Article Published in the Author Account of

Benjamin Yang

Book Summary: The Anatomy of Hope — How People Prevail in the Face of Illness

Abstract: In "The Anatomy of Hope," Dr. Jerome Groopman, Professor and Chairman of Department of Medicine, Harvard Medical School, tells extraordinary stories of hope in coping with conventionally hopeless diseases and suffering. Biologically, hope may stimulate the release of internal painkiller molecules.



Having completed his residency in Boston in 1978, Dr. Jerome Groopman moved to Los Angeles to begin a specialty fellowship in the study of blood diseases and cancer medicine at the University of California, Los Angeles (UCLA). With little money to help support the family he soon intended to start, Groopman supplemented his fellowship stipend by covering the practice of Dr. Richard Keyes, located in a rural town two hours north of Los Angeles. Based his practice in an area lacking other cancer specialists, Keyes hired young doctors to help with his practice and visit hospitalized patients during the weekends. When not on call at UCLA, Groopman would spend his weekends, working for Keyes.

It was here that Groopman first encountered the difficulty of balancing what he terms “false hope,” and “true hope.” On the one hand, Groopman recounts the story of a patient diagnosed with Stage D colon cancer, a patient for whom there was no realistic hope of survival. Yet, by keeping important facts about her prognosis and the likely outcome of available treatment options from that patient and her daughter, Groopman realized that he and Keyes had inadvertently seeded a false hope of recovery. Following her death, Groopman, by his own admission, allowed the pendulum to swing too far in the opposite direction. Rather than balancing probabilities with the chances of recovery and treatment alternatives, Groopman finds himself presenting his patients with stark statistical realities, only to realize that this could very easily cast a dark shadow of inevitability over a patient, rather than present an opportunity for rational hope of successful treatment.

Holding on to what he describes as the “ideology of the right to know” for some time, Groopman realized that he had taken the idea too far, and once again found himself offering only false hope to terminally ill patients. Somewhere lies the middle ground, upon which an understanding of the most likely outcomes is balanced by the opportunity to hope for a successful treatment, and the courage to endure the side effects that will be an inherent part of this treatment. Groopman was to see this middle ground when Richard Keyes was suddenly taken gravely ill.

In 1979, Keyes collapsed in his clinic and began to vomit bilious fluid (fluid derived from bile). Rushed to an emergency room, Keyes was admitted and soon diagnosed with cholangiocarcinoma, a condition from which there was little hope of survival. Originating in the cells of the bile duct, cholangiocarcinoma is a relatively rare form of cancer with a very poor prognosis, since cancer cells typically infiltrate the liver well before symptoms appear.

After Keyes had been transferred to UCLA for surgery, Groopman visited his friend and mentor, and saw immediately the despair and lack of hope in a man all too familiar with the graveness of his condition. Keyes was hesitant even to undergo surgery, ready to concede defeat without a fight, but did eventually do so at the hands of a surgeon by the name of Dr. Frank Andrews. It was during post-operative follow-up that Groopman would see first hand, how realistic hope could be seeded amidst such poor odds of survival.

Unable to find clear tumor margins, Andrews was concerned that he had left residual tumor cells within Keyes’s liver, where it would soon re-emerge, and Andrews wanted to pursue an aggressive course of post-operative radiation therapy. Groopman had already discussed this possibility with Keyes, who was dismissive of it instead focused upon the horrible side effects of irradiating the base of his liver, and deeply concerned about the well being of his wife after his inevitable death. Yet Andrews was somehow able to convince Keyes that radiation gave him a slim but very real chance of survival, while simultaneously advising Keyes that he should still plan for the worst. Andrews repeated his theme forcefully: that radiotherapy might not work, but that it could, and that it may at the very least buy Keyes precious time, and so Keyes was persuaded to undergo radiotherapy after all. He suffered greatly from the side effects of radiation, but ultimately his treatment proved successful, and Keyes emerged from the experience closer as a physician to the middle ground, where as Groopman puts it, both truth and hope can reside.

