The end is nigh

Saturday, 1st October, 2016

We are counting the hours now. That is the amount of time that Dr SD has given N to live. This follows blood reports coming in that show N's WBC counts exceeding 99.28 billion cells per Litre, a creatinine level of 2.43 and potassium level of 7.6 mMol/L. She has no infection, the blood culture report was clean. The leukocyte count is purely the cytokine response due to metastasis.

Anyway, we have put N on a 5% dextrose drip with 10 units of insulin to control the potassium levels. The creatinine is not that worrisome. N does show signs of kidney failure, though, which was probably brought on due to dehydration.

There is nothing we can do for the inflammatory response, that I can think of. It has not been caused due to an infection, or we could use antibiotics. Corticosteroids is an option, but hasn't been used much in end of life treatment from what I have read. Neither did any of the doctors suggest it. I re-read parts of my old immunology textbook to find it very lacking. It limits itself to infection, not to the pathway as such, so was not of much use to me.

It is sad that the awareness about the inflammatory response in cancer is lacking amongst medical practitioners in India. Perhaps targeting that pathway could have helped N. I regret not using the ayurvedic medicines now. Many were targeting that pathway.

However, I can see much headway being made in cancer medicine, which should help millions fighting against this terrible disease in the near future. It is sad that N will not be there to make any use of it.

I can see N's temperature going down steadily. It is now 96 F.

It is a waiting game now.

Crash and (not) burn!

What an eventful few days, ranging from heart-stopping agony to pure relief, and hopefully, a degree of recovery.

N's oral intake has been consistently reducing over the last 3 days, leading to reduced urine output, lowering blood pressure and visibly increasing discomfort. Our GP has basically recommended that we let N die, as painlessly as possible, giving her water when she asks for it, and not forcing any intake. This has, unsurprisingly led to dehydration, and its consequences at 4:00 AM on 28th September were scary.

We were urgently called to N's room by my uncle who had been woken by the nurse. N was exceedingly uncomfortable, seemed in agony and was breathing volubly and oddly. Her oxygen saturation was scarily low at 81. We called up my cousin, a doctor, currently living in the US, and he suggested we rush her to the hospital. This idea was immediately dismissed as it could mean that N would lose her life in an impersonal ICU with no one at her side. Taking the risk into consideration, a further patch of fentanyl was applied to at least ease her pain, and the backrest of the bed raised.

While N's children (my mother and uncle) sat by N, perhaps seeing her off for the last time, I rushed, along with my brother to a 24 hour chemist to procure an oxygen cylinder. It was impossible to get a proper sized one as most medical equipment stores were closed, so I returned with a refillable 1000 mL cylinder that could at most be deliver 0.5 L of oxygen per hour. Happily by the time we got back, N was enormously better, with her change in position (and perhaps eased pain?) bringing her oxygen back up to 97.

When the world woke up, we ordered a full sized cylinder, and returned the tiny thing that we had bought. It is now on stand-by, should the need arise.

Come afternoon, we were visited by a pain specialist, who does house calls and works in palliative care. Dr SD felt that N need not be left to die, and that hope was not lost. He suggested (much to my mother's disgust), that a naso-gastric feeding tube be inserted to give N some much needed nutrition. She agreed after being reassured that it would not cause her pain. However, he also felt that this could be done only after she is stabilised and her mouth, now infected, be treated. He suggested we have an IV line inserted in the mean time, a task that proved rather difficult for our nurse due to the dehydration.

What followed was an adventure to a nearby charitable hospital whose staff exceeded themselves in helping us. An experienced nurse attached to the hospital came over, after her shift ended to help us with N, completely out of the goodness of her heart. Faith in humanity was restored!

N is currently in repose. She did not like getting an IV line, and we would have respected her decision if her electrolyte imbalance were not interfering with her decision making abilities. Dr SD feels that N would probably stop needing the IV line in 2-5 days. Let's hope that she can have her nutrition orally by then.

A scare, regrets, things done and things to do...

24th September, 2016

N is very groggy. Liquid intake has gone down but urine output, pulse, oxygen saturation and blood pressure are tolerably okay. Some parameters could be better, but nothing is alarming. As night approaches, N gets a fever and we contact our GP. He tells us he'll try to meet us later. He comes over at about 11:00 PM, reads her reports once more, reiterates that things are very bad, and all that we can do is provide pain relief till the end. He suggests we use paracetamol and use sponging to bring down the fever when as required. He gives us a phone number of a pain specialist before leaving.

