He was not thrilled with these odds and presented a series of scenarios for me to consider in order to, and this is a direct quote, “save his ass.” I returned each verbal volley and stayed on course; from a sound and proven oncologic-principle perspective I insisted on removing all cancer-bearing tissue, even if it meant an APR. After thirty minutes of presenting his case, my lawyer patient sighed, shook his head, and agreed to proceed with the operation needed to remove the rectal cancer completely. His wife was supportive, but after her husband signed the surgical consent forms, she made us both laugh when she stated, “Don’t be a wimp, he’ll do all he can to save that ass.”
On the day of his operation, I was paged to call the direct number in the operating room where the procedure was scheduled. The circulating nurse answered the phone snickering and said, “You need to get in here and see something.” Unusual, but okay, a little preoperative levity. When I walked into the operating room my patient looked at me, then at the nurse and said, “Go ahead.” She pulled down the sheet covering him to expose his abdomen. There, written in large black block letters was the phrase SAVE THE ASSHOLE!
I was ready for him. I nodded knowingly, my surgical mask covering my smile, and responded, “You know, you are a lawyer. Most people think lawyers are assholes. Do you want me to save your actual asshole, or all of you?”
He roared with laughter, as did everyone in the operating room. Gesturing to the anesthesiologist, I said, “Put him out.” As my patient drifted off into drug-induced somnolence, he chanted the same words written on his stomach. I got the message. Sheesh!
This tale has a happy ending, figuratively and literally. The LAR and temporary ileostomy procedure were completed successfully. As my still-snoring patient was wheeled to the recovery room, I walked out to speak with his wife. She smiled slyly and asked if her printing was clear enough for me to read. I thanked her for her fine penmanship and recounted the conversation I’d had with her husband in the operating room. She laughed joyfully, tears streaming down her cheeks, and hugged me and thanked me for saving both assholes. This couple was quite a pair of characters!
Six weeks after the lawyer’s rectal cancer operation, I reversed his ileostomy and the flow through his gastrointestinal tract was returned to normal. I am pleased to report that the fine asshole, uh, I mean lawyer, is still alive, well, and cancer-free with all body parts functioning normally more than sixteen years after his sphincter-sparing operation.
Homo sapiens, we are an interesting species. Wonders never cease.
5
Opportunity Calling, Version 1.0
“The only thing that will redeem mankind is cooperation.”
Bertrand Russell
Cooperation: The action or process of working together to the same end
Eight months after I completed my surgical oncology fellowship and was a shiny, new assistant professor of surgical oncology, it came time for the annual Society of Surgical Oncology meeting. Since I was the most junior member of the faculty and, thus, the lowest person on the totem pole, I was asked to stay behind to take care of the patients and “watch the fort.” On the first day I received a phone call from my chairman. He explained he had forgotten that he had agreed to host a group of Italian surgeons who wanted to visit our institution before going to the meeting. I asked him when they would be arriving, and his terse reply was, “They are in my office now.”
Okay then. I ambled over to his office and met a senior Italian surgical oncologist from Genoa and eight young surgical oncology trainees from different institutions in Italy. We sat at the conference room table and spoke about management of various types of cancers for more than an hour. I then led the entourage to the operating suites, and we changed into scrubs. The nine surgeons jostled for position and watched while I performed two liver resections. At the conclusion of the operations, we changed back into our civilian clothing and returned to the conference room. I answered questions for another hour, after which the senior Italian surgeon graciously thanked me for my time. All of the young surgeons provided me with a copy of their business cards and I offered a copy of mine in return. I thought to myself, “Well, that was a pleasant experience,” but I didn’t imagine anything further would come from it.
Three months later my secretary walked into my office and informed me I had a call from Italy. I was mildly surprised as I answered the phone and was greeted by one of the young surgeons I had met a few months earlier. He told me he was arranging a multidisciplinary gastrointestinal cancer meeting at his host institute in southern Italy, and wondered if I would be available to travel there to provide two lectures at the meeting. I calmly said, “Let me check my schedule.” I held the phone away from my face as carefully as I could and tapped a few keys on my computer keyboard for ten to twelve seconds. I returned the phone to my ear and masking my excitement said, “Yes, yes I think I can make it.” I was sent requests for my lecture topics and my travel documents and four months later I flew to Naples, Italy.
I was greeted at the airport by the young Italian surgeon who had invited me to the meeting. I do not sleep well on planes so I was a bit fatigued after an overnight transatlantic flight. This was my first visit to Italy. I was a little drowsy until we began the drive to my hotel. After the third red light we sped through, amid honking horns and flashing headlights I turned to my host and asked, “Do most people not stop at red lights in Italy?” He replied, “In Napoli the stop light is only a suggestion.” The harrowing car ride to the hotel erased my sleepiness, and my bags and I were deposited at the front desk. Mario Andretti, also known as Francesco, told me he would be by later to take me to dinner and would also drive me to the G. Pascale Istituto Nazionale di Tumori (the G. Pascale National Cancer Institute) the next morning. I wasn’t thrilled by the prospect of further time in an automobile with this young maniac. Fortunately, the trip to dinner was very short, and I was introduced to delicious Neapolitan pizza. Conversely, the several mile ride to the hospital the next morning was more eye opening than the previous day’s escapades, and I spent the majority of the trip encouraging my host to keep an eye on the road while I gripped the seat and door handle anxiously. I subsequently learned over ensuing years visiting other Italian cities and speaking with colleagues who lived elsewhere in Italy that even they find driving in Napoli a terrifying experience so I did not feel quite so cowardly.
