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“Stop skipping dessert:” A Stanford neurosurgeon and cancer patient discusses facing terminal illness

"Stop skipping dessert:" A Stanford neurosurgeon and cancer patient discusses facing terminal illness

terminally_illWhen Paul Kalanithi, MD, a chief resident in neurological surgery at Stanford, was diagnosed at age 36 with stage IV lung cancer he struggled to learn how to live with conviction despite a prognosis of uncertainty. He found comfort in seven words from writer Samuel Beckett, “I can’t go on. I’ll go on.”

That mantra has given Kalanithi the strength to face his own mortality and have tough conversations with his wife and loved ones about the future. Tomorrow evening, he’ll join palliative-care specialist Timothy Quill, MD, for a discussion about end-of-life decision-making. The campus event is free and open to the public; no registration is required.

As a preview to the talk, Kalanithi talked with me about his experience as a patient and about the importance of end-of-life decisions.

How has your prognoses changed the way you talk to patients and their loved ones about grim news?

In large part, the way I talk to patients and their families hasn’t changed, because I had excellent role models in training. I remember witnessing a pediatric neurosurgeon talk parents through the diagnosis of their daughter’s brain tumor. He delivered not just the medical facts, but laid out the emotional terrain as well: the confusion, the fear, the anger and – above all – the need for support from and for each other. I always strove to emulate that model: to educate patients on the medical facts isn’t enough. You have to also find a way to gesture towards the emotional and existential landmarks.

Seeing it from the other side, it’s really hard, as a patient, to ask the tough questions. It’s important for the doctor to help initiate these conversations. I think it’s worth addressing prognosis and quality of life with patients, asking them what they think. My own assumptions about my prognosis were way off base. As a doctor, you can’t provide definite answers, but you can remove misconceptions and refocus patients’ energy.

Finally, I think, if you are the oncologist, it’s important to establish yourself as a go-to for any questions. Patients are bombarded with well-meaning advice, from dietary recommendations to holistic therapy to cutting-edge research. It can easily occupy all a patient’s time, when you ought to also spend time thinking about the priorities in your life. Physicians can also advise patients, as my dad would insist, that they can stop skipping dessert.

What is your advice to patients who are struggling with the certainty of death and the uncertainty of life?

I’ve written a little bit about facing terminal illness in The New York Times and The Paris Review. I found the experience difficult. I still find it difficult. It is a struggle. The problem is not simply learning to accept death. Because even if you do come to terms with finitude, you still wake up each morning and have a whole day to face. Your life keeps going on, whether you are ready for it to or not.

In some ways, having a terminal illness makes you no different from anyone else: Everyone dies. You have to find the balance – neither being overwhelmed by impending death nor completely ignoring it.

You have to find the things that matter to you, in two categories. The first is of ‘the bucket list’ sort. My wife and I always imagined revisiting our honeymoon spot on, say, our 20th wedding anniversary. But I didn’t realize how important to me that was until we decided to go back earlier (on our 7th anniversary, instead, about four months after I was diagnosed).

The second is, as all people should be doing, figuring out how to live true to your values. The tricky part is that, as you go through illness, your values may be constantly changing. So you have to figure out what matters to you, and keep figuring it out. It’s like someone just took away your credit card, and now you really have to budget. You may decide that you want to spend your time working. But two months later, you might feel differently, and say, you really want to learn saxophone, or devote yourself to the church. I think that’s okay – death may be a one-time event, but living with a terminal illness is a process.

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Cancer, Stanford News, Videos, Women's Health

The squeeze: Compression during mammography important for accurate breast cancer detection

The squeeze: Compression during mammography important for accurate breast cancer detection

After nearly 30 years of reluctantly enduring the pain of mammography, I finally understand why I shouldn’t complain. In fact, I think I should embrace the pain and ask the technician to squeeze my breasts even more tightly between the shelves of the mammography machine.

It’s only a brief moment of pain, after all, but it can make the difference between a breast cancer detected and a breast cancer missed. In a recent video on the topic, Stanford Health Care’s Jafi Lipson, MD, an assistant professor of radiology, explains the very important reasons for women to step up and take the squeeze without complaint. It will only take 30 seconds of your time – and it might save your life.

