I have seen the consultant surgeon this morning. Not very much new, I'm afraid. My main problems are colicky abdominal pains and diarrhea for which I am taking an anti-spasmodic and codeine phosphate. Th surgeon thinks these symptoms are caused by the mechanical effect of the presence of secondaries in the peritoneum and that the remedy is chemotherapy. I am seeing the medical oncologist this afternoon.
The special stains do not tell us anything new. They were negative for carcinoid, but even that is not helpful since the histology of adenocarcinoid can change to adenocarcinoma when it metastasizes, indeed such patients have a rather better prognosis. Although he thinks that the appendix is the most likely source of the tumor, he cannot be sure. The other option, large bowel, has been searched through very thoroughly on several occasions without finding a primary. The overwhelming majority of appendix tumors start life as carcinoid.
Were it not for the colic I would be very well. I have lost 14 pounds, but the weight loss has reversed and I have put on a couple of pounds since the nadir. My nutrition is important now, and the only restrictions on my diet are to avoid high residue products like peas and beans, sweet corn and cabbage, skins and pith.
I was encouraged when my friend George Stevenson brought me in a paper by Yan et al (Annals of Surgical Oncology 2008; 15:1440-6) which describes adenocarcinoid of the appendix that on peritoneal dissemination lacks the neuroendocrine component and appears as adenocarcinoma. Such patients have an improved survival over those who retain the carcinoid appearance, with a cumulative survival of 70% at 4 years and no further deaths thereafter.
This afternoon I saw the medical oncologist, Tamas Hickish. I will have a baseline CT next week with insertion of a Hickman like, starting chemotherapy at the end of next week of the beginning of the week afterwards.
Yesterday we watched the movie of 'The Kite Runner'. Although perhaps not as complete as the novel, it was a moving story and a rebuke to those who wish for an accommodation with the Taliban. These are appalling people who were quite justifiably deposed by George Bush and his allies. It is a common phenomenon found in the Western Democracies that they fail to complete the task that they embark on. They seem to lose heart when adversities stand in their way. Obama is talking about an exit strategy in Afghanistan. Will he be condemning millions of women to a second class life that includes no education, beheading for being raped, genital mutilation and forced marriage. Will the beard police return?
How this contrasts with the attitude of Christ who does not give up on us. "He who began a good work in you will carry it on to completion until the day of Christ Jesus" (Philippians 1:6).
I continue to receive messages of encouragement. From the Manabats in the Philippines and from Mary and Milena, two former colleagues of mine at the hospital whom I happened to meet in the corridor. Sometimes we despair when we have this diagnosis. When we know so many people are praying we wonder whether God is listening. Then he will send the chance meeting to encourage us and to let us know that he certainly is listening - so keep praying.
Friday, March 27, 2009
Thursday, March 26, 2009
Strutting and fretting
One thing that surprised me about being in hospital was how little the doctors influenced what was going on. When I was in charge of the wards I had the distinct impression that I was running things. Of course, it may be very different in surgery, where surgeons are in essence doing the same thing repeatedly and the whole subject may be protocolized. Standard operating procedures (SOPs) are relatively easy to produce and follow when one case doesn't vary very much from the next. In contrast, hematology patients are very different from each other. About the only leukemia that is at all stereotyped is chronic myeloid leukemia, where an identical molecular lesion produces a very similar clinical condition, but my readers will mostly know how heterogeneous is CLL, and AML or MDS is even more so. Non-Hodgkin's lymphoma breaks down into over 40 separate conditions.
When I was running the hematology lab we majored on SOPs, but then we were doing full blood counts on 750+ samples a day and very few other tests. We even had an SOP for answering the telephone (Good morning, this is the Hematology Lab. How may we help you?). The benefit of SOPs is that relatively unskilled workers can be trained to do complex tasks accurately and reproducibly. The danger of SOPs is inflexibility.
The surgery ward ran efficiently on a cadre of trained nurses and health care assistants (HCAs). There were some things that only nurses could do, like give injections, dole out pills and attach and detach intravenous pumps, but for most of the traditional nursing duties, like making beds, emptying bed-pans and giving bed-baths, the nurses and HCAs were interchangeable. Obviously, the use of HCAs to replace nurses is a cost saving. Many of the HCAs were from Eastern Europe or other foreign countries (though their English was always excellent) but, then, my nurses were also likely to be foreign (Indian, Chinese,) and their training was equally as good as those who were locally trained.
Many of my readers will know the Tom Stoppard play 'Rosencrantz and Guildenstern are dead'. For those who don't the author takes two minor characters from Hamlet and builds a play around them. They spend most of the play discussing the absurdities of life and death, the paradox of freedom and inevitability, of freewill and predestination. Mostly it is a two-hander, but at times the whole Shakespeare play rushes on to the stage and performs their bit of Elizabethan drama before exiting stage left, leaving the two alone, perplexed and totally misconstruing what has just happened.
The consultant ward round is like that. Of course, Hamlet is the main thing and Rozencrantz and Guildenstern mere strolling players in comparison. The great and important decisions are taken by the consultant and his retinue, while we patients are blown about by the forces of destiny.
Everything boxed and coxed, categorized and acted out word perfect without prompting makes for an efficient service where errors of omission do not occur. As long as the out of the ordinary does not come along.
The problem with this inflexibility arose over my drip. The houseman (now called a Foundation year one) has the task of writing up the intravenous fluids for the next 24 hours. At the beginning of March the F1s have only been employed for a couple of weeks and have difficulty in getting their routine work done in the day. In my day you stayed until the work was complete, but today the European Working Time Directive insists that you leave on time. Overstay the 5pm deadline and you get a ticket. Do it twice and you receive a reprimand. Habitual offenders may have to repeat the year.
There is a back up position, though. At night there is an F1 available to cover the whole hospital. Of course, this person does not know the individual patients and apart from catching up on the work left left over from the day she (and these days it is usually a she) has to deal with emergencies as they arise, so it wasn't until 2am that she got around to writing up my fluid chart. By which time the drip had been stopped for two hours and the cannula had clotted. In the old days the nurse in charge of the ward have put up a bag of whatever had gone before rather than let a drip stop, but today a nurse does not have that discretion. She has to obey orders precisely and if nothing is prescribed nothing can be given.
The F1 was very nervous as she tried to resite the cannula, and she failed. She summoned Night Sister and she failed twice. A more senior doctor was called for and she failed three times. Eventually an anesthesiologist was called and she got in first time - but it was the seventh attempt.
The next time I needed a new drip I insisted on an anesthesiologist first time. He turned out to be an old colleague whom I had only met over the telephone. He remembered that I had once done him a favor, and he certainly did one for me.
When I was running the hematology lab we majored on SOPs, but then we were doing full blood counts on 750+ samples a day and very few other tests. We even had an SOP for answering the telephone (Good morning, this is the Hematology Lab. How may we help you?). The benefit of SOPs is that relatively unskilled workers can be trained to do complex tasks accurately and reproducibly. The danger of SOPs is inflexibility.
The surgery ward ran efficiently on a cadre of trained nurses and health care assistants (HCAs). There were some things that only nurses could do, like give injections, dole out pills and attach and detach intravenous pumps, but for most of the traditional nursing duties, like making beds, emptying bed-pans and giving bed-baths, the nurses and HCAs were interchangeable. Obviously, the use of HCAs to replace nurses is a cost saving. Many of the HCAs were from Eastern Europe or other foreign countries (though their English was always excellent) but, then, my nurses were also likely to be foreign (Indian, Chinese,) and their training was equally as good as those who were locally trained.
Many of my readers will know the Tom Stoppard play 'Rosencrantz and Guildenstern are dead'. For those who don't the author takes two minor characters from Hamlet and builds a play around them. They spend most of the play discussing the absurdities of life and death, the paradox of freedom and inevitability, of freewill and predestination. Mostly it is a two-hander, but at times the whole Shakespeare play rushes on to the stage and performs their bit of Elizabethan drama before exiting stage left, leaving the two alone, perplexed and totally misconstruing what has just happened.
The consultant ward round is like that. Of course, Hamlet is the main thing and Rozencrantz and Guildenstern mere strolling players in comparison. The great and important decisions are taken by the consultant and his retinue, while we patients are blown about by the forces of destiny.
Everything boxed and coxed, categorized and acted out word perfect without prompting makes for an efficient service where errors of omission do not occur. As long as the out of the ordinary does not come along.
The problem with this inflexibility arose over my drip. The houseman (now called a Foundation year one) has the task of writing up the intravenous fluids for the next 24 hours. At the beginning of March the F1s have only been employed for a couple of weeks and have difficulty in getting their routine work done in the day. In my day you stayed until the work was complete, but today the European Working Time Directive insists that you leave on time. Overstay the 5pm deadline and you get a ticket. Do it twice and you receive a reprimand. Habitual offenders may have to repeat the year.
There is a back up position, though. At night there is an F1 available to cover the whole hospital. Of course, this person does not know the individual patients and apart from catching up on the work left left over from the day she (and these days it is usually a she) has to deal with emergencies as they arise, so it wasn't until 2am that she got around to writing up my fluid chart. By which time the drip had been stopped for two hours and the cannula had clotted. In the old days the nurse in charge of the ward have put up a bag of whatever had gone before rather than let a drip stop, but today a nurse does not have that discretion. She has to obey orders precisely and if nothing is prescribed nothing can be given.
The F1 was very nervous as she tried to resite the cannula, and she failed. She summoned Night Sister and she failed twice. A more senior doctor was called for and she failed three times. Eventually an anesthesiologist was called and she got in first time - but it was the seventh attempt.
The next time I needed a new drip I insisted on an anesthesiologist first time. He turned out to be an old colleague whom I had only met over the telephone. He remembered that I had once done him a favor, and he certainly did one for me.
Wednesday, March 25, 2009
Pain relief.
We expect it to be painful when someone slices your tummy open. I remember seeing a war film once where the soldiers hit the ground when showered with machine gun bullets. After the shooting stopped the sergeant told his men to start moving out, only to be greeted by one of his men asking, "What shall I do with these?" as the camera panned down to his abdomen where he held several coils of intestine in his hand. The very thought makes many people squirm, but it is just what an abdominal operation involves.
Naturally, some form of pain relief is necessary, and the best form is an epidural which stops the messages from nerve to brain, for although it seems as though we feel the pain in our tummy, in reality it is the brain that really does the feeling. Almost all other forms of pain relief involve impairing the function of the brain, sometimes so much that we are rendered unconscious.
It is also true that most forms of pain relief have serious side effects. Morphine and other opiates induce nausea and vomiting, suppress the cough reflex, slow down the bowel causing constipation and in large doses suppress the respiratory center causing one to stop breathing. The non-steroidal anti-inflmmatories can cause mucosal ulceration and depending whether they are cox-1 or cox-2 inhibitors affect the clotting mechanisms, either by leading to bleeding (cox-1) or thrombotic (cox-2). The one drug that is pretty free of side effect is acetaminophen (paracetamol), but overdoses (greater than 15 g or 30 tablets) are fatal, causing liver damage. Standard hospital guidelines allow a safety margin and require anti-poisoning measures after 24 tablets, but strangely the maximum permitted therapeutic dose in hospital in 8 tablets.
Since normally the required dose for pain relief is 2 tablets every 4 hours, this leaves anyone who is kept awake by pain with nowhere to go in the middle of the night. This happened to me. My pain was adequately controlled by paracetamol, but at 4 in the morning I needed another dose. The nurse informed me that I was not allowed any more paracetamol for another hour, but I could have some morphine.
I didn't blame the nurse, she was only obeying her instructions, but I do blame whoever wrote the instructions. It was not a local decision it is a central NHS decision. The maximal allowable dose is just one third of the toxic dose - even when there is a built in safety margin - and did I mention that there is a perfectly adequate antidote for paracetamol?
Had I been at home I could have taken paracetamol with impunity. As it was I suffered for another hour.
Naturally, some form of pain relief is necessary, and the best form is an epidural which stops the messages from nerve to brain, for although it seems as though we feel the pain in our tummy, in reality it is the brain that really does the feeling. Almost all other forms of pain relief involve impairing the function of the brain, sometimes so much that we are rendered unconscious.
It is also true that most forms of pain relief have serious side effects. Morphine and other opiates induce nausea and vomiting, suppress the cough reflex, slow down the bowel causing constipation and in large doses suppress the respiratory center causing one to stop breathing. The non-steroidal anti-inflmmatories can cause mucosal ulceration and depending whether they are cox-1 or cox-2 inhibitors affect the clotting mechanisms, either by leading to bleeding (cox-1) or thrombotic (cox-2). The one drug that is pretty free of side effect is acetaminophen (paracetamol), but overdoses (greater than 15 g or 30 tablets) are fatal, causing liver damage. Standard hospital guidelines allow a safety margin and require anti-poisoning measures after 24 tablets, but strangely the maximum permitted therapeutic dose in hospital in 8 tablets.
Since normally the required dose for pain relief is 2 tablets every 4 hours, this leaves anyone who is kept awake by pain with nowhere to go in the middle of the night. This happened to me. My pain was adequately controlled by paracetamol, but at 4 in the morning I needed another dose. The nurse informed me that I was not allowed any more paracetamol for another hour, but I could have some morphine.
I didn't blame the nurse, she was only obeying her instructions, but I do blame whoever wrote the instructions. It was not a local decision it is a central NHS decision. The maximal allowable dose is just one third of the toxic dose - even when there is a built in safety margin - and did I mention that there is a perfectly adequate antidote for paracetamol?
Had I been at home I could have taken paracetamol with impunity. As it was I suffered for another hour.
Tuesday, March 24, 2009
Torture
I'm not sure about waterboarding. They say it is very effective in extracting information and that although it induces a feeling of impending drowning, it leaves no marks and damages no tissue. Watching Jack Bauer on '24' torture traitors with a tazer does not seem immediately preferable. Yet scores of Westerns and cops and robbers movies have shown the 'good' guys beating a confession or information out of a villain.
It is a difficult dilemma. To stand up for human rights is a fine thing, but who would not have looked the other way if a CIA agent had been able to obtain information by torture that would have prevented 9/11? And if you think you would have stopped the torture consider whether you would have done so if your wife or son was one of the intended victims.
The whole question of what rights criminals retain is a difficult one, and even more so in the case of those detained who are presumed innocent until proved guilty or those detained on the basis of evidence that would not be admissible in a court of law.
Strange as it may seem, the law is there to protect the guilty as well as the innocent. Suppose you run over a child in a Malaysian village and kill him. A colleague of mine who served in the RAF during the Malayan crisis of the 1950s was told that on no account under such circumstances should he stop the car and get out; if he did so he would be torn limb from limb by the villagers, because there was no law there. Such a driver might well deserve punishment, but he might be entirely blameless; mob law admits no such nuances.
I don't know whether anyone has considered as a means of torturing, the injection of a drug that induces severe abdominal colic and diarrhea, but I would imagine it to be an effective means of extracting information. The past weekend was truly terrible. I was screaming with agony as the colic hit me. Had someone offered me an injection that would stop it in return for a confession, I would have given up the crown jewels. I would have confessed to anything from treason to pedophilia if they would only make it stop. I would have offered to have an arm or leg amputated rather than continue in such pain.
The real problem with torture is that you can't rely on the answer.
There is such a remedy for colic; it is called mebeverine, and since I have been taking it I am back to normal making a slow recovery from surgery. I have so far lost 15 pounds and am not yet eating properly, but I no longer have wound pain.
Proverbs 3:11-12 says "My son, do not despise the LORD's discipline and do not resent his rebuke, because the LORD disciplines those he loves, as a father the son he delights in.
I'm not sure what lesson the Lord is teaching me, but perhaps it is not to rely on my own wisdom, and not to be too proud the ask for advice. They say of a doctor who treats himself that he has a fool for a patient and a quack for a physician. My wife, who is non-medical, was urging mebeverine (colofac) on me for some hours before I accepted it and I only did that after I had managed to contact my surgeon's colleague (the surgeon was out of town) and he had agreed with my wife's prescription. What a vicious sin pride is.
It is a difficult dilemma. To stand up for human rights is a fine thing, but who would not have looked the other way if a CIA agent had been able to obtain information by torture that would have prevented 9/11? And if you think you would have stopped the torture consider whether you would have done so if your wife or son was one of the intended victims.
The whole question of what rights criminals retain is a difficult one, and even more so in the case of those detained who are presumed innocent until proved guilty or those detained on the basis of evidence that would not be admissible in a court of law.
Strange as it may seem, the law is there to protect the guilty as well as the innocent. Suppose you run over a child in a Malaysian village and kill him. A colleague of mine who served in the RAF during the Malayan crisis of the 1950s was told that on no account under such circumstances should he stop the car and get out; if he did so he would be torn limb from limb by the villagers, because there was no law there. Such a driver might well deserve punishment, but he might be entirely blameless; mob law admits no such nuances.
I don't know whether anyone has considered as a means of torturing, the injection of a drug that induces severe abdominal colic and diarrhea, but I would imagine it to be an effective means of extracting information. The past weekend was truly terrible. I was screaming with agony as the colic hit me. Had someone offered me an injection that would stop it in return for a confession, I would have given up the crown jewels. I would have confessed to anything from treason to pedophilia if they would only make it stop. I would have offered to have an arm or leg amputated rather than continue in such pain.
The real problem with torture is that you can't rely on the answer.
There is such a remedy for colic; it is called mebeverine, and since I have been taking it I am back to normal making a slow recovery from surgery. I have so far lost 15 pounds and am not yet eating properly, but I no longer have wound pain.
Proverbs 3:11-12 says "My son, do not despise the LORD's discipline and do not resent his rebuke, because the LORD disciplines those he loves, as a father the son he delights in.
I'm not sure what lesson the Lord is teaching me, but perhaps it is not to rely on my own wisdom, and not to be too proud the ask for advice. They say of a doctor who treats himself that he has a fool for a patient and a quack for a physician. My wife, who is non-medical, was urging mebeverine (colofac) on me for some hours before I accepted it and I only did that after I had managed to contact my surgeon's colleague (the surgeon was out of town) and he had agreed with my wife's prescription. What a vicious sin pride is.
