards to assist if speech was interfered with, assurances to Margaret that we could cope with any personality shift that might emerge uninhibited from her subconscious. Margaret suffered several seizures on 6 May, controlled by elevating her serum Dilantin levels, but otherwise no side effects. She was off pain medications by 5 May. She came home after nine days, strong and recovering well. (The main difficulty was respiratory infection for which we tried Keflex, then nothing, then Augmentin, with success just before radiotherapy began. There were also problems of thrush, from systemic disturbance contributed to both by antibiotics and dexamethosone (though the role of the dex was not mentioned until Margaret saw Helen Wheeler on 25 June. We finally realised, having treated the gastrointestinal and vaginal problems, that some of the sinus problem Margaret had might be thrush, not infection, and we improvised by opening a capsule of nystatin and making a weak solution from a small amount, droppering this up the nose to prompt benefit.)
We were then awaiting radiotherapy treatment at Canberra Hospital, but frustrated by the inadequacy of briefing ("If you want to know more, come to the first session with your wife") and aware that there was then only one radiotherapy machine in Canberra, for which there was a queue. Internet research also revealed the value of some new chemical treatments, notably temozolomide and thalidomide. To pursue wider opportunities for treatment we went to Sydney.
Margaret became a patient of Radiation Oncology of Sydney (Prof. Phillip Yuile) on 30 May and, after mask making and planning, treatment began on 6 June. On 25 June, on referral by Dr Yuile, Margaret saw Dr Helen Wheeler, neuro-oncologist. Yuile and Wheeler are members of the Sydney Neuro-Oncology Group (SNOG). It was their view that Margaret should consider chemical treatments after rather than with radiotherapy, given her general strength.
Radiotherapy finished after 30 sessions (5000cGy + 1000 boost) on 18 July. Margaret was cheerful and active throughout until the last week, when exhaustion progressively overcame her. We decided to stay in Sydney for maximum rest and observation by the traditional Chinese doctor, see below. For a time Margaret was up and about for only an hour or so daily, improvement was very slow. We treated the radiation burn with oral doses of vitamins A and E from the outset; after hair loss these were also applied to the skin (biting open the capsule to pour the oil on). There was a good recovery, impressive to doctors in China who admired the suturing and recovery on 3 September.
Margaret had from the operation to end of May reduced her dexamethosone dose progressively to nil, but was in some trouble when we arrived in Sydney at the end of May, and it was raised again to 12mg per day. This was progressively weaned during radiotherapy to zero on 17 July and not resumed until 24 August, see below.
Chinese traditional treatment - background - (click for more)
Margaret took to Sydney from a Canberra traditional Chinese medicine practitioner two prescriptions for herbal preparations (herbs not being readily available in Canberra). One was for immune system boosting to cope with the radiotherapy; one was for 'tumour killing', the latter supported by reports in Chinese from Shanghai University which claimed success against glioma. The immune system boosting herbal tonic was dispensed in Sydney by Robert Yang, a traditional practitioner; we held the second for use after radiotherapy. Robert modified and strengthened the tonic. He also arranged for us to meet members of a Chinese traditional medicine delegation visiting Sydney on 2 July. This turned out to be a lunch where I had been added to the speaker's list as a former Ambassador to China; I was determinedly brief, given the length of the speakers list.
Margaret sat at lunch with Professor Zhang Bei of the Sun Yat Sen University of Medical Sciences Cancer Hospital in Guangzhou and had an an extensive consultation with her. Zhang Bei is a traditional practitioner working in hospital where traditional and western medicine techniques are integrated. Zhang Bei reviewed Margaret's anti-tumour script, pronounced that it needed to be stronger, wrote another, advised that it had been in use in Guangzhou for some years as a concurrent adjunct to radiotherapy. Robert made up this preparation and Margaret began taking it twice daily on 4 July, along with the tonic. Zhang Bei also mentioned that she had a more powerful preparation which she could deliver later. Robert remained in consultation with Zhang Bei by phone over the following weeks; the two herbal preparations were modified and strengthened progressively.
Decision time focus, 24 August.
Margaret had appointments with Drs Yuile and Wheeler on 24 August, to be preceded by an MRI (a bit earlier than optimal - given the amount of oedema following radiotherapy - but brought forward to avoid rising Olympic fever in Sydney from the end of August).
