Dr. Karen Danielyan and Dr. Agop Y. Bedikian

An Ethical Dilemma with a Happy Ending

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By Agop Y. Bedikian MD

Special to the Mirror-Spectator

Life and death decision taking puts patients, relatives and caregivers in a very difficult situation. The decision taking is harder when a young patient has terminal cancer. The patients take the diagnosis of cancer as a death verdict. They are afraid of pain, suffering and disfiguring associated with it. The intense emotional effect and the adverse impact on body image drive some patients to depression and suicide. The general attitude among physicians in the West in the recent past changed from giving limited information to full disclosure about the disease, treatment and prognosis.

I devoted the first four decades of my life to treat patients with advanced cancer with the best therapies the clinical research could provide. More importantly, I always made myself available to them and their families as cancer therapy is complicated and affects the patients’ family in numerous ways. Very often, I received communication (letters, phone calls, e-mails etc.) from patients, families I have never met. They asked questions about the diagnosis, staging of the disease, management, and treatment options. I have never declined answering these requests. Most of the time, I do not hear from them again. On few occasions, I am involved in their therapy even though it is outside my field of subspecialty i.e. malignant melanoma. One such occasion was related to a young plastic surgeon from Armenia.

It all started with a phone call from the office of Mrs. Louise Manoogian Simone, the former president of Armenian General Benevolent Union. Her assistant, Barbara Boghosian, a member of the team responsible for AGBU Armenia Medical Programs was desperate. She said “excuse me for intruding; we wouldn’t have called you if we had an alternative. We have a young doctor in Armenia with the diagnosis of advanced lymphoma, we have been waiting for a second opinion from a pathologist in MD Anderson Cancer Center, and we have heard nothing during the past six weeks. We sent the pathology slides with the help of a charity organization in Houston; we chose your name from the short list of Armenian doctors and are seeking your assistance to expedite the process as the patient’s condition is deteriorating in the interim.”

I inquired about the patient’s medical history so that I could narrow down as to who may have received the pathology slides. Apparently, the patient was treated with antibiotics for tonsillitis in September 1999. The tonsillitis resolved but his flank pain persisted. A nephrologist thought it may be due to pyelonephritis. He was given multiple antibiotic treatments but he persisted in remaining febrile. In addition, he complained of weight loss and night sweats.

Dr. Karen Danielyan

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A complete physical examination showed that Dr. Karen Danielyan had an abdominal mass which histologically was diagnosed as lymphoma. It was decided to have confirmation of the diagnosis before he is brought to United States for treatment. I traced the pathology slides and took them to Dr. Mario Luna, the pathology colleague who had collaborated with me in several projects before. I asked him if he could have a look at the pathology slides ASAP and give me preliminary verbal diagnosis as a favor while I do the necessary paperwork to request official pathology consultation; in view of deteriorating condition of the patient in Armenia,. He looked at the slides under the microscope and said, ”this is not lymphoma, it is testicular cancer.” Immediately, I called the AGBU office in New York office and conveyed the new diagnosis and also I requested that the doctors in Armenia do a blood test to measure the serum Beta-HCH and alfa-fetoprotein levels; which are often elevated in association with metastatic testicular cancer. A day later, Mrs. Simone was told that the Beta-HCG level was over 200000, the highest dilution they could perform in their lab. Mrs. Simone told me that they can no longer bring the patient to the States for therapy as his condition has deteriorated significantly while waiting for the confirmation of the diagnosis. She asked me if I could help. I told her I will be visiting my daughter who was living in New York in few days and that I do not mind passing by the AGBU office in New York and find out the status of the patient then and what could be done in Yerevan. When I called his local oncologist for an update about the patient’s status, he told me that the patient’s serum bilirubin level was over twice the normal level and the liver enzyme level has tripled, indicating tumor progression in the abdomen. Then I inquired about the local availability of the anticancer drugs known to be effective against testicular cancer in addition to antiemetics and other supportive care medications.

Fully aware of the latest information about the patient and the limited availability of local resources for appropriate treatment, I told Mrs. Simone that the patient has very high chance of developing life threatening complication from chemotherapy because of hepatic and renal insufficiency. In addition, the prognosis of patients with similar liver and kidney dysfunction is very poor as half of them die in 6 to 8 weeks.

