"Dying Words"

Excellent piece from the New Yorker. The author really captures the pain and slight melancholy of oncology...and it reflects on our excellent clinical training at UCSF which has focused on death and dying for the past two weeks.

A speaker pointed out that we are currently learning about reproduction and palliative care simultaneously...eros and thanatos as we learned in English...sex and death always seem to go hand-in-hand.


Full Text :COPYRIGHT 2002 All rights reserved. Reproduced by permission of The Condé Nast Publications Inc.

Not long ago, I had an appointment with a patient who was likely to die within a year and a half. Maxine Barlow was a twenty-eight-year-old teacher in Boston. The only child of a middle-class family, she had recently become engaged to a financial analyst, Peter Wayland (all names have been changed). One morning in the shower, Maxine found a small lump in her breast, a little larger than a pea. A biopsy showed that it was breast cancer. Further tests revealed that the cancer had spread to Maxine's spine and liver, which meant that surgery could not fully remove it, and Maxine's surgeon referred her to me for chemotherapy.

Maxine and I met on a brisk autumn afternoon. Her appointment was my last of the day, since our conversation was likely to extend beyond the hour usually allotted to new patients. I had to explain the gravity of her condition and the possible choices she could make.
After I had examined Maxine, we were joined in my office by her parents and by Peter. They sat in a semicircle facing me, with Maxine between them. I moved my chair out from behind my desk.

"Let's review what was found at surgery," I began. Maxine reached for Peter's hand. Although I addressed Maxine, I also briefly met the gaze of her parents and of Peter, in order to engage everyone. "The cancer in the breast measured one and a half centimetres, about half an inch, and under the microscope the cancer cells were actively dividing," I said. "They should be treated aggressively. The tests we did on the tumor showed that it is not sensitive to hormones"--which ruled out Tamoxifen, a common hormone-blocker. "The scan showed that several deposits of tumor had spread from the breast to the bones in the neck. There also are four deposits in the liver. We can treat them with chemotherapy, which destroys the cancer cells wherever they might be lurking. The good news is that you stand a very strong chance of going into remission."

"So that means that she'll be O.K.?" Maxine's mother asked.

My stomach tightened in a familiar way. This part never got any easier.

"Remission does not mean cure," I said. "Remission means that all the cancer we can measure disappears. Therapy is palliative."

"What do you mean, 'palliative'?" Peter asked in a panicked voice.

"She has to be cured," Maxine's father said.

This distinction was important, and I needed to make sure, gently but unequivocally, that they understood. "There is a very good chance that we will see the metastatic deposits in your bones and liver shrink significantly, or completely melt away. But the most intensive chemotherapy or radiation available--even bone-marrow transplant--is not enough to destroy every cancer cell in your body. That is why, currently, we cannot say the cancer can be cured."
Maxine sat without speaking. Her eyes filled with tears, and I gave her some tissues.

"What is the point of treatment, then?" I asked. "Palliation. That means that even if the cancer cannot be cured it can be controlled. The best-case scenario is that the cancer becomes like a parasite," I said, purposefully invoking a stark image. "We knock it down with the therapy, and hope that it stays down for many, many months or years. You can live an active life--work, jog, travel, whatever. The bones and liver can heal. And when the cancer returns we work to knock it down again. All the while, we hold on to the hope that an experimental treatment will be found that is able to eradicate the cancer--to truly cure you."

Like Maxine, Mrs. Barlow was fighting back tears. Her husband stared at me. I paused before broaching a second critical issue.

"We talked about the best-case scenario. But we also have to acknowledge that there is a worst-case scenario."

I had found that this part of the discussion was best completed rapidly, as if removing an adhesive bandage.

"The worst-case scenario is that ultimately the cancer becomes resistant to all the treatments we have, and even experimental therapies are no use. Most people say that if they reach a point in the illness when their brain is impaired, and there is no likelihood of improving their quality of life, then nothing should be done to keep them artificially alive, through machines like respirators. It's essential, Maxine, that I know what you want done if we reach that point."

"I--I don't think I would want that," she said, haltingly.

"You mean that you would want only comfort measures to alleviate pain, and nothing done to prolong your life, like a respirator or cardiac resuscitation?"

"Yes, I think so," Maxine whispered.

I nodded. This was her "end-of-life directive." I would put it in writing in her medical chart.
"We have a plan of therapy and an understanding. Now let's look on the positive side," I said, trying to spark some of the determination she would need in order to endure the months of chemotherapy ahead. "You are young, your organ function is excellent--despite the deposits of tumor, your liver is still working well, and your blood counts are fine--so there is every reason to think that you will tolerate the drugs and we will make real progress."

I smiled confidently. Maxine struggled to do the same.

"But what are the exact odds for a remission?" Peter Wayland asked. "I mean, how many patients like Maxie stay in remission and for how long, on average?"

Maxine looked at him sharply. "Dr. Groopman said that there is every reason to think I'll go into remission," she said. "What more do we need to know now?"

She turned to me, her face full of uncertainty.