Sunday, March 22, 2009
Nasogastric tubes
As a medical student I had to insert a gastric tube to measure my own gastric acidity. I remember it as one of miserable days of my life. On that occasion I had to pass it via the mouth and it was only down for three hours. Following my two pint vomit they decided to insert one transnasaly.
At the age of 16 I played at center half for the school second XI. On one occasion I was about to head the ball over my own crossbar to concede a corner from a high cross, when our goalkeeper, Roger Millward, rushed out and in attempting to punch the football, punched me in the nose. When I came too my nose was broken, and this is why inserting a nasogastric tube was very painful, even though the nurse inserting it was Nurse Nightingale and extremely skillful with it.
I have taught generations of students that the word 'retch' is pronounced 'reach' and not 'wretch', but they will not learn. The presence of a tube at the back of the throat stimulated the gag reflex and causes retching. Many surgeons, Dr Fozard included, are not keen on the use of nasogastric tubes post-operatively, but when gastric stasis leads to vomiting, there is very little choice. The usual practice is to spigot the tube and wait until the stomach is clearly emptying before removing the tube as soon as possible. In my case the stasis was prolonged and the tube was down for several days. Eventually Dr Fozard took the decision to pull it up and immediately I felt better.
When I was about 14 I rapidly expanded my vocabulary and began to use long words instead of short ones. I would say 'commence' instead of 'start' or 'begin' and 'velocity' instead of 'speed'. I discovered the word 'recuperate' which for some reason I believed was a posh word for 'to belch'. I remember writing an essay at school in which I used 'recuperate' several times with this meaning. I couldn't understand why the boys in the class were laughing.
After abdominal surgery the first sign of recovery is the downward passage of wind. The nurses come round every morning and discretely ask, "Any wind?"
I see now that as a teenager I got thinks upside down. 'To recuperate' doesn't mean 'to belch', it means 'to fart'.
At the age of 16 I played at center half for the school second XI. On one occasion I was about to head the ball over my own crossbar to concede a corner from a high cross, when our goalkeeper, Roger Millward, rushed out and in attempting to punch the football, punched me in the nose. When I came too my nose was broken, and this is why inserting a nasogastric tube was very painful, even though the nurse inserting it was Nurse Nightingale and extremely skillful with it.
I have taught generations of students that the word 'retch' is pronounced 'reach' and not 'wretch', but they will not learn. The presence of a tube at the back of the throat stimulated the gag reflex and causes retching. Many surgeons, Dr Fozard included, are not keen on the use of nasogastric tubes post-operatively, but when gastric stasis leads to vomiting, there is very little choice. The usual practice is to spigot the tube and wait until the stomach is clearly emptying before removing the tube as soon as possible. In my case the stasis was prolonged and the tube was down for several days. Eventually Dr Fozard took the decision to pull it up and immediately I felt better.
When I was about 14 I rapidly expanded my vocabulary and began to use long words instead of short ones. I would say 'commence' instead of 'start' or 'begin' and 'velocity' instead of 'speed'. I discovered the word 'recuperate' which for some reason I believed was a posh word for 'to belch'. I remember writing an essay at school in which I used 'recuperate' several times with this meaning. I couldn't understand why the boys in the class were laughing.
After abdominal surgery the first sign of recovery is the downward passage of wind. The nurses come round every morning and discretely ask, "Any wind?"
I see now that as a teenager I got thinks upside down. 'To recuperate' doesn't mean 'to belch', it means 'to fart'.
Saturday, March 21, 2009
How it was in hospital
This is a chance to get off my chest the experience of the past two weeks while it is still fresh in my mind. The first thing I have to say is that I have never known such kindness and care as that I received from the nursing staff at my hospital.
I was admitted to the Royal Bournemouth Hospital early on the morning of my operation. This is the hospital that I worked at for my entire career. When I was first appointed in 1974 it was Victorian Establishment that had just 'growed like Topsy', with major developments in 1911, 1927, 1936, 1968, 1982 and 1986. The building that I originally worked in was demolished in 1993 and the new hospital built on the edge of the city opened in two phases in 1988 and 1992. It is a bright, airy, modern hospital that seems to have seen continual improvement since it opened. I was the first Medical Director of the new hospital.
The colorectal surgery department has an enviable reputation for high quality outcomes and low mortality and morbidity, a tribute to the meticulous planning and forethought of the head of department Dr Basil Fozard (you will see some of his innovations later). Dr Fozard has been at Bournemouth for about 12 years, having completed his training at the Mayo Clinic. I had already been pre-clerked before admission; so on the morning of the operation I knew precisely what awaited me as I sat and read in the day-room. I was able to walk to the operating theater suite. The anesthetist inserted a pink cannula in my wrist and injected a few drops of Hypnoval. He then sat me up to insert an epidural into my back and that's the last thing that I remember until I woke up in recovery. The surgeon came in and told me his findings, but I was still under the Hypnoval and I was in no fit state to fully understand.
My wife and daughter came in to visit me in the evening and here they encountered the first problem. It is now apparently the case that relatives can be given no information by the staff unless the patient has expressedly said that they might. There was therefore no-ne able to impart the news to them when they arrived, and it was I, in my drugged state, who blurted out the diagnosis. It was a terrible shock that they had not been expecting.
The rule has come in as an instruction from above because some patients have complained about their relatives being told. I have always thought that that was an unreasonable attitude to take unless there was some sort of estrangement involved. I have encountered husbands who wished to protect their wives from the news, but I have always countered that view by saying, "You have spent the past x years in the closest relationship it is possible to have, do you really intend to spend whatever time you have left telling lies to each other?"
The best person to break bad news is not the patient, but the doctor in charge, if he or she knows the job. He can speak from a position of knowledge, not only of the pathology, but also of how people react. He has an eye for the physiological reactions that accompany shock and is prepared with acts of comfort from a hand held to a cup of warm sweet tea.
To my mind the new rule is just one more of the vicious consequences of unthinking pandering to PC.
The major consequence of bowel surgery is paralytic ileus. This means the bowel stops its onward contractions (peristalsis) and just hangs about idly loitering. This always happens, especially if the bowel has been much handled (as when searching for a small primary). Post-operative treatment is aimed at making the period of ileus as short as possible. For many years morphine has been the mainstay of control of post-operative pain relief. However, morphine makes you constipated. Indeed, morphine alone can cause a paralytic ileus. Therefore, for Dr Fozard, the policy for pain relief is to use epidural anesthesia.
The problem for me was that the epidural only worked on the left side and the right was still painful. It happens occasionally and when it does the problem is more difficult. There was some Fentayl in the epidural to keep me in a haze, but I needed a PCA pump (patient controlled analgesia) to supplement this. This is a pump that delivers 1 mg of morphine at the press of a button, but then shuts out the patient for 5 minutes befor any more can be delivered. It is very effective, but the most immediate effect of morphine is nausea and vomiting. Generally, we offer an anti-emetic with morphine, but the choice is limited. Metaclopramide is a prokinetic agent that stimulates onward movement - possibly dangerous when the bowel has been resected and then rejoined, and ondansetron is constipating. Cyclizine is effective, but very sedating. As a result I had the morphine neat. This caused me severe spasm of the gullet.
Esophageal spasm produces a pain like angina, but can be relieved in the same way with glyceryl trinitrate, either under the tongue or as a spray. The new young doctor and I worked this out by Googling in the small hours of the morning, so she arranged to get a spray from the CCU. I tried it with instant pain relief. Then I vomited a couple of pints of brown fluid. What had been happening was that the body had contrived its own anti-emetic by constricting the gullet so hard it hurt. As soon as that was released - upchuck.
The response was to put down a naso-gastric tube and tomorrow I will tell you about that.
A great comfort to me throughout the period of hospitalization were the visits of Dr John Falkner Lee. John is a retired general practitioner. He and I were baptized on the same day in 1975 at Lansdowne Baptist Church. He is about 20 years older than I and shortly about to enter hospital to have one of his hip replacements replaced. Please pray for him. We were deacons together, elders together and always very close. For the past several years he has been on the staff of the hospital as Pastoral Visitor. On one of his visits he read to me from Zephaniah chapter 3.
The LORD has taken away your punishment; he has turned back your enemy. The LORD, the King of Israel, is with you; never again will you fear any harm. On that day they will say to Jerusalem, "Do not fear, O Zion; do not let your hands hang limp. The LORD your God is with you, he is mighty to save. He will take great delight in you, he will quiet you with his love, he will rejoice over you with singing."
Notice all those 'wills'; there is no 'might' in God, except that He is ‘might’y to save.
I was admitted to the Royal Bournemouth Hospital early on the morning of my operation. This is the hospital that I worked at for my entire career. When I was first appointed in 1974 it was Victorian Establishment that had just 'growed like Topsy', with major developments in 1911, 1927, 1936, 1968, 1982 and 1986. The building that I originally worked in was demolished in 1993 and the new hospital built on the edge of the city opened in two phases in 1988 and 1992. It is a bright, airy, modern hospital that seems to have seen continual improvement since it opened. I was the first Medical Director of the new hospital.
The colorectal surgery department has an enviable reputation for high quality outcomes and low mortality and morbidity, a tribute to the meticulous planning and forethought of the head of department Dr Basil Fozard (you will see some of his innovations later). Dr Fozard has been at Bournemouth for about 12 years, having completed his training at the Mayo Clinic. I had already been pre-clerked before admission; so on the morning of the operation I knew precisely what awaited me as I sat and read in the day-room. I was able to walk to the operating theater suite. The anesthetist inserted a pink cannula in my wrist and injected a few drops of Hypnoval. He then sat me up to insert an epidural into my back and that's the last thing that I remember until I woke up in recovery. The surgeon came in and told me his findings, but I was still under the Hypnoval and I was in no fit state to fully understand.
My wife and daughter came in to visit me in the evening and here they encountered the first problem. It is now apparently the case that relatives can be given no information by the staff unless the patient has expressedly said that they might. There was therefore no-ne able to impart the news to them when they arrived, and it was I, in my drugged state, who blurted out the diagnosis. It was a terrible shock that they had not been expecting.
The rule has come in as an instruction from above because some patients have complained about their relatives being told. I have always thought that that was an unreasonable attitude to take unless there was some sort of estrangement involved. I have encountered husbands who wished to protect their wives from the news, but I have always countered that view by saying, "You have spent the past x years in the closest relationship it is possible to have, do you really intend to spend whatever time you have left telling lies to each other?"
The best person to break bad news is not the patient, but the doctor in charge, if he or she knows the job. He can speak from a position of knowledge, not only of the pathology, but also of how people react. He has an eye for the physiological reactions that accompany shock and is prepared with acts of comfort from a hand held to a cup of warm sweet tea.
To my mind the new rule is just one more of the vicious consequences of unthinking pandering to PC.
The major consequence of bowel surgery is paralytic ileus. This means the bowel stops its onward contractions (peristalsis) and just hangs about idly loitering. This always happens, especially if the bowel has been much handled (as when searching for a small primary). Post-operative treatment is aimed at making the period of ileus as short as possible. For many years morphine has been the mainstay of control of post-operative pain relief. However, morphine makes you constipated. Indeed, morphine alone can cause a paralytic ileus. Therefore, for Dr Fozard, the policy for pain relief is to use epidural anesthesia.
The problem for me was that the epidural only worked on the left side and the right was still painful. It happens occasionally and when it does the problem is more difficult. There was some Fentayl in the epidural to keep me in a haze, but I needed a PCA pump (patient controlled analgesia) to supplement this. This is a pump that delivers 1 mg of morphine at the press of a button, but then shuts out the patient for 5 minutes befor any more can be delivered. It is very effective, but the most immediate effect of morphine is nausea and vomiting. Generally, we offer an anti-emetic with morphine, but the choice is limited. Metaclopramide is a prokinetic agent that stimulates onward movement - possibly dangerous when the bowel has been resected and then rejoined, and ondansetron is constipating. Cyclizine is effective, but very sedating. As a result I had the morphine neat. This caused me severe spasm of the gullet.
Esophageal spasm produces a pain like angina, but can be relieved in the same way with glyceryl trinitrate, either under the tongue or as a spray. The new young doctor and I worked this out by Googling in the small hours of the morning, so she arranged to get a spray from the CCU. I tried it with instant pain relief. Then I vomited a couple of pints of brown fluid. What had been happening was that the body had contrived its own anti-emetic by constricting the gullet so hard it hurt. As soon as that was released - upchuck.
The response was to put down a naso-gastric tube and tomorrow I will tell you about that.
A great comfort to me throughout the period of hospitalization were the visits of Dr John Falkner Lee. John is a retired general practitioner. He and I were baptized on the same day in 1975 at Lansdowne Baptist Church. He is about 20 years older than I and shortly about to enter hospital to have one of his hip replacements replaced. Please pray for him. We were deacons together, elders together and always very close. For the past several years he has been on the staff of the hospital as Pastoral Visitor. On one of his visits he read to me from Zephaniah chapter 3.
The LORD has taken away your punishment; he has turned back your enemy. The LORD, the King of Israel, is with you; never again will you fear any harm. On that day they will say to Jerusalem, "Do not fear, O Zion; do not let your hands hang limp. The LORD your God is with you, he is mighty to save. He will take great delight in you, he will quiet you with his love, he will rejoice over you with singing."
Notice all those 'wills'; there is no 'might' in God, except that He is ‘might’y to save.
Thursday, March 19, 2009
Home from hospital
I want to thank all those who have sent their good wishes, prayers and kind thoughts over the past couple of weeks.
It has been longer than I expected to fire up my computer again, and I am afraid that the news is not as good as I had hoped. Apparently I have cancer of the appendix that has spread sufficiently for me to need chemotherapy. The disease is not in my liver and the largest lymph nodes were removed
I returned from hospital today and I need some time of convalescence.
The histology came back as well differentiated adenocarcinoma that is CEA positive. There were some goblet cells, however, and it would still be compatible with goblet cell carcinoid, a very rare tumor with only 600 cases in the medical literature. but it will require special stains to distinguish (Chromogranin A). I will also need to know whether the k-ras gene is mutated in order to know whether the new EDGFR receptor monoclonal antibodies will be helpful.
I suppose the most optimistic factors and that I was really very well before the surgery, that the liver is not involved and that the CT in February was almost identical with the one in September.
This all suggests that the disease in very indolent (not another 'good' cancer!).
I have yet to be given a final diagnosis and the prognosis is still uncertain.
I will write later about various aspects of this experience, but I just want to say for now that the most comforting element of the whole episode was to recite to myself, "Thou wilt keep him in perfect peace, whose mind is stayed on thee: because he trusteth in thee" (Isaiah 26:3). Strange how the old King James version comes to me in times of need.
It has been longer than I expected to fire up my computer again, and I am afraid that the news is not as good as I had hoped. Apparently I have cancer of the appendix that has spread sufficiently for me to need chemotherapy. The disease is not in my liver and the largest lymph nodes were removed
I returned from hospital today and I need some time of convalescence.
The histology came back as well differentiated adenocarcinoma that is CEA positive. There were some goblet cells, however, and it would still be compatible with goblet cell carcinoid, a very rare tumor with only 600 cases in the medical literature. but it will require special stains to distinguish (Chromogranin A). I will also need to know whether the k-ras gene is mutated in order to know whether the new EDGFR receptor monoclonal antibodies will be helpful.
I suppose the most optimistic factors and that I was really very well before the surgery, that the liver is not involved and that the CT in February was almost identical with the one in September.
This all suggests that the disease in very indolent (not another 'good' cancer!).
I have yet to be given a final diagnosis and the prognosis is still uncertain.
I will write later about various aspects of this experience, but I just want to say for now that the most comforting element of the whole episode was to recite to myself, "Thou wilt keep him in perfect peace, whose mind is stayed on thee: because he trusteth in thee" (Isaiah 26:3). Strange how the old King James version comes to me in times of need.
Sunday, March 08, 2009
Waiting for surgery
A Green Woodpecker nodded and nibbled on our front lawn yesterday. For twenty minutes, not twenty feet from our front window, it strutted like a soldier on parade, its vermillion headpiece contrasting with its two-tone green uniform as it stiffly picked off insects that had been drawn above ground by the slightly warmer weather.
It was enough to attract us into the garden for the first clear up of the year. Two days ago we had woken up to blizzards with snow settling on the cars and drive, but Saturday was just about Spring. Now was the time to deadhead the hydrangeas, to cut back last year’s growth from the Sedum and to pull down the dead ivy from our cherry tree.
We gave the lawn a first cut, but first we had to buy a new lawnmower. We needed to be able to start it with an easy pull, and our old Mountfield was a terrible starter that needed strong stomach muscles as you yanked on the draw string. And I won’t be able to do that for a while.
On Tuesday, I go into hospital for abdominal surgery. This has been hanging over me since last September. At that time a CT scan found an enlarged lymph node in my right iliac fossa. Despite many investigations no explanation for it was found. I had hoped that it would just go away, but a recent CT scan shows it to be still there, and the only way of finding out what it means is to cut it out.
The radiologist suspects carcinoid, a rare slow growing tumor that typically secretes serotonin, but all the tests that I had for that were negative. Colonoscopy showed no cancer of the cecum and the biopsies were negative. So we really don’t know what we are going to find. I guess the explanation with the best outcome
is that there has been an old appendix abscess, but there are also more worrying possibilities. It could be a non-secretory carcinoid, or one that secreted another neuroendocrine hormone, like parathormone (I have a slightly raised blood calcium, but so do thousands of other normal people). Or it could be something more distressing.
In Julius Caesar, Shakespeare says, “Cowards die many times before their deaths. The valiant never taste of death but once.” Hemingway had a variation on this in ‘A Farewell to Arms’ “the brave dies perhaps two thousand deaths if he's intelligent. He simply doesn't mention them.” Whichever is true, waiting for an operation is a challenge. The more you know, the more you imagine the worse.