Being invited to give two lectures at a national cancer center in Italy in my first year as a faculty member was an honor and a thrilling event. But I was also gifted with an important lesson from the adventure. I toured the hospital with my Italian hosts, and I noticed the large number of liver cancer patients there. Intrigued, I began talking to the surgeons, medical oncologists, and epidemiologists at the meeting and discovered that hepatitis C infection is very common in southern Italy. I had been performing basic science and clinical research on liver cancer so I was startled to learn the number of patients they were treating on an annual basis. The epidemiologists there informed me that the entire Campania region of Italy is served by a single public health hospital, the Cotugno Hospital. Furthermore, by Italian national law, if you are a patient diagnosed with any type of potentially transmissible infectious disease, including hepatitis B or C, HIV, or tuberculosis, you are required to present yourself for a health evaluation at the regional public health hospital on an annual basis.
Eureka! Chronic hepatitis B or C infection is a common risk factor in patients who develop liver cancer. I asked the Italian physicians and staff if they were performing any type of screening or assessment to detect liver cancer in their large population of hepatitis-infected individuals. The answer was negative; they were not.
I delivered my two lectures at the meeting and then spent the next day and a half working with physicians at the public health hospital in Napoli. I recognized an unexpected opportunity to perform a clinical trial to screen high-risk patients to determine if we could diagnose this usually lethal liver cancer (the majority of patien
ts who develop symptoms of pain, weight loss, or jaundice are diagnosed with advanced disease) at an earlier, potentially curable stage of disease in asymptomatic individuals. Together with the physicians and epidemiologists on staff, we wrote a protocol to screen individuals who were chronically infected with hepatitis B or C. The next year in 1992 we initiated our screening trial, which consisted of placing posters throughout the Cotugno Hospital. These signs informed patients with chronic hepatitis B or C that we would perform a blood test, a serum alpha fetoprotein (AFP) level, and a transabdominal ultrasound of their liver to assess for abnormalities suggestive of liver cancer. Our initial objective and hope was to screen a thousand patients over the ensuing three years. Notably and incredibly from my perspective, every chronic hepatitis patient underwent a core biopsy of their liver during their initial assessment at the Cotugno Hospital. This provided a treasure trove of pathology data on the presence and severity of virus-induced injury to the liver.
From 1992 until we closed the program in 2006 we overshot our goal considerably. We screened and followed more than 22,500 individuals with chronic hepatitis B or C.1 Parenthetically, most patients diagnosed with liver cancer are not candidates for operations such as liver transplantation, surgical removal of the tumor, or thermal ablation of their tumors because almost invariably they present with cancer that is too far advanced to be considered for any of these potentially curative treatments. For this reason, in most countries fewer than 10 percent of patients diagnosed with liver cancer are considered for potentially curative therapy. Even among those who receive a transplant, surgical removal of their tumor, or thermal ablation of their tumor, only about half are still alive five years later. The average survival range is from six to eighteen months for all other patients who have more extensive cancer and are not candidates for a local therapy like surgery or thermal ablation. The primary objective of our screening protocol was to determine if we could diagnosis a higher proportion of high-risk chronic hepatitis-infected asymptomatic patients with liver cancer at an early stage, when surgical intervention was still possible.
We have learned, and will continue to learn, numerous useful pieces of information from our screening trial. First, we were able to diagnose almost 70 percent of patients with asymptomatic liver cancer while they still had stage I or II disease. Their tumors were small and not invading major blood vessels in the liver so potentially curative therapy could be offered. As a result, some of our liver-cancer patients have achieved long-term survival after receiving curative-intent treatments.
Second, we learned that patients diagnosed with liver cancer came from a subset of approximately 20 percent of the total group of patients screened. The patients who developed liver cancer had a liver biopsy that revealed cirrhosis.2 Therefore, the 80 percent of people who had no biopsy evidence of severe chronic inflammation or fibrosis (scarring or cirrhosis) of their liver caused by the hepatitis virus did not need to be screened as frequently as the others.3 In patients with hepatitis C and cirrhosis about one-fifth were diagnosed at the time of their first screening evaluation with elevated serum AFP levels and/or an ultrasound examination revealing a liver tumor. Patients who had either of these findings went on to get a CT or magnetic resonance imaging (MRI) scan followed by a tumor biopsy to confirm the diagnosis and extent of the liver cancer. The remaining four-fifths of the patients who developed liver cancer were diagnosed sometime during their ongoing semiannual screening exams.
