Archive for August, 2017

Treatment of Acute Stroke with IV tPA


Marco Gonzalez-Castellon, MD

Every year, more than 800,000 people have a stroke. Stroke is the number one cause of non-traumatic long term disability in the United States. Ischemic stroke is a treatable condition. Since 1996, there has been a specific treatment for acute ischemic stroke.

Recombinant tissue plasminogen activator (rt-PA) was approved by the Food and Drug Administration (FDA) for treatment of acute ischemic stroke. Recombinant tissue plasminogen activator is a potent blood thinner that reestablishes blood flow by dissolving blood clots blocking cerebral blood vessels. Reestablishing blood flow reduces stoke size improving the chances for recovery. The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA study showed that treated patients were at least 30 percent more likely to have minimal or no disability after three months. Since rt-PA is a potent blood thinner, there is risk of cerebral hemorrhage, however this complication was only seen in 6 percent of patients.

Treatment with IV rt-PA is time dependent and is more effective if its given within the first hours. Eligible patients must be treated within 4 ½ hours form symptoms onset to minimize complications. Best results are achieved in patients treated early; therefore it is vital to recognize the symptoms of stroke and call EMS.

The devastating effects of a stroke can be reduced if treatment is started right away.

Signs of a Stroke
The devastating effects of a stroke can be reduced if treatment is started right away. F.A.S.T is an easy way to remember the sudden signs of a stroke. If you suspect someone is having a stroke, call 911 for help right away.

Face Drooping – Does one side of the face droop or is it numb? Ask the person to smile. Is the person’s smile uneven?

Arm Weakness – Is one arm weak or numb? Ask the person to raise both arms. Does one arm drift downward?

Speech Difficulty – Is speech slurred? Is the person unable to speak or hard to understand? Ask the person to repeat a simple sentence, like “The sky is blue.” Is the sentence repeated correctly?

Time to call 911 – If someone shows any of these symptoms, even if the symptoms go away, call 911 and get the person to the hospital immediately. Check the time so you’ll know when the first symptoms appeared.

2017 Update on Evolving Therapies for Multiple Myeloma and AL Amyloidosis


Muhamed Baljevic, MD

A number of targeted immune therapies and small molecules are emerging as potential candidates with tremendous potential for the treatment of multiple myeloma and AL amyloidosis. With different strategies designed to either harness the power of our own immune system in the fight against cancer, or to target molecules found in myeloma or amyloidosis that play a role in cellular transport proteins or cell death, stronger and deeper responses are being achieved.

In a previous blog post, we have heard about several new drugs that are showing very promising activity in multiple myeloma. Now, more studies are confirming and updating their valuable role in the treatment of the same patients:

Selinexor which is a novel, first-in-class small molecule drug that inhibits exportin 1 is involved in nuclear transport. This oral drug is taken 1-2 times per week, and has strong antimyeloma effects. Previous combination with low-dose dexamethasone showed activity in heavily pretreated refractory multiple myeloma. Importantly, response rates were similar in the overall population and in patients with high-risk cytogenetic abnormalities, with adverse events, which were manageable with dose interruptions, dose reductions and supportive care. Expanding on this experience, recent combinations that added other myeloma drugs such as pomalidomide, bortezomib  or lenalidomide to this combination showed significant responses in all treatment combinations, and  in heavily pretreated patients with high risk features such as del17p and/or prior refractoriness to other standard rugs such as bortezomib. Importantly, these newer combinations were well tolerated.

Venetoclax is a drug that affects cell death pathways associated with CBL2 molecule. The overall response rate in patients with high BCL2 expression was 88 percent, with longer time to progression achieved in those expressing the protein strongly. This is particularly useful as we may be able to use BCL2 as a selective marker of higher response in patients. Response rates were even higher in patients who are not refractory to bortezomib and those who received only 1-3 prior types of therapy.

Pembrolizumab which is an immune checkpoint inhibitor showed significant effect in combination with pomalidomide with previously heavily treated myeloma patients. More recent studies have combined this drug with other myeloma drugs such as Lenalidomide, and showed overall response rate of 50 percent, with 15 percent achieving ≥ 90 percent reduction in myeloma disease burden.