25th September, 2016

Early hours
The fever does not reduce in spite of the paracetamol given to her earlier. It is now over 102 F. Worse, her limbs are cold. On taking a quick look online, the symptoms that we see seem to be consistent with what one expects to observe during the final week of life according to cancer.gov. I wish physicians had explained to us what to expect. We really expected N to have more time. A lot of the alternatives that I had planned would not be implementable within this suddenly reduced time frame. I can only thank the makers of the internet, organisations like the NHS, NIH etc. who make use of the "information highway"for the dissemination of information for all that I have gathered so that I even have an idea of what is going on without needing to purchase obscure and expensive medical texts.

Here are the symptoms, as observed in N:

• Decreased consciousness: N sleeps a lot more than she did, becomes irritable when woken (if she wakes)
• Decreased performance status: A vague criteria, but her oxygen saturation levels have been decreasing steadily from about 96+ to about 93. She seems more frail and needs much more support from others to even make her turn over in bed.
• Difficulty in swallowing liquids: N has reduced her nutrient intake drastically. We used to give her albumin in milk and coconut water, but she seems to find it difficult to swallow it, and often spits it out. 

This brings forth a lot of self-recrimination and regret:

• Why did we not seek a second opinion as soon as the cancer was detected once again, especially from an oncologist? It is obvious that an oncologist would have studied the problem in more depth and that we could have started a chemotherapy regimen rather than going in for surgery.
• Why did we not question the treatment process every step in the way? There were so many points where we could have not only detected that the cancer had metastasised, but also started treatment while N was relatively healthy.
• Why did we wait nearly two weeks before we decided that Dr P did not know what he was talking about -- that impacted stool as a diagnosis was not only absurd but an insult to every one's intelligence? We deferred to Dr P's judgement over our own. This is dangerous. A doctor's knowledge is not infallible and it is our duty to stand up to ridiculous ideas.
• Why did we allow Dr P2 to continue his negative pressure wound therapy when we could have used KCI's services (which we did switch to finally, and which are indubitably superior)? It is sad indeed when one gets better service from a technician than a plastic surgeon, even when the latter believes himself to be morally superior.
• Why did we not look more actively for specialists who could treat N at home?

Anyway, I digress. The difficulty in swallowing makes ingesting paracetamol tablets difficult and the fever levels are worrying. We therefore decide to inject it intra muscularly, which involves a trip to a 24 hours pharmacy to procure the drug and syringes. About half an hour later, the paracetamol has done its job, and the fever begins to reduce. Oddly enough we realise the fact by the warming up of N's limbs! Feeling relieved, we can now leave N in her nurse's care, who has been exemplary.

The Day

N's fever is now in control, more or less. The day passes without incident and with a couple of visitors. N sees them, is gracious, and suggests they go sit out with us and have tea -- a polite dismissal from a tired N. N also has a Skype call. Intake very limited once again. Does not need paracetamol.

Night passes without incident, though the nurse suggests that we get ourselves a Fowler bed for N. It would aid her in sitting up, and thus allow us to persuade her to drink without straining her as much. Will mobilise it in the morning.

26th September, 2016

Contacted a start-up that hires out medical equipment for the Fowler bed which is delivered in the evening and set up by night time. It also has an IV stand which is currently not in use. Have also initiated the process to procure an air mattress. 

Am contacted by Datar genetics in the afternoon. They apparently do whole gene expression profiling, and identify dtysfunctioning pathways using the KEGG database. They use a Thermo-Fischer platform. I was unaware that they are also in this space as I had heard of only the Illumina and Affymetrix platforms. I rather like the services that Datar offer, though it is a bit expensive (Rs 240000). The crux is however that it will take about 3 weeks to get the report. This might be too late for N. I have written back and stated that if the results can be expedited, I'd be game, or if the raw data could be made available within a couple of days as I could undertake the analysis myself (I have some experience with interpreting gene expression profiles). I'd get the age-sex matched controls' data from published papers. Did I mention how much I like open science and the internet that makes it all possible? Anyway, all that is subject to whether they can expedite the process. Otherwise, the point is moot.