Nevertheless, I face the future with equanimity. The sermon this morning was on 1 Peter 1:8: “Though you have not seen him, you love him; and even though you do not see him now, you believe in him and are filled with an inexpressible and glorious joy,” The worst that could happen is that I will see my Savior sooner. Were that to be the case, it would be very sad for those who love me, but for me, better by far.
It was enough to attract us into the garden for the first clear up of the year. Two days ago we had woken up to blizzards with snow settling on the cars and drive, but Saturday was just about Spring. Now was the time to deadhead the hydrangeas, to cut back last year’s growth from the Sedum and to pull down the dead ivy from our cherry tree.
We gave the lawn a first cut, but first we had to buy a new lawnmower. We needed to be able to start it with an easy pull, and our old Mountfield was a terrible starter that needed strong stomach muscles as you yanked on the draw string. And I won’t be able to do that for a while.
On Tuesday, I go into hospital for abdominal surgery. This has been hanging over me since last September. At that time a CT scan found an enlarged lymph node in my right iliac fossa. Despite many investigations no explanation for it was found. I had hoped that it would just go away, but a recent CT scan shows it to be still there, and the only way of finding out what it means is to cut it out.
The radiologist suspects carcinoid, a rare slow growing tumor that typically secretes serotonin, but all the tests that I had for that were negative. Colonoscopy showed no cancer of the cecum and the biopsies were negative. So we really don’t know what we are going to find. I guess the explanation with the best outcome
is that there has been an old appendix abscess, but there are also more worrying possibilities. It could be a non-secretory carcinoid, or one that secreted another neuroendocrine hormone, like parathormone (I have a slightly raised blood calcium, but so do thousands of other normal people). Or it could be something more distressing.
In Julius Caesar, Shakespeare says, “Cowards die many times before their deaths. The valiant never taste of death but once.” Hemingway had a variation on this in ‘A Farewell to Arms’ “the brave dies perhaps two thousand deaths if he's intelligent. He simply doesn't mention them.” Whichever is true, waiting for an operation is a challenge. The more you know, the more you imagine the worse.
Nevertheless, I face the future with equanimity. The sermon this morning was on 1 Peter 1:8: “Though you have not seen him, you love him; and even though you do not see him now, you believe in him and are filled with an inexpressible and glorious joy,” The worst that could happen is that I will see my Savior sooner. Were that to be the case, it would be very sad for those who love me, but for me, better by far.
Wednesday, March 04, 2009
Darwin's anniversary
This year marks the 200th anniversary of Darwin's birth and the 150th anniversary of the publication of Origin of Species.
Richard Dawkins claimed in 1989 that "it is absolutely safe to say that if you meet somebody who claims not to believe in evolution, that person is ignorant, stupid, or insane (or wicked, but I'd rather not consider that)."
I suppose it all depends on what you mean by evolution. If you mean that various species undergo selection of genetic characteristics by their environment which make them more or less likely to reproduce these characteristics in their progeny - in other words the survival of the fittest, then of course this is true. In fact, it is a tautology. In a struggle for existence, those that are fittest to survive will survive.
If, on the other hand, by evolution you mean that life has begun as a matter of chance because of the happenstance of various chemicals mixing leading to the formation of amino acids, then protein, then nucleic acids, then some form of cellular organization, then more complex cellular forms until finally the prolific array of different species that now inhabits the earth, including all those that have become extinct, then anyone who believes that has never examined the evidence critically.
Evolutionary theories probably began with Thales of Miletus who lived between 640 and 546 BC. Darwin's contribution to the debate derived from his observations of the genetic variation of domestic animals and then his observation of natural variation on his time on the Beagle, especially at the Galapagos Islands. The mechanism that he related demonstrated that small variations are potentially present in every species and that environmental niches are indeed available that suit one variation over another. Given physical separation - either natural or produced by man - then it is possible to produce extreme variations within a species - a Toy Poodle or a Great Dane, for example, though there are limits to that variation and no-one has yet produced a tiger from a tortoise or a rabbit from a greyhound.
Darwin was a man of his time and he had no clear understanding of the mechanism eg this variation. This had to wait for Mendel's genetic experiments with peas, and even that idea had no physical equivalent until Crick and Watson fathomed out the DNA code.
Modern neo-Darwinism postulates a molecular model of random mutations that are selected for by the same 'survival of the fittest' tautology that Darwin hit upon. However, as we know, although mutations occur and are particularly useful for developing the immune response in the lymph node, elsewhere they are usually deleterious and are the chief mechanism of cancer. To suggest that they are the driving force of evolution envisions a highly improbable landscape.
Francis Crick himself (although no creationist) puts the problem clearly in his 1981 book Life Itself, Its Origin and Nature:
To produce this miracle of molecular construction all the cell need to is to string together the amino acids (which make up the polypeptide chain) in the correct order... Here we need only ask, how many possible proteins are there? If a particular amino acid sequence was selected by chance, how rare an event would that be? This is an easy exercise in combinatorials. Suppose the chain is about 200 amino acids long; this is if anything rather less than the average length of proteins of all types. Since we have just 20 possibilities at each place, the number of possibilities is 20 multiplied by itself some two hundred times. This is conveniently written as 20 to the power of 200, that is a one followed by 260 zeros!
The number is quite beyond our everyday comprehension. For comparison, consider the number of fundamental particles (atoms, speaking loosely) in the entire visible universe, not just in our own galaxy with its 100,000,000,000 stars, but in all the billions of galaxies out to the limits of observable space. This number, which estimated to be 10 to the power of 80 is quite paltry by comparison to 10 to the power of 260. Moreover, we have only considered a polypeptide chain of rather modest length. Had we considered longer ones as well, the figure would have been even more immense.
Even a simple bacterial cell comprises not just one protein, but a whole host of proteins that interact together in complex union.
Put simply, there are not enough molecules in the whole universe for even a simple protein to have evolved by chance.
Brick one in the wall of doubt.
Richard Dawkins claimed in 1989 that "it is absolutely safe to say that if you meet somebody who claims not to believe in evolution, that person is ignorant, stupid, or insane (or wicked, but I'd rather not consider that)."
I suppose it all depends on what you mean by evolution. If you mean that various species undergo selection of genetic characteristics by their environment which make them more or less likely to reproduce these characteristics in their progeny - in other words the survival of the fittest, then of course this is true. In fact, it is a tautology. In a struggle for existence, those that are fittest to survive will survive.
If, on the other hand, by evolution you mean that life has begun as a matter of chance because of the happenstance of various chemicals mixing leading to the formation of amino acids, then protein, then nucleic acids, then some form of cellular organization, then more complex cellular forms until finally the prolific array of different species that now inhabits the earth, including all those that have become extinct, then anyone who believes that has never examined the evidence critically.
Evolutionary theories probably began with Thales of Miletus who lived between 640 and 546 BC. Darwin's contribution to the debate derived from his observations of the genetic variation of domestic animals and then his observation of natural variation on his time on the Beagle, especially at the Galapagos Islands. The mechanism that he related demonstrated that small variations are potentially present in every species and that environmental niches are indeed available that suit one variation over another. Given physical separation - either natural or produced by man - then it is possible to produce extreme variations within a species - a Toy Poodle or a Great Dane, for example, though there are limits to that variation and no-one has yet produced a tiger from a tortoise or a rabbit from a greyhound.
Darwin was a man of his time and he had no clear understanding of the mechanism eg this variation. This had to wait for Mendel's genetic experiments with peas, and even that idea had no physical equivalent until Crick and Watson fathomed out the DNA code.
Modern neo-Darwinism postulates a molecular model of random mutations that are selected for by the same 'survival of the fittest' tautology that Darwin hit upon. However, as we know, although mutations occur and are particularly useful for developing the immune response in the lymph node, elsewhere they are usually deleterious and are the chief mechanism of cancer. To suggest that they are the driving force of evolution envisions a highly improbable landscape.
Francis Crick himself (although no creationist) puts the problem clearly in his 1981 book Life Itself, Its Origin and Nature:
To produce this miracle of molecular construction all the cell need to is to string together the amino acids (which make up the polypeptide chain) in the correct order... Here we need only ask, how many possible proteins are there? If a particular amino acid sequence was selected by chance, how rare an event would that be? This is an easy exercise in combinatorials. Suppose the chain is about 200 amino acids long; this is if anything rather less than the average length of proteins of all types. Since we have just 20 possibilities at each place, the number of possibilities is 20 multiplied by itself some two hundred times. This is conveniently written as 20 to the power of 200, that is a one followed by 260 zeros!
The number is quite beyond our everyday comprehension. For comparison, consider the number of fundamental particles (atoms, speaking loosely) in the entire visible universe, not just in our own galaxy with its 100,000,000,000 stars, but in all the billions of galaxies out to the limits of observable space. This number, which estimated to be 10 to the power of 80 is quite paltry by comparison to 10 to the power of 260. Moreover, we have only considered a polypeptide chain of rather modest length. Had we considered longer ones as well, the figure would have been even more immense.
Even a simple bacterial cell comprises not just one protein, but a whole host of proteins that interact together in complex union.
Put simply, there are not enough molecules in the whole universe for even a simple protein to have evolved by chance.
Brick one in the wall of doubt.
Monday, March 02, 2009
Who's in charge?
Bruce Forsyth is Britain's premier TV game-show host. He is renowned for his use of catch phrases. At one time his favorite was, "I'm in charge!"
With financial markets in turmoil and the world in the worst recession since 1929, it makes you wonder whether anyone is in charge. Politicians, try to give the air of being in charge, but it is apparent that they are powerless. Every headline brings a reaction, but they give me the impression of being like England batsmen facing the West Indies pace attack of a former generation. They may be fending off short pitched deliveries and protecting their faces, but they have no plan to build an innings. A few weeks ago Gordon Brown claimed to have saved the world. It's a pity the world did not notice.
The bankers are certainly not in charge. If they were clever they took the money and ran. And they intend to hang on to it. The industrialists are not in charge. Nobody wants to buy their goods and they are laying off workers at an alarming rate. The armed forces are not in charge. Battered and bruised by conflicts for which they have no heart, they just want to come home.
Way back in 539 BC in the land that is modern day Iraq, the rulers were feasting, drinking and revelling, when they were shocked by the sight of a disembodied hand writing on the wall, "You have been weighed in the balance and found wanting." You can read about it in Daniel Chapter 5. It must have been a frightening experience but Belshazzar would have felt safe within the impregnable city of Babylon. How was he to know that Cyrus the Persian possessed sufficient engineering skills to divert the River Euphrates so that he could enter the city along the dry river bed?
Belshazzar that he was in control of events but powerful though he was he was like putty in the hands of history.
Cyrus was a great Persian king (it seems like Iraq and Iran have always been enemies). If you go to the British Museum you can see the Cyrus Cylinder. It was discovered in 1879 by the Assyro-British archaeologist Hormuzd Rassam in the foundations of the Esagila, the main temple of Babylon, where it had been placed as a foundation deposit. The text of the cylinder denounces Nabonidus (father of Belshazzar) as impious and portrays the victorious Cyrus as pleasing to the chief Babylonian god Marduk. It goes on to describe how Cyrus had improved the lives of the citizens of Babylonia, repatriated displaced peoples and restored temples and cult sanctuaries.
Among those people returned to their own country were the Jews who had been taken into exile by Nebuchadnezzar 70 years previously. The liberation of the Jews had been predicted by the Prophet Isaiah in chapter 44 "who says of Cyrus, 'He is my shepherd and will accomplish all that I please; he will say of Jerusalem, "Let it be rebuilt," and of the temple, "Let its foundations be laid." and in 45:13 "I will raise up Cyrus [a] in my righteousness: I will make all his ways straight. He will rebuild my city and set my exiles free, but not for a price or reward, says the LORD Almighty.".
It seems astonishing that so far ahead of time Isaiah should name the liberator, but in Ezra chapter 1 the event is reported <>
The Bible makes it clear that Cyrus was not working on his own. It reassures us that someone is in charge; someone who has control of the future. We used to sing a hymn:
God holds the key of all unknown,
And I am glad:
If other hands should hold the key,
Or if he truseted it to me,
I might be sad.
What if tomorrow's cares were here
Without its rest?
I'd rather he unlocked the day,
And, as the hours swing open, say,
"My will is best."
It seems to us that we face an uncertain future. Our savings are in jeopardy, our jobs are not safe, our pensions losing their value, our homes at risk. Many are worried about our health. Perhaps we face surgery or chemotherapy. WE may be frightened for our loved ones. Sometimes it seems that no sooner has one worry dissipated than another takes its place. Where can we turn for comfort?
Jesus said this, "Consider the lilies of the field, how they grow: they neither toil nor spin; and yet I say to you that even Solomon in all his glory was not arrayed like one of these. Now if God so clothes the grass of the field, which today is, and tomorrow is thrown into the oven, will He not much more clothe you, O you of little faith? Therefore do not worry, saying, ‘What shall we eat?’ or ‘What shall we drink?’ or ‘What shall we wear?’ For after all these things the Gentiles seek. For your heavenly Father knows that you need all these things. But seek first the kingdom of God and His righteousness, and all these things shall be added to you. Therefore do not worry about tomorrow, for tomorrow will worry about its own things. Sufficient for the day is its own trouble."
And St Paul wrote to the Christians in Rome who were suffering far more than we are, "We know that all things work together for good to those who love God, to those who are the called according to His purpose."
With financial markets in turmoil and the world in the worst recession since 1929, it makes you wonder whether anyone is in charge. Politicians, try to give the air of being in charge, but it is apparent that they are powerless. Every headline brings a reaction, but they give me the impression of being like England batsmen facing the West Indies pace attack of a former generation. They may be fending off short pitched deliveries and protecting their faces, but they have no plan to build an innings. A few weeks ago Gordon Brown claimed to have saved the world. It's a pity the world did not notice.
The bankers are certainly not in charge. If they were clever they took the money and ran. And they intend to hang on to it. The industrialists are not in charge. Nobody wants to buy their goods and they are laying off workers at an alarming rate. The armed forces are not in charge. Battered and bruised by conflicts for which they have no heart, they just want to come home.
Way back in 539 BC in the land that is modern day Iraq, the rulers were feasting, drinking and revelling, when they were shocked by the sight of a disembodied hand writing on the wall, "You have been weighed in the balance and found wanting." You can read about it in Daniel Chapter 5. It must have been a frightening experience but Belshazzar would have felt safe within the impregnable city of Babylon. How was he to know that Cyrus the Persian possessed sufficient engineering skills to divert the River Euphrates so that he could enter the city along the dry river bed?
Belshazzar that he was in control of events but powerful though he was he was like putty in the hands of history.
Cyrus was a great Persian king (it seems like Iraq and Iran have always been enemies). If you go to the British Museum you can see the Cyrus Cylinder. It was discovered in 1879 by the Assyro-British archaeologist Hormuzd Rassam in the foundations of the Esagila, the main temple of Babylon, where it had been placed as a foundation deposit. The text of the cylinder denounces Nabonidus (father of Belshazzar) as impious and portrays the victorious Cyrus as pleasing to the chief Babylonian god Marduk. It goes on to describe how Cyrus had improved the lives of the citizens of Babylonia, repatriated displaced peoples and restored temples and cult sanctuaries.
Among those people returned to their own country were the Jews who had been taken into exile by Nebuchadnezzar 70 years previously. The liberation of the Jews had been predicted by the Prophet Isaiah in chapter 44 "who says of Cyrus, 'He is my shepherd and will accomplish all that I please; he will say of Jerusalem, "Let it be rebuilt," and of the temple, "Let its foundations be laid." and in 45:13 "I will raise up Cyrus [a] in my righteousness: I will make all his ways straight. He will rebuild my city and set my exiles free, but not for a price or reward, says the LORD Almighty.".
It seems astonishing that so far ahead of time Isaiah should name the liberator, but in Ezra chapter 1 the event is reported <
The Bible makes it clear that Cyrus was not working on his own. It reassures us that someone is in charge; someone who has control of the future. We used to sing a hymn:
God holds the key of all unknown,
And I am glad:
If other hands should hold the key,
Or if he truseted it to me,
I might be sad.
What if tomorrow's cares were here
Without its rest?
I'd rather he unlocked the day,
And, as the hours swing open, say,
"My will is best."
It seems to us that we face an uncertain future. Our savings are in jeopardy, our jobs are not safe, our pensions losing their value, our homes at risk. Many are worried about our health. Perhaps we face surgery or chemotherapy. WE may be frightened for our loved ones. Sometimes it seems that no sooner has one worry dissipated than another takes its place. Where can we turn for comfort?
Jesus said this, "Consider the lilies of the field, how they grow: they neither toil nor spin; and yet I say to you that even Solomon in all his glory was not arrayed like one of these. Now if God so clothes the grass of the field, which today is, and tomorrow is thrown into the oven, will He not much more clothe you, O you of little faith? Therefore do not worry, saying, ‘What shall we eat?’ or ‘What shall we drink?’ or ‘What shall we wear?’ For after all these things the Gentiles seek. For your heavenly Father knows that you need all these things. But seek first the kingdom of God and His righteousness, and all these things shall be added to you. Therefore do not worry about tomorrow, for tomorrow will worry about its own things. Sufficient for the day is its own trouble."
And St Paul wrote to the Christians in Rome who were suffering far more than we are, "We know that all things work together for good to those who love God, to those who are the called according to His purpose."
Thursday, February 26, 2009
The Spectre of Socialized Medicine
Yesterday President Obama assured us that healthcare reform was at the top of his agenda. Opponents raise the spectre of socialized medicine and Britain's NHS is held up as an example of what lies down that path.
The truth is that both Britain and America have a mixed economy of social and private healthcare.
The great worry is that socialized medicine leads to rationing. At one time the NHS had a waiting list of five years for a hip replacement and there is a built in delay in getting the new cancer drugs, some of which have not been and may not be approved by NICE.