Previously: Despite genetic advances, detection still key in breast cancer, NIH Director highlights Stanford research on breast cancer surgery choices and Breast cancer patients are getting more bilateral mastectomies — but not any survival benefit

Cancer, Patient Care

Healing hands: My experience being treated for bladder cancer

Healing hands: My experience being treated for bladder cancer

We’ve partnered with Inspire, a company that builds and manages online support communities for patients and caregivers, to launch a patient-focused series here on Scope. Once a month, patients affected by serious and often rare diseases share their unique stories; this month’s column comes from a patient who has asked to remain anonymous.

“I hate to be the one to tell you this, but you have invasive bladder cancer.”

That’s certainly the last thing anyone wants to hear from their doctor. And it’s undoubtedly news that doctors must dread having to tell their patients.

I owe a debt of gratitude I can never fully repay to all of those whose healing hands, both literally and figuratively, reached out to help me

I heard those fateful words from my urologist in August 2012, at which time I was informed that my best course of action was to undergo chemotherapy treatments and have my bladder completely removed. Oh yeah, my prostate had to go as well.  “You’ve got to be kidding me,” I thought. “I’m 46, healthy, and serious health issues aren’t supposed to happen until I’m old – like 70 or something.”

So began my journey of cancer treatment, which included three rounds of neoadjuvant chemotherapy and culminated in the removal of my bladder and prostate. Like many who have to get on the roller-coaster ride that is cancer treatment, my road to recovery was rocky at times.

During a bladder biopsy and resection procedure, the doctor determined that the tumor in my bladder was blocking my right ureter, putting the kidney at serious risk. I was rushed to surgery where I received a nephrostomy stent. Two weeks later, a port-a-cath (for administering the chemo infusions) was placed in my chest; and three days after that, it had to be removed due to an infection. Then came the chemo, which was certainly no picnic – I suffered from a variety of side-effects, not the least which was becoming seriously neutropenic. Later, following surgery, my heart went into A-fib and I was whisked off to intensive care.

One of the ironies of my experience: Prior to the cancer diagnosis, I had never even spent a night in the hospital.

As most anyone who has gone through this experience can attest, it really kicks your ass physically, emotionally, spiritually, existentially, and about every which way in between. The good news today, though, is that I’m cancer free and my prognosis for long term survival is very good. I feel better physically than I’ve felt since this whole circus started, and I’ve resumed most of the activities I previously enjoyed before the cancer diagnosis. Nonetheless, healing emotionally from the trauma of the whole experience – including life with a urostomy – is still a work in progress.

Recently, I’ve been reflecting at depth on my journey with the Big C. During my treatment I interacted with an untold number of health professionals. From doctors and nurses to social workers and massage therapists, scores of health-care professionals and related practitioners were involved in helping me get better. I am in utter awe when I think about the years of training that each of these individuals received; the fortitude it must take to deal with the sick and infirm on a daily basis; the medical research behind the development of lifesaving chemo treatments; and surgical procedures like the cystoprostatectomy.

I owe a debt of gratitude I can never fully repay to all of those whose healing hands, both literally and figuratively, reached out to help me. Like my feisty little 70 year-old home health-care nurse Jackie, who told me, “During chemo, you’ve got to keep moving! Get out there and walk every day, stay active. You won’t feel like doing it, but do it anyway!” I followed her sage advice and sure enough, it really did help. Jackie also coaxed me through a very rough time after the removal of my port-a-cath when I was told I would need to stuff gauze in my gaping open chest wound on a daily basis. Jackie was right there, providing me with the encouragement and support that enabled me to get this done.

Then there were the various residents and fellows who provided for my care. The competency and kind bedside manner of the chief resident in urology helped me calm down and enabled me to wrap my head around what I was facing when I was first diagnosed. The expertise, professionalism, and compassion exhibited by the fellows who were involved in my surgery and subsequent care in the hospital were also appreciated.

And let’s not forget the attending physicians, whose years of education, training, and experience enabled them to do things that 100 years ago would be considered no less than an absolute miracle.

