The only patients who have an opportunity for prolonged survival after detection of this malicious disease are those with a reasonably small tumor that has not metastasized and can be removed with a surgical operation. This select group considered for surgical resection comprises fewer than 20 percent of PDAC patients. This grim reality becomes even harsher, because about three-quarters of these surgically treated patients develop recurrent PDAC from the microscopic metastatic deposits that are present, but undetectable at the time of their operation. I have several hundred patients with primary or metastatic liver cancers who have survived more than five and, in many cases, more than ten years after their surgical procedures. I can count on both of my hands without using all of the fingers the number of patients who are ten-year survivors after resection of PDAC.
The Whipple operation my patient mentioned in her text message has a long name in Doc Talk: a pancreaticoduodenectomy. How’s that for a medical mouthful? A word worthy of a spelling bee champion. Designed to remove cancers in the head or uncinate process of the pancreas, this procedure is one of the most challenging in gastrointestinal surgical oncology. The operation removes the head of the pancreas, the entire first portion of the intestine, called the duodenum, the last one third of the stomach that connects to the duodenum (unless the surgeon chooses an option called a pylorus-sparing procedure), the first few inches of the second part of the small intestine, the gallbladder, and a portion of the bile duct above the duodenum and the head of the pancreas. After all of these structures are removed, there are three surgical reconnections that must be performed. The remaining pancreas must be attached to the small intestine to allow pancreatic enzymes needed for normal digestion of food to drain into the intestine. Next, the bile duct must be attached to the small intestine to allow normal flow of bile from the liver to enter the intestine. Finally, the stomach itself must be reconnected to the intestine to allow food to pass into the small intestine for digestion into basic protein, carbohydrate, and fat molecules that are absorbed across the lining of the small bowel, and then fed up to the liver through the portal vein to allow processing and distribution. It all sounds like a delivery, sorting, warehousing, and redistribution enterprise.
This operation has long been considered a surgical tour de force. It is a complex procedure, which in the hands of experienced hepatopancreaticobiliary, or HPB (are we running out of letters yet?), surgeons, can last from four to ten hours. Similar to any operation of long duration and multiple steps, intra-operative and postprocedure complications can and will develop. It is common for cancers in this location to abut or even invade the portal vein. It was once thought that portal-vein incursion by PDAC was a contraindication to resection, but aggressive surgical groups worldwide have demonstrated that the portal vein can be removed and replaced with a vein graft from elsewhere in the body. The short- and long-term outcomes for patients undergoing vascular reconstruction are similar to PDAC patients without portal-venous involvement.
The greater problem is tumor involvement of the superior mesenteric artery. This critical vessel supplies the arterial blood flow to the entire small intestine and more than half of the colon. Unlike blood vessels in other areas of the body, medical science has not yet devised a surefire way to replace this blood vessel. Therefore, even with no evidence of metastatic disease, pancreatic cancer that abuts or encases this artery is labeled “locally advanced” and is considered unresectable—or borderline resectable, in the event the tumor shrinks away from the vessel with preoperative chemotherapy or chemoradiation treatment.
To the great frustration of oncology professionals, only a small fraction of patients are considered candidates for resection for pancreatic adenocarcinoma. Most patients already have advanced or metastatic disease at the time of diagnosis, so they are treated with various chemotherapy recipes or combinations of chemotherapy and radiation therapy in attempts to slow the growth of the cancer. Radiation therapy can assist in alleviating some of the pain caused when the cancer begins to grow into nerves in front of the spine. State-of-the-art chemotherapy drugs improve the average survival time by only a matter of months, however. A new drug was approved for general use in PDAC patients in 2016; it improved average survival rates by a whopping two months (almost). And chemotherapy or radiation therapy is not curative in patients with PDAC. This is a source of incredible angst and exasperation for patients, their families, and their physicians.
Researchers worldwide are actively looking for better and less toxic treatments for PDAC and other cancers. Currently, immunotherapy holds tremendous promise in the treatment of numerous types of cancer. There are many clinical trials using activated T-cells (circulating cells from the immune system) and agents that promote killing of cancer by these T-cells. The trials are still in their infancy and it remains to be seen if this latest set of promising agents coupled with cancer-killing T-cells will improve the long-term survival probability of patients with PDAC and other heinous malignant diseases.
My laboratory is actively engaged in novel, noninvasive electromagnetic-field therapies to treat PDAC. We have information in pancreatic cancer cells and in animals with PDAC indicating these electromagnetic-field treatments, which are nontoxic and harmless to normal tissues and organs, can alter the cancer cells themselves. This makes them more susceptible to killing by cytotoxic drugs, and can enhance blood flow into the tumor, increasing the delivery of anticancer drugs, nanoparticles, and activated immune cells. It is probable that this treatment will also enhance the killing of PDAC cells by standard ionizing irradiation, but the overarching goal in our laboratory is to develop less toxic therapies to improve the outcomes in our patients. We have not treated any human patients yet, but we are gaining important insights into how to use noninvasive electromagnetic fields to improve several types of treatment in cancer patients.