However, this indictment of the NHS does not tell the whole story. Even when it took 5 years to get a hip replacement on the NHS you could get one next week if you had health insurance. At the time I was practising around 20% of the population had healthcare insurance. This is a far lower percentage than in America, of course, but there are reasons for this, which I will explain. Health insurance for the 20% is largely provided by employers who naturally enough regard it as a good investment since it gives them control over when their employees will be absent on health grounds. The whole private healthcare industry is geared towards elective surgery, since it is this area that is easiest for socialized medicine to ration. If you were paying through your taxes for someone else's treatment you would be happy to cover treatment for cancer and heart attacks but you might be unsure about paying for their varicose veins or their sticking out ears to be remedied.
Private health insurance usually extended to the employees family. Many self-employed individuals were able to write off healthcare insurance as a business expense and saw it as a good investment.
The other element to my thesis is that America also enjoys socialized medicine. The largest plank in this is the VA service. Some commentators have suggested that this is the most efficient part of American healthcare. In addition there is Medicare and Medicaid and a separate provision for children. It is also true that there are government subsidies to the private insurance industry in the form of tax breaks. Finally, there are the county hospital ERs that provide free healthcare to the indigenous poor.
The UK currently spends about 7.4% of GDP on the NHS. Surprisingly, the American government spends a staggering 11% of a much larger GDP on healthcare. The healthcare purchased by insurance is on top of this.
There is no doubt in my mind that the very best healthcare is provided by doctors working in private practise. Isn't that what you would expect? The more you pay for something the more you are likely to receive for you money. After all, Honda makes very good cars, but Rolls Royce make better ones. In any business transaction you largely get what you pay for. It is also true that among the best paid doctors there are some flim flam men who are taking money under false pretenses, but that's the market for you.
The problem with the market is that we can't all afford Rolls Royces and some of us have to settle for a Ford. But even a Ford is expected to get us from A to B on time.
There was a time that the Ford provided by the NHS was a beat-up Edsel, but at that time only about 4% of GDP was being spent on it. I remember when I started as a hospital consultant I was single handed in haematology; now there are 5 people doing the job I was doing and 5 junior doctors being trained in the department where there were none before. There were 3 general physicians in my hospital; now there are 33. I have seen improvements in the quality of medicine that are almost unbelievable. Nonetheless, there are still blackspots in the system that need remedy.
The reason that private medicine has never been purchased by more than 20% of the population in the UK is that the NHS is so good. It is so good because it is very efficient, avoiding buying things that are unnecessary, using the power of central purchasing in the way that the Supermarkets do to drive down prices, yet at the same time allowing a high degree of local autonomy to take advantage of local situations.
I suspect that the reason that so many buy medical insurance in America is because the alternative is so awful.
Let's take some of the specific criticisms of the NHS. How about those long waiting times? Our own hospital has been at the forefront of getting these down. No-one has to wait more than two weeks to see a consultant about a suspected cancer. Hip replacement waiting times are down to six weeks. No-one in the country waits for more than 18 weeks for any procedure.
The NHS won't pay for expensive cancer drugs. There is some truth in this. But until recently the only way you could get rituximab for CLL in America was by terminological inexactitude. If you called your CLL a type of lymphoma then you could get the insurance companies to pay for it. You could do the same in the UK until the authorities got wise to the fact that there was no evidence that rituximab showed benefit in CLL. It was not until the German CLL8 trial reported that we were sure that rituximab improved the length of remissions in CLL. It is the pharmaceutical companies who are to blame for this. They could have conducted the relevant trials a decade earlier if they had had the will.
Doctors all round the world are still performing procedures for which there is no evidence of benefit. NICE has addressed this problem and is reducing the pressures on doctors to continue in their bad old ways. A good example would be the use of protein-pump inhibitors like omeprazole for indigestion. The bill for this is greater than the bill for all cancer chemotherapy put together. Even switching to ranitidine would make lost cancer chemotherapy affordable, but most indigestion responds perfectly well to antacids from the drugstore. If it doesn't then suspect peptic ulcer which can be cured by two weeks omeprazole and some cheap antibiotics.
The other criticism of socialised medicine is that it reduces doctors' incomes. The frightening example of Cuba is often brought up. And it is true. For my few private patients I was paid at 10 times the rate that the NHS paid me. On the other hand the NHS was paying me roughly the same as the Prime Minister was getting, so I shouldn't complain. Lots of people on salaries earn plenty - as we are finding out in the banking crisis.
There is a real problem with bureaucracy in anything run by the government and it is very important that the government is kept at arms length from anything to do with medicine. In the NHS every family doctor is an independent contractor, not a slaried employee. Nor is it necessary for a national health service to come from taxes; most European schemes are insurance-based. But with such a large number of Americans getting such poor healthcare, change is inevitable.
The truth is that both Britain and America have a mixed economy of social and private healthcare.
The great worry is that socialized medicine leads to rationing. At one time the NHS had a waiting list of five years for a hip replacement and there is a built in delay in getting the new cancer drugs, some of which have not been and may not be approved by NICE.
However, this indictment of the NHS does not tell the whole story. Even when it took 5 years to get a hip replacement on the NHS you could get one next week if you had health insurance. At the time I was practising around 20% of the population had healthcare insurance. This is a far lower percentage than in America, of course, but there are reasons for this, which I will explain. Health insurance for the 20% is largely provided by employers who naturally enough regard it as a good investment since it gives them control over when their employees will be absent on health grounds. The whole private healthcare industry is geared towards elective surgery, since it is this area that is easiest for socialized medicine to ration. If you were paying through your taxes for someone else's treatment you would be happy to cover treatment for cancer and heart attacks but you might be unsure about paying for their varicose veins or their sticking out ears to be remedied.
Private health insurance usually extended to the employees family. Many self-employed individuals were able to write off healthcare insurance as a business expense and saw it as a good investment.
The other element to my thesis is that America also enjoys socialized medicine. The largest plank in this is the VA service. Some commentators have suggested that this is the most efficient part of American healthcare. In addition there is Medicare and Medicaid and a separate provision for children. It is also true that there are government subsidies to the private insurance industry in the form of tax breaks. Finally, there are the county hospital ERs that provide free healthcare to the indigenous poor.
The UK currently spends about 7.4% of GDP on the NHS. Surprisingly, the American government spends a staggering 11% of a much larger GDP on healthcare. The healthcare purchased by insurance is on top of this.
There is no doubt in my mind that the very best healthcare is provided by doctors working in private practise. Isn't that what you would expect? The more you pay for something the more you are likely to receive for you money. After all, Honda makes very good cars, but Rolls Royce make better ones. In any business transaction you largely get what you pay for. It is also true that among the best paid doctors there are some flim flam men who are taking money under false pretenses, but that's the market for you.
The problem with the market is that we can't all afford Rolls Royces and some of us have to settle for a Ford. But even a Ford is expected to get us from A to B on time.
There was a time that the Ford provided by the NHS was a beat-up Edsel, but at that time only about 4% of GDP was being spent on it. I remember when I started as a hospital consultant I was single handed in haematology; now there are 5 people doing the job I was doing and 5 junior doctors being trained in the department where there were none before. There were 3 general physicians in my hospital; now there are 33. I have seen improvements in the quality of medicine that are almost unbelievable. Nonetheless, there are still blackspots in the system that need remedy.
The reason that private medicine has never been purchased by more than 20% of the population in the UK is that the NHS is so good. It is so good because it is very efficient, avoiding buying things that are unnecessary, using the power of central purchasing in the way that the Supermarkets do to drive down prices, yet at the same time allowing a high degree of local autonomy to take advantage of local situations.
I suspect that the reason that so many buy medical insurance in America is because the alternative is so awful.
Let's take some of the specific criticisms of the NHS. How about those long waiting times? Our own hospital has been at the forefront of getting these down. No-one has to wait more than two weeks to see a consultant about a suspected cancer. Hip replacement waiting times are down to six weeks. No-one in the country waits for more than 18 weeks for any procedure.
The NHS won't pay for expensive cancer drugs. There is some truth in this. But until recently the only way you could get rituximab for CLL in America was by terminological inexactitude. If you called your CLL a type of lymphoma then you could get the insurance companies to pay for it. You could do the same in the UK until the authorities got wise to the fact that there was no evidence that rituximab showed benefit in CLL. It was not until the German CLL8 trial reported that we were sure that rituximab improved the length of remissions in CLL. It is the pharmaceutical companies who are to blame for this. They could have conducted the relevant trials a decade earlier if they had had the will.
Doctors all round the world are still performing procedures for which there is no evidence of benefit. NICE has addressed this problem and is reducing the pressures on doctors to continue in their bad old ways. A good example would be the use of protein-pump inhibitors like omeprazole for indigestion. The bill for this is greater than the bill for all cancer chemotherapy put together. Even switching to ranitidine would make lost cancer chemotherapy affordable, but most indigestion responds perfectly well to antacids from the drugstore. If it doesn't then suspect peptic ulcer which can be cured by two weeks omeprazole and some cheap antibiotics.
The other criticism of socialised medicine is that it reduces doctors' incomes. The frightening example of Cuba is often brought up. And it is true. For my few private patients I was paid at 10 times the rate that the NHS paid me. On the other hand the NHS was paying me roughly the same as the Prime Minister was getting, so I shouldn't complain. Lots of people on salaries earn plenty - as we are finding out in the banking crisis.
There is a real problem with bureaucracy in anything run by the government and it is very important that the government is kept at arms length from anything to do with medicine. In the NHS every family doctor is an independent contractor, not a slaried employee. Nor is it necessary for a national health service to come from taxes; most European schemes are insurance-based. But with such a large number of Americans getting such poor healthcare, change is inevitable.
Wednesday, February 25, 2009
The magic of numbers
I remember the last time I had an accident in my car. I say an accident, but I was entirely culpable. I was late. It was dark and wet and I was driving too fast for the conditions. As I rounded a bend in the road, doing 43.2 mph I was confronted by the red tail lights of a stack of traffic held up in front of me. I ploughed into the back of a 4X4. No-one was hurt, but my car was damaged enough for me to have to abandon my journey.
The odd thing was that when I looked at the odometer it read 70,000.0 miles.
Of course, that number is no more significant than 72,865.7 but we want to attach significance to round numbers. That old car limped on to 131,875.3 miles, about which I have absolutely nothing to say. Perhaps it would have been more perfect had I scrapped it after the accident. Superstition would have forced me to.
Of course the realy significant number was the 43.2 mph and if you go to this website you will see why.
The odd thing was that when I looked at the odometer it read 70,000.0 miles.
Of course, that number is no more significant than 72,865.7 but we want to attach significance to round numbers. That old car limped on to 131,875.3 miles, about which I have absolutely nothing to say. Perhaps it would have been more perfect had I scrapped it after the accident. Superstition would have forced me to.
Of course the realy significant number was the 43.2 mph and if you go to this website you will see why.
Sunday, February 22, 2009
Religious Refugees
The UNHCR defines a refugee as a person who has fled his country owing to well founded fear of being persecuted for reasons of race, religion, nationality, membership of a particular social group or political opinion, is outside the country of his nationality, is unable or owing to such fear is unwilling to avail himself of the protection of that country. (In every case the male pronoun includes the female). Free countries have a duty to offer asylum to those in such danger.
There is a special problem with converts from Islam. According to Sharia law, leaving Islam is a crime on a par with treason that is punishable by death (or life imprisonment if it is a woman according to some readings). Not every Muslim takes this view, but many countries that operate according to Sharia law do. Even when the government of a country takes an enlightened view, family members and certain rural communities do not. Even enlightened governments are reluctant to interfere in the workings of families and local communities. In Pakistan, for instance, there have been many Christian converts from Islam who have been unmolested, but if you happen to live near the Afghan border, your father or brothers might kill you if you convert.
Recently, a Libyan asylum seeker who had converted to Christianity was beaten almost to death while in the West Drayton Removal Centre in the UK, by Somali and Yemeni detainees, as he left the makeshift church in the centre.
There is a great ignorance on behalf of officials of national immigration services (I am speaking in particular about the UK, Germany and New Zealand) about the danger that Christian converts from Islam are in, and a lack of cultural sensitivity. The UNHCR takes the view that converts are in no danger in Iran - a view that most in the West would regard as laughable were it not so serious. Then take the questions asked of converts to establish the genuineness of their conversions. "How do you prepare a turkey for Christmas?" "Recite the Roman Catholic Mass." "What were the names of the thieves crucified with Jesus on the Cross?"
Some immigrants have been offered Muslim interpreters. Do they not realise the risk of this. Although some interpreters may be scrupulously honest they will hardly be able to present the asylum seekers problems with any insight, and there may be an incentive to mistranslate so that the person is sent home for 'reconversion'.
However, it is not all bad news. In September last year an asylum seeker "George" a Syrian who had previously seen his application for asylum refused because the Inspector could not believe that George's father would truly hurt his son, finally won the right to stay in Britain.
There is a special problem with converts from Islam. According to Sharia law, leaving Islam is a crime on a par with treason that is punishable by death (or life imprisonment if it is a woman according to some readings). Not every Muslim takes this view, but many countries that operate according to Sharia law do. Even when the government of a country takes an enlightened view, family members and certain rural communities do not. Even enlightened governments are reluctant to interfere in the workings of families and local communities. In Pakistan, for instance, there have been many Christian converts from Islam who have been unmolested, but if you happen to live near the Afghan border, your father or brothers might kill you if you convert.
Recently, a Libyan asylum seeker who had converted to Christianity was beaten almost to death while in the West Drayton Removal Centre in the UK, by Somali and Yemeni detainees, as he left the makeshift church in the centre.
There is a great ignorance on behalf of officials of national immigration services (I am speaking in particular about the UK, Germany and New Zealand) about the danger that Christian converts from Islam are in, and a lack of cultural sensitivity. The UNHCR takes the view that converts are in no danger in Iran - a view that most in the West would regard as laughable were it not so serious. Then take the questions asked of converts to establish the genuineness of their conversions. "How do you prepare a turkey for Christmas?" "Recite the Roman Catholic Mass." "What were the names of the thieves crucified with Jesus on the Cross?"
Some immigrants have been offered Muslim interpreters. Do they not realise the risk of this. Although some interpreters may be scrupulously honest they will hardly be able to present the asylum seekers problems with any insight, and there may be an incentive to mistranslate so that the person is sent home for 'reconversion'.
However, it is not all bad news. In September last year an asylum seeker "George" a Syrian who had previously seen his application for asylum refused because the Inspector could not believe that George's father would truly hurt his son, finally won the right to stay in Britain.
Saturday, February 21, 2009
Cataloguing films
I am still cataloguing my movies on DVD and VHS. I now have about 900, including 90 children's films (mostly on VHS).
The directors who now mostly feature are Alfred Hitchcock with 19, David Lean with 14, Steven Spielberg, Billy Wilder and Peter Weir, each with 10, Clint Eastwood and Ingmar Bergman with 8 each, the Coen brothers and Douglas Sirk with 7 and on 6 come James Ivory, John Huston, Martin Scorsese, Michael Powell and Stephen Frears.
As far as male actors are concerned, Humphrey Bogart leads with 18, Anthony Hopkins is next with 14, then Clive Owen with 12 and John Mills with 9. Then tied with 8 films each are Al Pacino, Alec Guinness, Daniel Day Lewis, Morgan Freeman, Robert De Niro, Tom Cruise, William Holden and Alan Rickman.
For Female actors the order is Cate Blanchett and Judi Dench with 10, Helen Mirren and Nicole Kidman with 9, Ingrid Bergman, Kate Winslett, Julia Roberts and Diane Keaton with 8 and Helena Bonham-Carter and Meryl Streep with 7.
I'm not sure what this says about me. I suppose it says I like old war films (John Mills) and I tend to collect everything by certain directors; that I like Film Noir and good actors. Perhaps someone could suggest from these lists which films you think I don't have in my collection and those I ought to have.
Incidentally, I still haven't watched more than 200 of the films.
The directors who now mostly feature are Alfred Hitchcock with 19, David Lean with 14, Steven Spielberg, Billy Wilder and Peter Weir, each with 10, Clint Eastwood and Ingmar Bergman with 8 each, the Coen brothers and Douglas Sirk with 7 and on 6 come James Ivory, John Huston, Martin Scorsese, Michael Powell and Stephen Frears.
As far as male actors are concerned, Humphrey Bogart leads with 18, Anthony Hopkins is next with 14, then Clive Owen with 12 and John Mills with 9. Then tied with 8 films each are Al Pacino, Alec Guinness, Daniel Day Lewis, Morgan Freeman, Robert De Niro, Tom Cruise, William Holden and Alan Rickman.
For Female actors the order is Cate Blanchett and Judi Dench with 10, Helen Mirren and Nicole Kidman with 9, Ingrid Bergman, Kate Winslett, Julia Roberts and Diane Keaton with 8 and Helena Bonham-Carter and Meryl Streep with 7.
I'm not sure what this says about me. I suppose it says I like old war films (John Mills) and I tend to collect everything by certain directors; that I like Film Noir and good actors. Perhaps someone could suggest from these lists which films you think I don't have in my collection and those I ought to have.
Incidentally, I still haven't watched more than 200 of the films.
Friday, February 20, 2009
Cancer Screening
When the CT scanner first appeared people dreamed of everyone having a scan at regular intervals to detect early cancer. We have become used to the mantra that in cancer "Early diagnosis means early treatment means more cures and fewer cancer deaths". Screening has been so heavily backed by government information that we have all bought into it. In today's BMJ is a paper from Peter Gotzsche and his colleagues in Denmark which questions the value of mammography. They produce the following figures: If 2000 women are screened regularly for 10 years, one will avoid dying from breast cancer, but 10 healthy women will as a consequence become cancer patients and be treated unnecessarily. These women will have whole or part of their breast removed and some will also receive unnecessary radiotherapy or chemotherapy. Some will develop a secondary leukemia because of the therapy. Furthermore another 200 healthy women will experience a false alarm and suffer psychological trauma.
All this sounds counter-intuitive. Surely it is better to know what is going on?
