From the Publisher.
My Pick for Summer Beach ReadingThis isn't a new book. Cutting for Stone by Abraham Verghese was published in 2009 and immediately was a best seller. I just read it this year and the story immediately hooked me. This is a story of doctors, surgeons, trained in India or England in the 1940s, but transplanted to a mission hospital dependent on charitable donations in post-colonial Ethiopia. As one might imagine the facilities are marginal, but the attending doctors are quite resourceful and their attention to patients who travel many miles for care is dedicated and compassionate. But this is a novel, not a documentary, and we are swept up not only by the local color and life in an impoverished country, but also the philosophic and romantic activities of the doctors when they are not in clinic or surgery. The story of a surgeon and a nurse's twin children and their family and household help and living in a house at the Missing Hospital compound is so compelling that it is difficult to stop reading.
This is Abraham Verghese's first novel but not his first book or writing. He is a professor of medicine at Stanford University Medical School. Verghese's prose is the type of writing that is so fluid and descriptive that you feel you are right there in a missionary hospital in the 1950s. It is extraordinary that a doctor could do such an outstanding job in researching the history, geography, and the anthropology of the horn of Africa and India, and be able to craft a story that so cleverly incorporates general surgery and its advances by its protagonists. And the plot works so well, including a very fitting and conclusive ending that does not fail to satisfy. It is not often that I read a novel that delivers at every level.
Is it the Seed or the Soil?
In Lake Michigan an odd phenomenon has been noticed over the past few decades. Barnacle-like shell growths have encrusted the keel, turbine and propeller of vessels, piers, sanitation systems, and waterway navigation channels where there had been no encrusting in previous decades. The culprit: Two mussels, Dreissena polymorpha and Dreissena bugenis, the zebra mussel and quagga mussel. (1) The mussels have propagated so densely that on certain beaches one walks not on sand but upon a solid layer of shells. The density of mussels has been increasing dramatically, increasing 50% in the past 10 years. Oddly this increased concentration of mussels has created a swimming pool-like clarity in the water because of a decrease in fish and other organisms.
The foremost question is what accounts for the mussels' uncontrolled growth? The usual ecology answer is lack of a predator. Both Dreissena mussels originate in the waters in or near the Ukraine. The Dnieper River has been home for the mussels for centuries, yet the mussel population is stable and very low compared to Lake Michigan. There is no dramatic encrusting of vessels, docks, and beaches on the Dnieper or its tributaries. Why not? One cannot identify a specific organism or organisms that are a mussel predator. But from an ecologic viewpoint, the zebra and quagga mussels are not predatory in the Dnieper, sharing its environment or terrain equally with the local flora and fauna. In contrast, there is a distinct difference in the terrain of Lake Michigan, and that difference, not only in flora and fauna but also the water's chemistry, has enabled the mussel population to explode and to continue to do so. In other words, it is not the organism itself, alone, that makes it predatory or pathologic, but it is the environment or terrain that enables the transition from benign to aggressive. (1)
How does the Lake Michigan exploding mussel population bear any concern to human medicine? In the September 11, 2017 issue of The New Yorker, physician and Pulitzer Prize winning author, Siddhartha Mukherjee, MD, writes that the dilemma we face in treating the cancer patient may be very similar to why the quagga mussel is out of control in Lake Michigan but of no concern in the Dnieper. (1) When a woman develops breast cancer, the usual process is to proceed with a lumpectomy, then offer chemotherapy, radiation, and perhaps other therapies. The assumption is that breast cancer metastasis can be stopped with these measures; and although it may be overkill, both the patient and the oncologist can feel assured that all has been done in the cancer's earlier stages.
