Tuesday, June 12, 2018

Dr. Michael B. Furman: It's a Beautiful Day

Michael B. Furman, M.D.
"This might be my last full day on Earth," the doctor thought to himself as he began his carefully-planned day, the day before scheduled surgery to repair an expanding aortic aneurysm and to replace his malformed aortic valve. He had put off the dual-operation for a while as he meticulously read and reread the literature on the procedures and the options.

He arrived at the JCC earlier than usual (and surprised his regular workout companions). He took a swim to loosen up his muscles and then did an intense (but not too intense) spin class. After this, he presented a lecture on his craft to his “fellows” in training and then did a few cases with them. He left the orthopedic practice a bit early to go home and watch a movie, Les Miserables, with his (fraternal) twin daughters. He then gently kissed his girls and told them to work hard, and to always be their best.

Following this, came the hour-long drive on Route 83 from York to Baltimore with his wife Esther for a nice dinner before checking in at the hotel near Johns Hopkins for surgery the next morning. Yes, a good carefully-thought-out logical day.

The following morning, with the IV stuck in his arm, the calm anesthesiologist told him to count backward from 100. After a few seconds he thought, “This stuff is not working...”  His next conscious memory was of simply awakening and seeing his wife’s worried eyes as if no time had passed at all:  “Nothing to it.”

Dr. Michael B. Furman, you see, doesn't stray far from his roots as an engineer. He needs to know exactly how something works, and when he finally figures it out he doesn’t stop; the goal is to improve, to get things better, to try to get them just right.

He grew up in “small town” (his words) Scranton where his grandfather owned “Furman’s Army-Navy” surplus store (established in 1911). As a young child he played in the store; later on, he worked there too. The family was close, and everybody got together on Thanksgiving. One year he vividly recalls seeing his uncle in a new light; though he had once been a strong military man he was now stuck in a wheelchair with multiple sclerosis.  His wife was the “nurse she had not expected to be.” This sad image of impaired mobility, limited function, and decline made a strong impression on the ever-curious youngster.
Cornell Engineering Motto

In high school, he was “good in the sciences” and  he “liked to think things through." He graduated in 1978 and went to the University of Pennsylvania as a pre-med student. But he soon decided to follow his natural inclination and transferred to the engineering school. After receiving a degree in chemical engineering from Penn he went to Cornell for a Masters in Science. His thesis was a graphics-based computer program simulating the movement of red blood cells through capillaries. He liked this kind of work. Yet, pondering his options, and with not-so-subtle encouragement from his friends, he felt the pull of medicine and concluded that he “would be happier as a doctor.” Yes...a doctor, that seemed right. But he would be one with the sensibility of an engineer.

At Temple Medical School in Philadelphia the grueling first year was “all memorizing,” not the “fun, and play, and problem-solving” our protagonist had expected and had experienced while in engineering.  It was time to rethink his plan.  He took a year off and did research; it was not quite what he wanted, and he returned to medicine with renewed zeal.
Dr. Nathaniel Mayer

During a summer job after the second year (with more memorizing) he had the good fortune of working with Dr. Nathaniel Mayer, a pioneer rehabilitation specialist who was then keenly interested in gait mechanics and movement, with the ultimate goal always of improving “function” for his patients.

In the third year, the beginning of the “clinical” years of actually seeing patients, the restless medical student discovered that he loved medicine and the chance to solve practical problems for people who were suffering. He was intrigued by the “up and coming” field of rehabilitation medicine where “function and medicine came together.” He wrote a computer program (“On cards,” he remarked, with some nostalgia) to explain to students how specific muscles “do different things” to move the human body through the environment.

The Physical Medicine and Rehabilitation (PM&R) professor (and chair of the department) was impressed by his work and asked him to present it at their annual Academy meeting. Dr. Furman was excited by the opportunity, and this introduced him to the politics of the specialty.  He took to this naturally and quickly saw that it could help his developing interests in teaching and clinical research.

Before starting his own PM&R training at Temple he did a so-called rotating internship at the York Hospital where he was exposed to various relevant specialties; he “loved” the year in York.

After he was back in Philadelphia he called an occupational therapist for a blind date. The careful young man suggested lunch and a hike. Lunch, yes, there would be less pressure if it didn’t work out. It did, however, and he asked the young woman if she would join him for dinner and a movie that very evening.  The rest, as they say, is history. Dr. Furman told me that one day at Esther’s apartment in Germantown she had her back to him at the sink washing dishes and he said, ”You know, we will probably wind up together.” She turned around, looked at him, and matter-of-factly replied, “Yes, I know.”  Less than ten months later they were wed, “on a beautiful day” (despite the rain).
"Blind" epidural technique

Anyway, after the three years of residency, he took a spine fellowship in Atlanta focusing on in “interventional pain management.” Among other things, he studied techniques of spinal injections of steroids. These procedures had mostly been done “blindly” (this is, without the benefit of imaging) by anesthesiologists who did nerve blocks for surgery. This was a relatively new idea for PM&R specialists as they searched for better ways to manage difficult spinal pain. Pain that sometimes prevented their patients from even taking part in physical therapy. 