The problem with breast screening is not that cancers are missed, but that they are over-diagnosed. It is becoming clear that cancer may be diagnosed when the tumor is very small and despite its grim reputation, many cancers do not progress during the lifetime of the individual. Those of us who work with CLL are well aware of this fact: the commonest treatment applied is watch and wait. I am reminded of an obituary of a man from Oklahoma who died in his eighties, 52 years after his untreated CLL was first diagnosed. If it is true for CLL, why would it not be true for cancers of other tissues. Since CT scanning has become so sensitive we have been recognizing very small lumps in the lungs. Do these represent lung cancer? Or perhaps marginal zone lymphomas? Biopsy is the only way of finding out, but isn't that a bit invasive for what may be a false alarm? So we tend to watch and wait there too.
With mammogram results it is relatively easy to do a biopsy and this leads to the possibility of over diagnosis. For a start there is carcinoma-in-situ, which constitutes 20% of the diagnoses made. We know that fewer than half such cases lead to invasive cancer, but 30% are treated with mastectomy. Then there are patients who really do have cancer, but such an indolent cancer that it would never have become noticeable in the patient's lifetime.
Screening does not lead to fewer mastectomies; indeed in randomized trials 20% more mastectomies are performed in screened patients. You would think that this would be offset by a reduced number of mastectomies in older women whose late-occurring cancer had been forestalled. Unfortunately, this is not so. Radiotherapy is applied to some women whose cancer would not have progressed. It is known that radiotherapy doubles teh rate of mortality from lung cancer and heart disease.
Breast cancer rates are apparently increasing because mammography finds more cases. The cure rate is also improving, but the absolute number of women dying from breast cancer has not changed.
Similar results are available for PSA screening for prostate cancer. The disease is not 10 times more common than it was in the 1990s, but the number of people dying from prostate cancer every year has not changed - it remains the same in countries which adopt both a restrictive and a liberal policy on the use of PSA as a screening test.
I speak with some feeling as someone whose screening colonoscopy has led to two further colonoscopies, and octreatide scan and two CT scans, and still no diagnosis.
To explain the problem it helps to look at the maths. Suppose that a screening test is almost completely accurate; that it misses no positive cases and is 99.99% accurate. That means that one test in 10,000 will be a false positive. Not many tests are as accurate as this, but suppose you are screening for a rare disease with an incidence of 4 in 100,000 in the general population. That means that for every 10 positive tests, 6 will be false positives. (4 in 100,000 is the approximate frequency of CLL).
We underestimate the harm done by worrying patients. Few there are who face impending doom with equanimity.
All this sounds counter-intuitive. Surely it is better to know what is going on?
The problem with breast screening is not that cancers are missed, but that they are over-diagnosed. It is becoming clear that cancer may be diagnosed when the tumor is very small and despite its grim reputation, many cancers do not progress during the lifetime of the individual. Those of us who work with CLL are well aware of this fact: the commonest treatment applied is watch and wait. I am reminded of an obituary of a man from Oklahoma who died in his eighties, 52 years after his untreated CLL was first diagnosed. If it is true for CLL, why would it not be true for cancers of other tissues. Since CT scanning has become so sensitive we have been recognizing very small lumps in the lungs. Do these represent lung cancer? Or perhaps marginal zone lymphomas? Biopsy is the only way of finding out, but isn't that a bit invasive for what may be a false alarm? So we tend to watch and wait there too.
With mammogram results it is relatively easy to do a biopsy and this leads to the possibility of over diagnosis. For a start there is carcinoma-in-situ, which constitutes 20% of the diagnoses made. We know that fewer than half such cases lead to invasive cancer, but 30% are treated with mastectomy. Then there are patients who really do have cancer, but such an indolent cancer that it would never have become noticeable in the patient's lifetime.
Screening does not lead to fewer mastectomies; indeed in randomized trials 20% more mastectomies are performed in screened patients. You would think that this would be offset by a reduced number of mastectomies in older women whose late-occurring cancer had been forestalled. Unfortunately, this is not so. Radiotherapy is applied to some women whose cancer would not have progressed. It is known that radiotherapy doubles teh rate of mortality from lung cancer and heart disease.
Breast cancer rates are apparently increasing because mammography finds more cases. The cure rate is also improving, but the absolute number of women dying from breast cancer has not changed.
Similar results are available for PSA screening for prostate cancer. The disease is not 10 times more common than it was in the 1990s, but the number of people dying from prostate cancer every year has not changed - it remains the same in countries which adopt both a restrictive and a liberal policy on the use of PSA as a screening test.
I speak with some feeling as someone whose screening colonoscopy has led to two further colonoscopies, and octreatide scan and two CT scans, and still no diagnosis.
To explain the problem it helps to look at the maths. Suppose that a screening test is almost completely accurate; that it misses no positive cases and is 99.99% accurate. That means that one test in 10,000 will be a false positive. Not many tests are as accurate as this, but suppose you are screening for a rare disease with an incidence of 4 in 100,000 in the general population. That means that for every 10 positive tests, 6 will be false positives. (4 in 100,000 is the approximate frequency of CLL).
We underestimate the harm done by worrying patients. Few there are who face impending doom with equanimity.
Tuesday, February 17, 2009
Vitamin B
The B Vitamins are a group of water-soluble substances which are not otherwise related to each other. There are eight of them, but claims for vitamin status are made for another 23. A vitamin is a substance that is essential for healthy living that cannot be synthesized by teh body. The other 23 eithercan be synthesized by teh human body or are not essential for health. I will deal with teh eight true vitamins and then explain why some of the others are not true vitamins.
Vitamin B1 or thiamine is the substance that is necessary in the diet to prevent beriberi. Chinese medical texts referred to beriberi as early as 2700 BC. Symptoms of beriberi include severe lethargy and fatigue, together with complications affecting the cardiovascular, nervous, muscular, and gastrointestinal systems. The origin of the word is from a Sinhalese phrase meaning "I cannot, I cannot", the word being doubled for emphasis. Two types of beriberi are recognized: the 'wet-type' affects the heart; through a combination of heart failure and weakening of the capillary walls, it causes the peripheral tissues to become edematous. Dry beriberi causes wasting and partial paralysis resulting from damaged peripheral nerves.
In 1884, Takaki Kanehiro, a British-trained Japanese doctor of the Japanese Navy, observed that beriberi was endemic among low-ranking crew who often ate nothing but rice, but not among crews of Western navies and officers who consumed a Western-style diet. Kanehiro initially believed that lack of protein was the chief cause of beriberi. He conducted one of the first cliical trials using the crews of two battleships; one crew was fed only white rice, while the other was fed a diet of meat, fish, barley, rice, and beans. The group that ate only white rice reported 161 crew with beriberi and 25 deaths, while the latter group had only 14 cases of beriberi and no deaths. This convinced Kanehiro and the Japanese Navy that diet was the cause of beriberi. But Kanehiro wrongly thought that protein was the missing element in the diet (Kwashiorkor, which is caused by protein deficiency also causes heart failure).
In 1897 Christian Eijkman, a military doctor in the Dutch Indies, discovered that chickens fed on a diet of cooked, polished rice developed paralysis, which could be reversed by discontinuing rice polishing (he mistakenly attributed that to a nerve poison in the endosperm of rice, from which the outer layers of the grain gave protection to the body. In 1897, Christiaan Eijkman in the Dutch East Indies, discovered that feeding unpolished rice instead of the polished variety to chickens prevented paralysis in the chickens. In 1898, Sir Frederick Hopkins postulated that some foods contained "accessory factors" — in addition to proteins, carbohydrates and fats, — that were necessary for the functions of the human body.
Eijkman was awarded a Nobel Price in Psysiology and Medicine in 1929, because his observations led to the discovery of vitamins). An associate, Gerrit Grijns, correctly interpreted the connection between excessive consumption of polished rice and beriberi in 1901: he concluded that rice contained an essential nutrient in the outer layers of the grain that was removed in polishing. In 1911 Casimir Funk isolated an antineuritic substance from rice bran that he called a “vitamine” (on account of its containing an amino group). Dutch chemists, Jansen and Donath, went on to isolate and crystallize the active agent in 1926, whose structure was determined by R.R.Williams, a US chemist, in 1934. Thiamin (“sulfur-containing vitamin”) was synthesized in 1936 by the same group. It was first named “aneurin” (for anti-neuritic vitamin).
Thiamine occurs naturally in unrefined cereals and fresh foods, particularly whole grain bread, fresh meat, legumes, green vegetables, fruit, and milk. Beriberi is therefore common in people whose diet excludes these particular types of nutrition.
Beriberi may be found in people whose diet consists mainly of polished white rice, which is very low in thiamine because the thiamine-bearing husk has been removed. It can also be seen in chronic alcoholics with an inadequate diet (Wernicke-Korsakoff syndrome), as well as being a rare side effect of gastric bypass surgery. If a baby is mainly fed on the milk of a mother who suffers from thiamine deficiency then that child may develop beriberi as well.
Wernicke’s encephalopathy (WE) is the type of thiaqmine deficiency most frequently seen in Western society. Although it may also occur in patients with impaired nutrition from other causes, it is usually seen in alcoholics. It is a striking neuro-psychiatric disorder characterized by paralysis of eye movements, abnormal stance and gait, and markedly deranged mental function.
Alcoholics may have thiamin deficiency because of the following: 1) inadequate nutritional intake: alcoholics tend to intake less than the recommended amount of thiamin. 2) decreased uptake of thiamin from the GI tract: active transport of thiamin into enterocytes is disturbed during acute alcohol exposure. 3) liver thiamin stores are reduced due to hepatic steatosis or fibrosis. 4) impaired thiamin utilization: magnesium, which is required for the binding of thiamin to thiamin-using enzymes within the cell, is also deficient due to chronic alcohol consumption. The inefficient utilization of any thiamin that does reach the cells will further exacerbate the thiamin deficiency. 5) Ethanol per se inhibits thiamin transport in the gastrointestinal system and blocks phosphorylation of thiamin to its cofactor form, TDP.
Korsakoff Psychosis is generally considered to occur with deterioration of brain function in patients initially diagnosed with WE. This is an amnestic-confabulatory syndrome characterized by retrograde and anterograde amnesia, impairment of conceptual functions, and decreased spontaneity and initiative. Because of their loss of memory they invent the most fantastic explanations for their circumstances.
However, most people on normal diets do not require vitamin B1 supplements.
Vitamin B1 or thiamine is the substance that is necessary in the diet to prevent beriberi. Chinese medical texts referred to beriberi as early as 2700 BC. Symptoms of beriberi include severe lethargy and fatigue, together with complications affecting the cardiovascular, nervous, muscular, and gastrointestinal systems. The origin of the word is from a Sinhalese phrase meaning "I cannot, I cannot", the word being doubled for emphasis. Two types of beriberi are recognized: the 'wet-type' affects the heart; through a combination of heart failure and weakening of the capillary walls, it causes the peripheral tissues to become edematous. Dry beriberi causes wasting and partial paralysis resulting from damaged peripheral nerves.
In 1884, Takaki Kanehiro, a British-trained Japanese doctor of the Japanese Navy, observed that beriberi was endemic among low-ranking crew who often ate nothing but rice, but not among crews of Western navies and officers who consumed a Western-style diet. Kanehiro initially believed that lack of protein was the chief cause of beriberi. He conducted one of the first cliical trials using the crews of two battleships; one crew was fed only white rice, while the other was fed a diet of meat, fish, barley, rice, and beans. The group that ate only white rice reported 161 crew with beriberi and 25 deaths, while the latter group had only 14 cases of beriberi and no deaths. This convinced Kanehiro and the Japanese Navy that diet was the cause of beriberi. But Kanehiro wrongly thought that protein was the missing element in the diet (Kwashiorkor, which is caused by protein deficiency also causes heart failure).
In 1897 Christian Eijkman, a military doctor in the Dutch Indies, discovered that chickens fed on a diet of cooked, polished rice developed paralysis, which could be reversed by discontinuing rice polishing (he mistakenly attributed that to a nerve poison in the endosperm of rice, from which the outer layers of the grain gave protection to the body. In 1897, Christiaan Eijkman in the Dutch East Indies, discovered that feeding unpolished rice instead of the polished variety to chickens prevented paralysis in the chickens. In 1898, Sir Frederick Hopkins postulated that some foods contained "accessory factors" — in addition to proteins, carbohydrates and fats, — that were necessary for the functions of the human body.
Eijkman was awarded a Nobel Price in Psysiology and Medicine in 1929, because his observations led to the discovery of vitamins). An associate, Gerrit Grijns, correctly interpreted the connection between excessive consumption of polished rice and beriberi in 1901: he concluded that rice contained an essential nutrient in the outer layers of the grain that was removed in polishing. In 1911 Casimir Funk isolated an antineuritic substance from rice bran that he called a “vitamine” (on account of its containing an amino group). Dutch chemists, Jansen and Donath, went on to isolate and crystallize the active agent in 1926, whose structure was determined by R.R.Williams, a US chemist, in 1934. Thiamin (“sulfur-containing vitamin”) was synthesized in 1936 by the same group. It was first named “aneurin” (for anti-neuritic vitamin).
Thiamine occurs naturally in unrefined cereals and fresh foods, particularly whole grain bread, fresh meat, legumes, green vegetables, fruit, and milk. Beriberi is therefore common in people whose diet excludes these particular types of nutrition.
Beriberi may be found in people whose diet consists mainly of polished white rice, which is very low in thiamine because the thiamine-bearing husk has been removed. It can also be seen in chronic alcoholics with an inadequate diet (Wernicke-Korsakoff syndrome), as well as being a rare side effect of gastric bypass surgery. If a baby is mainly fed on the milk of a mother who suffers from thiamine deficiency then that child may develop beriberi as well.
Wernicke’s encephalopathy (WE) is the type of thiaqmine deficiency most frequently seen in Western society. Although it may also occur in patients with impaired nutrition from other causes, it is usually seen in alcoholics. It is a striking neuro-psychiatric disorder characterized by paralysis of eye movements, abnormal stance and gait, and markedly deranged mental function.
Alcoholics may have thiamin deficiency because of the following: 1) inadequate nutritional intake: alcoholics tend to intake less than the recommended amount of thiamin. 2) decreased uptake of thiamin from the GI tract: active transport of thiamin into enterocytes is disturbed during acute alcohol exposure. 3) liver thiamin stores are reduced due to hepatic steatosis or fibrosis. 4) impaired thiamin utilization: magnesium, which is required for the binding of thiamin to thiamin-using enzymes within the cell, is also deficient due to chronic alcohol consumption. The inefficient utilization of any thiamin that does reach the cells will further exacerbate the thiamin deficiency. 5) Ethanol per se inhibits thiamin transport in the gastrointestinal system and blocks phosphorylation of thiamin to its cofactor form, TDP.
Korsakoff Psychosis is generally considered to occur with deterioration of brain function in patients initially diagnosed with WE. This is an amnestic-confabulatory syndrome characterized by retrograde and anterograde amnesia, impairment of conceptual functions, and decreased spontaneity and initiative. Because of their loss of memory they invent the most fantastic explanations for their circumstances.
However, most people on normal diets do not require vitamin B1 supplements.
Sunday, February 15, 2009
Current affairs
politicsNo blogging for week because I have been busy preparing a sermon for this evening and for leading a Bible study last Thursday. So a few comments on what has been in the news this week.
Gert Wilders, the Dutch MEP was denied entry to Britain to show his film 'Fitner' to parliamentarians in the House of Lords. Readers of this blog will know that I have seen this film and provided a link to it on the internet. It is a short film that juxtaposes scenes of atrocities committed by Muslims (9/11, 7/7, Madrid and a hostage beheading) with the parts of the Koran that certain Muslims use to justify their actions. Banning Wilders did not stop anyone watching it. Indeed the added publicity ensured that many more people went to the various websites that feature it.
It is obviously true that not all Muslims ascribe to these views any more than Christians and Jews any longer feel the need to totally wipe out the Amalekites. The problems is that some Muslims do, and many of them live in the Western democracies. People over here are frightened by them. Free speech is not an optional extra to protect people who agree with you. The Muslim member of the House of Lords was out of order when he persuaded the Home Secretary to ban Wilders and the Home Secretary was both wimpish and authoritarian.
Jade Goody was treated for metastatic cervical cancer and it was announced that the disease is untreatable and that she has little time left. She is the ultimate in the 'famous for 15 minutes' syndrome. She first came to fame for her outrageous behavior on 'Big Brother' and then was cast off 'I'm a Celebrity Get Me Out of Here' for racist speech. She was held up as an example of the colossal ignorance of the 'underclass'. Then on the Indian version of 'Big Brother' she was told on camera that she had advanced cancer. While the TV world looked on she lost her hair to chemotherapy. She has expressed a desire to die on camera as a warning to the world. Since cervical cancer is mostly caused by Human Papilloma Virus, which is a sexually transmitted infection one wonders whether her display will reduce promiscuity.
And as if outrageous behavior had yet to reach its limit, we now have a 12 year-old apparently fathering a child on a 15 year old girl. The boy is clearly pre-pubertal and the claim is probably untrue, but exactly what do the parents think they are doing? Trying to make money from their children's misfortune is the obvious answer. The welfare state will provide the children with somewhere to live and £30,000 a year in benefits, apparently. then there is what the newspapers and TV will pay for the stories. It may all come to nothing since two older boys are now claiming to be the father. It seems to me that the teenagers should be taken into care and the parents prosecuted - and the baby adopted.
But adoption itself in hazardous. One couple have had their three children adopted against there will because social workers thought they had been abusing their middle child. Doubts have now arisen as to the justice of the claim. It seems that the child failed to thrive on formula milk and was switched to a soya substitute that lacked vitamin C. Experts have claimed that the apparent injuries were due to scurvy. Nonetheless, the Appeal Court has ruled that the adoptions are irreversible. As the father said, "If our children had been kidnapped and then recovered, would the children have had to stay with the kidnappers because they had got used to them?"