Some drama again today. N's fever shot up once again to over 102 F, and oral paracetamol was not an option. The day nurse is not as competent as our night nurse and needed prodding to inject her with paracetamol, which she did with a degree of muttering. 

By the time the shift changed, the fever was going down. At 9 PM we shifted N onto the Fowler bed, after which we had our dinner. N's Fentanyl was also upped to 75 micrograms by this time due to her pain, which is disappointing. We will have to get some more patches, as we have only two more 25 microgram patches left. I hate the paperwork, and they never issue more than 6, so I'll have to visit that horrible hospital again (hopefully -- I'd rather not think of the alternative) for a prescription and a refill even though I'd rather never see the face of N's doctor ever again. 

There has been some good news too, though, N's fever came down to normal by 11:00 PM. That is a relief, as it is the first time after the 24th that it has reduced to this level. I wonder if the fever reduction could be correlated to N's comfort level in terms of the bed and the increase in Fentanyl dosage. She seems more alert than she has in the last three days. Suddenly there is hope again. 

We will be contacting the pain specialist first thing in the morning tomorrow. Hopefully he could save us a degree of bother by arranging for Fentanyl himself...here's to wishful thinking!

Mostly disappointments and life goes on...(thankfully)

23rd September, 2016:

Met Dr S. She felt that N is too frail to receive chemotherapy. My mother is relieved as she feels that N's recent treatment regimen has been nothing but exploitative on the part of her doctors. She, with reason, is disgusted with the lack of information and the patronising attitude of N's primary surgeon.

While I don't think Dr P misled us, I have maintained at all times that his team has been unprofessional and at times ignorant. Indeed, I have called them out on it. This is particularly true for Drs C, U, S2 and P2 who have withheld information, not responded to calls and have been downright rude while having only a school child's knowledge of science.  When someone does not know that negative pressure creates a vacuum, (while they casually do "negative pressure wound therapy" dressings), it should raise red flags. I sometimes wonder why there is no core science curriculum for clinicians in India after high school. Patronising someone is irritating enough. Being patronising when one is a complete and utter idiot is disgusting. I am unsurprised by the statistic that 60% of Indian doctors fail to get a licence in the UK. Most are rote monarchs produced by a flawed education system. The better ones go abroad.

To be fair, there were a few excellent ones as well, Dr V was brilliant, and Dr I was not bad. Our GP, Dr RP is brilliant and a true asset to the profession.

Anyway I digress -- physician stupidity (and I have been unfortunate to be subjected to a lot of it), always causes me to rant. Dr S felt N is frail, and my mother, disgusted with doctors, hospitals and health "care" did not think that not undergoing chemotherapy was something to be sad about. She does not see the point in prolonging N's life with torture and I find it hard to argue the point.

I was however, hopeful of immunotherapy. Unfortunately Roche India's reply came in and they stated that they had no permission to market the drug in India, so I am stuck with an unaffordable treatment option. I will try writing to Roche in Switzerland but I am not particularly hopeful. If there seems to be any headway, I will arrange to have N's PDL1 expression undertaken.

A Vaidya came for a home visit as well. I asked the Viadya for the formulation. He listed a total of 11 constituents of which two bhasmas contain mercury, so we haven't given them to N. If the accumulation time is slow, I may go ahead with them anyway, there isn't much to lose at this point, and the effects would perhaps have been apparent only years later. Years that she obviously doesn't have. Even so we have refrained. Besides, my mother felt he was grasping as he had brought pre-prepared medicines (before even seeing N), for which he charged Rs 5000, though it is a small sum compared to biologicals that are available in the Indian market (Rs 75000 for a breast cancer drug by Roche). Admittedly, I feel that there are better formulations available, and better Vaidyas too. I intend to Skype with one in a couple of days. The other wants to see N personally before prescribing or diagnosing.

24th September, 2016:

The nurse almost overdosed N with painkillers. Gave her an ultracet over the two 25 microgram fentanyl patches applied. N's complaints of pain need to be monitored exceedingly closely, as many complaints stem from irritation rather than pain (as was the case today). Removed one patch. So far so good, though drowsy. Mouth is dry, but no respiratory distress or anything nasty. Observed her for about an hour. The nurse in the next shift is much more competent, thankfully.