I mused about the fear a diagnosis of PDAC incites in patients and their family members after I received the heartwarming text from my patient. I believe she has a very high probability of becoming a ten-year survivor. It has not been an easy road for her, however. During the nine years after her operation she endured four hospitalizations for a condition called ascending cholangitis: bacteria from her intestine colonized her bile ducts and caused a life-threatening infection. During two of these hospital admissions she wound up in the intensive-care unit for more than a week with high fevers, and she actually required a ventilator for several days during one of the episodes. Each time aggressive medical therapy and antibiotics brought her back from the brink. She also required two additional operations for small-bowel obstructions. Patients who undergo major abdominal operations are known to have an increased risk of developing scarring within the peritoneal cavity, which can lead to narrowing or obstruction of the intestine. Some of these patients can be managed without an operation, and their bowel function returns to normal. My “Nine-Year Lady” unfortunately twice developed complete obstruction of her small bowel, three years and then again seven years after her initial pancreaticoduodenectomy, necessitating operations to remove a small section of scarred intestine that was in danger of perforating. Despite these problems, thankfully, her PDAC has never recurred.
My patient is one of the most grateful and radiant individuals I have encountered in my medical career. Throughout her recurrent hospitalizations and recovery she has remained upbeat and positive. She is mischievous and energetic; every time I see her in the clinic I am guaranteed a hug and kiss. She likes bright-red lipstick so the clinic staff must always quietly remind me to wipe my cheek after I see her lest I bounce into another patient’s examination room with, literally, one rosy, red cheek!
I despise this hideous, difficult-to-treat disease, and I deplore what it does to the lives of far too many patients and their families. My colleagues and I are fueled by this negative emotion to search tirelessly for improved treatments for PDAC. This can be said about any type of cancer, or for that matter any type of disease a physician focuses on in his or her pr
actice and research. It is our desire to improve not only survival but also the quality of life for our patients. That is the “driver mutation” in the genome of a physician-investigator. When it comes to PDAC, I hope someday it will not be quite so unusual to receive a text message celebrating long-term success. Such a message is a great start to a day. I texted my reply:
Good morning to you! You are welcome!
I want many more good mornings for patients.
16
The Wrestler
“Remember you will not always win. Some days, the most resourceful individual will taste defeat. But there is, in this case, always tomorrow—after you have done your best to achieve success today.”
Maxwell Maltz
Resourcefulness: The ability to find quick and clever ways to overcome difficulties
I have fond memories of both of my grandfathers from when I was a boy growing up in the American Southwest. My mother’s father was a master gardener. In an arid environment he was able to grow plants that should have thrived only in tropical rain forests. Botanists from the Department of Biology at the local university surveyed his garden, and promptly asked him to help with problems they were experiencing in their greenhouses. There were large fruit trees scattered throughout my grandfather’s backyard, perfect for climbing and eating apples, peaches, or cherries fresh off the branch. Their dense foliage made it possible to hide and pounce down on unsuspecting younger brothers or cousins wandering too near the danger zone. Not saying I ever did such a thing, just saying it was possible. You know?
Every Friday night members of our extended family ate dinner at my mother’s parents’ house. I poignantly remember an after-dinner ritual. My grandfather would retire to his recliner, toothpick in his mouth, and instruct one of his grandchildren to turn on the color television in the bulky, multicomponent–console, with built-in radio, turntable, and speakers. It was time to watch Friday-night boxing. There was no remote control; we kids were the channel changers and volume-knob manipulators. My grandfather was usually not an emotional man, but he would become quite animated and occasionally agitated watching a fight, particularly if there was a boxer he favored in the match. We grandchildren enjoyed watching him more than we did the pugilists on the flickering television screen.
My father’s father, on the other hand, was a wrestling fan. By wrestling, I mean the brawling seen on Saturday-afternoon television, featuring men in tight shorts and outlandish costumes, some wearing colorful capes and hoods or masks over their heads. They entered the ring to either wild applause or catcalls and hisses, bouncing off the ropes to clothesline their onrushing opponent or jumping from the turnbuckles to land on their hapless rival laid out on the mat below. Even to a boy it was obviously bad theater and fraud, but I enjoyed watching my grandfather yelling at the television, berating the bad guys and the referees. He knew every hero and villain, and he would hurl epithets at the masked men in tight wrestling suits while openly cheering for those he admired. I still remember some of their names. Gene Kiniski, The Sheik, Ray Mendoza, Dory Funk Jr., Terry Funk, Mad Dog Vachon, Hard Boiled Haggarty, Raul Reyes, Killer Kowalski, and Johnny Valentine. My grandfather particularly loved the chaos of tag-team matches, guaranteed to degenerate into a free-for-all with all the combatants in the ring, throwing chairs, and occasionally even body-slamming the referee to the canvas. When I grew older I mistakenly pointed out that these matches were all rehearsed and the outcomes were scripted, that this wasn’t real sport. He fixed me with a glare and informed me I was getting, “a little too big for my britches.” He asked me if I thought a 250-pound man climbing to the top of the ropes to hurl himself on his foe below, or the prostrate, seemingly stunned wrestler on the mat absorbing the flying blow should be considered as anything less than athletic.