The financial crisis deepens with Gordon Brown catching most of the stick. He got the plaudits in the good times and must expect criticism in the bad ones. They latest suggest is 'quantitative easing', a euphemism for printing money. The Retail Price Index of inflation was 0.1% this month. This was mainly due to a fall in mortgage interest rates and a cut of 2.5% in VAT. However the Consumer Prices Index, which is the government's favored measure was 3.1%, still way above the 2% target. So have we got inflation or deflation?
The real problem in the economy is the failure of the banks to lend money to people needing cash to keep their businesses active, or to replace their car or to improve their house. The government has given the banks billions of taxpayers money so that they can lend, but it seems that that money is being used to replenish their own financial reserves and pay their employees huge bonuses. Since several of the banks are now nationalized, the government has it in its power to remedy that behavior. However, so many of the bankers are advising the government that I doubt it will happen. The Bank of England thinks 2010 will be better. Presumably because we will by then be shot of the Labor Party.
ADDED LATER 26/5/09. The 12 year old was not the father.
Gert Wilders, the Dutch MEP was denied entry to Britain to show his film 'Fitner' to parliamentarians in the House of Lords. Readers of this blog will know that I have seen this film and provided a link to it on the internet. It is a short film that juxtaposes scenes of atrocities committed by Muslims (9/11, 7/7, Madrid and a hostage beheading) with the parts of the Koran that certain Muslims use to justify their actions. Banning Wilders did not stop anyone watching it. Indeed the added publicity ensured that many more people went to the various websites that feature it.
It is obviously true that not all Muslims ascribe to these views any more than Christians and Jews any longer feel the need to totally wipe out the Amalekites. The problems is that some Muslims do, and many of them live in the Western democracies. People over here are frightened by them. Free speech is not an optional extra to protect people who agree with you. The Muslim member of the House of Lords was out of order when he persuaded the Home Secretary to ban Wilders and the Home Secretary was both wimpish and authoritarian.
Jade Goody was treated for metastatic cervical cancer and it was announced that the disease is untreatable and that she has little time left. She is the ultimate in the 'famous for 15 minutes' syndrome. She first came to fame for her outrageous behavior on 'Big Brother' and then was cast off 'I'm a Celebrity Get Me Out of Here' for racist speech. She was held up as an example of the colossal ignorance of the 'underclass'. Then on the Indian version of 'Big Brother' she was told on camera that she had advanced cancer. While the TV world looked on she lost her hair to chemotherapy. She has expressed a desire to die on camera as a warning to the world. Since cervical cancer is mostly caused by Human Papilloma Virus, which is a sexually transmitted infection one wonders whether her display will reduce promiscuity.
And as if outrageous behavior had yet to reach its limit, we now have a 12 year-old apparently fathering a child on a 15 year old girl. The boy is clearly pre-pubertal and the claim is probably untrue, but exactly what do the parents think they are doing? Trying to make money from their children's misfortune is the obvious answer. The welfare state will provide the children with somewhere to live and £30,000 a year in benefits, apparently. then there is what the newspapers and TV will pay for the stories. It may all come to nothing since two older boys are now claiming to be the father. It seems to me that the teenagers should be taken into care and the parents prosecuted - and the baby adopted.
But adoption itself in hazardous. One couple have had their three children adopted against there will because social workers thought they had been abusing their middle child. Doubts have now arisen as to the justice of the claim. It seems that the child failed to thrive on formula milk and was switched to a soya substitute that lacked vitamin C. Experts have claimed that the apparent injuries were due to scurvy. Nonetheless, the Appeal Court has ruled that the adoptions are irreversible. As the father said, "If our children had been kidnapped and then recovered, would the children have had to stay with the kidnappers because they had got used to them?"
The financial crisis deepens with Gordon Brown catching most of the stick. He got the plaudits in the good times and must expect criticism in the bad ones. They latest suggest is 'quantitative easing', a euphemism for printing money. The Retail Price Index of inflation was 0.1% this month. This was mainly due to a fall in mortgage interest rates and a cut of 2.5% in VAT. However the Consumer Prices Index, which is the government's favored measure was 3.1%, still way above the 2% target. So have we got inflation or deflation?
The real problem in the economy is the failure of the banks to lend money to people needing cash to keep their businesses active, or to replace their car or to improve their house. The government has given the banks billions of taxpayers money so that they can lend, but it seems that that money is being used to replenish their own financial reserves and pay their employees huge bonuses. Since several of the banks are now nationalized, the government has it in its power to remedy that behavior. However, so many of the bankers are advising the government that I doubt it will happen. The Bank of England thinks 2010 will be better. Presumably because we will by then be shot of the Labor Party.
ADDED LATER 26/5/09. The 12 year old was not the father.
Sunday, February 08, 2009
The Prodigal Son
I guess this story and the one about the Good Samaritan are the best known of Jesus' parables. Most people think they know it well. A young man, as young men do, gets fed up with his straight-laced family and wants to see the world. He asks his dad for the money that is coming to him when his father dies and he takes it and splits. He spends the next few years in riotous living. You can imagine him doing a Paris Hilton, getting into all kinds of scrapes and having enough money to bail himself out of them. He would have been a popular chap; lots of fair-weather friends.
You can see where it's heading. All good things come to an end. His money runs out, his friends desert him. There's famine in the land. He tries to get a job but the only work he can get is looking after pigs, which for a Jew would have been especially degrading. In the end he comes to his senses, realizes how much better he would have been had he not left home and goes back to mum and dad, who, as parents do, take him back. They may seem a bit soft, but that's what parents are like, a mother’s love has no limits. After all, he is their flesh and blood.
So, it's a cautionary tale about keeping to the straight and narrow, telling us that we ought to obey our parents and warning us about the sort of life that the young man embarked on.
I guess that's how many people see it, but it is a profound misunderstanding of the text.
To understand a text, we have to look at the context - otherwise it becomes a pretext. This is one of three parables in Luke 15 about losing things: a lost coin, a lost sheep and a lost son. It tells us about the concern the owner has about losing things.
I guess most of us have lost something vital. My son was due to fly to Switzerland on Friday, but his girlfriend lost her passport. They searched high and low for it. They tore her place apart, but it was nowhere to be found and the holiday had to be postponed. Most of us have lost our keys. Do you have one of those devices that causes your key ring to emit an electronic noise when you blow a whistle or clap your hands? I wish I did. I'm always putting my keys down somewhere and not remembering where. When I've lost something like that I can't settle at anything else. I must find it. It plays on my mind.
The lady who lost her coin, the shepherd who lost a sheep - these stories are telling us that our Father's concern for a sinner who goes astray is no less.
To simply say that the returning prodigal was accepted, because that's what parents do, misses the point. The German Poet, Heinrich Heine, who had converted from Judaism to Christianity in order to preserve his German citizenship, was asked on his deathbed by a priest whether he thought that God would forgive his sins. He replied, "Dieu me pardonnera; c'est son metier" - God will forgive me; that's His job.
To assume that we are going to get forgiven so perfunctorily, misreads the younger son's heartfelt repentance. The Bible tells us that he ‘came to his senses’. It reminds us of Legion, the man from whom Jesus cast many Demons. The people came out and found the man sitting at Jesus’ feet, ‘dressed and in his right mind’. Repentance is not a formula for getting forgiven – it literally means ‘think again’. It involves starting with a different premise. In all three parables it is repentance that is stressed. In Luke 15:7, the parable of the lost sheep, Jesus says, “I tell you that in the same way there will be more rejoicing in heaven over one sinner who repents than over ninety-nine righteous persons who do not need to repent.” and in Luke 15:10, the parable of the lost coin, He says, “In the same way, I tell you, there is rejoicing in the presence of the angels of God over one sinner who repents."
Is the young man truly repentant? These days we see many people who swap sides when the going gets tough. Footballers who are proud to pull on the shirt of Portsmouth (or Tottenham or West Ham) and talk about the history of the club and how proud they are to be thought of in the same lineage as Jimmy Dickinson (or Danny Blanchflower of Bobby Moore). Then Real Madrid or Liverpool or Chelsea flash their check books and loyalty is easily bought. Was this prodigal just seeing which side his bread was buttered on? I don’t think so. He accepted that he had forfeited his sonhood and was eager to be a slave in his father’s house.
And if this attitude belittles the son’s repentance, it also diminishes the hurt done to the father. To ask for your inheritance while your father still lives, is tantamount to saying, "I wish you were dead." To take that amount of capital out of the business must have seriously affected how it was run. Presumably the father would have had to borrow to realize the cash. That would have been an added burden on the revenues of the farm.
We have to remember that this parable would have been shocking to his hearers. They would know all about unreasonable love. They would remember what Isaiah had said in chapter 49 v 15: "Can a mother forget the baby at her breast and have no compassion on the child she has borne? Though she may forget, I will not forget you!” In illustrating God’s extreme grace, Isaiah turns to a mother’s nature. Ask a mother, “If your son were making false returns on his Income Tax declaration, would you shop him?” or “Supposing your son was a murderer, would you hand him over to the police?” Time and again mothers help their sons to get away – and who would blame a mother?
Notwithstanding, a mother’s love, the Jew’s life was defined by the Law. In Jewish eyes a woman was weak. A Jewish man would thank God everyday that he was not born a woman. In a court of law a woman’s word was worth much less than a man’s. A man was not sentimental. This young man had broken the Fifth Commandment and the Tenth Commandment and probably the Seventh as well. The Jews believed in forgiveness. The young man could have taken an animal to the Temple and made a sin-offering, but no, he traipses back to his father and his father in his weakness rushes out to meet him with open arms like a mere woman.
I imagine a Jew of the day would have found this depiction of God offensive. And in a way I agree with them. It really won’t do to brush away sin as if it didn’t matter. Two weeks ago the Manchester United midfielder, Michael Carrick, burst into the penalty area and was tripped by the Everton center half. United had already scored from a penalty awarded when the same player had been tripped earlier, and this time the referee waved away the claim. When questioned afterwards, Sir Alex Fergusson, the United manager said, “Of course it was a penalty, even more blatant that the first one. But you can’t expect to get two penalties in a match like this.”
Like many fans I was outraged. Surely we have a right to expect the referee to be fair. No matter how much of an advantage United might have had, fouls can’t simply be ignored. I would be very worried by a God who simply ignored sin as if it had never happened. Winking at my indiscretions is one thing, but if my enemy harms me I want him punished. It’s not fair!
It is interesting to note the actions of the father. As well as putting shoes on his feet, a cloak on his back and a ring on his finger, he has the fattened calf slaughtered. Is it special pleading to see the killing of an animal as having a special meaning? The Jews knew all about animal sacrifices. They knew about the nature of surrogacy. The sacrifice on the Day of Atonement was, as here, a young bull.
Looking backwards we can see that it was the very teller of the story who was to be sacrificed as a surrogate for the prodigal son and for all prodigals since. We can see him as the atoning sacrifice for our sins. God doesn’t wink at our sin, but he doesn’t hold them against us. He has taken the punishment for them on himself in the body of the Son.
So, it’s not just a warning for the young; it’s a description of God’s amazing grace; of how the lost can be saved and the damned redeemed. It’s a message that tells us that no-one is too bad to save; that no-one is so far gone that they cannot be rescued and that God in his great love is not willing that any should perish, but that all should turn from their wicked ways and live. And when we look at the context – that Jesus was sitting down with Tax-collectors and sinners – we see that it is a point well made.
But I don’t think that is the main point of the story. The main point concerns the older brother.
When I was younger I had a lot of sympathy for the older brother. After all, he was the sensible one. He’d kept his nose clean, slaved away at home, been a good example, always been there to help around the house, obeyed the rules and now he felt he was being taken for granted. On the other hand his brother had been an absolute wastrel, spent the family money of wicked things, gone missing when his father had to take out a bigger loan to keep the farm going – not only had he been the cause of the loan in the first place, but he’d not been around to help about the farm to pay off the interest – and now his big plans had all collapsed he had come scurrying back to Papa with his tail between his legs. No wonder he felt hard done by.
There is a story of Elizabeth Elliot’s that I have stolen from Chris Kelly. It’s not a Biblical story, but it is a parable. One day Jesus asked his disciples to carry a stone for him. They each picked up a stone from the ground. Clever old Peter picked up a tiny pebble that slipped easily into his pocket. No burden at all to carry that around. After they had been walking around the Galilean countryside all morning they stopped for lunch. Jesus asked them all to brink their stones to him and we waved his hand over them and turned them into bread. “That’s your lunch,” he said. Poor old Peter had less than a mouthful. After lunch Jesus asked the disciples to do the same again. Peter was not going to be fooled a second time. This time he picked up a boulder. As they walked over the hills of Judea, Peter struggled with his load. Shifting it from one shoulder to the other and then holding it next to his chest, then on his head, he fell further and further behind. Eventually, he caught them up. They had been sitting by the side of the lake for half an hour or so. “Ah, Peter,” said the Lord, “You’ve finally got here. You can chuck the rock in the lake now.”
“What? Aren’t you going to turn it into bread?”
“Peter, were you carrying that stone for me, as I asked, or were you carrying it for yourself?”
The older brother wasn’t being the dutiful son because he loved his father. He was doing it for the reward. He liked being thought of as ‘the good son’. He had the respect of the servants and the neighbors. He was a pillar of the community. He had a good image. And what is more he had expectations. Do you remember the oily character in Pride and Prejudice, Mr. William Collins, who was so nauseatingly obsequious to his patron, Lady Catherine de Bourgh? He too had expectations. The Bennet’s house at Longbourn was entailed to him – if Mr. Bennet were to die, Mrs. Bennet and her five daughters would be turfed out of home and hearth to make way for him. I think Jane Austen had the older brother in mind when she drew Mr. Collins.
The contrast between the two brothers turns on the word ‘slave’. The older brother complains that he has been slaving for his father for years without reward; the younger son regards becoming a slave in his father’s household as the source of his future joy.
Context is all important. Jesus told these three parables because the Pharisees were muttering. Their complaint was that “This man welcomes sinners.” The point Jesus is making is that not only does God welcome sinners, but the Pharisees are like the older brother who doesn’t welcome sinners.
Remember the Pharisee’s prayer, “God, I thank you that I am not like other men – robbers, evildoers, adulterers – or even like this tax collector.”
It is certainly a fine thing not to be a robber, evildoer or an adulterer. But if he thought he was not like other men, he was certainly mistaken.
The Apostle John writing in his old age says, “If we claim to be without sin, we deceive ourselves and the truth is not in us…If we claim we have not sinned we make Him out to be a liar.”
The truth is that even good people need a Savior. Even religious people need salvation. I am afraid that our churches are full of people who think they are safe and are not. They have lived good lives. Everybody thinks well of them. They could stand as MPs and be scrutinized by the scandal sheets and no-one would find anything to make a story about. No hidden mistress, their income tax returns are spotless, no unfortunate ‘perks’ they would be embarrassed by; they go to church twice on Sundays, they tithe religiously, they are always at Holy Communion. They are politically correct, watching their words carefully; “Paki” and “Golliwog” are not even in their vocabulary; they turn their TV off at the mains every night; they drive a hybrid car; their houses have roof insulation nine inches thick and their walls are insulated with polyurethane foam.
Yet these very good people still fall short of the standards Jesus has set. President Carter was a very good man. He may not have been a good President, but his lifestyle was exemplary. He was mocked about the story in Playboy. “Have you ever committed adultery?” he was asked.
“I have committed adultery in my heart,” he replied. He was just being honest. Applying to himself the interpretation of the Ten Commandments that Jesus had opened up in the Sermon on the Mount.
When the prodigal son was yet far off, his father, watching the road, perhaps standing on the roof of his house and scanning the horizon, spotted him. Was there something about the way he walked? Something about his gait or his body shape that he recognized. “I am the good shepherd,” said Jesus elsewhere, “I know my sheep.”
Can’t you feel the excitement, the anticipation, the overwhelming joy as the father ran to his son, threw his arms around him and kissed him? No wonder Jesus said there would be rejoicing in heaven.
What about the older brother? When he heard the music and the dancing he became angry. He skulked around outside and refused to go in. Not a lot of joy there. And it is a characteristic of the Pharisees. Would you not expect them to be pleased, for example, about the story of Zacchaeus, the reformed tax-collector? How about when they saw Lazarus raised from the dead? Or Blind Bartimaeus able to see again?
Supposing Joni Earickson suddenly got up from her wheelchair; would you rejoice? Or would you think it was a trick? When Jonathan Aitken was converted in prison did you suspect he was just trying to curry favor? To re-establish himself as a politician who was accepted in polite society. Did you feel the same about Chuck Colsen, the notorious Watergate plotter?
Have you met joyless Christians; people who are always picking holes in somebody else’s sweater? Oh, they are there. They don’t like the new hymn book. They don’t like the PowerPoint projector. The communion wine should be alcoholic/non-alcoholic (take your choice). They don’t like small groups. They find large meetings too impersonal. Church doesn’t do anything for me.
No wonder they are joyless. Without a Savior they never know whether the good they have done is enough. Is it enough to have double glazing? Should I perhaps get triple glazing? Should I set the house temperature at 68 rather than 70?
The prodigal son was humbled. He fell from a great height. One moment he was surrounded by rich friends, moving in the highest society. In today’s terms he would be lunching at the Savoy with merchant bankers, think it hilarious to send back a £500 bottle of wine because it was ‘corked’; then leave a £1000 tip. In the evening a little dinner party with Jude Law and a bevy of blondes and after the meal, a snort of cocaine. He would be pictured in ‘Hello’ in his Armani suit and Paul Smith shirt.
Just a blink later and he is wallowing with the pigs, his money gone, and he squabbles with the hogs to eat their food. Not difficult for him to be realistic about his situation. Humility comes easy to a man who has been brought down low.
Not so his brother. When you think you’re doing well, when you have a religious ritual to go by, when you’re good, it’s hard to see you need a savior. Did you see David Beckham in the England match on Wednesday? He’s done well to come back to international football hasn’t he? Except that he harassed the referee over what he thought was a wrong decision and got himself a yellow card. When you are convinced you are in the right humility is a hard currency to deal in. Pride keeps us from the kingdom.