The prime goal for the PM&R physiatrist is “to get people moving” and allow them “to get their lives back.” Dr. Furman envisioned the potential benefit of the spinal injections and concluded that precise and, most especially, safe, use of these techniques, when combined with various non-pharmacologic treatments, could ease patients along the path to wholeness again.
Engineer's Mind
 (from RoCkiNg EnGineRS)

It turned out that he so liked the feel of community medicine during his internship in York that he returned in 1995 (his parents and his wife’s parents lived in the Philadelphia area then; they would be not too far away) to practice with the orthopedic group. He was able to feed his interests in teaching, research, and medical politics in addition to doing clinical practice. He could use his critical insights and engineer’s mind to make things better. 
The far-sighted orthopedic surgeon Dr. Joseph Danyo saw this and encouraged him to start a fellowship (one of the first) in the field of image-guided intervention for pain. Dr. Furman did not hesitate, and the first fellow graduated from the program in 1998.

The program itself has remained successful despite lots of new competition, and there have been over 70 fellows over the past 20 years  (most still keep in touch and get together frequently). This success reflects the quality and passion of the teaching.

To that end, Dr. Furman is the lead author and creative force behind the standard textbook on the subject, and he has presented many well-received lectures (complete with “Furmanisms” as he calls them) to his interested colleagues around the country and internationally.
Dr. Furman's Textbook

In the words of David “DJ” Kennedy, M.D., now the PM&R Chairman at Vanderbilt, in his forward to the second edition of the text, the “Atlas of Image-Guided Spinal Procedures” transformed “multifaceted procedures into a series of simpler algorithmic tasks...offering clarity where only complexity existed.” The book is essential reading for anyone in the field.  

Dr. Furman enjoys teaching and takes this task very seriously. As he noted, "To teach is to learn twice” (echoing, it seems, the words of Joseph Joubert in the early 1800s). The Schwenck and Whitman (1987) version expends this: “To teach well is to learn twice as well, so that in the encounter the teacher learns more than the student.” This keeps clinician, sharp. Continuing their important thoughts on the subject: “Clinical teaching is essential in moving the profession of medicine forward.” Dr. Furman agrees, as does his professional society, as shown by their decision to recognize his efforts with their upcoming 2018 Legacy Award and Lectureship in October.
The Karate Kid and Mr. Miyagi
(Shu-Ha-Ri) 

(By the way, Dr. Furman has a deep and long-term interest in the martial arts and he told me about the important concept of “Shu-Ha-Ri.” That is, one first learns from the master by imitating his moves and understanding them (the Shu). The next step in the student-teacher process is to separate from the teacher with a higher degree of understanding, and to be able to break the rule when necessary (the Ha). The final step is to “become the rule” and to transcend it (the Ri). He followed this sequence as a student and now serves as the master. But I digress…)

Teaching is vitally important in management of patients. Teaching them how to deal better with pain, or teaching them how to cope with other orthopedic, skeletal, or neurologic limitations takes time and effort. Careful explanation of the planned intervention and providing expert guidance about reasonable “expectations” is critical for the best outcome, he notes.

Though Dr. Furman treats patients with a wide array of problems, with his special expertise in the interventional spinal procedures he sees many with chronic back pain, either with or without leg pain (sciatica). 

Though it is said that nearly 90% of acute back pain episodes resolve within six weeks, 70% reoccur, and as many as 7% will progress to chronic persistent back pain. Since acute spinal pain is so common (nearly universal), chronic pain, by extension, is an enormous problem for society. In fact, low back pain is felt to be the second-most-frequent reason for visits to a physician for a chronic condition.

Unfortunately, such pain is notoriously difficult to treat. Many individuals with chronic back pain are unable to continue working, cannot enjoy even simple pleasures of life, and feel that their lives are miserable. To make matters worse, the precise cause of their debilitating pain is often difficult or impossible to determine.

What, I wondered, about the “ruptured disk” people talk about?  Isn’t that the cause of a lot of back pain? A 2018 Medscape review (by Wheeler) notes that, “Although disk herniation has been popularized as a cause of spinal and radicular pain, asymptomatic disk
 herniations on computed tomography (CT) and magnetic resonance imaging (MRI) scans are common, (and) there is no clear relationship between the extent of disk protrusion and the degree of clinical symptoms.”

There are seemingly a few specific situations where surgery for chronic lower back pain is usually beneficial, such as when the spinal canal is severely narrowed, or when a part of the disk has broken off or fragmented, for example, but surgery is not needed for most patients. 

For them, a  “multidisciplinary” treatment program is more appropriate. The focus is on function (that word, again), utilizing a broad range of physical techniques in addition to analgesics, pain modifiers that change the pain signals traveling through the nervous system, and anti-inflammatory medicines. It is stressed that emotional, social, and work-related issues that may affect the patient’s recovery need to be identified and addressed. 

