Research

Research

UMass Memorial pioneers cancer surgery technique

By Susan Gonsalves, Correspondent
Posted May 16, 2017 at 3:05 PM
Updated May 16, 2017 at 3:07 PM

WORCESTER — UMass Memorial is the first center in the U.S. to participate in an international trial looking at the role of an innovative surgical technique for rectal cancer treatment.

And Justin Maykel, MD, chief of the Division of Colon and Rectal Surgeries, is one of the most experienced in using the transanal total mesorectal excision (taTME) procedure and will serve as director for the U.S. centers participating in this Color III trial.

“It’s a hot topic in our field,” Dr. Maykel said. “People are curious as to what role this (surgery) is going to have for patients with rectal cancer.”

UMass Memorial was one of the early adopters of the technique. Dr. Maykel began performing it in 2014 and estimates he has done about 60 of the surgeries.

Because the technique is still new, long-term outcomes data is not available, he said. However, cancer outcomes to date are equal to the more invasive open approach and he feels taTME provides additional quality of life benefits.

“There is no downside to offering it to patients with rectal cancer to the mid or low portion or patients who must undergo rectal surgery for extensive polyps, ulcerative colitis or Crohn’s disease,” Dr. Maykel said. “The operation holds up to any other approach that we have. We really
believe this is the best way to do it.”

Open surgery, he said, leaves a large abdominal incision, putting the patient at risk for wound infections, hernias and other complications.

Patients who can’t be candidates for laparoscopy because of obesity, prior pelvic surgery or large tumor size, are good candidates for taTME.
In the 1980s, Professor Bill Heald in the United Kingdom popularized the TME approach, Dr. Maykel said, which involves removing the rectum and all the lymph nodes and surrounding tissue in one discreet specimen and leaving all the normal pelvic structures behind.

“TME had a major impact on cancer recurrence rates and patient survival,” Dr. Maykel said. 

In the new technique, surgeons remove rectal cancers through the anus, if possible, rather than cutting through the patient’s abdomen. If the tumor is too large to fit through the anus, the doctors make a small incision in the abdomen.

Performing that technique in a minimally evasive manner (taTME) is the next step in the progression, he said. “taTME provides a lot of solutions to the problems of open and lap surgeries.”

“It’s a complicated surgery with a lot of unique steps to it,” he explained. “There is new instrumentation and views of patient anatomy.”

He said that the operation gives surgeons a view of the anatomy they would not have seen before. It involves creating a new operating field from below in place of what they’d normally visualize from above.

“The No. 1 goal of treating rectal cancer is to cure patients of the cancer,” Dr. Maykel said. “The second is to preserve their sphincters and avoid having to have a permanent colostomy bag. So, we divide the rectum beyond the level of the tumor, and it gives surgeons a better view of that step.”

UMass Memorial’s four surgeons, Dr. Maykel and Drs. Jennifer Davids, Paul Sturrock and Karim Alavi work as a team in the operating room.

Dr. Alavi, MD, MPH, director of UMass Memorial Colon and Rectal Surgery Fellowship, agreed that partnering with colleagues helps to achieve the best results. “Extra sets of eyes help with the anatomy challenges,” he said. “They help you to stay in the (surgical) planes.”

He has seen patients having shorter recovery times and hospital stays as a result of the operation.

Patients typically receive chemotherapy/radiation, have the surgery and then are administered more chemo.

Instead of a week in the hospital after an open surgery, taTME patients go home four or five days later. Recovery time out of work is reduced from four to six weeks to two to four—although each patient is different.

Dr. Alavi estimated that he has performed 40 taTME procedures to date.

In addition, surgeons travel to UMass to observe operations, and Dr. Maykel and Dr. Alavi travel to other sites to proctor surgeons who are learning the procedure.

Dr. Maykel noted that although the taTME surgery is catching on across Europe, it’s still rare in this country and will likely be available only at leading academic medical centers, at least in the short term.

“I see this approach being offered to a patient traveling to a high-volume center and not every hospital. It is a highly specialized procedure with technical complexities and has a steep learning curve.”

The taTME and lap procedures cost about $1,000 more than open surgeries, although insurance covers all types and the patients’ co-pay is the same, Dr. Maykel said.

UMass Memorial did not provide estimates of total cost, but Dr. Maykel said hospitals have to make a $25,000 to $30,000 investment in an insufflation system. Staplers are not used in taTME but a necessary disposable access device costs $700 but eliminates the need for other instruments.
“It’s basically cost-neutral and not any more expensive than the way we do other things.” 

Dr. Alavi said an unexpected advantage of the taTME approach is the ability to partner with industry to advance technology.

Dr. Maykel served as co-director of the first taTME instructional course at the American Society of Colon and Rectal Surgeons in Los Angeles last year and also taught a course sponsored by Florida hospitals.