Before (left) and after (right) PET scans of a patient with multiple myeloma treated with BCMA-targeted CAR T-cells. Photo credit: National Cancer Institute

CAR T-cells are highly exciting and rapidly emerging form of therapy for many cancer types, multiple myeloma included. CAR T-cells work by recognizing targets on cancer cells, and those that have been engineered to target B-cell maturation protein (BMCA) on myeloma cells are of particular importance, as this protein is expressed most uniformly on myeloma cells, and not normal cells. Previously encouraging results in myeloma have been upstaged by an even bigger news of response in 33 of 35 patients (94 percent) with relapsed or refractory multiple myeloma, who  experienced clinical remission after treatment with CAR T-cells targeting BCMA. Substantial but reversible toxicity was comparable to that observed in previous CAR T-cell studies. In a follow up of an earlier reported first-in-human multicenter study of bb2121 anti-BCMA CAR T cell therapy for relapsed/refractory multiple myeloma, 100 percent of patients showed response. It must be noted that the experience and expertise with CAR T-cell therapy in multiple myeloma is still limited, and further larger studies will be needed to confirm safety and utility of this immune therapy in multiple myeloma.

While an ongoing work has surely expanded our understanding and proficiency in using the therapies previously introduced, myeloma and amyloidosis community is working hard on bringing novel treatment modalities to the clinical arena, where many patients have already benefited from their efficacy. Few of the notable mentions include:

Subcutaneous Therapy with Daratumumab

Daratumumab is a monoclonal antibody that targets CD38 protein on myeloma cells. This drug has been a block-buster in myeloma treatment arsenal since it’s early days by showing very strong activity on its own in heavily pretreated myeloma patients. This efficacy has been enhanced in combination therapies with other myeloma drugs such as pomalidomide, bortezomib  or lenalidomide . A major challenge in its widespread use however has been intravenous mode of infusion requiring long-infusion visits due to possible allergic reactions. However, a new strategy to administer daratumumab as subcutaneous therapy may make daratumumab available to wider patient populations. The phase Ib study included 53 patients with relapsed/refractory multiple myeloma who received subcutaneous daratumumab. The overall response rate for one group of treated patents was 38 percent, including 13 percent with high degree responses where reduction in myeloma was ≥ 90 percent. One quarter of patients had infusion-related reaction, which occurred during the first 4 hours of infusion, without severe reactions noted. This is a significant improvement from 50 percent infusion-related reaction rate expected and observed previously with intravenous mode of delivery.

Radium-223 Dichloride

This is an alpha particle-radiation-emitting compound that has strong additive effects when combined with bortezomib. A phase 1b/2 trial is evaluating the safety and efficacy of radium-223 dichloride in combination with bortezomib and dexamethasone in early relapsed multiple myeloma.

NEOD001 Monoclonal Antibody

Amyloidosis is the general term used to describe extracellular deposition in body tissues of small fibril portions of a variety of proteins, as they circulate in human plasma. These deposits may result in a wide range of organ dysfunctions depending upon their type, location, and the amount of deposition. Traditional treatment for amyloidosis involves the use of chemotherapy directed at the plasma cells responsible for the production of amyloid protein. This unfortunately does nothing for already deposited amyloid by the time diagnosis is established. NEOD001 is a monoclonal antibody that specifically targets amyloid fibrils, assisting in their dissolution from the tissues where they deposited. First-in-human phase I/II study of NEOD001 evaluated this therapy in 27 patients with AL amyloidosis who competed chemotherapy, but had persistent organ dysfunction that remained. Time to response was very fast, within 2-4 months. In 14 patients with heart amyloid involvement, 57 percent responded and 43 percent had stable disease, while in 15 kidney-amyloid patients, 60 percent responded and 40 percent had stable disease. This therapy is likely to transform our ability to effectively manage amyloidosis, as it was also demonstrated hat the effectiveness of it was not related to the depth of response to prior chemotherapy, nor the time passed since last chemotherapy before the delivery of NEOD001.

Remarkable Recovery: Local boy thriving after triple organ transplant

Alex Leach had never had food or even tried water in his life. But now, after a triple organ transplant, Alex’s life is brand new. But as you’ll see in this story from WDAY, his zest for life will never change.

Robotic Thyroid Surgery Doesn’t Leave a Visible Scar

We’re One of a Few Academic Medical Centers Offering Robotic Thyroidectomies

Katie O’Callaghan was working the checkout line at her parents’ grocery store in Hastings, Nebraska, when a customer noticed a lump on O’Callaghan’s neck. The 24 year old, who was four months pregnant with her first child, brought it up at her next OB/GYN appointment. A biopsy later revealed she had thyroid cancer.

Estelle Chang, MD.

Estelle Chang, MD

“I couldn’t believe it,” says O’Callaghan. “Being pregnant with my first child was intimidating enough, let alone discovering I had cancer.”