But when pain is too intense to allow participation in physical therapy, or when “conservative” (the non-surgical) therapies have been tried and failed and there is no clear-cut or urgent surgical condition an "interventionist" like Dr. Furman may be called in to help. With careful selection of patients, and the right image-guided technique for injecting the anti-
inflammatory steroid where it will provide the most benefit, there are very good results, often with sustained pain relief at six months or a year or more.  Relieved of the burden of pain, patients can enjoy life again.


So, Dr. Michael Furman--physician, engineer, educator, and author--and the scores of fellows he has trained over the past 20 years, can often intervene effectively and safely when stubborn disabling spinal pain gets in the way of recovery. And when chronic back pain is finally under control, is managed better, it can be “a beautiful day.”

Come to think of it, Dr. Furman’s planned “last full day on Earth” sounds pretty close to what he might like to do most days. 

Shu-Ha-Ri.





References:

Furman, Michael B., with Leland Berkowits, Isaac Cohen, Bradley S. Goodman, Jonathan S. Kirschner, Thomas S. Lee and Paul S. Lin. Atlas of Image-Guided Spinal Procedures. Elsevier, 2018.

Joseph Joubert.  Joubert: A Selection from His Thoughts.  1899.

Schwenck, Thomas, and Whitman, Neal. The Physician as Teacher. Williams and Wilkins, 1987.

Wheeler, Anthony. Low Back Pain and Sciatica. Medscape Jan 2, 2018 (emedicine.medscape.com/article/1144130)

Sunday, April 15, 2018

Dr. Michelle Weiss: A Love Story


Michelle Weiss, M.D.
The twelve-year-old girl had an accident; she fell off her bike, hit her head, and broke her teeth.  As a result of the concussion she couldn’t remember the details of the event, but she remembered the feeling. While lying on the bed in the ER and “in the midst of all this confusion” her family pediatrician arrived. His smiling face brought her “such comfort,” and she was extremely grateful simply for his presence. Looking back, she believes that this started her “going down the track of medicine.”


Ellis Island circa 1910
As a daughter of first-generation Americans (whose own parents came through Ellis Island from Eastern Europe) she was taught the value of education. She and her two sisters (one, a twin) were made to believe that there were “no limits” on what they could do in life. That is, as long as they would be either a teacher (like her mother), an accountant (like her father), a lawyer (as her two sisters would eventually become), or a doctor (as she herself would be).  

Dr. Michelle Weiss was a natural and joyous learner, and during her sophomore year at the University of Rochester she excelled and received early acceptance to the medical school. She “recalculated” and quickly switched her major from Biochemistry to Psychology (with an informal Art History “minor”). Everything seemed fine, and she was happy and on her way.But the following year, a month before he had planned to present her with an engagement ring, her boyfriend had an epileptic seizure and died. This threw her “off-target” for quite a while.

As she finished college and then immersed herself in medical school studies she “loved” everything she did. She told me, in fact, that she “loved every minute” and “loved” all of her rotations in the medical specialties. She was most moved, however, by her time spent in pediatrics.On the peds-oncology floor she saw that nobody was “burned out” as they took care of the desperately sick children. How could they be, she thought, as the resilient kids played together, and sold cups of sweetened lemonade?

CHOP
Taken by this, Dr. Weiss did a three-year pediatric residency at Children’s Hospital of Philadelphia (affectionately known as CHOP). Needless to say, she “loved” this, too, as “everybody worked together.”  She recalled, by the way, that a small container of McDonald’s fries (the old recipe!) could create an instant friendship. (The very first Ronald McDonald House was opened, at CHOP, in 1974, with the help of the Philadelphia Eagles.)

But how did Dr. Weiss eventually narrow down her broad interests to become a pediatric allergist/immunologist? The only one in York?

Scene from "Billy Elliot"
The story goes way back. In elementary school, she watched with delight as a fellow student began to show talent, even by the sixth grade. The gym teacher’s son was athletic and charming. In high school, he was a “magnificent” dancer who could “fly through the air like Billy Elliot.” At NYU he majored in the arts. Sadly, he developed AIDS and died before he graduated college.  This affected Dr.Weiss deeply. In fact, she was so "shook up" that she needed to know more. So she took a graduate class in immunology at Rochester (while still an undergraduate).

Kathleen Sullivan M.D., Ph.D.
Her interest in immune T cells, B cells, and histamine release continued through medical school and residency training. And after the three years of general pediatrics she did a two-year fellowship in allergy and immunology at CHOP with the prominent immunologist and noted HIV researcher Dr. Steven Douglas. She worked closely with Dr. Kathleen (Kate) Sullivan (currently chief of Allergy and Immunology at CHOP) who was “kind, and brilliant beyond belief.” It was Dr. Sullivan who taught Dr. Weiss to “go out of your way to help people...to go the extra mile.” Anything less was not acceptable.

Around this time she was finally (doctors are the worst patients) treated for the allergic rhinitis she had suffered from every fall for years. There was sneezing and a runny nose and Dr. Weiss felt terrible. A colleague casually suggested that she should try the antihistamine Seldane. She did, and immediately felt better.  She said that she wished that she had known about this before, as she could “breathe again.” For her, it was, “a miracle drug! " (Seldane was taken off the market in 1997 due to serious heart arrhythmias and was replaced by its safe metabolite, fexofenadine, or Allegra.)