To all those in the health-care field who touched my life during this journey, my unending gratitude. To those who are answering the call to provide professional medical care for others, my sincerest respect.

The author of this article lives in Virginia and works in administration at a large hospital.

Cancer, Clinical Trials, Research, Science, Stanford News, Stem Cells

Drug may prevent bladder cancer progression, say Stanford researchers

Drug may prevent bladder cancer progression, say Stanford researchers

Bladder cancer is an insidious foe. About 70 percent of the time the condition is diagnosed while still confined to the bladder lining (in these cases, it’s known as a “carcinoma in situ,” or CIS). However, a subset of these localized cancers will go on to invade tissue surrounding the bladder and become much more deadly.

Now, developmental biologist Philip Beachy, PhD, a Howard Hughes Medical Institute investigator, and his colleagues have found that low doses of a drug called FK506 currently used to prevent the rejection of transplanted organs can prevent the progression of CIS into invasive bladder cancer in mice. Beachy collaborated with collaborated with urologist Joseph Liao, MD, and pulmonary specialist Edda Spiekerkoetter, MD, to conduct the research, which was published today in Cancer Cell. As Beachy explains in our release:

This could be a boon to the management of bladder cancer patients. Bladder cancer is the most expensive cancer to treat per patient because most patients require continual monitoring. The effective prevention of progression to invasive carcinoma would be a major advance in the treatment of this disease.

Beachy and Liao are members of the Stanford Cancer Institute. Together they’re hoping to initiate clinical trials of FK506 in people with CIS to learn whether the drug can also prevent progression to invasive cancer in humans.

The findings of the current study build upon previous research into the disease in Beachy’s laboratory and a long-time interest by Beachy in a molecular signaling pathway governed by a protein called sonic hedgehog. Beachy identified the first hedgehog protein in 1992; the protein (and the hedgehog pathway) have since been shown to play a vital role in embryonic developments and many types of cancers. Sonic hedgehog, Beachy has found, is produced by specialized stem cells in the bladder as a way to communicate with neighboring cells. They learned it’s required for the formation of CIS, but that it must also be lost in order for the cancer cells to invade other tissues. As Beachy explained in our release:

This was a very provocative finding. It was clear that these [sonic-hedgehog-expressing] bladder stem cells were the source of the intermediate cancers, or carcinomas in situ, that remain confined to the bladder lining. However, it was equally clear that sonic hedgehog expression must then be lost in order for those cancer cells to be able to invade surrounding tissue. We wondered whether the loss of this expression leads to increased tumor cell growth.

The researchers found that sonic hedgehog expression works in a loop with another class of proteins called BMPs. (You can read more about this in our release.) FK506 works by activating the BMP portion of the pathway in the absence of sonic hedgehog. Ten out of ten mice with CIS who received a low dose of the drug (low enough not to cause immunosuppression) were protected from developing invasive bladder cancer after five months of exposure to the carcinogen. In contrast, seven of nine mice receiving a placebo did develop the invasive form of the disease within the same time period.

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Cancer, Neuroscience, Stanford News, Technology, Videos

Stanford celebrates 20th anniversary of the CyberKnife

Stanford celebrates 20th anniversary of the CyberKnife

Just about 30 years ago, Stanford neurosurgeon John Adler, MD, traveled to the Karolinksa Institute in Sweden, home to Lars Leksell, MD, and a device Leksell had invented called the Gamma Knife. Leksell had long been a visionary figure in neurosurgery, and Adler – inspired by the device that enables non-invasive brain surgery - began to imagine a next step, driven by the addition of computer technology.

Coming up with an idea, of course, can happen in a matter of minutes. Adler had no idea that it would take 18 years before his next step, the CyberKnife, would treat its first patient. Stanford Hospital was the first to own a CyberKnife, and Adler unhesitatingly admits that without the agreement of hospital administrators to purchase that very first device – designed to treat tumors, brain and spine conditions, as well as cancers of the pancreas, prostate, liver and lungs - its development would not have been completed.