We also had discussions via Robert Yang with Zhang Bei regarding her stronger treatment By some error which persisted in communication by phone this was thought to be 'one treatment' but was eventually established after arrival in China as 'one treatment per day for 60 days'. Zhang Bei wished to see the patient to prescribe dosage and observe any side effects. When we proposed visiting Guangzhou, she offered to come to Australia again. Given difficulties associated with her treating a patient in Australia with an unknown substance, we elected to go there, subject to clearance by Australian doctors of Margaret's fitness to travel. Zhang Bei asked that Margaret bring with her a recent MRI and blood count. The optimal time seemed to be after the 24 August appointments.
Margaret had a full blood count on 22 August (all normal except liver function enzymes elevated by Dilantin) and an MRI on 23 August. The radiologists report read, in part:
"There is an irregular mass measuring 3cm in diameter in the left frontal lobe with surrounding marked vasogenic white matter oedema... The features are of a partially haemorrhagic mass within the left frontal lobe which may represent residual/recurrent tumour, radiation necrosis or a combination of the two. Direct comparison with previous imaging is imperative."
There was however, no previous post-operative MRI imaging for comparison. I had raised the need for MRI before radiotherapy in Sydney and Canberra but was assured it was inappropriate, though I was aware that it was best practice in the United States and was also done elsewhere in Australia.
The conclusion of the consultations with Sydney doctors on 24 August was that Margaret might proceed to seek the treatment in Guangzhou, and that a clearer MRI would be available later; appointments were made for 10 October, with the MRI to precede that.
Dr Wheeler expressed concern that Margaret should take dexamethosone to protect against oedema during air travel. A dose of 4mg daily was begun promptly, Dilantin levels checked on 25 and 28 August, dex raised to 2 x 4mg on 28 and 29 August during travel; discretion to give Margaret an additional 8mg if in trouble in flight. After hours contact information for Dr Wheeler, which was a nice reassurance..
We travelled by road Sydney-Canberra on 25 August, then flew Canberra-Sydney on 28 August, Sydney-Guangzhou on 29 August. Our family doctor in Canberra, Rob Reid, reviewed Dilantin levels on 25 and 28 August [39 and 40]. Dilantin dosage remained at 250mg twice daily.
There were no difficulties on the short flight Canberra-Sydney. I assured Margaret that I too felt queasy at one point in the nine hours to Guangzhou, when we had to spend an hour cutting through the top of a typhoon in the South China Sea at 35000ft.
Sun Yat Sen University of Medical Sciences - first meeting - (click for more).
We had had in mind taking a rest day on arrival Guangzhou, but instead went promptly to the hospital, wanting to get things started.
We were received at 11am Wednesday 30 August by:
Zeng Yi-Xin MD Ph.D., Professor Cancer Biology; Director, Cancer
Centre; President, Tumor Hospital; Director, Cancer Institute.
Zhang Bei Professor and Vice Chairman, Dept of Traditional Chinese
Medicine, Department of Comprehensive 1, Cancer Center.
Chen Zhong-Ping MD Ph.D., Professor and Chairman, Neurosurgery/Neuro-Oncology.
Prof. Zeng [speaks good English, has worked in Tokyo and Philadelphia, I think] explained that the hospital seeks to integrate treatments, and is organised on a disease basis, on the model of M D Anderson in Texas, with departments for brain, stomach, liver, and so forth.
Prof. Zhang after consultation with Margaret through an interpreter, friend of friends of ours, made available the strong medicine we had come for, and it was at this stage that we established that it was to be taken for 60 days, not once. "Well, we haven't won the Nobel Prize yet" observed Prof. Zeng cheerfully. This anti-tumour medicine was in what I would describe as an instant-coffee-equivalent form - herbs boiled in huge quantity, solids removed, liquid dehydrated, with water to be added (capsules could have been used, but the quantity needed would be of the order of 18 capsules a day). In addition she provided a script for an anti-oedema, anti-inflammatory, pro-immune system herbal to be dispensed in Australia, and enough of that for use while in China (every second day). (The 'instant coffee' form was passed by AQIS at Melbourne; the herbs would not have been - they should only be obtained through practitioners in Australia. The prescription was faxed ahead to Robert Yang in Sydney. He had difficulty with one ingredient and there was a gap in Margaret's use of this herbal; the one week to response referred to by Zhang Bei, see below, should sensibly be dated from Tuesday 14 September.)
Prof. Chen [excellent English, has worked with Mohr at McGill in Montreal, also in Vancouver] expressed concern at the absence of a pre-radiotherapy MRI for comparison, agreed that the 23 August MRI was unclear. He and Dr Zeng said Margaret needed a PET scan to be able to consider gamma knife treatment. They were disbelieving of my statement that I thought neither available in Australia, but assured us that we could have such treatment in Guangzhou if we wished. I questioned whether Margaret could have the gamma knife on top of the full load of regular radiotherapy. They thought it commonplace.