Early on during her fellowship she was offered a month-long pulmonary elective in Israel. Without hesitation, she went. But the rounds on patients in the hospital were in Hebrew and she was (uncharacteristically) not prepared.  So she played the role of tourist, and with a small group tagging behind, she became known as “the map girl.”

Shabbat at the Western Wall
One Friday night they were invited, with others, to the Western Wall, and then to a private residence for a Shabbat dinner. She was 28 and lonely. Most of the guests were much younger, but as Dr. Weiss looked around the lovely home she spotted a young man who, she thought, might be about her age. He was from Australia; they immediately hit it off.  They toured with the group for a while, but it wasn’t long before he wanted the girl “who knew her way around” all to himself. She went along with the plan, and, before long, they fell in love.

Martin (the Aussie) went back home, and she returned to CHOP. A few months later she made her way to Australia to see him.  He was smitten, and did not equivocate: "I am quitting my job, putting my house up for rent, giving my dog away, and moving to Philadelphia. Let's see if this works."

He arrived in Philadelphia in September (it was 1993) and proposed on November 1st. They got married at City Hall on November 30th, and the wedding was in July 1994. A few months later they were starting their family. As Dr. Weiss was finishing her fellowship she had to think about where to practice.  Her parents lived just outside New York City and her sister was in Owings Mills.  Family is vitally important to her and she split the difference, and moved to York.  She worked with  Dr. Greg Lanpher for a few years, and she went out on her own in 1997 (while carrying her second child).

Private practice has had its challenges in the era of corporate medicine but Martin worked behind the scenes to smooth things out as much as possible for his wife, and Dr. Weiss could focus solely on her patients.  When the demands of electronic documentation became too burdensome in the last few years, they adjusted.

The practice of allergy and immunology has, of course, changed substantially over the past 25 years.  There is a much better understanding of the genomic aspects of the so-called innate and adaptive arms of the (exceedingly complex) immune system. The precise molecular mechanisms of specific diseases are now known, opening up novel treatments.  She notes that, “our diagnostics are so much better.”

But, obtaining a meticulous history (from the patient or the parents) is still essential in the detective work to find out which allergens in the environment (inside or outside), or in the diet, set off the abnormal immune response.  This is a skill that Dr. Weiss has carefully honed over the years and it takes time to elicit and record it accurately. She spends the time.

What’s new? What should we know about? Dr. Weiss thought a minute and then remarked that, "everything we knew about food allergies was thrown out the window two years ago.”

It seems that reactions to food are the most common cause of trips to the ER for life-threatening anaphylaxis. The usual culprits in children are cow’s milk, eggs, and peanuts. Yes, peanuts. The incidence of peanut allergy doubled in recent years and there may be as many as 200 deaths yearly in the U.S. attributable to this.  While there is still no effective treatment other than avoiding even a speck of peanuts, there is now good reason for hope.


Israeli Peanut Treat
Dr. Weiss noted that it had been accepted dogma that exposure to peanuts should be avoided in infants and young children to prevent the development of peanut allergy. But this idea was questioned after it was found that Jewish children in Britain had ten times the rate of peanut allergies of Jewish children in Israel of similar genetic and socioeconomic backgrounds. Why? “Bamba,” a ubiquitous 50% peanut/puffed-corn doodle. Israeli infants are given this to suck on.  Eureka! Early exposure seemed to be protective, not harmful.

The proof. A 2015 NEJM study of allergy-prone infants (with eczema or an egg allergy) showed that only 1.9% of those who were given peanut-containing products developed a peanut allergy compared to 13.7% of the infants for whom peanuts were carefully avoided. The official guidelines about feeding infants peanut products were changed in 2017 to reflect this compelling data (and real-life experience). Parents will be able to breathe easier when they do not have to worry about that.

Speaking of breathing, Dr. Weiss is quite pleased that asthma can usually be controlled without using repeated doses of systemic steroids (such as prednisone) that have potentially harmful side effects. She noted that the newer inhaled steroids are very effective, and are safe for use in very young children. In 2015 there were 3,615 deaths in the U.S. attributed to asthma; 219 of those were in children under 19. Alarmingly, the death rate for children under eleven years old had increased nearly 80% since 1980.

Proper and aggressive treatment of chronic asthma and acute exacerbations with beta-agonists, inhaled steroids, leukotriene receptor antagonists (like Singulair), and maybe even the IgE-binding antibody omalizumab (there’s that -mab thing again), she believes, could reduce the numbers substantially.  

What about bee stings, I asked? She said that if there is a history of a severe life-threatening reaction, and a positive skin test to bee or wasp venom, desensitization can easily be done. With the periodic injections the eventual cure rate is 98.6%.  “Not enough people know about this,” she said.

There is much more. Dr. Weiss reads the literature closely (though she is not especially fond of the required periodic exams), has presented more than 20 carefully-prepared Grand Rounds to the medical staff, and has given noon lectures for the residents to enlighten them. She spends much time educating her patients and their anxious families. All of this is done with the same “love” she experienced in her work during her training years, the “love” she found in her Mid-East travels, and the “love” she shares with her family and close friends.