This year, Adler and his Stanford colleagues are celebrating the 20th anniversary of the CyberKnife. Stanford has two, one of just a handful of medical centers with that distinction, and it has accumulated the longest and largest history of patient care with the device. To honor Adler and those Stanford physicians who continue to explore its ever-lengthening list of applications to patient care, a new video featuring Adler was created. It’s a quick glimpse of the determination – and luck – required to make that leap from inspired idea to groundbreaking therapy.

Previously: CyberKnife: From promising technique to proven tumor treatment

Cancer, Infectious Disease, Pediatrics, Research, Stanford News

Summer’s child: Stanford researchers use season of birth to estimate cancer risk

Summer’s child: Stanford researchers use season of birth to estimate cancer risk

Four_seasons

One of the hardest parts of unraveling childhood cancers is understanding what causes them. In recent years, evidence has been mounting that cancer and many other chronic diseases begin early in life – and perhaps even in utero. To untangle some of these early causes of cancer in children and young adults, Stanford epidemiologist and family physician Casey Crump, MD, PhD, is partnering with researchers at Lund University in Sweden, a working relationship was set up by Marilyn Winkleby, PhD, MPH, professor emeritus of medicine here. The team is using Sweden’s national registries for birth certificates and medical records to track how factors during gestation and soon after birth – called perinatal factors – affect cancer risks.

Because Sweden has a national health care system, it’s relatively easy to track the course of illness in individuals. By comparison, the U.S.’s health care system is fragmented across dozens of health care providers and insurers, so getting medical records for a single person that might span decades is a much more difficult prospect.

Crump’s team is focusing on cancers that are common in childhood and early adulthood: brain tumors, leukemia and lymphoma among them. Two papers published earlier this year examine how the time of year a child is born affects cancer risk. The most recent, published ahead of print in April in the International Journal of Cancer, examined whether the season of birth was linked to the risk of developing either Hodgkin’s lymphoma or non-Hodgkin’s lymphoma later in life. Crump explained:

Lymphomas are among the most common cancers in childhood but the causes are still largely unknown. It’s been hypothesized that infectious exposures, such as Epstein Barr virus and others may play an important role, but it’s still unclear what the critical age window of susceptibility might be. We had an opportunity to use season of birth from birth records as a proxy for infectious exposures in the first few months of life, and see the relationship between that and subsequent risk of Hodgkin’s and non-Hodgkin’s lymphoma – following these people from birth through childhood and on into young adulthood.

The researchers found that children born in spring or summer had a higher risk of developing non-Hodgkin’s lymphoma later in life compared to kids born in winter. The team didn’t find any similar seasonal pattern for risk of Hodgkin’s lymphoma. The results lend additional support to the “delayed exposure hypothesis.” Children born in spring or summer may not be exposed to critical pathogens during a critical early period of immune system development, leaving them vulnerable later in life. Children born in the fall or winter, by comparison, do get that important exposure at just the right time. Crump was quick to note that season of birth provides only a rough estimate of these exposures, since the team didn’t have accurate measures of exposures to Epstein Barr or other viruses, but he also added that these results “shed additional light on possible pathways of risk that may contribute to the development of non-Hodgkin’s lymphoma.”

A similar study published in January in the International Journal of Epidemiology found that children born in spring and summer had a higher chance of developing melanoma later in childhood or early adulthood. The team hypothesized that spring and summer babies are exposed to more UV radiation in warm summer months in the first few months of life – an exposure that fall and winter babies are less likely to have.

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Cancer, Genetics, Stanford News, Videos, Women's Health

Despite genetic advances, detection still key in breast cancer

Despite genetic advances, detection still key in breast cancer

Just a few years before the launch of the first national breast cancer awareness month, I found a small lump in my left breast. I still remember the cold chill that ran through me – and stayed with me until several days later when a surgeon discovered that the lump was not a tumor. His parting words have never left me: “Remember how you’ve been feeling.” He wanted to make sure I would go on to have regular mammograms.

Spreading the word about the disease and the importance of detecting it in its early stages was – and is – the point of the national awareness campaign. In the almost 30 years since that first campaign, advances in imaging technology have enabled earlier detection of breast cancer, genome sequencing has identified some of the mysteries behind the development risk, and selecting the most effective surgery and chemotherapy is more and more of an individualized choice.

