Barriers will not stop convergence of medical technologies

15 May Barriers will not stop convergence of medical technologies

When a patient presents to a doctor, many assessments have to be made leading to complex “decision trees” throughout the process of what is unglamorously called “managing the patient.”
During residency, which is not the free-for-all carnival that “Gray’s Anatomy” would have us believe, one of the most important judgment calls that is learned is whether the patient is “sick” or not. This is not in the sense that the patient is faking illness but rather the concept that young doctors gradually learn from experience, whether a patient is on the uptrend or downtrend towards recovery.
“Mrs. Jones spiked a fever last night, her foot is not looking that good. She looks sick. I think we need to send her to the ICU.”
“Billie was brought to the ER last night by his mom. He fell from his crib, was doing fine but this morning, but seems irritable. We need a CT scan of his head.”
One of the most important of such decisions is whether a disease is of a surgical or a medical nature. A surgical disease is one that requires some form of intervention such as, of course, surgery (although various vascular interventions and radiation techniques would also fall in this category), while a medical condition implies a pharmaceutical approach to treatment.
Conditional therapy
Many diseases have both medical and surgical manifestations. An infection, for example, might involve antibiotics (a medical approach). An infected abscess, however, would require a surgical approach to drain it and reduce the body’s infectious load. A dislocated shoulder typically requires an intervention (not necessarily surgical but at least some form of manual manipulation), as it is highly unlikely that taking a pill will do the trick.
Cancer is another condition that is treated either surgically or medically (or both). Earlier (or more localized) tumors are often excised surgically, while more advanced disease undergoes chemotherapy. And in many cases, the increasing realization that even localized disease can often harbor cancer stem cells throughout the body means that surgery is not uncommonly combined with more generalized medical therapies.
Some conditions – such as back pain – can have either surgical or medical treatment options in which it is not definitively clear which approach is necessarily better. This concept was addressed in my column earlier this year reporting on the pivotal spine patient outcomes research trial (SPORT), where I concluded that patient choice was probably more important a factor in the selection of treatment modality than necessarily any hard evidence-based scientific criteria.
And there are some diseases which have been historically surgical and which are now medical and vice-versa. Some may be surprised to learn that tuberculosis was once treated by excising diseased lung tissue surgically. TB is now, of course, pretty much a medical disease. Before the advent of heart transplantation and other such circulatory support (such as left-ventricular assist devices), heart failure was mostly a medically treated disease.
So, what are the factors that make a disease surgical vs. medical?
In general, a surgical disease is one which has the following characteristics:
• Local in extent.
• Requiring rapid treatment.
• Has a surgical intervention with a sufficiently favorable risk-benefit balance.
These are not hard-and-fast rules as there are certainly medical diseases such as asthma that are local (e.g. affecting the bronchi in the lungs) and in which a medicine (such as an inhaled beta-2 agonist) is rapidly effective. Nonetheless, these basic criteria help to explain how doctors make that all-important decision on whether to send the patient to the OR or manage them medically.
Is diabetes a medical or a surgical disease?
Nearly everyone will correctly identify diabetes as a medical disease caused by a relative lack of insulin in these patients. The paucity (and in some cases complete lack) of insulin has many effects. The most important is an increase in blood sugar which results from the fact that liver and muscle cells, which normally under the influence of insulin take up glucose, don’t do so. It is predominantly the high blood glucose levels that lead to a diverse range of dangerous (and even potentially fatal) complications.
The discovery of insulin by Banting and Best in 1921 and the development of replacement insulin therapy soon thereafter has been one of the greatest achievements of modern medicine. It earned Banting and Best the Nobel Prize and, more importantly, has saved and prolonged countless millions of lives throughout the world. By virtue of careful glucose checks and subcutaneous insulin injections, generations of diabetics have been able to lead relatively normal lives although admittedly encumbered somewhat by their daily injection regimens.
Despite this great accomplishment, the disease is by no means conquered. Due to lifestyle changes (some would say the clash of Neolithic genes with modern Western culture), the U.S. and indeed the entire world is experiencing an epidemic of diabetes. And while blood glucose levels can be controlled by insulin, the inexorable pace of complications still leads to very high levels of morbidity and mortality among these patients.