Several years later, another of Groopman’s colleagues would be diagnosed with cancer, and subsequently demonstrated the right to hope, even against all odds. George Griffin, Harvard Professor and highly respected Chairman of the Department of Pathology was diagnosed with stomach cancer, a disease to which he had devoted his life’s work.

Diagnosed with a classic case of undifferentiated carcinoma, Griffin knew all too well that he had developed the very worst form of stomach cancer. Griffin knew more of his disease, its prognosis, and his chances of survival than perhaps anyone else. Yet rather than needing to be persuaded to undergo treatment, it appeared to many that he needed exactly the opposite. Despite a six month survival rate of only 2-3%, and against all recommendations, Griffin insisted upon receiving high dose multi-agent chemotherapy in combination with intensive radiotherapy, even though there was no evidence to support such toxic therapy having any effect upon stomach cancers that were as advanced as his. Visiting Griffin, Groopman found his colleague apparently close to death in a hospital bed, having suffered a chemical burn upon the entire length of his alimentary canal as a result of the intensive chemotherapy.

It would be three weeks before Griffin would recover from his first round of chemotherapy and radiation, but shortly thereafter, Griffin was back in hospital scheduled for surgery. Surgery would be considered normal treatment for stomach cancer in cases where the tumor obstructed either the stomach or the esophagus. However, Griffin was not subject to such complications, and his decision to undergo surgery baffled and alarmed his clinical colleagues. Once again, his treatment seemed a futile attempt to avoid the inevitable, likely to result in yet more suffering for Griffin, and his wife, a fellow pathologist. Griffin’s surgery lasted several hours, and due to the spread of his primary tumor resulted in the removal of a large proportion of his stomach, the lower part of his esophagus, and a thick chain of enlarged lymph nodes. The latter would likely prove to be irrefutable evidence of the metastatic spread of Griffin’s primary tumor, but when examined by pathologists, there was no evidence of live cancer cells to be found.

Had Griffin’s cancer been cured after all, or was it hiding in distant sites, only to re-emerge and resume its relentless growth? Griffin was simply not prepared to wait, and in another decision that would both shock and sadden his colleagues, he was admitted to hospital to begin a second round of intensive chemotherapy and radiation, much the same as the first round that he had endured and barely survived, only weeks before. Once again, Groopman visited his desperately ill friend in hospital, and once again found himself questioning the wisdom of such aggressive treatment in the face of such appalling odds of success.

Thirteen years later, the two men met one another for lunch, and Griffin explained that despite virtually all his colleagues having written off his decision to undergo aggressive combination therapy as nothing more than madness, he believed that he had had the right to undergo it. He had been right to hope for a successful treatment regimen.

Clearly changed by the experience of two of his colleagues surviving their cancers, and after years of treating patients who died despite his best efforts, Groopman faced a new challenge that would require him to draw upon everything he had learned about hope.

Shortly before the Christmas of 1995, Groopman was confronted by the case of a man referred to as Dan Conrad, a Vietnam veteran now working as a construction worker. Conrad had been admitted to the ER after having breathing difficulties at work, and an X-ray showed a mass the size of a grapefruit pressing on his airways. A subsequent CAT scan (computerized axial tomography, whereby multiple X-ray images are combined to give a cross-sectional image) revealed worse news still, showing the mass to have extended down through his diaphragm into the abdominal cavity, where it had reached almost a foot in diameter. A biopsy identified the tumor as an aggressive non-Hodgkin’s lymphoma that would require immediate and dramatic treatment.

In much the same way as he had observed Frank Andrews do so with Richard Keyes, Groopman confronted Dan Conrad with the reality of his situation using what he describes as “purposeful determination,” and informed Conrad of his diagnosis. On the one hand, surgery was not an option for this type of tumor, especially in Conrad’s case where it had invaded his abdomen to such an extent. However, on the other hand, Groopman made it clear that although the tumor was an aggressive and fast growing one, this very fact made it highly sensitive to the chemotherapy and radiation treatments, since both work most effectively against rapidly dividing cells. Groopman explained that certain combinations of anticancer agents had proven to be both highly effective in fighting this type of lymphoma, and safe, and that if he was willing to try it, Conrad could be treated with a new experimental antibody treatment that held great promise.