But what makes the tumor cell metastasize? In 1889 a British doctor, Stephen Paget, who was son of famed pathologist, James Paget, studied the chart files of 735 women who died from breast cancer. More than 300 of the women had well-defined metastases; 241 were found in the liver, 70 in the lung, and 17 in the spleen. Why does breast cancer metastasize more frequently to certain organs and not others? Paget conjectured that even when breast cancer metastasizes to bone, why aren't all bones subject to metastasis? He stated that one never hears of a metastasis to the hand or foot. Paget was making the argument that breast cancer metastasis may depend on how the tumor cell responds and interacts with distant organ tissues. But medicine largely ignored this question for one hundred years. Siddhartha brings up a medical student mnemonic, "Bacon Lettuce Tomato with Kosher Pickle," which is used to remember that the tumors that invade bone are breast, lung, thyroid, kidney, and prostate. Why do these tumors have a predilection for metastasizing to bone but other tumors don't? Is it dependent on the tumor cell's interaction with the organ's microenvironment? Tumor cells are genetically programmed to metastasize and proliferate; yet some do and some don't. Why?
Siddhartha discusses the intriguing work of cancer researcher Joan Massague. In 2001 Massague read a report published in the 1970s from the NIH about a mouse's ovarian pedicle implanted with breast cancer cells forming a small tumor. When the tumor's vein was cannulated, thousands of cancer cells were observed to be emanating from the tumor minute by minute without cessation. Further studies confirmed the natural vascular output of cancer cells from a proliferating tumor. In other words, tumors produce vast quantities of circulating cancer cells but they mostly fail to metastasize. Why? Massague explained that despite the output of cancer cells there must be a great degree of cell death or cell dormancy, "sleeper" cells. He contends that the majority of cells die and when they do succeed in reaching an organ, the cells face a hostile terrain that will cause them to die leaving only a few surviving cells. The metastasis requires that those surviving cells awaken from their dormancy and multiply in conditions that enable tumor cell growth--tumor cell and tissue terrain compatibility. But what provides the right conditions in the terrain?
For Johns Hopkins oncologist Kenneth Pienta, MD, the Lake Michigan quagga scenario is a perfect comparison to a cancer patient who is experiencing ongoing metastasis. Rather than think that metastasis is based on the pathogenicity of the particular tumor cell, one should think about the terrain instead. What is it about the organ tissue that permits the tumor cell to succeed in its tissue growth? When the cancer cell arrives in its new environment, that organ's microenvironment changes to a milieu conducive for the tumor cell's progressive growth. Pienta explains that we should think not about what the tumor cell is doing to us, but what we are doing to the tumor cell.
But that brings up the awkward and messy issue of ecology - what factors in the terrain enable the quagga mussel or the tumor cell to grow? "Invasion" ecologists, like Anthony Ricciardi, PhD, at McGill University, talk about changes in Lake Michigan's water temperature, salinity, calcium content, and lack of predators (such as fish and ducks), to account for the mussels explosive growth. Ecology studies are difficult and each factor affects the next one, including "nutrition, predation, climate, and topography subject to feedback loops." The 14th century theologian and philosopher, William of Ockham, is famous for his law of parsimony known as Occam's Razor. As a problem-solving technique, Occam's Razor considers the hypothesis with the least number of explanations to have the highest likelihood of being truthful. Occam's Razor frequently is used in science and medicine to explain phenomena and make a diagnosis. But ecological hypotheses are often complex and contextual and multi-equationed and do not work well with Occam's Razor. Such is the case with the quaggas and metastatic tumor cells.
Mina Bissell's work in the 1980s is well known to cancer researchers and also argues for the terrain connection. For many decades it has been known that one could inject a virus into a chick's wing and a tumor would grow within the wing. Bissell demonstrated that if you injured the chick's other wing, a tumor would also grow in that wing, which has not been injected with virus. The strange thing was that if the virus was injected while the chick was only an embryo, no tumor would appear. A different environment determines the tumor cell's existence.