So with the miracle cure of injected insulin in hand, how can this still remain a problem?
Gray’s area
Clearly the systemically administered medical treatment, effective as it is, doesn’t fully address the problem. In this regard, a little Gray’s Anatomy (of the real kind) is in order.
The blood supply to and from most tissues in the body follows a relatively simple formula. Oxygen-rich arterial blood from the heart enters these organs which then drain into veins that lead back to the heart. The pancreas, which is the organ that secretes insulin in response to glucose levels, doesn’t actually follow this simple paradigm. Blood flowing to the pancreas does, indeed, come from the heart but the blood (now supplemented with insulin) leaving the pancreas actually enters a special vein called the portal vein. Instead of leading directly back to the heart, the portal vein flows through the liver as an intermediary on its way back to the heart.
As with the pancreas, the blood from the intestines (glucose rich after a meal) also enters the portal vein and likewise flows through the liver. The liver is the major organ for glucose storage and metabolism and more importantly this close anatomic/physiologic confluence of the glucose load with the glucose regulator insulin means that for a non-diabetic person, glucose control is much more precisely controlled. This is not just a physiological mechanism but a result of very specific anatomic relationships.
In the case of a diabetic patient whose subcutaneously injected insulin essentially enters the peripheral venous circulation, then taking a tour through the heart and then around the systemic arterial circulation before reaching the liver, the anatomic dissociation between glucose load and glucose control is readily apparent. For a diabetic patient to achieve normal glucose levels, the distribution of insulin throughout the tissues is may very well be quite different from that of a non-diabetic whose insulin comes from the pancreas. This may imply (though not proven) that for diabetics some tissues could be essentially over-medicated with insulin while others relatively under-medicated.
I should stress that these are purely conjectural statements. While based on well-known principles of pancreatic anatomy and physiology, they are not necessarily scientifically proven, nor should they be considered as a basis for modifying any particular patient’s treatment. In addition, this discussion pertains to insulin-dependent diabetes and important measures such as diet and exercise, which are critical for all diabetics, including those with non-insulin dependent diabetes.
The point, however, is that a surgical (namely, a more anatomically localized) approach to diabetes may be necessary to achieve to improve current treatment. Islet-cell transplantation in which functioning beta cells are transplanted into the pancreas (and presumably in proper anatomic position as well) hence represents not just a fancy insulin replacement regimen but also a direct cure for the disease. It would be my view that resources should be even more aggressively applied towards this line of attack.
Implantable, electronically controlled insulin pumps are also gaining ground as part of the treatment armamentarium. Current incarnations of these devices serve an important function in improving the quality of life for these patients (e.g. not having to do multiple, daily self-injections) yet still administer their insulin outside the pancreatic-portal axis. While enormously more convenient, smart insulin pumps – however intelligent they may be – will likely not represent a definitive treatment.
Their own devices
In the future, further minimally invasive techniques may make it possible to have such devices placed within the portal vein measuring both post-intestinal glucose levels as well as injecting the insulin directly into that flow. In this way, such a pump could truly be called an artificial pancreas.
Another, more space-age possibility may be for a device to be implanted in the portal vein which can convert an otherwise inactive, systemically administered insulin into its active form.
Like anything, breakthroughs in technology will not be the only factor bringing these advances to the bedside (or more accurately inside the patient). The surgery/medicine divide is not just a scientific/technical issue but also reflective of significant cultural differences among specialties. The official name of my medical school alma mater – the Columbia University College of Physicians and Surgeons – exemplifies this traditional dichotomy between medicine and surgery.
The Food and Drug Administration also is structured along these lines. For example, the Center for Drug Evaluation and Research (CDER) is a completely different organization from the Center for Devices and Radiological Health (CDRH). It is not surprising that the regulatory pathways for drugs (e.g. medicine) are quite different than those for devices (e.g. surgery).
Convergent (or combination) medical technologies will indeed require a closer interplay between these two very different ways of approaching the patient. Despite the technical and cultural challenges, we have seen and will continue to see more of such convergence – whether it is for cancer or even diabetes. Traditions may be at risk but ultimately it’ll be patients who benefit.
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