Are they irredeemable, these joyless Christians? Listen to what the Apostle Paul says of himself. “If anyone else thinks he has reasons to put confidence in the flesh, I have more: circumcised on the eighth day, of the people of Israel, of the tribe of Benjamin, a Hebrew of Hebrews; in regard to the law, a Pharisee; as for zeal, persecuting the church; as for legalistic righteousness, faultless.”
Elsewhere, he describes himself as the ‘chief of sinners’.
Only the Holy Spirit could change Paul, but the Holy Spirit did just that.
As I examine my heart, I invite you to do the same. Am I an older brother? Do I lack joy? Do I lack humility? If any of these accusations stick then turn to the Savior now. Pray that the Holy Spirit will give you the joy of your salvation. For he is not only able to do so, he is more than willing.
You can see where it's heading. All good things come to an end. His money runs out, his friends desert him. There's famine in the land. He tries to get a job but the only work he can get is looking after pigs, which for a Jew would have been especially degrading. In the end he comes to his senses, realizes how much better he would have been had he not left home and goes back to mum and dad, who, as parents do, take him back. They may seem a bit soft, but that's what parents are like, a mother’s love has no limits. After all, he is their flesh and blood.
So, it's a cautionary tale about keeping to the straight and narrow, telling us that we ought to obey our parents and warning us about the sort of life that the young man embarked on.
I guess that's how many people see it, but it is a profound misunderstanding of the text.
To understand a text, we have to look at the context - otherwise it becomes a pretext. This is one of three parables in Luke 15 about losing things: a lost coin, a lost sheep and a lost son. It tells us about the concern the owner has about losing things.
I guess most of us have lost something vital. My son was due to fly to Switzerland on Friday, but his girlfriend lost her passport. They searched high and low for it. They tore her place apart, but it was nowhere to be found and the holiday had to be postponed. Most of us have lost our keys. Do you have one of those devices that causes your key ring to emit an electronic noise when you blow a whistle or clap your hands? I wish I did. I'm always putting my keys down somewhere and not remembering where. When I've lost something like that I can't settle at anything else. I must find it. It plays on my mind.
The lady who lost her coin, the shepherd who lost a sheep - these stories are telling us that our Father's concern for a sinner who goes astray is no less.
To simply say that the returning prodigal was accepted, because that's what parents do, misses the point. The German Poet, Heinrich Heine, who had converted from Judaism to Christianity in order to preserve his German citizenship, was asked on his deathbed by a priest whether he thought that God would forgive his sins. He replied, "Dieu me pardonnera; c'est son metier" - God will forgive me; that's His job.
To assume that we are going to get forgiven so perfunctorily, misreads the younger son's heartfelt repentance. The Bible tells us that he ‘came to his senses’. It reminds us of Legion, the man from whom Jesus cast many Demons. The people came out and found the man sitting at Jesus’ feet, ‘dressed and in his right mind’. Repentance is not a formula for getting forgiven – it literally means ‘think again’. It involves starting with a different premise. In all three parables it is repentance that is stressed. In Luke 15:7, the parable of the lost sheep, Jesus says, “I tell you that in the same way there will be more rejoicing in heaven over one sinner who repents than over ninety-nine righteous persons who do not need to repent.” and in Luke 15:10, the parable of the lost coin, He says, “In the same way, I tell you, there is rejoicing in the presence of the angels of God over one sinner who repents."
Is the young man truly repentant? These days we see many people who swap sides when the going gets tough. Footballers who are proud to pull on the shirt of Portsmouth (or Tottenham or West Ham) and talk about the history of the club and how proud they are to be thought of in the same lineage as Jimmy Dickinson (or Danny Blanchflower of Bobby Moore). Then Real Madrid or Liverpool or Chelsea flash their check books and loyalty is easily bought. Was this prodigal just seeing which side his bread was buttered on? I don’t think so. He accepted that he had forfeited his sonhood and was eager to be a slave in his father’s house.
And if this attitude belittles the son’s repentance, it also diminishes the hurt done to the father. To ask for your inheritance while your father still lives, is tantamount to saying, "I wish you were dead." To take that amount of capital out of the business must have seriously affected how it was run. Presumably the father would have had to borrow to realize the cash. That would have been an added burden on the revenues of the farm.
We have to remember that this parable would have been shocking to his hearers. They would know all about unreasonable love. They would remember what Isaiah had said in chapter 49 v 15: "Can a mother forget the baby at her breast and have no compassion on the child she has borne? Though she may forget, I will not forget you!” In illustrating God’s extreme grace, Isaiah turns to a mother’s nature. Ask a mother, “If your son were making false returns on his Income Tax declaration, would you shop him?” or “Supposing your son was a murderer, would you hand him over to the police?” Time and again mothers help their sons to get away – and who would blame a mother?
Notwithstanding, a mother’s love, the Jew’s life was defined by the Law. In Jewish eyes a woman was weak. A Jewish man would thank God everyday that he was not born a woman. In a court of law a woman’s word was worth much less than a man’s. A man was not sentimental. This young man had broken the Fifth Commandment and the Tenth Commandment and probably the Seventh as well. The Jews believed in forgiveness. The young man could have taken an animal to the Temple and made a sin-offering, but no, he traipses back to his father and his father in his weakness rushes out to meet him with open arms like a mere woman.
I imagine a Jew of the day would have found this depiction of God offensive. And in a way I agree with them. It really won’t do to brush away sin as if it didn’t matter. Two weeks ago the Manchester United midfielder, Michael Carrick, burst into the penalty area and was tripped by the Everton center half. United had already scored from a penalty awarded when the same player had been tripped earlier, and this time the referee waved away the claim. When questioned afterwards, Sir Alex Fergusson, the United manager said, “Of course it was a penalty, even more blatant that the first one. But you can’t expect to get two penalties in a match like this.”
Like many fans I was outraged. Surely we have a right to expect the referee to be fair. No matter how much of an advantage United might have had, fouls can’t simply be ignored. I would be very worried by a God who simply ignored sin as if it had never happened. Winking at my indiscretions is one thing, but if my enemy harms me I want him punished. It’s not fair!
It is interesting to note the actions of the father. As well as putting shoes on his feet, a cloak on his back and a ring on his finger, he has the fattened calf slaughtered. Is it special pleading to see the killing of an animal as having a special meaning? The Jews knew all about animal sacrifices. They knew about the nature of surrogacy. The sacrifice on the Day of Atonement was, as here, a young bull.
Looking backwards we can see that it was the very teller of the story who was to be sacrificed as a surrogate for the prodigal son and for all prodigals since. We can see him as the atoning sacrifice for our sins. God doesn’t wink at our sin, but he doesn’t hold them against us. He has taken the punishment for them on himself in the body of the Son.
So, it’s not just a warning for the young; it’s a description of God’s amazing grace; of how the lost can be saved and the damned redeemed. It’s a message that tells us that no-one is too bad to save; that no-one is so far gone that they cannot be rescued and that God in his great love is not willing that any should perish, but that all should turn from their wicked ways and live. And when we look at the context – that Jesus was sitting down with Tax-collectors and sinners – we see that it is a point well made.
But I don’t think that is the main point of the story. The main point concerns the older brother.
When I was younger I had a lot of sympathy for the older brother. After all, he was the sensible one. He’d kept his nose clean, slaved away at home, been a good example, always been there to help around the house, obeyed the rules and now he felt he was being taken for granted. On the other hand his brother had been an absolute wastrel, spent the family money of wicked things, gone missing when his father had to take out a bigger loan to keep the farm going – not only had he been the cause of the loan in the first place, but he’d not been around to help about the farm to pay off the interest – and now his big plans had all collapsed he had come scurrying back to Papa with his tail between his legs. No wonder he felt hard done by.
There is a story of Elizabeth Elliot’s that I have stolen from Chris Kelly. It’s not a Biblical story, but it is a parable. One day Jesus asked his disciples to carry a stone for him. They each picked up a stone from the ground. Clever old Peter picked up a tiny pebble that slipped easily into his pocket. No burden at all to carry that around. After they had been walking around the Galilean countryside all morning they stopped for lunch. Jesus asked them all to brink their stones to him and we waved his hand over them and turned them into bread. “That’s your lunch,” he said. Poor old Peter had less than a mouthful. After lunch Jesus asked the disciples to do the same again. Peter was not going to be fooled a second time. This time he picked up a boulder. As they walked over the hills of Judea, Peter struggled with his load. Shifting it from one shoulder to the other and then holding it next to his chest, then on his head, he fell further and further behind. Eventually, he caught them up. They had been sitting by the side of the lake for half an hour or so. “Ah, Peter,” said the Lord, “You’ve finally got here. You can chuck the rock in the lake now.”
“What? Aren’t you going to turn it into bread?”
“Peter, were you carrying that stone for me, as I asked, or were you carrying it for yourself?”
The older brother wasn’t being the dutiful son because he loved his father. He was doing it for the reward. He liked being thought of as ‘the good son’. He had the respect of the servants and the neighbors. He was a pillar of the community. He had a good image. And what is more he had expectations. Do you remember the oily character in Pride and Prejudice, Mr. William Collins, who was so nauseatingly obsequious to his patron, Lady Catherine de Bourgh? He too had expectations. The Bennet’s house at Longbourn was entailed to him – if Mr. Bennet were to die, Mrs. Bennet and her five daughters would be turfed out of home and hearth to make way for him. I think Jane Austen had the older brother in mind when she drew Mr. Collins.
The contrast between the two brothers turns on the word ‘slave’. The older brother complains that he has been slaving for his father for years without reward; the younger son regards becoming a slave in his father’s household as the source of his future joy.
Context is all important. Jesus told these three parables because the Pharisees were muttering. Their complaint was that “This man welcomes sinners.” The point Jesus is making is that not only does God welcome sinners, but the Pharisees are like the older brother who doesn’t welcome sinners.
Remember the Pharisee’s prayer, “God, I thank you that I am not like other men – robbers, evildoers, adulterers – or even like this tax collector.”
It is certainly a fine thing not to be a robber, evildoer or an adulterer. But if he thought he was not like other men, he was certainly mistaken.
The Apostle John writing in his old age says, “If we claim to be without sin, we deceive ourselves and the truth is not in us…If we claim we have not sinned we make Him out to be a liar.”
The truth is that even good people need a Savior. Even religious people need salvation. I am afraid that our churches are full of people who think they are safe and are not. They have lived good lives. Everybody thinks well of them. They could stand as MPs and be scrutinized by the scandal sheets and no-one would find anything to make a story about. No hidden mistress, their income tax returns are spotless, no unfortunate ‘perks’ they would be embarrassed by; they go to church twice on Sundays, they tithe religiously, they are always at Holy Communion. They are politically correct, watching their words carefully; “Paki” and “Golliwog” are not even in their vocabulary; they turn their TV off at the mains every night; they drive a hybrid car; their houses have roof insulation nine inches thick and their walls are insulated with polyurethane foam.
Yet these very good people still fall short of the standards Jesus has set. President Carter was a very good man. He may not have been a good President, but his lifestyle was exemplary. He was mocked about the story in Playboy. “Have you ever committed adultery?” he was asked.
“I have committed adultery in my heart,” he replied. He was just being honest. Applying to himself the interpretation of the Ten Commandments that Jesus had opened up in the Sermon on the Mount.
When the prodigal son was yet far off, his father, watching the road, perhaps standing on the roof of his house and scanning the horizon, spotted him. Was there something about the way he walked? Something about his gait or his body shape that he recognized. “I am the good shepherd,” said Jesus elsewhere, “I know my sheep.”
Can’t you feel the excitement, the anticipation, the overwhelming joy as the father ran to his son, threw his arms around him and kissed him? No wonder Jesus said there would be rejoicing in heaven.
What about the older brother? When he heard the music and the dancing he became angry. He skulked around outside and refused to go in. Not a lot of joy there. And it is a characteristic of the Pharisees. Would you not expect them to be pleased, for example, about the story of Zacchaeus, the reformed tax-collector? How about when they saw Lazarus raised from the dead? Or Blind Bartimaeus able to see again?
Supposing Joni Earickson suddenly got up from her wheelchair; would you rejoice? Or would you think it was a trick? When Jonathan Aitken was converted in prison did you suspect he was just trying to curry favor? To re-establish himself as a politician who was accepted in polite society. Did you feel the same about Chuck Colsen, the notorious Watergate plotter?
Have you met joyless Christians; people who are always picking holes in somebody else’s sweater? Oh, they are there. They don’t like the new hymn book. They don’t like the PowerPoint projector. The communion wine should be alcoholic/non-alcoholic (take your choice). They don’t like small groups. They find large meetings too impersonal. Church doesn’t do anything for me.
No wonder they are joyless. Without a Savior they never know whether the good they have done is enough. Is it enough to have double glazing? Should I perhaps get triple glazing? Should I set the house temperature at 68 rather than 70?
The prodigal son was humbled. He fell from a great height. One moment he was surrounded by rich friends, moving in the highest society. In today’s terms he would be lunching at the Savoy with merchant bankers, think it hilarious to send back a £500 bottle of wine because it was ‘corked’; then leave a £1000 tip. In the evening a little dinner party with Jude Law and a bevy of blondes and after the meal, a snort of cocaine. He would be pictured in ‘Hello’ in his Armani suit and Paul Smith shirt.
Just a blink later and he is wallowing with the pigs, his money gone, and he squabbles with the hogs to eat their food. Not difficult for him to be realistic about his situation. Humility comes easy to a man who has been brought down low.
Not so his brother. When you think you’re doing well, when you have a religious ritual to go by, when you’re good, it’s hard to see you need a savior. Did you see David Beckham in the England match on Wednesday? He’s done well to come back to international football hasn’t he? Except that he harassed the referee over what he thought was a wrong decision and got himself a yellow card. When you are convinced you are in the right humility is a hard currency to deal in. Pride keeps us from the kingdom.
Are they irredeemable, these joyless Christians? Listen to what the Apostle Paul says of himself. “If anyone else thinks he has reasons to put confidence in the flesh, I have more: circumcised on the eighth day, of the people of Israel, of the tribe of Benjamin, a Hebrew of Hebrews; in regard to the law, a Pharisee; as for zeal, persecuting the church; as for legalistic righteousness, faultless.”
Elsewhere, he describes himself as the ‘chief of sinners’.
Only the Holy Spirit could change Paul, but the Holy Spirit did just that.
As I examine my heart, I invite you to do the same. Am I an older brother? Do I lack joy? Do I lack humility? If any of these accusations stick then turn to the Savior now. Pray that the Holy Spirit will give you the joy of your salvation. For he is not only able to do so, he is more than willing.
Friday, February 06, 2009
NICE picture
This morning in the post I received this remarkable picture. "What's remarkable about it?" you may ask, "Just an old couple cutting a cake." Edith and John are celebrating their Diamond Wedding anniversary.
Eighteen years ago John had been given just a few weeks to live. He had been diagnosed with kidney cancer which was regarded as inoperable. His lungs were almost totally replaced by secondary cancer and he had very large lymph nodes in his abdomen. There was no effective chemotherapy for kidney cancer, and in fact the recommended treatment was the female sex hormone, progesterone. This did no good, but it was pretty harmless.
About that time there had been a television program about a new type of agent called interleukin-2 (IL-2). It was a terrible treatment. Patients suffered terrific shivering attacks, their blood pressures dropped, they went into kidney failure, some died of heart failure, some developed horrific rashes, but some got better.
John came to see me. I wasn't sure who mentioned IL-2 first, it may well have been him. Ar first I dismissed it out of hand. It was not a licensed product. It was impossibly expensive (£9000 then seemed an awful lot of money when you find it difficult to get the NHS to pay an extra £300 for mitoxantrone).
John offered to raise the £9000 but even then there was a rule that if you paid for your drugs privately your whole treatment had to be private. Had we gone down that route we would have been talking about £25,000+.
Instead I suggested that John make a contribution to our research fund so that we could start a clinical trial of interleukin-2 in kidney cancer. I wrote a protocol and got ethical approval even though I knew that without funding I would only be able to treat one patient.
We weren't really sure what to expect, but my team were up for it and we gave John the drug. The toxicity was bad, though not as bad as it had appeared on television. All the secondaries disappeared and the cancerous kidney shrunk to such a size that it could be removed.
When we took this result to the company that made it, they funded me to treat another 24 kidney cancer patients, 25 melanomas and 10 colon cancer patients. We had one other kidney cancer complete remission, and she also is still alive, and 5 complete remissions in melanoma patients, but they all relapsed within a year. One of the colon cancer patients had a partial remission.
Several points to learn from this. The median is not the message, as Stephen J Gould said. Despite a poor median survival, some patients do very well on strange treatments that have no apparent survival benefit. Patient drive and determination is sometimes the most important factor. The looser arrangements for clinical trials that used to obtain had their good points as well as their bad ones.
In 1991 I was at the peak of my powers. Everything I touched turned to gold. My confidence was high and I felt I had magic in my fingers. What a dangerous state for any man to aspire to! If I felt like that now I would seek absolution.
Tuesday, February 03, 2009
What is a CR?
I spent yesterday wrestling with the CLL Guidelines - both the 1996 and the 2008 versions - trying to evaluate a clinical trial results as part of a Review Panel. It used to be quite easy, though pretty meaningless. To say you had a complete remission (CR) in CLL you had to have disappearance of all disease that could be detected by physical examination, and restoration of the blood count to reasonable levels - neutrophils > 1500/cu mm, lymphocytes <4000/cu mm, platelets >100,000/cu mm and Hb >11 g/dL. This had to last for two months, and at the end of those two months a bone marrow biopsy had to contain fewer than 30% lymphocytes and to be of reasonably normal cellularity.
Of course, the 1996 guidelines were written before imaging became a routine practice, so hepatomegaly meant that you could feel the liver below the edge of the ribs and splenomegaly meant that you could feel the spleen below the edge of the ribs.