Dr. Weiss remembers the smiling pediatrician who met her in the ER when she was vulnerable and frightened, and she channels that smile as she engages with, and brightens, the world around her. We smile back in return.


Robert Indiana's "LOVE" Sculpture in Philadelphia



Tuesday, March 27, 2018

Eamonn Boyle, M.D. says, "Most Things Get Better..."

Having “no grand plan” for his life after high school the young man was idling in front of a bookcase when he spotted a volume on zoology and thought to himself, “That might be interesting.” A few months later, in 1963, he entered the government-sponsored seven-year medical school program at University College, Dublin. Half of the lads (there were very few women) left after the first demanding year.

Eamonn Boyle, M.D., F.A.C.P.
Our protagonist did well and continued his studies. He enjoyed zoology, but also chemistry, biology, physics and, especially, botany.  Dr. John Harman,  “a great pathology professor,” introduced him to the study of inflammation, how the body defends and protects itself, and Dr. Ruy Pérez-Tamayo taught him about tumors. But his interests were still broad and as Dr. Eamonn Boyle (the young man of the story) finished his studies he wondered, “What am I going to do now?”

While preparing to “put in papers” for an internship at the hospital where he trained (as did most of his fellow graduates)  he ran into his alphabetically-arranged classmate Frank Bonner (Bonner, Boyle, etc., you know how it was in the old days when life was simple and orderly). Frank was from Philadelphia, and said, “Why don’t you come to America? I think I can get you in. They’re missing a player!”

So he landed his rotating internship and two-year medicine residency at Bryn Mawr Hospital from 1970 to 1973.  His interest in oncology that was sparked while in medical school became more definite as he closely watched and learned all he could from the “legendary and revered” (according to her 2005 obituary), Dr. Abigail Silvers.  

She let Dr. Boyle know that even if you could not cure their cancers, patients still had general medical needs, and that you could alleviate their symptoms and relieve their suffering, and that they “didn’t all die in one day.” He was deeply affected by her humanity and thought, “This would be a good fit.”  And, he reasoned, treatment for cancer “is only going to get better with the passage of time, since most things get better.”   
Emil Freireich, M.D.

After his time in suburban Philadelphia, he took a fellowship at the M.D. Anderson Cancer Center in Houston, Texas, one of the first comprehensive cancer centers and (according to U.S. News) ranked #1 for 11 of the past 14 years. He spent five intense years in Texas as he worked alongside true cancer treatment pioneers, including Dr. Emil Freireich.

While sleep-deprived (he was on call every third night) but well-fed (they provided “three squares”) at Bryn Mawr he had met a local student-nurse who would later agree to become his wife. When thinking about where to go into practice (academic medicine was not for him) proximity to Philly, where her family lived, was important.   

He interviewed for a position in Lancaster but there was no need for a full-time oncologist at the small Catholic hospital. The radiation therapist there referred him to York Hospital “just down the road” since Dr. Ross Moquin was unexpectedly leaving practice.   On the short drive from Lancaster to York that beautiful cool Mother’s Day weekend the trees and flowers were in bloom and the rolling hills were a welcome break from flat and steamy Houston.  He could be comfortable here, he thought. 

He liked what he saw, particularly when he met several of the general internists at the hospital, including Drs. Leo Samuelson and Jack Kline.  Dr. Moquin queried him and quickly said, “The job is yours.”  Dr. Boyle began to see patients here in 1978, joining Dr. Miodrag Kukrika who had been in York for a few years and, together, they formed “Cancer Care Associates.”  Their practice expanded and evolved over the next 40 years.

The field of oncology, of course, has also changed dramatically in four decades.

Blood Smear of ALL
In the beginning.  Watching children with acute lymphoblastic leukemia (ALL) quickly succumb to their devastating illness Dr. Sidney Farber felt helpless. In 1947 he and his team used the folic acid antagonist aminopterin to block DNA synthesis. Many of the children had their disease go into remission, but they all subsequently developed resistance to the single drug and relapsed and died. 

Treatment was then refined by the aforementioned Dr. Freireich as he gave the kids several agents in combination (similar in concept to the treatment for tuberculosis, it was noted), and the therapy was then continued beyond the acute stage.  

Thus began the era of “multiple-drug induction followed by maintenance chemotherapy.”  By 1971 the cure rate in ALL was 50%.  Dr. Boyle witnessed this, and there was new optimism as he noted that, “Little children could go from inevitably dying, to being cured most of the time.”  The cure rate now at St. Jude is 90+%. 

After the spectacular success with ALL, curative treatment for advanced Hodgkin’s lymphoma followed in 1965, and advanced testicular carcinoma became a very treatable disease in 1975.  For a young optimistic cancer doctor, this was evidence that aggressive chemotherapy might also even halt, for example, metastatic breast, colon, prostate, and lung cancers. As Dr. Boyle said, “That was the proof (we needed).”