Good point. I wouldn’t want to do it.
Cancer patients and caregivers grapple with malignant disease every day. Surgical oncology is an unusual, but not unique, subspecialty area in surgical care. Many surgeons will enter the lives of their patients for an acute illness or event, perform the indicated operation to improve their condition, care for them in the hospital, and then see them for one or two postoperative visits before discharging them on to the rest of their lives. Some surgical subspecialties, including surgical oncology, follow their patients longitudinally. All oncology-related specialties follow their patients for years, if not their lifetime, after a diagnosis of cancer. We watch for the success of our treatment, evidence of any recurrent or new metastatic disease, and we treat any symptoms or problems related to the therapies we deliver. We get a chance to know our patients and their families, and to watch how they respond to living with the ever-present specter—the possible return of malignant disease.
I admire the pluck and defiance of my patients who have a never-give-up attitude. One particular patient comes to mind when I think about fortitude. When I walked into the examination room to meet him, he sprang to his feet, grasped my hand and shook it vigorously, smiled a dazzling white smile, and then gave me a bear hug. Effusive. His first words: “Doc, you’re going to help me beat this thing!” At this point he was still shaking my hand, his grip getting tighter, so I politely asked him to release my hand lest I be unable to perform an operation on him because of damaged digits. He laughed and immediately cut me loose, allowing circulation to return to my fingers. We sat down to talk. I was not surprised this gentleman had an impressive grip. He was in his late forties and built like a running back or rugby player. I actually asked him if he had been a football player. He feigned disgust and exasperation and said, “No, I’m a real athlete. I am a wrestler.” As I explored his history it turned out he had been a collegiate wrestler of significant accomplishment and repute. After graduation he had founded a successful business and spent his time raising his family, expanding his business acumen, and refereeing high school and college wrestling matches around his home state.
I was seeing this man for a diagnosis of colorectal-cancer liver metastasis. Eight months prior to our initial meeting, he noticed some blood in his bowel movements and made an appointment with his primary-care physician. His doctor noted that he did have blood on a rectal exam and that he was slightly anemic. The patient had no family history of colon cancer. A gastroenterologist was consulted and a colonoscopy revealed a colon cancer. The patient underwent an operation in his hometown to remove the malignant colon tumor. Pathology revealed cancer in several lymph nodes near the primary tumor, and a biopsy of a liver tumor confirmed metastasis in the right lobe of his liver. He had stage IV disease, signifying blood-borne spread of malignant cells with successful implantation and growth of cells from the colon cancer to another organ, his liver.
The patient recovered from his colon operation at a “meteoric pace” (according to his hometown surgeon when I spoke to him), and then received six months of systemic intravenous chemotherapy. He was referred to me to address the sole clinically evident site of malignant disease, the tumor in the right lobe of his liver. I use the phrase clinically evident purposefully; the radiologists and I did not detect any suspicious tumors or lesions in his lungs, lymph nodes, or peritoneal cavity on our state-of-the-art CT scans. This remarkably fit, healthy young man had just a solitary liver metastasis smack-dab in the middle of the right lobe. An almost Pavlovian circumstance for a hepatobiliary surgical oncologist who loves to attack and remove liver malignancies.
This gentleman was one of the most energetic, positive, let’s-get-this-done people I have met—in any area of my life. We talked for about half an hour during our first visit, and I completed a physical examination. I reviewed his CT scans and pathology information; he had a five-centimeter liver tumor, which was originally almost eight centimeters in diameter. The reduction indicated a positive response to chemotherapy. Numerous studies have indicated that patients showing shrinkage of their tumors with chemotherapy tend to have a longer survival time after surgical and other anticancer therapies. But, as I’ve said, it’s all statist
ics and probabilities; the bottom line is we can never know what’s going to happen specifically to any one patient. The wrestler told me he was ready for me to operate and “get this devil out of me” as quickly as possible. The next week I performed an exploratory laparotomy.
Surgeons are multisensory creatures. We like to visually inspect the area of operation, but we also like to feel. I palpated my patient’s lymph nodes near the blood vessels heading into his liver. Several of them felt hard like small stones, but not enlarged. I removed all of these regional lymph nodes and then completed a routine right hepatectomy. Upon checking the remainder of the belly cavity visually and tactilely, there was no evidence of tumor at any other site.
My patient was up walking laps in the hallways of the surgical unit the night of his operation. Several nurses told me they were exhausted just watching him. He was indefatigable. He consistently had a huge smile on his face and greeted everyone with a bone-crushing handshake. He left the hospital only four days after his operation. As he stated, “All systems are working, I’m outta here.”
See ya!
I saw him in the clinic the following week and we reviewed the results from the surgery. I explained that the pathologist had found not only the single liver tumor we knew was present, but also three additional two-to-three-millimeter tumors near it. None of these tumors were close to the liver transection line, meaning we had achieved a negative-margin operation. Furthermore, three of the twelve lymph nodes removed from around the blood vessels supplying his liver contained metastatic colorectal cancer.
In My Hands Page 11