Had intended to go to meet a very respected Vaidya today, but my mother (and N) shot down the idea. Considering the fact that N seemed drugged to her eyeballs, I agreed. Will try to persuade them to meet the Vaidya another day.

Also, changed the vacuum dressing at home (called a technician). He did a much better job than the surgeon (as the technician had the last time, as well). The wound is very clean and has closed considerably. It should be fully closed in five to ten days' time.

It is pouring outside, and there was a bit of a scare. A wire started sparking. The electrical source was identified and shut down and the electricity suppliers called on the phone. The latter put us on hold for about half an hour. Happily we had resolved the situation (by identifying and shutting down the supply) by the time they put the call through. Absolutely useless!

We are still alive and have a roof over our heads as I write this. Hopefully tomorrow will be less eventful.

* I will list the formulation given by the Vaidya in this blog. later, along side their constituents and potential activity. I have undertaken the exercise and have it on paper.

Updates...

We went to get N's HRCT scan of the lungs done today. It seems that the dye is injected only for contrast scans, so N's high creatinine is irrelevant for a run of the mill CT. In spite of an appointment at the centre, there seemed to be an agonising wait, so the scan was cancelled. The scan is important as the lungs and the bones are the most probable targets of metastasis in bladder cancer, so we'll probably schedule it for later and have someone sent over earlier merely for the purpose of "reserving a place".

Disheartening news followed, the pharmacy we contacted through Roche has quoted CHF 15,250 for 1 vial of Tecentriq. This is prohibitively expensive for even a relatively well off Indian and doesn't even include shipping charges (~CHF 2500). While I have written to Roche to ask whether it may be made available cheaper in developing countries, I cannot be optimistic about my chances.

Meanwhile, we have contacted a couple of Ayurvedic oncologists. We will be visiting what seems to be a leading centre on Friday and will be arranging for a home visit from another practitioner as well. Let's see what they say and the therapeutic path they choose.

Scheduled to meet the oncologist later today. Mother refuses to consider chemotherapy, especially after our GP (someone I trust and respect enormously), has described it as fighting a losing battle. I can't say that I disagree but would reserve judgement until we at least meet the woman.

An eventful couple of days

Monday, 5:30 pm:
My parents visited N's primary surgeon, Dr P, who was slightly defensive and shocked at the spread. Ultracet has been replaced by a 25 microgram patch of Fentanyl, an opioid analgesic which is 80 times more potent than morphine, but is safer overall. The dosage, of course, has been titrated taking the potency into consideration. The prescription involved a lot of paperwork. Dr P suggested we speak with an oncologist to plan N's treatment. My mother opted out as she was very overwhelmed.

Monday, 8:30 pm:
My father and I met the oncologist. Unlike Dr P, she was not dismissive of chemotherapy (GemCarbo treatment), pointing out that N has fought her way through a major surgery with relative ease in spite of advanced cancer but underlining the fact that the therapy would, considering her age, be fraught with risk. Asked her about immunotherapy and targeted therapeutics. While aware of them, Dr S stated that her experience with these therapies were limited and mostly theoretical. However, she did acknowledge that they could be a viable alternative for N. Dr S prescribed tests to check the spread of the cancer (CT scan of the lungs, scheduled for tomorrow) as well as some blood work to exclude/confirm infection as a cause for elevated WBC levels.

Most of our questions remained unaddressed. Dr S understandably pointed out that most of them could be answered only after seeing N in person. The meeting with N is scheduled for tomorrow at 6:45 pm to evaluate whether N could be a potential candidate for chemotherapy or whether we would have to limit ourselves to alternatives/palliative care. Dr S was, surprisingly enough, more optimistic than myself on looking at the reports, though we'll wait and watch.

Tuesday
My mother maintains that she will not subject N to chemotherapy and has sourced homeopathic medicines from Delhi. I am uncomfortable giving N medicines whose constituents I am unaware of. Some may argue that homeopathic medicines are nothing but water (or whatever carrier), but I think that homeopaths in India don't really follow homeopathy as in the West, but use higher concentrations. While this may be a good thing therapeutically, I'd be more comfortable with water, as at least then, I'd be sure that nothing interacts with what she is having. Homeopaths are generally very secretive about their treatments as they compound their own formulations and that annoys me. I am tempted to send the medicine for chromatographic analysis.