In the middle.  The intense and complicated chemotherapy regimens of the 1980s and early 1990s often made patients feel terrible, and as their white blood cell counts dropped precipitously they sometimes developed life-threatening infections.  This “slowed down” but did not really cure many cancers. Colony-stimulating factors helped limit anemia and falling white counts, but that was not enough. Discouraged, Dr. Boyle waited patiently for something better.

(From "Rewire Me")
Along the way, he noted that there were “rough areas” (emotionally) but that he “never thought of doing anything else.” He was a “round peg in a round hole” as a front-line practitioner serving the York community.  As he reflected on this, he noted that the “relationship with people” as he gently guided them along in their cancer travels and helped them cope with the “assault on their personhood and control” was “the biggest thing” for him. As it is for most physicians, he believes.  

But he feels that, ”There could be a little bit more done psychologically for the cancer patient who has trouble keeping the balance," and that "this (struggle) relates to their nature before the cancer, and how much cancer and its treatment is interfering with their life.” 

The current era.  (Here is where things get really complicated, and Dr. Boyle, with patience, and in his gently nudging way, took the time to allow me to get things reasonably straight.) Cancer, he noted, is now recognized "fundamentally" as a gene disorder. Damaged genes (hence called oncogenes) go haywire, causing the affected cells to grow uncontrollably, to spread to other organs, or to block the effects of the body’s usually-protective immune system.  

The damage to the DNA of the genome may be caused by environmental factors including tobacco, chemicals, radiation, and others, still unknown. A number of viruses may alter host genes or introduce new genes that may eventually lead to cancer.

Location of BRCA Genes
There may also be an inherited (i.e., hereditary)  tendency (Dr. Boyle was careful to emphasize this latter point) to develop to certain cancers, such seen in carriers of mutated tumor-suppressor BRCA1 and BRCA2 genes that substantially increase the risk of breast and ovarian cancers. But even here, subsequent gene damage is necessary for the development of a cancer cell.

It was dreamed decades ago that by knowing the exact genome of the cancer cell it might be possible to design agents to attack only those specific altered functions.  It took some time, but this "sequencing" of the gene can now be done relatively easily, and an antibody to the precise target, a so-called monoclonal antibody, can be created in any amounts needed (yes, this is truly amazing science and technology). 

Rituxan, the first monoclonal antibody therapy was introduced in 1997. It attacks the B cells of the immune system that have a unique cell-surface marker called CD20.
  
Structure of Rituximab (Wikipedia)
Other therapeutic antibodies, including what are known as checkpoint inhibitors, have been developed. These include, among others, Herceptin in 1998 for breast cancers, Avastin in 2004 to block the vascular supply to certain tumors, Erbitux, an epidermal growth factor inhibitor, in 2009, for colon, lung and head and neck tumors, and Keytruda, in 2017, that blocks the cancer’s own sneaky self-protective adaptive system to then permit the patient’s immune cells to do their job and attack and destroy the tumor.  

There is already a genetic test to see if the patient will not respond to Erbitux or Keytruda, so, less guessing, making Dr. Boyle's job is a wee-bit easier.

Dr. Boyle notes that in addition to the advanced “biologic” monoclonals (whose tongue-twister generic names all end in -mab, by the way) conventional drugs with simple chemical structures have been designed to attack specific tumor cells.  This may be done by blocking a protein, or enzyme, necessary for the activity of the rogue cells.  Gleevec (released in 2001)  for chronic myelogenous leukemia and certain stomach tumors, and Imbruvica (in 2015), for chronic lymphocytic leukemia, are examples of this.  

More immunology; old and new. Since the 1980s the BCG vaccine used to prevent tuberculosis in countries where TB is endemic has been employed surprisingly effectively to treat minor bladder cancers.  At Duke University a vaccine derived from the patient’s tumor itself is being tested with remarkable success in treating glioblastoma, the highly aggressive and feared primary brain tumor. In fact, it has, on average, tripled survival times. 

Recent experiments in mice showed that when they are vaccinated with their own induced stem cells they eradicated many different types of tumor cells, raising the hope that the same will occur in our species.

Cartoon of CAR-T
The newest immune system therapy, noted Dr. Boyle, is called CAR-T(cell).  This takes the patient’s own T killer-cells and engineers them to have a specific surface marker. It then makes a bunch of these cells to infuse back into the patient.  This has been partially effective in otherwise resistant childhood leukemia and certain stubborn lymphomas. CAR-T is given as a single treatment. Novartis has currently priced its version at $475,000 (while Gilead charges a measly $373,000).  

Multiple Factors in Disease
The future. After a cancer diagnosis or, better yet, after finding a pre-cancer picked up by sophisticated screening, we will calmly sit down with our doctor and be offered perfectly-customized “precision” care uniquely matched to our genetics and epigenetics (the turning-on and turning-off of specific genes), the offending gene mutations of the cancerous cells, the activity (or lack thereof) of our protective immune system, and our personal history of other risk factors and unique biology. There will be less fear, fewer side effects from treatment, less suffering, occasional miraculous cures, and longer survival.

"But, won’t cancer one day be totally eradicated?" I asked. 