Third, we learned that new blood tests can be helpful in diagnosing liver cancer at an early stage. We discovered that serum levels of a novel biomarker, soluble interleukin-1 receptor, rose in liver cancer patients six to twelve months before AFP levels became elevated. We are continuing to study this and other novel biomarker blood tests in an attempt to increase our diagnostic accuracy. We recognize that we have a wealth of future data as we are following patients who originally had high circulating hepatitis C viral loads but were successfully treated with antiviral therapy. It will be critical to monitor these patients longitudinally to understand if there is reduction in their risk of developing liver cancer. Our cache of data will be mined for the next ten to twenty years to reveal additional findings.
One of the fascinating aspects of life as an academic physician is the opportunity to visit and interact with colleagues around the world. I have visited places I never imagined I’d see when I was a boy daydreaming my way through books about faraway and seemingly unreachable locales. I was blessed with an invaluable lesson from my first international experience. Now, every time I visit a new hospital in another country or around the United States where scientists and clinicians are interested in the multidisciplinary management of cancer patients, I inquire about the problems they face and the research they are performing. From our conversations we often identify common ground and potentially synergistic approaches to initiate collaborative basic and clinical research projects. Thanks to modern technology and communication in real time, we can perform large cooperative studies to improve our ability to prevent, diagnose, and more effectively treat cancer.
My first trip to Italy could have been nothing more than a pleasant diversion and an opportunity to enjoy Neapolitan pizza. However, as Louis Pasteur noted, “Fortune favors the prepared mind.” The good fortune to perform collaborative and cooperative research that can affect and improve the lives of our patients is always an opportunity I want to seek. The data and results accrued in our Italian liver-cancer screening trial has led to several European Community grants to expand the studies to other areas of Europe. I have returned to the G. Pascale Istituto Nazionale di Tumori, which sounds even better when vocalized, many times in the past twenty-four years. Happily, more motorists actually now stop at red lights. And walking across the street is no longer like running an undulating, dangerous obstacle course. I will continue to visit occasionally to assess and review the amassing data. The opportunity opened to me all those years ago will continue to reveal new avenues for research projects in Europe and the United States.
And, the Neapolitan pizza is always worth the journey.
Molto bene!
6
Does Your Dogma Bite?
“Creativity is just connecting things. When you ask creative people how they did something, they feel a little guilty because they didn’t really do it; they just saw something. It seemed obvious to them after a while. That’s because they were able to connect experiences they’ve had and synthesize new things.”
Steve Jobs
Creativity: The use of imagination or original ideas to create something; inventiveness
I like the silly humor in a scene from the movie The Return of the Pink Panther. Peter Sellers, playing the bumbling Inspector Clouseau, enters an inn to request a room for the night. After the usual language miscommunications between Clouseau and the innkeeper, the inspector stops and looks down at a small dog sitting near the door. He inquires if the innkeeper’s dog bites, and the elderly man blandly replies no. Clouseau reaches down to pet the dog, which promptly nips his hand.
“I thought you said your dog does not bite!” complains Clouseau.
“That is not my dog,” calmly replies the innkeeper.
I love dogs. No matter how my day was at work, I have a happy homecoming when I’m greeted joyfully by my pack of pooches. Tails wagging, four dogs (Yes, four. I told you I am fond of them!) greet me as I enter the house from the garage, each jostling for position to be the first for an ear or belly rub. Frequently, a toy is dropped at my feet informing me it’s time to go to the back yard for a game of fetch or rope tug. While dogs are great fun, playful, and wonderful companions, they can also chew your expensive new shoes to pieces or leave malodorous droppings in your house that you have to follow your nose to find. Dogma is much like this. Dogma develops in part because human nature likes to embrace things that are known, familiar, and comfortable. But dogma, like dogs, can be destructive or problematic. Dogma can suppress or discourage thoughtfulness and innovation. T
his is particularly dangerous in institutions where the leadership supports dogma and the climate does not advocate or encourage questioning of entrenched beliefs. In cancer care, dogma can be potentially deadly if we involved in patient care and research don’t constantly remind ourselves to question the adequacy of currently available treatments.
In surgical oncology, dogma can develop as readily as in any other area of medicine. As a poignant example, in 1988 Kevin Hughes and others published a paper in Surgery describing the survival rate of patients with colorectal-cancer liver metastases that were surgically removed.4 The authors reported that one-third of patients who underwent complete surgical removal of their liver tumors were still alive five years after the operation, most with no evidence of recurrence of their cancer. The paper is a seminal reason why surgical treatment of colorectal-cancer liver metastases, stage IV disease, is a common practice today, particularly since chemotherapy alone rarely cures these patients. For patients with colorectal cancer that has spread only to their liver, we can improve their probability of long-term survival by surgically removing or destroying their malignant liver tumors.