This was a crucial moment in our interview. There were several ways that I could answer Peter's question. I could give the bald statistics--that more than fifty per cent of people with cancer like Maxine's die within two years--or I could put it more gently, and say that she had a chance, if a low one, of surviving for more than two years. I could even say, somewhat vaguely, that she was young and strong and had as good a chance as anyone of surviving, on the principle that she would benefit more from encouragement than from statistics. As I looked at Maxine, I sensed that she preferred neither the extreme of ignorance nor the extreme of excruciating detail but some middle ground.

"Statistics don't say anything about any particular individual, only about groups," I said. "There can be wide variability in the behavior of any cancer in each person, because each of us is different--different genetically, living in a different environment--and we metabolize the treatments differently.

"I want my patients to be informed," I said, looking now at Peter. "When Maxine said she understood there is a very good chance of remission, that is accurate. It could last months or it could last years. Putting precise numbers on it at this point doesn't really tell us anything more about Maxine. In the meantime, we need to plan for the best while acknowledging the worst."
Oncologists give bad news to patients some thirty-five times per month on average, telling a patient that he has cancer, that his tumor has come back, that his treatment has failed, that no further treatment would be helpful. And yet there is no agreement among specialists about how to deliver such news. More than forty per cent of oncologists withhold a prognosis from a patient if he or she does not ask for it or if the family requests that the patient not be told. A similar number speak in euphemisms, skirting the truth. Today, in most of Europe doctors often do not tell patients that they are dying.

Until recently, many doctors rarely informed their patients that there was nothing to be done for them; conventional wisdom had it that patients ought to be spared the anguish of knowing that they were going to die. The renowned physician Sir William Osler, who, at the turn of the last century, wrote the seminal textbook "The Principles and Practice of Medicine," emphasized the importance of keeping the patient optimistic. "It wasn't the style to be specific," Dr. David Golde, a former physician-in-chief at Memorial Sloan-Kettering Cancer Center, said of his medical training, which began in 1962. "The patient's questions and the doctor's answers--both avoided detail. And doctors never volunteered to give more information. Of course, there were no formalized end-of-life directives. The doctor's duty to ease the path was unspoken." When I asked him what he meant by not being specific, he said, "The doctor would say, 'Yes, you have a serious disease.' "

In 1969, a book called "On Death and Dying," by Elisabeth Kubler-Ross, which later became a best-seller, made death an acceptable subject for discussion between patients and doctors for the first time. In the nineteen-eighties, cultural and political changes in America--some precipitated by AIDS--introduced the notion that a patient had a right to know everything his doctor knew. In 1993, Sherwin Nuland's book "How We Die," which won the National Book Award, described in detail the psychology and physiology of death.

As medical practice grows more sophisticated more people are living longer with the knowledge that they may be dying. Decisions made in the late stages of illness are increasingly an aspect of treatment. Dying requires emotional and physical stamina from the individual and his family. And the difficulty of negotiating all this has an effect on doctors as well as patients. A recent article reported that more than half of the oncologists interviewed say that the frequent witnessing of death leads to an overwhelming sense of fatigue and futility; the profession has one of the highest burnout rates in medicine.

Despite this, during my nine years of medical school and professional training in the nineteen-seventies, I was never instructed in how to speak about dying to a gravely ill patient and the patient's family. It was presumed that, as medical students, we learned how to deliver bad news through careful observation of our mentors, just as we learned how to lance a deep abscess by watching doctors and then trying it ourselves. But most physicians preferred to speak to their patients in private. And the subject was never raised in our classrooms.

As an oncology fellow, I began my career believing that it was essential to provide details to my patients. Sharing statistics seemed like the obvious thing to do: surely a patient should have access to everything I knew. Early on, I had a case somewhat similar to Maxine's. Claire Allen was a small, straw-haired librarian in her forties with breast cancer; she was married, with two young children. Like Maxine, she had multiple metastases to bone and liver. We met in my clinic office, and she looked at me expectantly.

"Claire, with this disease, a remission would ordinarily last three to six months," I told her bluntly. "A person could expect to survive between one to two years."

She appeared to take the news stalwartly, but I later learned from her husband that she had left the appointment deeply shaken. She told her children that she had only one Christmas left. Her face was full of despair whenever I saw her. And yet Claire lived for nearly four years. She was able to travel, work part time, and take care of her children, but was unable to stop thinking that she could die at any moment.

Chastened, I tried a different approach. Henry Gold, a short-order cook in his sixties, had acute leukemia that had resisted all treatment. At one point, he asked me what else could be done. I reassured him that there were drugs that had not yet been tried, even though I knew they were unlikely to help. When Henry started to bleed around his lungs, I had the interns drain the hemorrhage with chest tubes; I insisted that he be intubated, supported on a respirator in the I.C.U., and given numerous blood transfusions. His heart developed a dangerous arrhythmia, so I gave orders for cardiac medications and electroshock. I never asked Henry what he wanted. He stayed alive for more than a week on the respirator, a catheter in his heart, tubes in his throat, unable to speak to family and friends who had come to his bedside.