Regrettably, but with soft gentle honesty, Dr. Boyle said, "I don’t think so." He noted, instead, that "cancer may be tied up in the way we are.” Implying that this is an integral part of our animal biology, of our evolutionary zoological heritage.

The Pulitzer Prize-winning author of The Emperor of All Maladies, Dr. Siddhartha Mukherjee, agrees:
"The Emperor.."


Cancer, we have discovered, is stitched into our genome. Oncogenes arise from mutations in essential genes that regulate growth. Mutations accumulate in our genes when the DNA is damaged by carcinogens, but also by seemingly random errors in copying genes when cells divide. ..Cancer is a flaw in our growth, but this flaw is deeply entrenched in ourselves. We can rid ourselves of cancer, then, only in as much as we can rid ourselves of the processes in our physiology that depend on growth--aging, regeneration, healing, reproduction...It is possible that we are fatally conjoined to this ancient illness, forced to play its cat-and-mouse game for the foreseeable future of our species...But if cancer deaths can be prevented before old age it will transform the way we imagine this ancient illness...It would be a victory over our own inevitability, (p. 462-3).


I think Dr. Eamonn Boyle would be satisfied with that.

Required Reading: Mukherjee, Siddhartha. "The Emperor of All Maladies; A Biography of Cancer."  New York; Scribner, 2010.

Sunday, March 11, 2018

John Mathai, M.D., F.A.C.S., F.A.C.C.

The 23-year-old young man arrived at midnight in Pune after a fifteen-hour train ride from Trivandrum.  He slept on a bench on the platform and awoke to someone sticking him in the side. He looked up and the policeman said, “You have a suitcase. Put your feet on top of it so  no one will steal it.”   He left the station and thought, “What have I done now?"  His appointment was in a few days.  He washed up and walked into the main parking area of the busy Indian railway station.

Coastal SW India
With no hotel reservations, he looked around.  He spotted a priest and thought to himself, “He must be an honest guy.”  He went up to him and told him that he was there for an interview and was looking for a place to stay for a few nights. The priest said he had a friend at the university who could give him a room. He was instructed to take a bus and to meet him at a specific stop.  It was very hot, and, after arrival, the young man looked around anxiously for the priest and waited, and was relieved when he finally saw him on his bicycle.  

Lodging at the empty school was arranged (it was summer) and he was told where he could get his suit pressed.  He did what was suggested and he had the interview.  With a “first place” in surgery and “second place” in medicine he was, of course, selected.  He would go to the States for a general internship at Somerset Hospital in Somerville, New Jersey.
.   
John Mathai, M.D.
Dr. John Mathai was that young man with dreams. He finished medical school in lush Kerala on the southwest coast of India in 1962 and decided to go into surgery like his father, a tuberculosis specialist. The hope was to leave India and study and practice in Great Britain where he could learn from the best, and be one of them. He would be a Fellow of the coveted Royal College of Surgeons.  

That would be nice, but he didn’t have the right contacts.  However, he could first get to the U.S. through an Indian foundation and then go to England from there. Thus, the preceding little story.

Yet, arranging the trip to New Jersey was not so simple. India was at war with China and doctors were being denied passports; maybe he would have to stay.  But “someone with money,” noted Dr. Mathai, petitioned the Supreme Court, and it was decided that “it was everyone’s right to get a passport.” He did that and was on his way.

With the help of the then-current “Fly Now; Pay Later” program (this was before credit cards, so we can all “fly now and pay later” ), and a split ticket, he left Bombay.  He flew from there through Cairo to Rome on TWA, and then to New York City on Pan Am.

With the help of his cousin who worked for the Federal Reserve Bank, he had filled out the proper governmental forms so he could take money out of the country for travel. How much did he have with him? Why, the maximum, of course...75 rupees (about fifteen dollars!).  And one flimsy suitcase.

Approaching New York in winter the pilot announced,"Even with snow on the ground we will be landing on schedule."  Dr. Mathai was puzzled at first and didn’t recognize the last word since he was used to the British (and Indian) pronunciation of it as “shedule.”  Was “Skedule” another city? He thought for a moment and then understood.  

More connections…

A sign held up by an airline employee alerted him that the assistant director of the hospital was there to greet him, and he was ready. Walking through the terminal together to get to the car they came upon an escalator.  Having not seen “this animal” before he was baffled as the moving steps appeared and disappeared. Dr.Mathai said, “I watched how these guys got on this thing and I got up my courage and stepped on.”   He was a quick learner.

Mumbai, not N.J.
The director drove through New York City and Dr. Mathai witnessed some of the things he had read about while he was in India, and that was fine. But the most impressive sight by far was the scene when they got to the turnpike.  He was utterly “amazed” by the orderliness of the traffic, with all the cars in a line, and all going in the same direction!  This was not the chaos that he felt in India.
   
After the internship year in Somerville his plan was still to go to England, of course.  So, at a camera shop just off Times Square, he bought a fine Voightlander (he still cherishes it) to preserve his memories of being in America.  Of being in a country where, he noted, “Everything works.”