If the patient did not fulfill the criteria for a CR the next test was to see if the conditions for a partial remission (PR) were met. These required a >50% decrease in the lymphocyte count, a >50% reduction in the size of the lymph nodes and a >50% reduction in hepatosplenomegaly plus the restoration of (or considerable improvement in) one of the elements of the blood count (ie platelets over 100,000/cu mm, Hb over 11 g/dL and neutrophils over 1500, or if these are not achieved a >50% increase over the baseline levels).
Patients who fail treatment might have progressive disease (PD) which was defined as a >50% increase in the sum of the products of at least two lymph nodes on two consecutive determinations at least 2 weeks apart (at least one node must be > than 2cm) or the appearance of new nodes that could be felt. Or a >50% increase in the size of the liver or spleen below the ribs or the appearance of one of these which was not previously present, or a >50% in the absolute number of circulating lymphocytes (as long as the number is greater than 5000/cu mm.
(It should be noted that all the >50% signs in this essay mean greater or equal to 50%; I don’t know how to make the sign for greater or equal to.)
Those who don’t improve enough to be called a PR or who don’t deteriorate enough to be called PD were designated as having stable disease (SD).
Although this system was fairly easy to operate it was a bit of a joke. This wasn’t a CR like the CRs of acute leukemia where getting a CR is a prelude to a cure. Everybody knew that obtaining a CR in CLL (and that itself was pretty rare) didn’t mean a cure. It was possible that 30% of the cells in the bone marrow were still leukemia cells. And since lymph nodes in the belly couldn’t be felt there could be a couple of kilograms of cancer there undetected. In fat people it’s almost impossible to feel lymph nodes in the armpits and in very thin people you can often feel very small lymph nodes, which may be enlarged because of infection rather than CLL. A spleen has to enlarge threefold to be felt below the ribs, and measuring the liver by physical examination is fraught with difficulties; for example, if the lungs are over expanded, as in emphysema, a normal sized liver can be felt below the ribs.
The new guidelines were prompted by a number of things. It had long been recognized that some patients apparently achieved CR, but their marrow biopsies, while mainly being free of CLL, contained lymphoid nodules. Were these lymphoid nodules foci of CLL or just reactive nodules of normal tissue? They clearly needed to be studied separately and so such patients were designated nPR. We do know that such patients have a shorter time to progression than those with CR. Then there were some patients who seemed to be in CR but their blood counts did not return to normal. It seemed that their bone marrow had been damaged by the CLL. Of course, it could have been the case that residual CLL was suppressing their bone marrow and preventing normalization. The 1996 guidelines regarded this as a controversial issue, but decided that they should be called PR – except that if Hb was still <11 g/dL, neutrophils <1500/cu mm and platelets <100,000 /cu mm they had to be regarded as stable disease.
The other confusing thing about the guidelines was that despite stressing that size measurements are to be determined by physical examination, they add “and appropriate radiographic techniques” for lymph node sizing, and “or appropriate radiographic techniques if in a clinical trial” for liver and spleen measurement, as if physical examination and ‘appropriate radiological techniques’ were interchangeable. We know for certain that radiological techniques will detect disease that is undetectable to the examiner’s hand.
For evaluating clinical trials it turns out that measurements are not noted down in the notes, and investigations are forgotten. There may be ‘after’ CT scans but no ‘before’ or vice versa.
So do the new guidelines help?
Now CR needs all the following criteria as assessed at least three months after the completion of treatment:
1. No clonal lymphocytes. This is more stringent than before – all you needed then was fewer than 4000 lymphocytes.
2. No significantly enlarged lymph nodes. In clinical trials CT scanning is now positively encouraged. So we are talking about the largest diameter of lymph nodes anywhere in the body, not being greater than 1.5 cm.
3. No hepatomegaly or splenomegaly by physical examination. We have now reverted to physical examination even though a CT scan will have been done to look for enlarged lymph nodes. The guidelines advise that if liver or spleen were found to be abnormal before treatment then a scan should be performed at evaluation; this should also be done if the evaluation was inconclusive by physical examination.
4. No constitutional symptoms.
5. Neutrophils >1500 / cu mm, platelets >100,000 /. Cu mm Hb >11 g/dL (untransfused). For more than 20 years I have been protesting that to choose the same Hb level for men and women is insane.
6. If all these points have been achieved a bone marrow aspirate and trephine biopsy should be performed. The marrow should be examined by flow cytometry and immunohistochemistry to look for clonal B cells. If clonal cells are found then the case is demoted to PR. It must be stressed here that the flow cytometry is not the powerful 4-color flow used to detect MRD, but the simpler 2-color flow that detects one cell in 100.If lymphoid nodules are found in the trephine, then immunohistochemistry should distinguish between CLL and reactive nodules. The nPR category therefore disappears. If the marrow is hypercellular, then it should be repeated in 4-6 weeks, provided the blood counts have recovered. In some cases it is necessary to continue to postpone the marrow, but this time interval should not exceed 6 months.
7. The question of apparent CR with a failure to recover the bone marrow also seems to have been resolved. Those who fulfill all the criteria for a CR including the marrow examination, but who have a persistent anemia, thrombocytopenia or neutropenia unrelated to CLL but related to drug toxicity are designated CRi (‘i’ stands for incomplete marrow recovery). In view of the fact that a PR still requires recovery of at least one of the marrow lineages, I am not clear whether CRi can be applied to a patient with complete pancytopenia.
PR is similar to before – slightly confusing. There are four things that must be achieved:
1. A decrease in blood lymphocytes to fewer than 50% of the starting value.
2. A reduction in the size of the lymph nodes. This has to be assessed by CT in a clinical trial, and is defined as a decrease of 50% or more of the ‘sum products’ of up to six lymph nodes ‘Sum products’ are the figure you get when you multiply the perpendicular diameters of individual lymph nodes. It doesn’t say which six nodes, but most people would take the six biggest ones – of course if only three are enlarged you’d just do it with three. If there is just one big node then you can take a 50% reduction in its diameter. As far as lymph nodes are concerned there must be no increase in size in any of them, though in small nodes of less than 2cm diameter, an increase of less than 25% is not considered significant. There must also be no new enlarged node that wasn’t enlarged before.
3. A decrease in the size of the liver or spleen by 50% or more defined by CT in clinical trials. This is the one I take issue with. Enlarged spleens are often 18 cm long when measured by CT. A 50% reduction in size to 9cm would make it smaller than normal – up to 12 cm – and measurement of livers will have a similar drawback. We don’t want treatment that will make the liver shrink to the size of someone’s with cirrhosis. What they mean is a 50% reduction in the enlargement of either organ, but since we don’t know what the normal was for that patient, we are unable to calculate an answer. Livers and spleens vary with body size – they are certainly larger in men than women. Until this issue is resolved I recommend that any liver or spleen that can’t be felt by clinical examination should be regarded as normal.
4. One of the following should be present: neutrophils >1500 / cu mm, platelets >100,000 / cu mm, Hb >11 g/dL, or if not then at least one should show a 50% improvement over baseline.
A further proviso is that at least one of these parameters should persist for at least 2 months. It is not clear to me from the paper whether this refers to all the 4 measurements or just one of those in section 4. I’m assuming it means any of the four sections.
Systemic symptoms don’t come into it. Although CR requires these to remit, a PR does not, although they have to be noted.
PD is generally obvious from blood counts and therefore need not be looked for by CT scanning, though clearly from the instructions in the paper, it can be. So if any of the following occur PD is said to have occurred:
1. Any new lesions appearing such as an new lymph node enlarged to >1.5 cm diameter, splenomegaly, hepatomegaly or any other organ infiltration.
2. An increase by 50% or more of the greatest diameter of any previous lymph node.
3. An increase of 50% or more of the sum of the product of diameters of multiple nodes.
4. An increase in the size of liver or spleen by 50% or more or the appearance of spleens or livers that can now be felt.
5. An increase of50% or more in the absolute lymphocyte count, as long as it is greater than 5000.
6. Transformation to aggressive histology (eg Richter’s syndrome). This should be confirmed by biopsy.
7. The appearance of cytopenia unrelated to treatment or autoimmunity. This can only be assessed after treatment and so is defined as a fall in Hb by 2g/dL or to less than 10g/dL or by a decrease in platelet count by more than 50% or to below 100,000 per cu mm, that occurs at least 3 months after treatment ends and associated with an infiltrate of clonal lymphoid cells in the marrow. Note, the guidelines say nothing about late neutropenia.
SD is anything between PR and PD.
The duration of a response is measured from the end of the last treatment, but, confusingly, progression-free survival is measured from the first day of treatment.
Trials that are designed to eradicate the CLL should include testing for minimal residual disease (MRD). Either 4-color flow cytometry or allele-specific oligonucleotide PCR should be used using a threshold of one cell in 10,000. It is permissible to use blood for this assay except within 3 months of completing therapy, especially when alemtuzumab, rituximab or other antibodies have been used, in which case, bone marrow should be used.
Although the new guidelines make sense, there are still some ambiguities and in places the application of common sense runs counter to the wording of the document.
Of course, the 1996 guidelines were written before imaging became a routine practice, so hepatomegaly meant that you could feel the liver below the edge of the ribs and splenomegaly meant that you could feel the spleen below the edge of the ribs.
If the patient did not fulfill the criteria for a CR the next test was to see if the conditions for a partial remission (PR) were met. These required a >50% decrease in the lymphocyte count, a >50% reduction in the size of the lymph nodes and a >50% reduction in hepatosplenomegaly plus the restoration of (or considerable improvement in) one of the elements of the blood count (ie platelets over 100,000/cu mm, Hb over 11 g/dL and neutrophils over 1500, or if these are not achieved a >50% increase over the baseline levels).
Patients who fail treatment might have progressive disease (PD) which was defined as a >50% increase in the sum of the products of at least two lymph nodes on two consecutive determinations at least 2 weeks apart (at least one node must be > than 2cm) or the appearance of new nodes that could be felt. Or a >50% increase in the size of the liver or spleen below the ribs or the appearance of one of these which was not previously present, or a >50% in the absolute number of circulating lymphocytes (as long as the number is greater than 5000/cu mm.
(It should be noted that all the >50% signs in this essay mean greater or equal to 50%; I don’t know how to make the sign for greater or equal to.)
Those who don’t improve enough to be called a PR or who don’t deteriorate enough to be called PD were designated as having stable disease (SD).
Although this system was fairly easy to operate it was a bit of a joke. This wasn’t a CR like the CRs of acute leukemia where getting a CR is a prelude to a cure. Everybody knew that obtaining a CR in CLL (and that itself was pretty rare) didn’t mean a cure. It was possible that 30% of the cells in the bone marrow were still leukemia cells. And since lymph nodes in the belly couldn’t be felt there could be a couple of kilograms of cancer there undetected. In fat people it’s almost impossible to feel lymph nodes in the armpits and in very thin people you can often feel very small lymph nodes, which may be enlarged because of infection rather than CLL. A spleen has to enlarge threefold to be felt below the ribs, and measuring the liver by physical examination is fraught with difficulties; for example, if the lungs are over expanded, as in emphysema, a normal sized liver can be felt below the ribs.
The new guidelines were prompted by a number of things. It had long been recognized that some patients apparently achieved CR, but their marrow biopsies, while mainly being free of CLL, contained lymphoid nodules. Were these lymphoid nodules foci of CLL or just reactive nodules of normal tissue? They clearly needed to be studied separately and so such patients were designated nPR. We do know that such patients have a shorter time to progression than those with CR. Then there were some patients who seemed to be in CR but their blood counts did not return to normal. It seemed that their bone marrow had been damaged by the CLL. Of course, it could have been the case that residual CLL was suppressing their bone marrow and preventing normalization. The 1996 guidelines regarded this as a controversial issue, but decided that they should be called PR – except that if Hb was still <11 g/dL, neutrophils <1500/cu mm and platelets <100,000 /cu mm they had to be regarded as stable disease.
The other confusing thing about the guidelines was that despite stressing that size measurements are to be determined by physical examination, they add “and appropriate radiographic techniques” for lymph node sizing, and “or appropriate radiographic techniques if in a clinical trial” for liver and spleen measurement, as if physical examination and ‘appropriate radiological techniques’ were interchangeable. We know for certain that radiological techniques will detect disease that is undetectable to the examiner’s hand.
For evaluating clinical trials it turns out that measurements are not noted down in the notes, and investigations are forgotten. There may be ‘after’ CT scans but no ‘before’ or vice versa.
So do the new guidelines help?
Now CR needs all the following criteria as assessed at least three months after the completion of treatment:
1. No clonal lymphocytes. This is more stringent than before – all you needed then was fewer than 4000 lymphocytes.
2. No significantly enlarged lymph nodes. In clinical trials CT scanning is now positively encouraged. So we are talking about the largest diameter of lymph nodes anywhere in the body, not being greater than 1.5 cm.
3. No hepatomegaly or splenomegaly by physical examination. We have now reverted to physical examination even though a CT scan will have been done to look for enlarged lymph nodes. The guidelines advise that if liver or spleen were found to be abnormal before treatment then a scan should be performed at evaluation; this should also be done if the evaluation was inconclusive by physical examination.
4. No constitutional symptoms.
5. Neutrophils >1500 / cu mm, platelets >100,000 /. Cu mm Hb >11 g/dL (untransfused). For more than 20 years I have been protesting that to choose the same Hb level for men and women is insane.
6. If all these points have been achieved a bone marrow aspirate and trephine biopsy should be performed. The marrow should be examined by flow cytometry and immunohistochemistry to look for clonal B cells. If clonal cells are found then the case is demoted to PR. It must be stressed here that the flow cytometry is not the powerful 4-color flow used to detect MRD, but the simpler 2-color flow that detects one cell in 100.If lymphoid nodules are found in the trephine, then immunohistochemistry should distinguish between CLL and reactive nodules. The nPR category therefore disappears. If the marrow is hypercellular, then it should be repeated in 4-6 weeks, provided the blood counts have recovered. In some cases it is necessary to continue to postpone the marrow, but this time interval should not exceed 6 months.
7. The question of apparent CR with a failure to recover the bone marrow also seems to have been resolved. Those who fulfill all the criteria for a CR including the marrow examination, but who have a persistent anemia, thrombocytopenia or neutropenia unrelated to CLL but related to drug toxicity are designated CRi (‘i’ stands for incomplete marrow recovery). In view of the fact that a PR still requires recovery of at least one of the marrow lineages, I am not clear whether CRi can be applied to a patient with complete pancytopenia.
PR is similar to before – slightly confusing. There are four things that must be achieved:
1. A decrease in blood lymphocytes to fewer than 50% of the starting value.
2. A reduction in the size of the lymph nodes. This has to be assessed by CT in a clinical trial, and is defined as a decrease of 50% or more of the ‘sum products’ of up to six lymph nodes ‘Sum products’ are the figure you get when you multiply the perpendicular diameters of individual lymph nodes. It doesn’t say which six nodes, but most people would take the six biggest ones – of course if only three are enlarged you’d just do it with three. If there is just one big node then you can take a 50% reduction in its diameter. As far as lymph nodes are concerned there must be no increase in size in any of them, though in small nodes of less than 2cm diameter, an increase of less than 25% is not considered significant. There must also be no new enlarged node that wasn’t enlarged before.
3. A decrease in the size of the liver or spleen by 50% or more defined by CT in clinical trials. This is the one I take issue with. Enlarged spleens are often 18 cm long when measured by CT. A 50% reduction in size to 9cm would make it smaller than normal – up to 12 cm – and measurement of livers will have a similar drawback. We don’t want treatment that will make the liver shrink to the size of someone’s with cirrhosis. What they mean is a 50% reduction in the enlargement of either organ, but since we don’t know what the normal was for that patient, we are unable to calculate an answer. Livers and spleens vary with body size – they are certainly larger in men than women. Until this issue is resolved I recommend that any liver or spleen that can’t be felt by clinical examination should be regarded as normal.
4. One of the following should be present: neutrophils >1500 / cu mm, platelets >100,000 / cu mm, Hb >11 g/dL, or if not then at least one should show a 50% improvement over baseline.
A further proviso is that at least one of these parameters should persist for at least 2 months. It is not clear to me from the paper whether this refers to all the 4 measurements or just one of those in section 4. I’m assuming it means any of the four sections.
Systemic symptoms don’t come into it. Although CR requires these to remit, a PR does not, although they have to be noted.
PD is generally obvious from blood counts and therefore need not be looked for by CT scanning, though clearly from the instructions in the paper, it can be. So if any of the following occur PD is said to have occurred:
1. Any new lesions appearing such as an new lymph node enlarged to >1.5 cm diameter, splenomegaly, hepatomegaly or any other organ infiltration.
2. An increase by 50% or more of the greatest diameter of any previous lymph node.
3. An increase of 50% or more of the sum of the product of diameters of multiple nodes.
4. An increase in the size of liver or spleen by 50% or more or the appearance of spleens or livers that can now be felt.
5. An increase of50% or more in the absolute lymphocyte count, as long as it is greater than 5000.
6. Transformation to aggressive histology (eg Richter’s syndrome). This should be confirmed by biopsy.
7. The appearance of cytopenia unrelated to treatment or autoimmunity. This can only be assessed after treatment and so is defined as a fall in Hb by 2g/dL or to less than 10g/dL or by a decrease in platelet count by more than 50% or to below 100,000 per cu mm, that occurs at least 3 months after treatment ends and associated with an infiltrate of clonal lymphoid cells in the marrow. Note, the guidelines say nothing about late neutropenia.
SD is anything between PR and PD.
The duration of a response is measured from the end of the last treatment, but, confusingly, progression-free survival is measured from the first day of treatment.
Trials that are designed to eradicate the CLL should include testing for minimal residual disease (MRD). Either 4-color flow cytometry or allele-specific oligonucleotide PCR should be used using a threshold of one cell in 10,000. It is permissible to use blood for this assay except within 3 months of completing therapy, especially when alemtuzumab, rituximab or other antibodies have been used, in which case, bone marrow should be used.
Although the new guidelines make sense, there are still some ambiguities and in places the application of common sense runs counter to the wording of the document.
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