Stanford has a powerful team of physicians addressing all aspects of breast cancer science and care. On Oct. 16, breast-imaging specialist Jafi Lipson, MD, assistant professor of radiology, and breast cancer surgeon Amanda Wheeler, MD, clinical assistant professor of surgery, will give a free lecture, “The Latest Advancements in Screening and Treatment for Breast Cancer,” at the Sheraton Palo Alto. And throughout the month, Stanford Health Care will post short educational videos and infographics on a variety of breast-cancer topics, including types of breast cancer, options in surgical reconstruction, and why enduring the pain of compression in mammography is worth the effort. Today, Stanford Health Care kicks off the month with a video featuring Stanford breast cancer expert Alison Kurian, MD, explaining the role that genetics play in disease development (above).

Because one in eight women will develop breast cancer in her lifetime, I would urge all of us to keep in mind the reality of this disease – and to honor those we know who have survived, or not, by paying attention.

Previously: NIH Director highlights Stanford research on breast cancer surgery choicesBreast cancer patients are getting more bilateral mastectomies —  but not any survival benefitBreast cancer awareness: Beneath the pink packaging and At Stanford event, cancer advocate Susan Love talks about “a future with no breast cancer”

Cancer, Clinical Trials, In the News, NIH, Patient Care, Research

National Cancer Institute looking for “Exceptional Responders”

OLYMPUS DIGITAL CAMERAHope is a powerful force in cancer treatment. For patients and their families, the hope is that, no matter how unlikely, the treatment plan will cure the patient and eradicate the disease. Sadly, this is sometimes a long shot. But sometimes, against all odds, the therapy is unusually successful. Now the National Cancer Institute is trying to learn why.

This week the institute launched a study into the phenomena of “Exceptional Responders” – that is, cancer patients who have a unique response to treatments (primarily chemotherapy) that have not been effective for most other patients. As they describe in a Q&A about the effort:

For this initiative, exceptional responders will be identified among patients enrolled in early-phase clinical trials in which fewer than 10 percent of the patients responded to the treatments being studied; patients who were treated with drugs not found to be generally effective for their disease; patients who were treated in later-phase clinical trials of single agents or combinations; and even patients who were treated with established therapies. In this pilot study, malignant tissue (and normal tissue, when possible) and clinical data will be obtained from a group of exceptional responders and analyzed in detail. The goal is to determine whether certain molecular features of the malignant tissue can predict responses to the same or similar drugs.

The researchers would like to obtain tumor samples, as well as normal tissue, from about 100 exceptional responders. They’ll compare DNA sequences and RNA transcript levels and other molecular measurements to try to understand why these patients were such outliers in their response to treatment. In at least one previous case, an exceptional responder with bladder cancer led researchers to discover a new molecular pathway involved in the development of the disease, and suggested new therapeutic approaches for other similar patients.

Do you know someone who might qualify for the study? More from the Q&A:

Patients who believe they may be exceptional responders should contact their physicians or clinical trialists to see if they can assist in submitting tissue for consideration. [...] Investigators who have tissue from a potential exceptional responder should send an email to NCIExceptionalResponders@mail.nih.gov. The email should include a short description of the case, without patient identifiers; information about whether tissue collected before the exceptional response is available; whether informed consent was given to use tissue for research; and the patient’s vital status.

Photo by pol sifter

Cancer, Global Health, Health Policy, Infectious Disease, Public Health

Treating an infection to prevent a cancer: H. pylori and stomach cancer

Treating an infection to prevent a cancer: H. pylori and stomach cancer

Hpylori-pic-thumb-460x385-2092

The number of newly diagnosed stomach cancer cases in the United States is less than a tenth of the number of prostate cancer cases or breast cancer cases, which may be part of the reason it doesn’t get the same attention as breast and prostate cancer. But the mortality rate is much higher for stomach (or gastric) cancer. Nearly 11,000 Americans will likely die from gastric cancer this year, with only 28 percent of cases surviving five years or more. For comparison, the five-year survival rate for prostate cancer is nearly 99 percent and for breast cancer, it’s more than 89 percent.