David Adams, PhD, an Australian physiologist and geneticist, tells the story of how his father had a spontaneous regression of melanoma in 1992. The tumor appeared as a lengthy black streak and then within weeks involuted, turning grey, and disappeared never to recur. Years later he died of prostate cancer. What circumstances in the body would make one tumor disappear and another metastasize? Adams, in Siddhartha's New Yorker article, discusses an interesting series of melanoma cases involving donated kidneys. (1) In the typical case, a patient is diagnosed with melanoma and treated achieving full remission and no recurrence. That melanoma patient is accepted as a kidney donor years later. Following transplantation, despite being given the typical immunosuppressive therapies, the recipient's kidney rapidly develops multiple black lesions typical of melanoma. The donated kidney is, of course, removed. Of note, the donor remains perfectly healthy with no sign of melanoma. It was the placement of the donated kidney into a new environment, within the patient having chronic kidney disease, which enabled the dormant melanoma cells to metastasize, never having proliferated in the donor's body. Same tumor cells, different terrain!
This work intrigued Adams, and he wanted to explore how the terrain could make a difference in how tumor cells proliferate. Near where Adams now works in England was a research facility that genetically modified mouse strains to determine their physiologic effects on the heart, brain, and other organs. Adams wanted to use these animals for cancer research in a different fashion than had been standardized. For years biologists have been injecting a variety of tumor cell lines into one modified mouse strain to determine whether the tumor would grow and metastasize with certain genetic modifications. Adams wanted to see what would happen if he injected one tumor cell line into a variety of genetically modified mice to see which developed tumors and developed metastases. In other words, instead of testing the tumor cell line's pathogenicity, Adam's wanted to understand how the tumor cell line faired in different environments, different terrains: tumor cell and terrain interaction.
In 2013 Adam's colleague and wife, Louise van der Weyden, PhD, injected mouse melanoma cells into 24 different mouse strains. After a few weeks she studied the mice for metastases in the lungs. The results were startling; there were great differences between the mice that developed metastases. Van der Weyden details that some mice had hundreds of pinprick size metastases, others had fully blackened lungs. In others there were relatively few lesions.
Adams and van der Weyden continued their work and reported in 2015 that after 810 mouse strains were injected with melanoma, many developed metastases. But 15 strains were moderately resistant. They were able to find gene variations in 12 of the 15 strains that were known to impact immunological resistance. One strain was particularly remarkable with hardly any lung metastases developing even after two months. Adams and van der Weyden then tested this highly resistant mouse strain with breast, lung, and colon cancer injections known to generally metastasize in average mice. Again that mouse strain did not develop metastases for each of the tumor types. It was determined that this mouse strain had a gene variant, Spns2, that enables production of natural killer (INK) immune cells. This was the same gene variant that Massague determined resisted metastases.
In 1962 a British cancer researcher, D.W. Smithers, MD, wrote, "cancer is no more a disease of cells than a traffic jam is a disease of cars." The cars themselves do not cause the traffic jam--it is a myriad of road conditions including weather, traffic lights, number of cars, and car accidents that lead to the jam. Similarly, the cancer cells themselves do not cause cancer metastases. The cells require a cooperative terrain to metastasize. Which leads us, unfortunately, back to Occam's Razor: how do we sort out what factors in the terrain's ecology determine whether the quagga mussels will explode or cancer cells metastasize?
Diet and Risk of Prostate Cancer Recurrence by Jacob Schor, ND
In medical school more than 40 years ago, we were taught that nearly 80% of men who lived to age 80 would acquire prostate cancer but a majority would die of cardiovascular disease or another cause. It is much the same today with more than 90% being diagnosed with localized disease, yet more than 25,000 die because of prostate cancer each year in the US. For many patients with localized disease a recommendation of "watch and wait" is the opted course of action. But would it be prudent for those patients to modify their diet or use supplementation?