On a chilly morning two days after our first meeting, Maxine returned to the clinic for her first round of chemotherapy. She had insisted on coming alone; Peter would pick her up afterward. The chemotherapy suite is a large, open space that holds twenty or so patients receiving intravenous drugs, some behind curtains, others talking or watching television. Maxine looked at the patients she passed. Most were wearing hats or kerchiefs to cover their bald heads. Several reclined in their chairs, thin and pale, too weak to sit up. It was clear that some of them would soon die.

A half hour after Maxine's chemotherapy treatment, Peter still had not arrived. Maxine's cell phone rang. "He's tied up," she explained to me, and we arranged for a car service to take her home. When I called Maxine later that evening to see how she was doing, Peter answered the phone and told me that she was sleeping.

"She's going to die, isn't she?" he said. He explained that he had been searching the Internet, and had read that in cases like Maxine's patients survived on average eighteen months, and that a remission lasted three to six months at best.

"Peter, as I said when we met, statistics don't tell you what is going to happen to any one person, just groups."

I got off the phone as quickly as I could. There could be no "back channel" discussions with friends or family; if Maxine had wanted to, she could have logged on to the Internet.

Over the next seven months, the metastases in Maxine's bones and in her liver decreased significantly. Although she was frequently tired and lost her hair, she was able to work part time, and even took a weekend trip to Manhattan with her parents and went to Newport for a friend's wedding. Then, on a routine visit at the end of May, after her eighth month of therapy, I noticed that one of her eyes wandered, and she seemed to be tilting her head to the right.

"Are you having any trouble seeing?"

She said that sometimes it was difficult to read.

"Any double vision?"

Yes, she said, on a few occasions that week, when she was walking down stairs.

Movement of the eyes is controlled by a set of cranial nerves at the base of the skull. An initial MRI scan of the brain did not turn up anything abnormal, but scans do not always detect small deposits on the cranial nerves. I explained that a spinal tap was the best way to determine if the cancer had spread to the brain; it would allow us to search for tumor cells in the spinal fluid.
Maxine lay on her side as a medical resident performed the procedure. I tried to distract her. We talked about the Red Sox, who had started the season strong, and whether, as usual, they would end up losing games in the homestretch. After sterilizing and anesthetizing the area between the fourth and fifth lumbar vertebrae, the resident passed a fine trocar into the spinal canal. Maxine twitched. Drops of fluid fell from the trocar into a test tube that he held under it. Normal spinal fluid is clear; Maxine's was cloudy.

"It's over," I said. "Stay down for an hour, so you don't get a headache."

She asked what it meant if the cancer had gone to her cranial nerves.

I was almost certain, based on the cloudiness of the spinal fluid, that this was the case. How much did Maxine want to know?

"It is a major setback," I said.

"I'm not sure I want to ask how long a remission lasts if the cancer is in my brain," she said.

"Are you sure you want to talk about this now?"

Maxine closed her eyes and nodded.

"People usually live several weeks to a few months without any treatment," I said. "But that represents the average. There are people who live longer. Treatment with radiation and chemotherapy instilled into the spinal fluid may or may not extend life, but it can reduce some of the most annoying complications, like the double vision."

Maxine was silent. "Is it even worth being treated?" she finally asked.

"You are the only one who can answer that question," I said. "If we don't treat it, it will quickly spread to other cranial nerves and parts of the brain and spinal cord. The quality of your life would be markedly impaired. I want to help sustain as much quality of life for as long as possible."

Maxine opened her eyes.

"I don't want to die," she said, beginning to sob. "I didn't think it would happen so fast, so soon. I'm not ready to die."

"I don't want to lose you," I said. There was nothing more I could say now that would help.

"Let's go step by step, and talk after the results from the spinal tap."

Later that day, I went to the pathology laboratory. Under the microscope, numerous large cells, with distorted nuclei, filled what should have been an empty field. "Carcinoma," the pathologist said.

Over the next few weeks, we began radiation treatment and a new round of chemotherapy, infused into her spinal fluid. At first, Maxine's double vision improved. But after three weeks or so she found that she couldn't move her left eye, and we put a patch over it. Shortly thereafter, the left side of her face began to droop. A second MRI showed that the cancer had spread to the membranes lining the cerebral cortex and spinal cord. It was evening when I came into Maxine's hospital room. She was watching television.

She turned to me as I switched off the TV.

"Peter left me."

I nodded, saying that I had noticed that he was not around the past few days.

"He's been seeing someone else the past three months."

I remained silent.

"I always felt, deep inside, that he was weak." Maxine paused. "No, not just weak. He's a schmuck. A real schmuck."

"Do you know what that word literally means in Yiddish?" I asked.

Maxine laughed.

I took her hand. She tried to press back, but had little force. The nerves from the cervical spinal cord were being compressed by the deposits of cancer.

"I'm not sure how much strength I have left," Maxine said. She was in a fragile condition. It was time to assess clinical issues.