But to Groopman’s profound disappointment, Conrad seemed totally unconvinced, showing a “chilling lack of spirit.” Despite repeated attempts to persuade him otherwise, Conrad had decided to refuse treatment altogether, unable to face its side effects, resigned to a fate that he saw as inevitable.

It would be several days before Groopman would come to understand Conrad’s decision to refuse treatment, during which time his condition steadily deteriorated, his breathing becoming increasingly labored. The answer was fear: fear that he would suffer the same way a fellow Vietnam veteran had suffered after his diagnosis. Conrad’s army friend had also been told by his doctors that he could be cured, but had suffered badly from the side effects of his chemotherapy, had contracted pneumonia, and had spent days in the intensive care unit, only to die after a week of relentless suffering. Dan Conrad had seen it all, and was terrified by the prospect of suffering the way his friend had.

Finally, with a clear understanding of what was driving Conrad’s fear, Groopman was able to convince him, not that he could be cured, but to proceed with his treatment one step at a time. The potential for a cure was there should Conrad decide to stay the entire course of treatment, but Groopman promised him that if he decided to do so, Conrad could choose to end his treatment at any point.

Ten weeks after going to the ER, Dan Conrad, a man previously convinced that he was to die from a lymphoma, left the hospital alive. Having received chemotherapy and radiation, and having undergone surgery to remove a bowel obstruction caused by his tumor, Conrad underwent a second round of chemotherapy, and did indeed elect to try the experimental antibody therapy. By the end of his treatment, the mass in Conrad’s chest had been reduced to a shadow on the X-rays, and the mass in his abdomen had been reduced to less than half its original size. He would continue his treatment as an outpatient, and considered cured if survival lasts ten years or more. Conrad is one of the first patients to receive the monoclonal antibody (then an investigational drug and now approved as Rituxan) therapy in combination with more conventional chemotherapy and radiation therapy.

Having recounted several tales of cancer patients confronting their disease, some of whom would win their battles, some of whom would not, a clear message emerges from Groopman’s text.

Not that hope is sufficient for recovery, and not that strong religious convictions will triumph over disease, rather that hope and belief in the possibility of a cure, can give patients the courage to endure the severe side effects and complications inherent to the aggressive treatments required to effect a cure. In Chapter 6, Groopman illustrates this point further in an interesting tale of his own battle, not with a life-threatening illness, but with a chronic back pain.

Shortly before moving from Boston to Los Angeles, Groopman ruptured a lumbar disc while training for the Boston marathon. Six months after surgery that at least partially resolved the problem, Groopman collapsed from an agonizing pain in his lower back. After seeing numerous specialists, an orthopedist recommended further surgery designed to fuse and thereby stabilize his spine, and told Groopman that he would be running within weeks. As he awoke from the surgery, Groopman once again found himself in excruciating pain, unable to move his legs. He would spend weeks essentially bed ridden, unable to control the pain, even with narcotics.

His problem was diagnosed to be caused by inflammation and scarring, and Groopman declined any further surgery and opted instead for physical therapy. Gradually, Groopman would learn ways in which to function on a day-to-day basis without triggering painful episodes of back spasms, and began to live his life within the limits now imposed upon his body. Then, after living like this for some nineteen years, he was persuaded to visit a licensed massage therapist. As he feared he would in doing so, Groopman had stepped beyond the “invisible fence” that he describes as having surrounded him, and spent several days incapacitated by severe muscle spasms.

After weeks of unrelenting pain, Groopman went to see Dr. James Rainville, a specialist in rehabilitation medicine at the New England Baptist Hospital, Boston and a man for whom the answer was clear. Having thoroughly examined Groopman, Rainville’s diagnosis was that Groopman had been “worshiping the volcano god of pain”, and that he could expect to make a full recovery. Astonished, Groopman was told that he must exercise more not less, and that he must push the boundaries of movement, and the pain associated with it further. Convinced that there was essentially nothing physically wrong with him, Rainville told Groopman that he must learn to ignore the pain. Only then could his muscles be steadily and increasingly challenged with exercise until they became re-educated, and relinquished their painful memories.