On a global scale, an estimated 700,000 people will die from gastric cancer this year, as Stanford infectious disease specialist Julie Parsonnet, MD, and her co-authors note in a Viewpoint piece in the most recent issue of the Journal of the American Medical Association. The authors also point out that worldwide, about 77 percent of gastric cancer cases are linked to chronic infections of Helicobacter pylori, a helix-shaped bacteria that was identified in the early 1980s and found to be linked to gastric ulcers a few years later, as well as to gastritis, an inflammation of the stomach lining that is a precursor to stomach cancer.

Researchers are still trying to understand exactly how H. pylori causes cancer or even how it colonizes the gastrointestinal track – they believe it’s picked up via food or water. Until recently, there was a dearth of randomized clinical trials that looked at the effectiveness of screening and treatment for H. pylori as a method for preventing stomach cancer.

Ignoring gastric cancer in the hope that it will soon disappear is not a tenable health policy

In the opinion piece, the authors describe the recommendations of a working group that met in December 2013 at the behest of the International Agency for Research on Cancer. Taking the burden of the disease and the availability of treatment options in consideration, the group considered gastric cancer “a logical target for intervention,” according to the authors of the JAMA piece. They go on to write:

Screening and treatment for H pylori is generally acceptable and affordable. An inexpensive serological test can determine who may be infected, with a sensitivity and specificity that could be sufficient for population-based prevention programs. Low-cost treatment regimens using 2 or 3 generic antibiotics plus a proton pump inhibitor for 7 to 14 days can eradicate the infection in more than 80% of cases, depending on the antibiotic resistance patterns of H pylori within the population. Economic modeling studies indicate that H pylori screening and treatment strategies are cost-effective under a large range of assumptions about effectiveness and costs. However, the models are limited by reliance on observational data rather than randomized trial results, by a lack of information on possible adverse effects of treatment, and by limited data from lower-income countries.

Researchers still have many gaps in their understanding of the best methods to prevent stomach cancer, but several trials may answer some of those questions in the coming decade.

Stomach cancer is not the only cancer known to be linked with an infection. Doctors routinely test whether women who come in for a PAP smear are infected with the human papilloma virus (HPV), which is linked to cervical cancer. Chronic hepatitis B and C infections are known to be linked to liver cancer. In time, screening for H. pylori to prevent stomach cancer may become routine. Until then, Parsonnet and her coauthors say in their conclusion, “Ignoring gastric cancer in the hope that it will soon disappear is not a tenable health policy.”

Previously: Researchers identify potential drug target in ulcer bug that infects half the world’s population, Good-bye cancer, good-bye stomach: A survivor shares her tale and Image of the Week: Helicobacter pylori colonizing the stomach
Photo by Shuman Tan and Lydia-Marie Joubert

Applied Biotechnology, Bioengineering, Cancer, Research, Stanford News

New “decoy” protein blocks cancer from spreading

New "decoy" protein blocks cancer from spreading

14299-metastasis_news

Cancer becomes most deadly when it’s on the move – jumping from the breast to the brain or the pancreas to the liver and then onward.

But now, a team of Stanford researchers led by radiation biologist Amato Giaccia, PhD, and bioengineer Jennifer Cochran, PhD, have created a protein that may be able to thwart the metastasis.

They published their results this week in Nature Chemical Biology.

“This is a very promising therapy that appears to be effective and nontoxic in preclinical experiments,” Giaccia said in a Stanford release. ”It could open up a new approach to cancer treatment.”

The researchers created a protein that mimics Axl, a protein found on the surface of cancer cells. This decoy protein intercepts incoming messages – intended for the original Axl – cueing the cancer cells to find a new home.

The decoy Axl worked wonders in mice. Mice with breast cancer given the treatment had 78 percent fewer new tumors, and mice with ovarian cancer had 90 percent fewer new tumors than mice with cancer not given the treatment.

Becky Bach is a former park ranger who now spends her time writing about science or practicing yoga. She’s a science-writing intern in the Office of Communications and Public Affairs.

Previously: Studying the drivers of metastasis to combat cancer, A computer kit could lead to a better way to design synthetic molecules, Common drug class targets breast cancer stem cells, may benefit more patients, says study
Photo by Rod Searcey

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