"Remember once I asked you what your wishes were if we reached a point when further therapy would not improve the quality of your life?"

Maxine nodded. "So you think it's just a few days?" she asked. Her voice was hollow.

"Probably more than just a few days," I said. "Probably weeks. Or maybe longer--I've been wrong before."

"And really nothing can be done?"

Like all patients, Maxine was finding it almost impossible to give up hope.

"Nothing that I know of," I said. "And to continue to give you chemotherapy would not improve the time we have left. But anything I can do to make the time that we have left good for you, I'll do."

Maxine turned away. "How do I actually die from the cancer?"

"You lose consciousness, go into a coma, and either you stop breathing or your heart stops. But you're not aware of any of it."

She was silent as I sat holding her hand.

The first time I witnessed death was in my second year of medical school. My father had had a massive, unexpected heart attack, and I went to meet my mother at the hospital in Queens. The sheets were drenched with sweat. His eyes were filmy and repeatedly rolled upward. Coarse, grunting noises punctuated his breathing, and his chest heaved. His limbs jerked wildly. This went on for nearly half an hour, as a large clock on the wall ticked off the minutes. Then, after a last convulsion, a pink foam poured from his mouth, his head snapped back, the little color remaining in his skin drained away, and he was still.

I held my mother, numb with disbelief. The doctor on call, whom we did not know and who had stood by as we watched, closed the curtain around the bed. He looked at me holding my mother, and said weakly, "It's tough, kid."

Although I later learned that the flailing movements of my father's limbs were the result of neurological reflexes, and that he had not been conscious, I could not stop wondering if he had suffered. The ugliness of these final minutes often invades otherwise comforting memories of times we spent together. When I became a physician, I vowed that I would do everything I could to temper such gruesome experiences for the patient and for the family.
During the Middle Ages and the Renaissance, death was supposed to be met with words of welcome. This was the core of ars moriendi--"the art of dying." The "art" prepared and purified the person by linking his experience to Jesus' death on the Cross. Treatises like William Caxton's, printed in 1491, instructed laymen to think about the end of life, even when they were healthy, and dictated what words they should expect to hear and say when death was near:
"This time of your departing shall be better to you than the time of your birth, for now all sickness, sorrow, and trouble shall depart from you forever. Therefore be not aggrieved with your sickness and take it not with grutching but take it rather all by gladness."

Today, the physician frequently finds himself assuming a role that was once the exclusive province of religious authorities. Yet the palliative care he offers is primarily meant to ease physical suffering; he is not trained to alleviate emotional pain. In medical terms, a "good death" is a death with the least physical suffering possible. As ars moriendi suggests, though, there is a historical notion of a "good death" that is more complicated; it is as much about a cultivated attitude toward leaving life as it is about the physical act. Is there more, then, that physicians should do to make dying in a hospital after illness less emotionally taxing?
Last January, one of the first academic studies of how effectively oncologists communicate critical information to their patients was published. A hundred and eighteen patients cared for by nine oncologists participated in the research. The doctor-patient interactions were recorded on audiotape. The study tried to determine two things: whether the information disclosed to the patients was sufficient for them to make an informed decision about further treatment, and whether the doctor encouraged the patient's participation in choosing among treatments.
Although the oncologists knew that they were being taped, in more than a quarter of the consultations the patients were not told that their disease was incurable; a similar percentage were not informed of the side effects associated with the proposed anti-cancer therapy. Only five patients of the hundred and eighteen--some four per cent--received what the researchers considered adequate information. In nearly ninety per cent of the taped discussions, the oncologists failed to ask the patients if they understood the information being presented to them. These results are in keeping with prior research indicating that more than a third of patients with incurable metastatic cancer believe that the treatment offered by their doctors will actually cure them.

Suffering is not the only cost. Many in the medical profession have speculated that doctors' uncertainty in guiding patients through the end of life is one of the primary causes of rising health-care costs. More money is spent on care during the last weeks of life than on the months or years of care that precede it. The kinds of interventions that are routine in an intensive-care unit--pumps to sustain circulation, respirators to ventilate the lungs--cost hundreds of thousands of dollars. Some physicians don't want to acknowledge that a patient is going to die, and regularly order tests and procedures at a point when no reasonable gain can come of them. Studies show that a doctor does not shorten the life of the patient when he chooses to provide palliative rather than intensive care.

...[cut some parts]

After I talked with Maxine, I arranged for her to be transferred to a special hospice unit, and soon she began to drift in and out of consciousness. The cancer pressing on the cranial nerves connected to the back of her throat and her tongue had made it difficult for her to swallow. The nurses had to suction her saliva to prevent her from choking. Shortly before noon a week later, I was paged and told that Maxine's death appeared imminent.

Maxine's parents were sitting by her bed when I came in. They stood up, and Mrs. Barlow hugged me, crying. Mr. Barlow's face was frozen with grief.