Good news:
A lot of relatives came to visit N. She was very heartened and spoke at length after a long, long time. Her appetite remains poor though and she absolutely refuses solid food, though she confesses that she enjoys the smell of cooking. I think I'll buy a few books to keep N entertained. She is partial to Gulshan Nanda, though she absolutely loved Yashpal's Jhootha Sach.

Also, an update:
Have received a reply from Roche. It seems that Tecentriq is not available in India and that there are no trials of the drug underway here, either. They did refer me to an international pharmacy in Geneva, however, and listed out the protocol for importing the drug to India. Will do so if affordable.

Have not started N on any treatment (conventional or otherwise) so far, except palliative. Will have to make a decision in a few days along with N, who has been told very little of the metastasis. This makes me uncomfortable as well. If I were in her position, I'd like to know. Will need a way to break it gently, soon. I can only imagine the emotional turmoil it will cause her; after all, it devastated us when we heard. Came across a very promising article on chemotherapies in advanced bladder cancer to help us choose and understand.

7:42 pm:
Test reports out:
Creatinine: High (1.22)
Liver function tests: Normal
CRP: High (101.2)

Procalcitonin results awaited, expected 24th September.

This may mean that CT scan may need to be rescheduled...will have to modify diet (especially protein intake) as well. Will contact physician for input. Will a diuretic be started? Her feet did seem slightly swollen...

A hospital free weekend of research

The weekend was fairly okay. N's urostomy bag leaked into the wound dressing, so both were changed at home. Had a routine CBC done, as usual; WBCs gradually increased as usual. N is on Augmentin 625, twice a day, which does not seem to help control "infection".

Was prescribed Ultracet thrice a day for pain. It seems to relieve her, but works for only 4-5 hours, rather than 8. Have spaced the medication in such a way that the pain seems minimal. Scheduled to speak with doctor again on Monday, 19th. Due to it being a weekend, N is not stressed by doctors' visits and poking and prodding.

We on the other hand, are going through options:

Chemotherapy seems to be too toxic for someone N's age and health. There seems to be no purpose in prolonging life by a few weeks to a few months under what amounts to torture.

Roche's Tecentriq, newly approved immunotherapy drug, which binds to the protein PDL-1 associated with some bladder cancers sounds like a good option, if her tumour expresses PDL-1 excessively (we haven't yet checked). Targeted cancer therapeutics is theoretically head and shoulders better than chemotherapy. Unfortunately, this option seems to be available only in the USA and it is prohibitively expensive in that country (USD 12,500 per month). I have written to Roche (India) to check for its availability in this country and pricing. We have not received a reply, yet. I intend to exhaust any contacts available in that company to see if we can get this treatment here.

Ayurveda is another option that we are exploring. While much maligned in the West and often dismissed as quackery, the pharamcotheraputics of many of the drugs in the Ayurvedic system are sound. I feel that the problems in Ayurveda are more on the lines of lack of standardisation and problems in quality control as the system is mostly unregulated. These problems are being actively looked into and research on actives as well as formulations are being undertaken world wide. As a matter of fact, I feel that if properly systemised and updated the holistic approach of Ayurveda is actually superior to conventional medicine, especially towards multi-factorial diseases like cancer. Anyway, I digress.

CancerResearch UK has on their site listed some promising drugs in slowing tumour growth. Admittedly most studies here are on rats and mice, however considering the fact that (a) these medicines have been used for over 2000 years in India (b) the safety record of conventional drugs for this disease is pretty iffy, Ayurveda seems to be a viable alternative. Using formulations from GMP following Ayurvedic drug companies (Himalaya, Patanjali, Dabar etc.) should also mitigate many of the perceived safety risks.

I have meanwhile, compiled a list of anti-cancer formulations that are used in Ayurveda and am exploring how they work, which pathways they target etc. I will probably put them online once I get them in order. Considering the fact that they have been compiled in relative haste, I apologise in advance for their relative incompleteness.

I contacted an Ayurvedic clinic in Hyderabad. I have yet to receive a reply. Meanwhile I am looking for competent Vaidyas in the Mumbai region.

On the bright side, my uncle, N's son, will be coming over to visit N from the USA. This should please her, as she misses him awfully.