Many nutritionists advise cancer patients to avoid red meat. However, as Schor details in his paper in this issue, research reveals that instead of beef, the big concern should focus on poultry and eggs, as their consumption nearly doubled the risk of prostate cancer progression. Additional dietary recommendations that help in preventing cancer relapse include limitation of drinking whole milk, as well as the eating of refined grains, sugars, and high-fat dairy. Studies have also confirmed the benefit of increasing vegetable intake and consuming vegetable fats and less saturated fats. As with most cancers, increased exercise, weight management, and smoking cessation are beneficial. As for supplements it is advised that genetic testing may be in order before recommending vitamin E, selenium, and lycopene.
How to Approach the Cancer Patient by Prof. Serge Jurasunas
While the prognosis for localized cancer is excellent, the same is not true for metastatic disease. The conventional treatment of surgery, chemotherapy, and radiation treatment has a long track record of dismal outcomes for advanced cancer. The recent addition of specialized biological response modifiers (BRM) has offered some hope for prolonging survival but has not turned around the awful odds for cancer that has spread. Jurasunas argues that all patients should avail themselves of a "new paradigm of cancer" that employs informative diagnostic testing to understand tumor functioning as well as nutritional interventions capable of modifying immune and metabolic activity. Restoring mitochondrial functioning and cellular respiration are critical for cancer care.
Jurasunas includes numerous markers to understand cancer activity including P53 gene function. He notes that when the P53 gene is mutated or misfolded it is incapable of expressing anti-tumor activity. Among nutritional supports helpful in restoring normal P53 functioning are rice bran arabinoxylan compound (RBAC), curcumin, enzyme yeast cell preparation, fish peptides, Horvi-enzyme therapy, probiotics, resveratrol, and EGCG.
Jurasunas strongly advocates that cancer patients receive emotional and psychological support without which their cancer protocol may fail.
Cover Story: Cancer Care--Conventional, Complementary, Alternative? by Barbara MacDonald, ND
We all have patients who believe religiously in natural medicine employing naturopathy, food, meditation, prayer, exercise, and other natural supports to maintain their health and their family's health. Of course, much of their ill health is manageable without allopathic medical intervention. But what about when they are diagnosed with cancer? Unlike many patients who are newly diagnosed with cancer, these individuals shun conventional chemotherapy, radiation, and surgery. Many want to opt for a "natural" medicine approach for their cancer much like they have done all their lives. Is this the wisest course of action?
Barbara MacDonald, ND, a naturopathic physician who has specialized in naturopathic oncology care and is the author of The Breast Cancer Companion: A Complementary Care Manual (2016), thinks not. She cites a recent Yale University School of Medicine study comparing those patients who combined conventional and alternative care to those who had only unconventional care, 78% of the former group survived five years compared to only 55% in the latter group. (2) MacDonald proposes that those who are thinking of only employing alternative approaches seriously consider integrating conventional care. Timing is everything--surgery is frequently only available when the disease has not metastasized.
Timing is also vital when undergoing chemotherapy and radiation treatment. Misguided advice by oncologists that naturopathic care will interfere with chemotherapy has led some patients to postpone herbal and nutraceutical supplementation when botanicals and intravenous vitamin C would mitigate adverse effects and maximize chemotherapy benefits. Integrative cancer care, particularly under the direction of an experienced practitioner, offers a better outcome than conventional care alone.
Jonathan Collin, MD
(1.) Mukherjee S. The invasion equation: Will a tumor spread? That may depend as much on your body as on your cancer. The New Yorker. Sept. 11, 2017.
(2.) Johnson SB, Park HS, Gross CP, Yu JB. Use of alternative medicine for cancer and its impact on survival. JNCI. Published online Aug. 10, 2017.
 Printer friendly
 Cite/link
 Email
 Feedback
| |
| Author: | Collin, Jonathan |
|---|---|
| Publication: | Townsend Letter |
| Date: | Aug 1, 2018 |
| Words: | 2938 |
| Previous Article: | Glutamine and Sickle Cell Disease: Another Example of Why Healthcare Is So Expensive. |
| Next Article: | A New Perspective on Prevention of Viral-Induced Cancers. |
| Topics: | |