Maxine was no longer conscious. Every few seconds, her chest heaved, and she gasped. She was entering what is called the agonal phase--taken from the Greek agon, which means struggle--a period that precedes death and can last from a few minutes to hours.

I warned Maxine's parents that this was usually harrowing, and that sometimes family members preferred not to witness it.

"I want to be with my baby," Maxine's mother said.

Maxine's hands began to twitch and her breathing moved into a syncopated pattern called Cheyne-Stokes, a short set of staccato breaths bracketing a long pause.

Mrs. Barlow raised her head.

"Maxie, we love you, and God loves you."

Mr. Barlow sat straight, his hands clasped in his lap.

Sometimes as a patient dies there is a convulsive burst of muscular activity, like a grand-mal seizure. I braced myself for it when Maxine's fingers began to twitch, as if she were grasping for an invisible object. These muscle contractions continued for some forty minutes. Then a harsh rattling sound came from her chest. I glanced at the nurse, who was next to the morphine infusion. There was a single explosive jerk of Maxine's body, a sharp arching of her chest, followed by a series of fluttering movements in the muscles of her neck.

The Barlows stood up. Maxine's skin was already changing to an ashen hue. I placed my stethoscope over her heart. "I am sorry," the nurse said. I reached over and took Mr. Barlow's hand, and then turned and embraced Mrs. Barlow as she cried.

I left the Barlows and went to the nurses' station to fill out Maxine's death certificate. I designated the primary cause as respiratory failure due to metastatic breast cancer to the brain and handed the chart with the death certificate to the floor clerk. The time of death was 12:57 P.M.

Source Citation:Groopman, Jerome. "DYING WORDS." The New Yorker 78.32 (Oct 28, 2002):

Small Step for Man

What amazes me about oncology is how science moves at a pace that is both slow and exhilarating. It seems that even the smallest steps toward improvement seem vast, and yet only highlight evermore how that elusive "cure" continually escapes us.

Of course, there are a few break-throughs in cancer therapeutics that seems awe-inspiring...whoever invented the bone marrow transplant (wow), the MOPP regimen for chemotherapy, how chemoradiation can cure Hodgkin's, how Gleevac can suppress CML. And even the "smaller" advances, like how you can harvest bone marrow stem cells from a donor's peripheral circulation using G-CSF seems so amazing and wonderful because you can spare donors a radical pelvic surgery and give patients faster engraftments (so that there are "1) shorter hospital stays 2) fewer treatment-related deaths 3) fewer infections 4) fewer transfusions and 5) lower cost"). It's when you can make advances in research that translate into enormous human benefit that makes me feel so inspired.

At the same time, there is always more work to be done. We watched a Frontline clip about a patient receiving alternative medicine for his pancreatic cancer, and it reminded me that there are still so many things to do.

Oh, and reading about bone marrow transplants have made me resolve a few things:
1) Have 3 children so that they can donate bone marrow stem cells to each other (just in case)
2) Save cord blood

Gambler's Dilemma

There's a strange paradox in leukemia/lymphoma world -- the more aggressive disease has a higher acute mortality rate, but also a greater sensitivity to chemotherapy which offers the possibility of a cure. Meanwhile, the chronic disease is more indolent (median survival is 10 years), but essentially incurable.

**This is purely a thought experiment, but in pathology lab today, the professor remarked that we are lucky that life does not force us to decide whether we (or patients) have the acute or chronic disease -- but that since survival differences between both disease eventually wash out...there is no clear answer to the question. Would you rather have a severe, sudden disease with a shorter median survival period but the possibility of salvation...or the slowly fatal chronic disease that offers you more time? A reckless gambler might bet on the first horse, the deliberate tortoise (or conservative gambler) might choose the latter.

Personally as a young, grudgingly optimistic gambler, I am more inclined to choose the more aggressive disease since it offers me a shot at being free and clear -- despite the more dismal median survival.

Paul also decided that he would rather have the acute disease, remarking, "Invariably fatal just doesn't sit well with me."

But, isn't being alive invariably fatal?

What do you think?

Static shock

I woke up today already a little agitated because I had forgotten to call home to wish Jeremy a happy birthday yesterday night after teaching MSP and then overslept this morning until 7:50 a.m., decided that it wasn't worth coming in 20 minutes late to lecture because it was getting almost embarassingly predictable so I slept a little more and arrived in time for the 9 a.m. lecture.

Probably a good move since my brain was more alert and I actually learned more, but one detail that the lecturer mentioned gave me a little mental static shock. He mentioned that patients with multiple myeloma do not have good prognoses and that bone marrow transplants are palliative measures designed to reduce recurrences and extend survival.

Someone whom I admire very much received a BMT for multiple myeloma -- and it almost made me cry realizing that things in life are so unfair.

Thoughts on Cancer

Cancer has always fascinated me on both a scientific and non-scientific level. As a deranged cellular process, the disease reveals an intricate system of checks and balances and underscores how little we actually know about the maddeningly complex “cross-talk” that Bruce Alberts compared to cell “thinking.”