Wanting a second opinion, O’Callaghan was referred to Estelle Chang, MD, an otolaryngology head and neck surgeon at Nebraska Medicine, who completed a six-month Advanced Robotic Head and Neck Endocrine Surgery Fellowship at Severance Hospital of the Yonsei University Health System in Seoul, South Korea. During her fellowship, Dr. Chang studied the latest, minimally invasive, thyroid and parathyroid surgery techniques.

“Traditionally, thyroidectomy has been performed using a 4 to 8 centimeter incision in the front of the neck, which can leave a visible scar,” explains Dr. Chang. “Robotic thyroidectomy is a minimally invasive surgical technique that is used to remove all or part of a thyroid gland without leaving a visible scar. This is the future and we should be at the forefront.”

At Nebraska Medicine, three robotic thyroidectomy approaches are offered for patients:

  • Underarm
  • Facelift (behind the earlobe)
    • If the patient wants a complete facelift at the end of the procedure, that’s a possibility
  • Through the mouth

    Katie O’Callaghan was shocked to learn at 24 years old, she had thyroid cancer.

    Katie O’Callaghan was shocked to learn at 24 years old, she had thyroid cancer.

“We can tailor to the patient, depending on the size of the tumor and the patient’s physical characteristics,” explains Dr. Chang. “This type of surgery is a great option for Caucasians who tan easily, African-Americans and Asians. They all tend to have a difficult time with scarring.”

Not wanting a scar on her neck, O’Callaghan opted for Dr. Chang to perform the facelift approach. For the safety of the baby, surgery was put on hold until after O’Callaghan gave birth to her son. On May 22, O’Callaghan became the first patient to undergo a robotic thyroidectomy at Nebraska Medicine. Dr. Chang made the incision behind O’Callaghan’s earlobe and surgery took approximately three hours. O’Callaghan was kept overnight for observation and released the next day.

“I knew I was in good hands at Nebraska Medicine,” says O’Callaghan. “Currently, I have no cancer in my body and I feel great. By looking at me, you’d never know I had thyroid surgery. I’m really happy with the outcome.”

Thyroid nodules are very common and occur in approximately 30 percent of all people in the United States. By the age of 60, more than half of women will have a thyroid nodule. The vast majority of the nodules are benign, with about 5 to 10 percent being cancerous. Symptoms of thyroid cancer can involve swollen lymph nodes in the neck, difficulty swallowing or breathing – but most patients don’t experience any symptoms.

“While thyroid cancer can be seen in people of any background, age or gender, most cases occur in women, people less than 55 years old, and those with Caucasian or Asian backgrounds,” says Nebraska Medicine surgical oncologist Abbey Fingeret, MD. “Fortunately, in most cases, it can be completely cured with surgery.”

Abbey Fingeret, MD

Abbey Fingeret, MD

Dr. Fingeret is currently the only endocrine surgery fellowship-trained surgeon in the state of Nebraska. She completed her fellowship at Harvard University and Massachusetts General Hospital, performing more than 500 thyroid operations. Dr. Fingeret also finished a three-month Advanced Robotic Endocrine Surgery Fellowship in South Korea. This summer, she looks to perform her first robotic thyroidectomy at Nebraska Medicine.

“I truly believe in the mission of Nebraska Medicine,” says Dr. Fingeret. “We are here to offer state-of-the-art care, where the patient always comes first. It’s my honor and privilege to be part of this exceptional team of ancillary staff, clinicians and researchers.”

“Nebraska Medicine treats all aspects of thyroid ailments and endocrine-related disorders,” adds Harris Frankel, MD, chief medical officer. “We have a large and experienced multidisciplinary team, which includes physicians from ENT, Endocrinology, General Surgery and Cancer Services. When you walk in the door, you can be seen by an endocrinologist and thyroid surgeon on the same day.”

We are one of a few academic medical centers in the country offering robotic thyroidectomies. Patients with multiple medical problems who shouldn’t be under anesthesia for extended periods of time are not ideal candidates. Robotic surgery can also be used to remove other benign masses of the neck, such as lipomas and thyroglossal duct cysts.

Patient Shares Emotional Story of Her Quest for a Kidney

Below is a Blog Written by Kimberly Pilar, Kidney Transplant Patient

I was first diagnosed with kidney failure in January 2004 when I was just 20 years old. I was in my third year of college at the University of South Dakota in Vermillion. Everything changed that day. I was no longer a normal college student. Before I knew it, I was sent back home to Sioux City, Iowa, and was admitted to the hospital. From there, I learned my kidney function was at just 7 percent. I started peritoneal dialysis right away. I was told I needed a kidney transplant to regain a normal life. I was speechless. No one in our family had a history of kidney failure. The search began for a donor.

Kimberly and her cousin, Theresa (in pink), who donated her kidney to her.