As it turned out, though, Dr. Mathai didn’t leave after his internship.  There were four years of general surgery at Albert Einstein Hospital in Philadelphia,“York and Tabor,” (where I, the writer, just happened to have been whelped).  He then needed to specialize, and first considered neurosurgery; it was fascinating, but too “depressing.”  But “somehow” he was “attracted to Dryden Morse” a heart surgeon at Hahnemann who had worked with Dr. Charles Bailey (“the father of direct heart surgery” according to Dr. Denton Cooley).   

Pioneer: Dr. Favorolo at Cleveland
Dr. Morse took a special interest in Dr. Mathai and mentored him in the exploding field of open heart surgery in the mid-1960s. The young surgeon considered going to the Cleveland Clinic next, where bypass grafting was being perfected, but was convinced instead to pursue his passion at the university level, and he planned to go to the University of Maryland with the renowned trauma innovator Dr. R Adams Cowley.

Not so fast, buddy boy!  This was the time of the Vietnam Tet Offensive in 1968 and Dr. Mathai was called to serve his new country. He passed his perfunctory physical (”Can you see? Can you walk?”) at the Draft Board in Philadelphia and was ready to go to war, but Dr. Cowley “needed” him in his program.  He pulled strings and used his military contacts and, as a result, Dr. Mathai was able to start his Thoracic Surgery residency.

After completing that grueling program Dr. Cowley steered him to York where he joined the staff in 1970.  He  started work ominously (he felt) on August 6th, “the date of Hiroshima,” and soon realized that he was, in his words, “the only foreigner” on the clinical medical staff, and that “nobody looked like (him).”

Surgical Team in Cleveland
He quickly fit in, however, and was urged by Dr. Jack Gracey (of Cardiology) and Paul Keiser (the CEO of the hospital) to start a full cardiac surgery program.  This had to be approved by the medical staff but they were bitterly divided and needed to be convinced. So Dr. Mathai took a fellowship at the Cleveland Clinic where he met Dr. Joe Hooper.  They became friends and decided to work together to start things in York.  With chutzpah, they brought the Clinic’s Cardiac OR nurse manager, and the capable Physician’s Assistant working with her, to the York Hospital.  The plan was to “duplicate exactly” what was done in Cleveland, and the program here began in 1975.

Two Types of Bypasses
The team was very careful in selecting patients, and the statistics for the first year were excellent.  The service then continued with several other surgeons (including Drs. Peter, Levin, Fried, Haupt., etc.), and Dr. Mathai practiced open heart surgery at York day and night until 2007 when the health system changed.  He then did cardiac procedures for several productive years at  Holy Spirit Hospital in Camp Hill and Pinnacle in Harrisburg with Dr. Brad Levin before unforeseen circumstances forced him in another direction.  After a few months, he started a practice limited to vein surgery, and he enjoys seeing patients even now. 

Dr. Mathai returned to India several times a year for 30 years to work with a Hindu charity, and for the last 20 he went to private hospitals, mostly the Kerala Institute of Medical Sciences.  He has seen many changes over the decades and notes that the facilities in his homeland are now comparable “and sometimes a little better” than hospitals here.

Today, at 79 (that’s correct), Dr. Mathai can look back at his own career and see the history of coronary artery bypass graft surgery.  The first successful CABG was done by Dr. Robert
Goetz (from Frankfurt by way of South Africa) on May 2, 1960, at Albert Einstein in New York.  Unfortunately, his “colleagues were violently against the procedure” and, as a result, he was not permitted to further pursue his exciting technique (the actual artery-to-artery anastomosis itself took...are you ready?...17 seconds!).  

Time passed before Dr. Rene Favorolo (a fiery Argentinian) at the Cleveland Clinic did the first aortocoronary bypass using the patient’s own saphenous vein as the donor vessel in 1967, and by 1970 he and his colleagues had performed more than 1,000 such procedures.  

A Robotic Procedure
Surgeons throughout the United States adopted this technique and have been modifying and perfecting the operation ever since. The number of bypasses performed yearly in the U.S. peaked in 2000 at around 500,000 and has steadily declined since as advances in coronary stenting (by clearing the blocked artery from within rather than going around it)  and preventive therapies (to halt progression or even reverse some of the plaque build-up) have appeared. In fact, coronary artery bypass grafting is now often done robotically, without the need to split the sternum, without the need to open the chest, without the need for the surgeon to touch the patient.  

When It's Over...
Over his nearly 40 years practicing heart surgery, Dr. Mathai has seen and done much as he has been part of and has adapted to changes in medicine.  As stated by the Nobel Laureate cardiologist Dr. Bernard Lown, "No doubt what one does is largely the result of who one is." This is clearly so for the resourceful and resilient Dr. John Mathai who noted that change is woven into the fabric of life, that the trace of the heart’s rhythm changes moment to moment, until one day it doesn’t.

Complex open heart surgery and, specifically, coronary artery bypass, like all significant medical interventions, has been the product of the prodigious talents and sustained efforts of many dedicated individuals. Individuals whose path may not be a straight line, and whose journey may start in a faraway land, on a train platform, in the dark of night.  

We thank them all.