Until last year, I considered cancer to be an isolated biological process. It was easy to see how the cell cycle can be sabotaged, how certain checkpoints can be bypassed and normal cellular proliferation permitted to run amok. In my head, there was a solid cadre of proteins automatically associated with cancer…p53, Bcl-2, Rb.

However, a syllabus chapter on neoplasms last year changed my view of cancer cells by pulling together information in a suggestive fashion. In normal tissue like the gut or skin, we have stem cells that continually divide into daughter stem cells and cells destined to terminally differentiate and die. Only these stem cells enjoy limitless replicative potential, and differentiation means that the cell has a one-way ticket to dying without any heirs. The syllabus also talked about how cancers can be pathologically graded based on differentiation, and that less differentiated cancers are fiercer adversaries – as though the degree to which a cell has regressed back from its terminally differentiated state reflects how feral and uncontrollable the cell has become.

And then I wondered if cancer cells had achieved the impossible…did they manage to somehow reverse the laws of nature and learn how to de-differentiate in a misguided bid for “stem cell-hood” and immortality?

In another tangent, I had never been interested in the links between inflammation and cancer until an analysis from a pilot project at Stanford showed that the only proteins associated with survival were two cytokines, IL-1 and IL-7. Suddenly, I was interested in how inflammation can affect cancer survival. The connection had never been vitally interesting before, even though it was also mentioned in the syllabus in passing. Another event that sparked my interest in the connection between immunity and cancer was writing about an ongoing UCSF brain tumor vaccine trial for Synapse, which described harvesting the tumor cells and cultivating protein complexes to boost immune response to the tumor. Although it still seems unclear to me how the whole immune system vs. cancer situation exactly works, I really like the connections.

No one else will agree with me, but the most outstanding lectures in Cancer block so far were given by Dr. Doug Hanahan on the topics of angiogenesis and metastasis. For some reason, his lectures really seemed to address where my thoughts on cancer biology have been turning to. There was an interesting mention of an “angiogenic switch” and the idea that there are “bad” inflammatory cells, fibroblasts, etc. that somehow aid cancer cells. In the metastasis lecture, I was intrigued by the notion that metastasis resembles a “re-awakening” of the far-flung migratory habits of cells during embryonic development. Re-reading Hanahan’s syllabus chapters made me intellectually excited. In the end, these two processes – angiogenesis and metastasis – are two of the keys to fully understanding cancer and how to cure it.

We Shall OverCome

Ovarian Cancer Support Bands

(youth sizes "for the petite ladies")

Last Friday, a classmate named Mike Frederick presented the best damn Clinical Sciences Journal Club in recent memory. It was a paper demonstrating the effectiveness of oophorectomies (surgical removal of ovaries) as prophylaxis against ovarian cancer in patients with BRCA1 and/or BRCA2 mutations.

The strength of Mike's presentation rested upon his courage to discuss how ovarian cancer has affected his life. He began the presentation with the sound a woman singing opera -- the voice belonged to be his sister, who passed away from ovarian cancer the summer before Mike started medical school at UCSF. Mike wove his own family history and his personal experiences together in a way that amused, touched, and educated the audience (a crowd of MS1's and MS2's, journal club has always been a proudly student-run affair). My eyes were constantly tearing up, and it was so memorable watching Mike onstage showing us videos of his family and photos of his sister...in between Kaplan-Meier curves and data tables of the patient population in the study.

What will really stay in memory is how the presentation was so quintessentially "Mike" -- a guy who is proud of his family, a down-to-earth, unapologetically opinionated farm boy from Nipomo, CA, who can bake banana cream pies from scratch and tell you the difference between a starfish and a sea star while he skin dives for abalone. A guy who formerly boasted tonsils the size of testicles (before he had them removed last year) and who has helped to make UCSF medical school an amazing place to be.

Rule of Thumb

O'Brien S et al. N Engl J Med 2003;348:994-1004

Loosely paraphrased from Dr. Andrew Ko's lecture:

"A lot of times you might wonder what makes a clinical study significant or useful. There are a lot of ways to determine this, but a mentor of mine during my oncology fellowship at Stanford gave me this rule of thumb: if a person sitting in the back of the room can measure out the space of his or her thumb between the two survival curves on a Kaplan Meier graph, then the study is something to write home about."

Simple. Cute. Useful.

The Blind Man's Dilemma

Writing this right now is utter insanity because I have not started reading the syllabus yet and it's Friday night before a Monday exam. However, I wanted to write this down before it becomes forgotten.

The aged Chinese man sitting in the closet-sized exam room was looking at an obscure point in space about 1 foot away from my head. He was a friendly grandfatherly character, with black plastic glasses, eyes clouded by cataracts, and a distinct scholarly air perhaps manifested by his fastidiously pressed striped shirt, bright red suspenders, and black trousers. Around his shoulder was a green cloth bag.