Rather than remaining confined by the increasingly limited boundaries imposed by pain, within which Groopman had learned to live over the preceding nineteen years, Groopman could rebuild his body, and return to a normal life. After the pain of his massage-induced back spasms, the very thought of more vigorous exercise terrified Groopman, but Rainville succeeded in igniting the desire to fight and the hope of success. Much as he had advised Dan Conrad to do, Groopman went step-by-step, beginning with several weeks of gentle stretching before enrolling in a more vigorous exercise program in Rainville’s classroom. Sure enough, each exercise session resulted in severe pain, but over the course of several months, the constant pain became first intermittent, and then rare. Groopman had exited his labyrinth of pain.

Having recovered from his spinal injury, Groopman began to investigate what was known about the biology of hope, i.e., the biological mechanisms whereby hope can contribute to recovery. In the first of many examples presented in Chapter 7, Groopman describes studies in which researchers have examined the reaction of placebo-treated volunteer patients subjected to painful stimuli.

In what are regarded as classical studies, Dr. Fabrizio Benedetti at the Department of Neurosciences, University of Turin in Italy, studied the reaction of volunteers to pain, inflicted upon them using an inflatable compression cuff placed around the arm, that was designed to quickly cut off the circulation. Wired to monitors that recorded physiological changes in response to painful stimuli, the volunteer is subjected to compression of the cuff, and increases in heart rate, sweating, blood pressure and muscle contraction are recorded. Prior to another pain stimulus, the volunteer is given an injection of morphine, and as expected, a volunteer pre-treated with morphine feels no pain, and shows no reaction. However, after being subjected to this sequence several times over, the volunteer unwittingly receives not morphine, but an injection of nothing more than saline. Yet upon compression of the cuff, the now placebo-treated volunteer has no reaction to the painful stimulus, and reports no feeling of pain.

Benedetti’s explanation of this remarkable phenomenon is that the volunteer’s belief that he or she is receiving another dose of a potent painkiller, and the expectation that it will prevent any pain, stimulates the release of endorphins and enkephalins, the body’s own endogenous painkillers. Other substances within the central nervous system such as Substance P and cholecystokinin, have the opposite effect, in that they can amplify pain responses. It is believed that expectation and belief can interfere with the release of these substances, in particular cholecystokinin, and thereby enhance the effects of analgesic medications, and endogenous endorphins and enkephalins.

In a still more remarkable example of how belief and expectation, and the desire to recover can influence clinical outcomes, Groopman goes on to describe the results of a study published in the New England Journal of Medicine in July 2002. Researchers at the Baylor College of Medicine in Houston, Texas studied the level of pain relief required to increase limb function in 180 patients suffering from arthritic knees. Half of these patients underwent arthroscopic knee surgery either lavage (the flushing out of toxins etc.) or debridement (removal of necrotic or infected material from a wound), and half of them underwent only a “sham” placebo surgery. The latter patients were prepared for surgery in the same way as their cohorts, and spent the same amount of time in the operating theater, during which time they received surgery that involved little more than minor incisions around the knee together with saline lavage. All patients received the same post-operative care, and all were cared for by nurses “blinded” to the type of surgery performed. Amazingly, equal benefits were observed among patients undergoing sham surgery when they were compared with those who had actually undergone arthroscopic surgery.

Groopman elaborates upon these themes with a number of interesting examples of how hope, desire and expectation can have such palpable influences upon biological processes in the remainder of Chapter 7.

In conclusion, a book that some, who pay too much attention to its references to religious beliefs and convictions, might so easily dismiss simply as a text about “mind over matter,” proves instead to be a compelling story, and a highly rewarding and enlightening read. Individuals who have found themselves questioning how they might react to the diagnosis of a life-threatening disease and who are facing one now should read this book.

[Discovery Medicine, 4(23):351-355, 2004]

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