Kimberly and her cousin, Theresa (in pink), who donated her kidney to her.

I received my first kidney transplant at Nebraska Medicine. My cousin, Theresa – who was only 25 at the time – offered to give me one of her kidneys. It is an incredible gift and the words “thank you” just seem so small. On Nov. 2, 2004 (Election Day), we underwent our surgeries. I was completely terrified of all the things that could happen. Not Theresa (Or not that she would show me.). She was my rock that day. I looked at her strength and tried to gather my own. For her. For her sacrifice.

Our surgeries were a great success. Theresa and Kenny (the kidney) gave me my life back. I no longer needed to do peritoneal dialysis. Recovery took some time but it was worth the pain.

In 2009, we were devastated when Theresa was diagnosed with breast cancer at just 29 years old. I watched this vibrant, beautiful woman become frail and sick. It was heartbreaking. She fought hard for three years but lost her battle with cancer June 4, 2012. Even today, talking about her brings tears to my eyes. It breaks my heart every day that I couldn’t save the woman who saved me. All I could do was be there for her every day and show her how much I loved her. That also made the gift she gave me even more special. I was able to give life to a piece of her.

So you can imagine my heartbreak when I began losing her gift. I was getting fevers every night for about a week. Only at night. During the day I felt fine, so I waited a week to call my transplant coordinator. She suggested I come to Omaha. It was Halloween night, 2014. I went through several tests and was later admitted to the hospital. I spent our 10-year “kidney-versary” in the hospital trying to save Theresa’s kidney. They couldn’t find a reason for the fevers and decreased kidney function. I went home for about a week before going back to Nebraska Medicine. This time it was three weeks of tests. They finally figured out after an endoscopy and colonoscopy that I had somehow contracted a virus called CMV. It is a very dangerous virus and my counts were off the charts. The virus attacked my transplanted kidney and began to kill it off. They started me on hemodialysis in hopes to rejuvenate my kidney. We spent a couple months hoping it would bounce back but it didn’t. They said I would need another kidney transplant. My heart broke that my piece of Theresa was dying and needed to be replaced.

For two and a half years, I waited. Bag packed just in case I got the call. I had visited another transplant center in Des Moines, Iowa, and was told it would be hard to match me with a donor due to high antibodies in my system. They told me I was looking for a needle in a haystack and that search could be 5 to 10 years. We were all devastated. Theresa’s sister started a Facebook page looking for donors called “Kidney 4 Kimmy.” I had a great response from the Facebook page. People from all over the country were reading my story. If just one person decided to register as an organ donor, I consider the page a success.

Kimberly is seen here with her brothers.

Kimberly is seen here with her brothers.

On June 28, 2017 I received the call I was waiting for at 11:20 p.m. I ran downstairs to my roommate and woke her up while still on the phone with Nebraska Medicine. I could barely speak. Was this really happening? I had to have my roommate call my parents – as I was crying. My parents drove to my house, picked me up and by midnight, we were on our way to Omaha. We arrived about 1:45 a.m. and were taken right into a room. I went through some blood work for final cross-matching and X-rays. Some doctors and nurses came in to talk us through what was going to happen in the next few hours. They needed to make sure the donor kidney was viable for transplantation and everything matched me.

At about 10:15 a.m., the transplant surgeon, Arika Hoffman, MD, said everything looked great and we were ready for surgery. By 10:30 a.m., we were being taken to Pre-op. It seemed like a whirlwind. Next thing I remember was waking up in my room with a new kidney. I am so very thankful to the entire team at Nebraska Medicine. The surgeons, nephrologists, nurses, care techs – everyone was so amazing and supportive over my five-day stay.

I remember looking at my mom the day we left and crying on her shoulder. I still couldn’t comprehend what had just happened. I had waited for this moment for over two and a half years and it was now over. All that was left was to heal and praise God for the gift I was given.

I did not know my donor. I will never be able to know him/her. I will never be able to hug them and thank them for the gift they have given me. I hope to one day meet their family and thank them for the amazing life they allowed me to have thanks to their lost loved one.

I want to thank my parents, brothers and their families, my entire extended family and friends for all the love, support, and prayers offered to me over the last 13 years.

To Nebraska Medicine, I couldn’t imagine having my second transplant anywhere else and am so happy to call you family. Dr. Hoffman and fellow surgeons, Dr. Clifford Miles and staff, you are truly amazing and my lifesavers. I will never be able to thank you enough. Every nurse and care tech on the Solid Organ Transplant Unit was truly incredible. I couldn’t have made the progress I did without you all.

Thank you, thank you, thank you.

Kimberly Pilar

Kidney Transplant Recipient