The CT scan had shown cancer in his prostate, bladder, and in the right pelvic region and his kidneys were backed up with fluid -- but he knew that his case was difficult. As the doctor began describing how he must begin chemotherapy within a week as a palliative measure to shrink his large prostate cancer and permit him to urinate again (a quality of life issue), the blind man interrupted the scheduling by saying, "Wait, not before my birthday party! It's on the 28th."

The oncologist reminded the blind man that the tumor would only grow larger if they waited 2 weeks, but the blind man remained adamant.

"Can you guarantee that I won't feel nauseated and half-dead from the chemo?" he asked.

"No, of course not," said the honest doctor.

"Well, now that's a problem. I want to feel good during my 82nd birthday party."

"It's up to you," said the doctor, "The chemo is not going to cure you, but the tumor is just going to grow bigger."

The blind man seemed to relax after he heard the words "not going to cure you."

During the physical exam, the blind man lay down on the bench without removing his green cloth bag. It was a curious omission, but it became clear after the doctor lifted the patient's shirt and pointed out how there was a tube emerging from the blind man's back, wrapping around the front and ingeniously hidden by a seam in the black trousers (mended by his wife). The tube emerged from the trousers and dove into the green cloth bag (created by his wife's female friend). Since the blind man could not urinate with the prostate cancer blocking the ureters, there was a tube implanted to drain the kidney, allowing the urine to emerge from a plastic pipe and draining into a plastic bag hidden by the innocuous green cloth. In my mind, the man was carrying an external "pee-bag" around.

Talking to the blind man, it was clear that he was well-educated and that he knew that his case was (in his words) "terminal." He looked forward to gathering his friends and family for his birthday, and he seemed so spirited, saddened, and strong. He proudly said that he would like to finish a manuscript before he dies, apparently he was a scholar in Asian-American studies, and I knew that he still looked forward to the future and had goals.

Somehow, when I am talking to elderly cancer patients, I feel like they have reached the delicate balance of acceptance and hope that continually escapes me.

Erasing Memories

No comments for now, but a very potent and vivid piece from CNN.com...

"She was worried about the lump and worried about the children who were worrying about her. She was, however, most worried about the anesthesia. "What if I don't wake up?" just wasn't a question I could answer sufficiently for her. Some people take no solace in statistics (that, for example, there are two or three deaths per 1 million patients anesthetized) — these patients are the medical cousins of the folks still crossing the country by train or bus rather than "risking the airplane." So I warned her that there might be a little pain and agreed to do her biopsy under a local anesthetic — but only if she would allow an anesthesiologist in the room, just in case.

The lump was growing near — maybe on — the inner end of Ellen's collarbone, meaning that during the biopsy I might have to use a tool that goes "crunch." It's pretty hard to numb up bone with a local anesthetic so I was glad to have Frank, the anesthesiologist, there at the head of the table with some IV sedatives, in case Ellen got panicky or was in too much pain. She was adamant about not going under, but agreed to "some sedation" if we thought it was necessary.
I can understand not wanting to lose consciousness. It's arguably the most precious thing we have. And although serious complications from anesthesia are truly rare these days, so are bone tumors — and she clearly had one of those. Ellen had a history of cancer too — it had not been a cancer that was likely to spread to the bone and there hadn't been any sign of it for years, but it had been a malignancy. This lump was growing at the end of the clavicle, in the place where arthritis often produces a lumpy enlargement. But Ellen's lump had come on too fast; it felt fleshy and, most significantly, unlike arthritis, it wasn't tender at all. As hard as I pressed on the lump that day in the office, it didn't hurt. That's why I booked the biopsy.

I've been in many operating rooms over the years, with the highest-tech, ultra high-quality equipment around, but I don't think I've been in one where the intercom, a low tech app if there ever was one, really worked. And we found that was true in our room that day.
Ellen's procedure got off to a fine start. She was O.K. with the needle-sticks for the lidocaine and she stayed calm and collected under the layers of paper and plastic that we used to drape off the surgical site. When I got in there, I saw that the lump was growing from the bone. I warned her it might hurt but she didn't make a peep when I used the tool that crunches and bit off a piece of bone for the pathologist.

I ordered up a touch prep — a quick microscopic look at the cells of the specimen. We would know in 15 minutes if there were cancer in the lump. While the specimen was in the pathology lab, we washed out the wound and started to sew it back up, layer by layer. The inch-long incision was on a very conspicuous part of this youngish woman's body, right where a necklace or the neckline of a fancy dress might lead the eye. I sutured slowly. We were still waiting for the pathology report anyway. It was quiet in the room. I made small talk with Ellen and the nurses. Ellen was O.K. but nervous. She talked about her kids, about how much driving she did everyday shuttling them around. The topic of the tumor, and what it had looked like, was given wide berth by all of us. I finished stitching, but I had to stay scrubbed — we couldn't take off the drapes until pathology told us they had a sufficient specimen. There wasn't much else to discuss; it was real quiet and, rare for the OR, a little bit awkward.

"Dr. Haig?" A voice over the intercom, harsh and loud.

"Yes," I said. "Is this path lab?"