I stressed the fact that we have only one shot to reverse the deteriorating process in this patient. Therapy of such patients would require oncologist with detailed knowledge about the pharmacokinetics of the anticancer drugs chosen for treatment to make the appropriate dose adjustment based on the deteriorating kidney and liver functions. These drugs should be administered in a fashion different than that is a common practice in Armenia. Then Mrs. Simone told me that despite the grave prognosis, she has not given up on this doctor, she will do whatever it takes to try to save him. She asked me what would I need if I take charge of the management of this case. I told her that I need a person willing to administer the anticancer drugs as per my instruction with no modification or delay, monitor the patient closely and inform me via e-mail at least twice a day. I would prefer working with a person with limited knowledge in cancer care than with an oncologist because that will eliminate the tendency and temptation to modify the treatment or alter the way the drugs are administered. In addition, I asked her commitment to purchase and delivery of the needed cytotoxic and supportive care drugs including antiemetics, antibiotics and bone marrow stimulant growth factors to make them available when needed locally. I provided her with the list of the drugs we needed and started to take the necessary steps to initiate systemic chemotherapy using the then locally available cytotoxic drugs while we procure and ship the long list of needed drugs. Dr. Armine Kharatian, (Anesthesiologist, colleague and friend of the patient) agreed to assist me in the delivery of the therapy, monitoring and supporting the patient based on instruction sent from Houston through the internet.

Within few days, we were ready to start chemotherapy with appropriate dose modification. In view of the patient’s compromised renal function, I omitted the use of cisplatin, started the chemotherapy with Adriamycin and Cytoxan at reduced doses on January first, 2000. With the return of serum creatinine to normal before the second chemotherapy course, cisplatin was added to the regimen. When the drugs procured and sent from the US became locally available, I incorporated them in the treatment regimen as appropriate. Within 6 weeks, there was significant improvement of the renal and liver function test results accompanied with clinical improvement as well. At the time, the patient was offered travel to the States for treatment; he declined preferring receiving therapy close to her family. The patient received therapy with close monitoring for possible nephropathy and neuropathy before each course. With this regimen, his beta HCG dropped by about 99 percent and his metastases shrunk by 90 percent compared with his pre-therapy evaluation. Concerned about the peripheral neuropathy (which could prevent him to practice plastic surgery), the treatment was modified. The cisplatin dose was reduced and, etoposide, and bleomycin were introduced in the treatment. After 2 courses of this regimen, his beta HCG decreased to 15 (normal level is < 5). Bleomycin was subsequently discontinued in view of the possibility of pulmonary damage that may prevent future surgical procedures for resection render him free of disease. In summer of 2000, he was started on therapy regimen including etoposide, Actinomycin D, methotrexate, and leucovorin rescue. After 3 courses his beta- HCG returned to normal level. The repeat Ct Scans of chest and abdomen showed residual abnormalities in the lungs, liver metastases and necrotic mass adjacent to the left kidney partially obstructing the left ureter in the abdomen. In view of persistent abnormalities on CT scans despite the return of serum beta-HCG to normal we could not be sure that the last cancer cell had died.

When the patient recovered from the generalized effects of the systemic therapy, the patient came to Houston for resection of the residual abnormal areas seen on the CT scans. He underwent extensive abdominal surgery under the direction of Dr. Richard Babaian. The left kidney and the necrotic abdominal mass were removed; the microscopic examination of the specimens showed calcification consistent with metastatic necrotic germ cell tumor. There were no viable cancer cells was present. Left testis showed mature teratoma with scar, no other germ cell tumor component. There were viable cancer cells. Over 2 dozen lymph nodes were removed; none showed viable cancer cells.  Six weeks later, Dr. Ara Vaporciyan resected over 2 dozen pulmonary nodules and lymph nodes; microscopic examination they showed necrosis and fibrosis but no viable cancer cells in them.

During the subsequent year, the patient had follow-up visits every 3 months together with repeat radiologic tests and determination of serum Beta-HCG. The results were negative for tumor recurrence. Then the patient had yearly evaluation with no sign of tumor recurrence. After 5 years, all tests were discontinued. On August 18, 2000, I received an e-mail from Karen he said “I finally climbed Mount Ararat. This I dedicated this climbing to my Mother and you, my doctor, two persons who gave life to me. I reached a peak height of 5,135 meter above sea level. It was difficult. It is at 5,000 meter level, that the eternal ice starts. With love, Karen.”

Topics: Armenia

The last time I saw Karen was during my visit to Yerevan in June 2016. He was practicing plastic surgery and remains free of cancer. He had built a new surgical unit about 10 miles from his clinic in Yerevan. This happy outcome could not be achieved without the foresight, determination, persistence and support of Mrs. Louise Manoogian Simone. As a result of her support, hundreds of Armenian children are living a normal life without the stigma of cleft lips, palates and club feet under Karen’s care.

(Agop Y. Bedikian was born in Beirut, Lebanon. He is a graduate of the Hovagimian-Manougian Secondary School for boys. He studied medicine at the American University of Beirut. In 1975, he completed his residency in Internal medicine at the Washington University Medical Center in St, Louis, Mo. and moved to Houston. After completing a fellowship in Medical Oncology at the MD Anderson Cancer Center, he joined the medical staff. His activities included conducting clinical trials with new anticancer drugs, treating patient and teaching fellows, pharmacists and nurses. At present, he is Emeritus Professor of Medicine and Medical Oncology at MD Anderson.)

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