The discussion was hectic, not least for first morning after arrival (discarding the principle of resting after travel and before international negotiations, yet again, after the manner of statesmen and other fools). It turned into something of a yin-yang, boy-girl division, with Margaret ensconced with Zhang Bei and myself with the big male professors. We left the meeting with Margaret wishing only to take the traditional medicine. In conversation between us later in the day we realised that Margaret had not appreciated that the 'gamma knife' was in fact a form of radiotherapy, but had picked up on the word knife and thought it an operation and was understandably reluctant. I had read internet material on the gamma knife in May, but as it seemed so far away, beyond reach, in the United States, I had not discussed it with Margaret just as I had not shared with her an exhausting weight of other technical stuff.
We consulted our family doctor, Rob Reid, by phone, on the afternoon of 30 August, who confirmed that to the best of his knowledge there were two, hard to access and expensive PET machines in Australia and no gamma knife. He was strongly in favour of Margaret having the PET scan to see if the gamma knife treatment would be practicable, conveying this to both Margaret and myself. Margaret, following these discussions, opted for the PET scan. (Later on 30 August I talked to my brother Warren, Sydney psychiatrist, whose advice was similarly positive along the same lines as Rob Reid.)
I rang Dr Chen, who arranged for the PET scan for the following morning 31 August, and, having no operation that day, accompanied us to the PET Centre at the Nanfang Military Hospital, the PET machine at the civilian hospital (two machines in Guangzhou) being busy that day.
Later on 31 August Dr Chen rang me to say he had looked at the PET scans. They did not show as neat a target for gamma knife as he though perhaps the case from the 23 August MRI, but did show that the haematoma uninterpretable in the 23 August MRI was all necrosis, no life at all. Around it, however, were, he suspected some small areas of tumour. While he did not himself think these very easy targets for gamma knife, he was not an expert and we could go with him to see the experts in gamma knife.
On Friday 1 September Dr Zhang Bei made a house call to see how Margaret was doing. The only prospective side effect from her herbal was a rash; Margaret had none. Zhang Bei expressed the view that the MRI planned for early October should be deferred to 60 days from commencement of her herbal on 30 August. She expected that an MRI around early October would show no tumour growth; delay to 60 days should show reduction or absence of tumour. She also anticipated that within a week the new tonic she added should reduce oedema. Pain tablets to be taken only when necessary to break a cycle of pain, not in heavy doses or routinely. Whereas Dr Chen was of the view that it might be appropriate for Margaret to have further surgery to remove necrosis, Zhang Bei's opinion was that the necrosis would be dealt with by natural processes and she did not favour any operation. (DA comment: given the whole 'balancing' intent of the Chinese traditional medicine, its value would no doubt be disrupted by anaesthesia and surgery.) Zhang Bei believed the gamma knife treatment would go hand in hand with her treatment. She emphasised that she collaborated daily with Chen in such integrated treatment.
We had discussion about nutrition and other subjects with Zhang Bei. Earlier, Margaret having valued acupuncture. Zhang Bei said it should never be used in cancer [a] because too stimulating, [b] because of risk of spread of the cancer. Her advice on nutrition/diet was to eat high protein, high yin, avoid prawns. Black tea, not green tea, warm drinks not cold drinks and eat female chicken rather than male. And best of all black skinned chicken. I have confirmed now that that means what we call Chinese silkies - these little fluffy headed hens have black skin, including the white feathered ones. Of course in Guangzhou, though not here, it was possible to buy fresh, free range black skinned female chicken in the market. It did taste good. On the protein, I would also note that our Western tendency is to eat muscle protein only. Add to the meat muscle offal (liver, etc.) and marine shellfish and dairy and eggs.
Margaret had been initially, briefly, of the view, after the PET scan, that it provided an excellent benchmark for measuring the impact of the traditional medicine, and that she would have no other treatment. I think in this she was influenced by her behaviourist honours psychology training - change only one variable at a time. But after some thought, she shifted to the realisation that the opportunity for the gamma knife treatment was too good to miss. As Warren Argall later expressed expressed it, the gamma knife might kill all tumour or, if not, it would reduce tumour to a size which could be more susceptible to attack not only by the Chinese medicine, but also western chemical treatment options at a later date. And so Margaret decided in favour of consideration of the gamma knife treatment.