"Yes, can I put on Dr. Morales?" the voice replied, referring to the pathologist looking at the microscope slides of Ellen's specimen.

"Have him call in on the phone," I said. The drill, which everyone knew, was that the circulating nurse would hold the phone to my ear while the pathologist told me what he saw.

But instead of an "O.K." there was silence, and then, "Scott, this is Jorge, can you hear me?"

"Yes, but hold on, we're under local in here," I said. "You'd better call the desk and have them put you through to the phone in the room."

"Scott, I can barely hear you but, listen, this is a wildly pleomorphic tumor, very anaplastic. I can't tell..."

"Hold on, Jorge — let me use the..." But he couldn't hear me and kept on talking.

"...what the cell type is, but it's a really, really, bad..."

The circulator was moving toward the intercom on the wall, but she wasn't going to make it.

"...cancer."

Ellen's shuddering gasp, then shrieks came from under the drapes: "Oh, my God. Oh, my God.
My kids. Oh, my... my arm..."

The burning pain in Ellen's arm was due to the rapid application of propofol, a paper-white liquid medication, which the perceptive Dr. Frank had plugged into Ellen's IV the second he heard the c-word. When he saw her reaction, he pushed. The drug, sometimes called "milk of amnesia," stings some patients sharply in the veins, but what it also does is erase your last few minutes. (Think of the "neuralyzer" from the Men in Black movies.) Oh, and it puts you to sleep. An amazing molecule, a great anesthesiologist and a great save.

Not everyone agreed. I looked up at three sets of eyes, the nurses' eyes, that bored into Frank and me accusingly. How can you do that? they demanded to know. Don't you need consent or at least fill out some kind of form before you steal a patient's last 10 minutes? But all I could say was, "Awesome job, Frank." Somehow with that, and with the calm sleep on their patient's face, we were given not forgiveness, but a reprieve.

Ten minutes later Ellen woke up, happy and even-keeled, not even knowing she'd been asleep. From the recovery room she was home in time for dinner. "The procedure went smoothly, but we'll have to wait for the final pathology reports," I said, which was not exactly the whole truth, but it let me get the oncology people cued up, a proper diagnosis, and Ellen herself emotionally prepared. I would give her the bad news at a more appropriate time.

The ending was not quite happy; it was a recurrence of the cancer she'd had years before — fairly rare for that type of tumor. Ellen died of it about six years later. I confess I never told her about the incident with the intercom.

Over a decade later, I'm still not sure that was right.

Questions of withholding bad news, wiping out bad memories — plastering over wayward cracks in our minds with chemicals — are answered thousands of times everyday, without ever being asked. Ethics committees and experts exist in our hospitals, but what they have to say counts precious little down in the trenches, where intercoms fail and human minds treat human minds, in real time. You would think, by now, that the distinction between treatments using words (or ideas) and chemicals (or electric currents) is starting to blur. (If an hour of psychotherapy accomplishes the same thing as 20 mg of Prozac — that is, a boost in mood and serotonin levels — is there a difference?) But it is not. Everyone I know who deals with medicines that affect minds seems to operate with a very clear functional distinction between personhood — the realm of virtue, vice, responsibility and creativity — and brain chemistry. That distinction was clear in the eyes of my nurses that day. Something more important than a chemical balance in Ellen's brain had been violated — only a little and, obviously, with benevolent intent. But it hadn't been as simple as pushing a rewind button. Something there had borne the unmistakable quality of wrong.

As mundane, as miserably human as a soccer mom "dying young" of cancer might be, I found such value and such meaning in the way Ellen clung to her consciousness, the personhood she needed to care for her family. Much of what we read about brain science in the media today would have us believe that we're nothing more, really, than very fancy machines. And surely what we're learning about the physical brain is exciting and powerful — but thinking honestly, it remains so limited. We can trace the brain pathway of a drug "high," we can call it pleasure, but that tells us nothing about what so many people choose instead — deeper things that somehow beat out mere pleasure as the reasons for doing what we do. Those comforts — of ultimate meaning, virtue, peace and joy — have little to do with molecules."

Dr. Scott Haig is an Assistant Clinical Professor of Orthopedic Surgery at Columbia University College of Physicians and Surgeons. He has a private practice in the New York City area.

Cancer and Health Disparities

Yesterday, I attended a lunch elective on African American Health Disparities. It was a talk given by Dr. Mack Roach, the chair of Rad Onc at UCSF, who strongly believes that research focuses too much on attributing biological/genetic differences between races to cancer outcomes. It was a fascinating talk filled with numerous study results and I realized a few things:

1) It's almost impossible to separate which cancer outcomes are biologic and which are psychosocial given the limits of our current studies.

2) Dr. Roach is correct in that there is an inherent bias for positive studies and this impedes funding/publishing, etc. His work showing that racial differences do NOT affect outcomes has been hard to publish for this reason. It makes me glad that we have someone at UCSF pushing for this counterview.

3) I get really excited seeing a powerpoint with lots of data from cancer studies

4) Is my fate as an oncologist sealed?