On Saturday 2 September, Dr Chen took us to the Guangdong Minimally Invasive Neurosurgery Medical Centre (one of two gamma knife establishments in Guangzhou), where we met with "very famous" Professor Hua Shen-Ling. After discussion between the experts, Professor Hu said that the situation was suitable for gamma knife treatment; if nothing was done, traditional medicine or chemotherapy might have a small chance, if lucky, but this was a high grade glioma; with the gamma knife there was some hope that surviving tumour cells could be killed. This was discussed with Margaret and she decided to have the treatment. The consent form, which I, not the patient, was obliged to sign, as next of kin, included the following: local anaesthetics were required, there could be problems for heart and lungs [rare]; there would be oedema to be dealt with; and, most important, some tumours were resistant to the treatment, in which case a patient would normally be treated again (how we'd collect on this warranty raises some interesting prospects of further travel). Margaret had eight treatments of five and a half minutes, the total lasting an hour (after half a day's preparation and planning). Margaret afterwards had an intravenous dose of 250ml mannitol and 10mg dexamethosone, on that day and also, as an outpatient, on 3 and 4 September. Dexamethosone oral doses were thereafter maintained at 4mg twice daily until after plane travel to Australia.
We had planned initially to return to Australia on the evening of 4 September, but with the extra activity and advice to rest after the gamma knife treatment, we stayed in Guangzhou until the evening of Friday 8 September. Drs Zhang and Chen came to dinner on Wednesday 6 September, at which time Margaret still had very limited energy. Her energy levels improved on the Thursday. Nonetheless, we took care not to overspend energy, and wheelchair assistance was used at airports (Guangzhou, Melbourne and Canberra) on 8 and 9 September. Margaret had no difficulties on the plane and after return, though we both were very tired. On Sunday 10 September, a very sunny spring day, she went out for a walk alone in the morning. I think we missed a dose of Dilantin [250mg] on the evening of Sunday 10. I had sought to reduce the dexamethosone to 18 hourly promptly after the end of travel, but Margaret reported headaches, and the dosage came back to around 14 hourly.
Margaret awoke pained, hungry and troubled at 5am Monday 11. I gave her Dex and Dilantin and muesli. Around 5.30 her perturbation increased, and she slipped into a couple of seizures. These were not as severe as those on 6 May. During the second seizure Margaret brought up all the food and medication just taken, but there were no injuries.. I had neglected to record the length of time of the seizures, an immediate question of hospital staff on arrival there by ambulance around 6.30am; my best guess was no more than 5 minutes each.
Margaret's serum Dilantin level was found to be 26; the level had clearly eroded as a result of faster metabolism caused by the dexamethosone, also the missed dose Sunday night. I had discussed appropriate Dilantin dosage with Chinese doctors; they had been surprised that Margaret was taking so much. But they conceded that Margaret was bigger than most of their patients (Margaret weighing 75kg, up since starting dex; Dr Chen weighing 55kg. One photo I did not take, but I still remember the scene, was of Margaret on a bed at the gamma knife hospital, a petite southern Chinese nurse looking at her, looking at the petite sized southern Chinese hospital pajamas in her hands, back at Margaret, back at the pajamas... coming to terms with the astonishing size of some foreigners.)
After 300mg IV Dilantin in Acute Care, Margaret moved to Ward 14B and was able to eat and drink a little before taking dexamethosone orally at lunchtime. Dex was set at 4mg three times daily, Dilantin 250mg twice daily again. Margaret recovered rapidly overnight. Her Dilantin level was checked again on Wednesday and, being 35, Margaret was sent home, for the level to be checked again Friday 15 September. Home has been pretty restful.
Another factor in management/mismanagement of dex and Dil levels was a gap in Zhang Bei's tonic supply, as referred to above. The anti-oedema impact of this tonic should be expected now one week from 14 September, which should assist weaning off dex.
Margaret's Friday Dilantin level was 36, essentially as it was on Wednesday; dosage raised by Dr Reid forthwith to 300mg twice daily (what I had suggested at the hospital Wednesday, sigh) with review next week in light of further serum Dilantin testing and any reduction possible in dexamethosone dose ( = reduction in Dilantin metabolism).
The Balance of Stress, Exertion, Risk and Opportunities
Margaret, while cheerful if tired, has had a nasty shock with the seizures and hospitalisation and is not as positive as on return home. As we were leaving China we were of the view that what we had achieved greatly enhanced her prospects. Hopefully her spirits will rise during the next week; there is of course, considerable mental weariness and confusion consequent to all that she has been through in the past several weeks - as there was after the craniotomy and radiotherapy. Hopefully the downturn in mood will be transitory, and current sleepiness and weakness will just reflect exhaustion and recovery.