Deborah Dauphinais of Leominster said that she was blindsided last October when she learned she had rectal cancer. Because of the size of her tumor, Dr. Maykel recommended the taTME method. 

“I was scared to death. I had no prior surgeries and didn’t know what to expect,” Ms. Dauphinais said. “Dr. Maykel explained it all and was really there for me. He has the best bedside manner and is unbelievably talented.”

Following a Valentine’s Day surgery, Ms. Dauphinais said she was up and around and back on her feet again in two weeks. She used no pain medication and only felt little pulls on an inch-and-a-half scar low on her pelvis. 

Best of all, she only had to use a bag for six weeks as doctors were able to reconnect ends of her colon.

“I put my life in his hands,” Ms. Dauphinais added. “His experience and new way of doing the operation presents a much better outcome. He knows his stuff.”

Stephen Lyle, M.D., Ph.D.

Associate Professor and Director,
UMass Cancer Center Tissue Bank
Dept’s. of Cancer Biology and Pathology
UMass Medical School

Over the past several years, doctors and cancer scientists have realized that tumors, similar to normal tissues, are made up of a mixture of cells. Thus, a patient does not just have one type of cancer cell but many different cancer cells that may behave differently. Some cells within the tumor are cured easily by chemotherapy and radiation while other cancer cells may survive, only to re-grow or spread to other organs; and this represents a major challenge to effectively treating cancer patients. Recently, we have recognized that colon cancers contain small numbers of “cancer stem cells” that may be especially resistant to chemotherapy and radiation treatments and thus may be responsible for recurrence of the tumor after therapy. The research laboratory of Dr. Stephen Lyle is studying rare cancer stem cells within colon cancers so that we can better eliminate these cells and kill cancer at its root.

Work in the laboratory of Stephen Lyle focuses on stem cells and cancer, including colorectal cancer. There are three important reasons to think about adult stem cells and cancer.

  • Normal adult stem cells possess the self-renewal properties of cancer cells and thus can serve as a model system for study.
  • Stem cells may be targets of carcinogenic pathways. Since adult stem cells reside in the body for your life-time, they can accumulate multiple genetic mutations which lead to cancer. Can we protect our stem cells and prevent cancer?
  • Do cancers, as abnormal tissues, contain a subpopulation of cells with stem cell qualities; “cancer stem cells”? If so, what are their properties and how can this be exploited therapeutically?

We are developing ways to identify and target “cancer stem cells” in colon cancer.

Publications

  • Grossman SR, Lyle S, Resnick MB, Sabo E, Lis R, Rosinha E, Liu Q, Hsieh C-C, Bhat G, Frackleton AR, Hafer LJ. P66 Shc tumor levels show a strong prognostic correlation with disease outcome in stage II colon cancer. Clin. Can. Res. 2007, Oct 1;13(19): 5798-804.
  • Li H, Fan X, Stoicov C, Liu JH, Zubair S, Tsai E, Ste Marie R, Wang TC, Lyle S, Kurt-Jones E, Houghton J. Human and mouse colon cancer utilizes CD95 signaling for local growth and metastatic spread to liver. Gastroenterology. 2009 Sep;137(3):934-44

Collaborative work between the labs of Drs. Stephen Lyle and JeanMarie Houghton was profiled on the cover of the journal “Gastroenterology.”

Steven R. Grossman, MD, PhD

Associate Professor of Cancer Biology and Medicine
Co-Director, GI Cancer Program
UMass Medical School/UMass Memorial Cancer Center

Our laboratory focuses on the function of proteins in cells that normally prevent cancers, such as colorectal cancer. These powerful cancer fighting proteins include p53 and p14ARF. Most colon cancers demonstrate the loss by mutation or lack of expression of one of these tumor suppressors. Our goal is to understand how these proteins fight cancer at the cell level, in order to design therapies that could restore their function in cancers where they have been inactivated-specifically targeting treatments to the types of distinct changes that occur in an individual cancer patient. Our first therapeutic drug candidate arising from this work is currently being tested in a mouse model of colon cancer. This therapeutic candidate targets an enzyme –CtBP- that is normally inactivated by p14ARF, and our research predicts might be hyperactivated (overexpressed) in colon cancer tumors that have lost ARF.

Publications

  1. Kovi RC, Paliwal S, Pande S, Grossman SR. An ARF/CtBP2 complex regulates BH3-only gene expression and p53-independent apoptosis. Cell Death Diff 2009; Oct 2, Epub ahead of print.
  2. Paliwal S, Kovi RC, Nath B, Chen YW, Lewis BC, Grossman SR. The Alternative Reading Frame Tumor Suppressor Antagonizes Hypoxia-Induced Cancer Cell Migration via Interaction with the COOH-Terminal Binding Protein Corepressor. Cancer Res. 2007; 67:9322-9329.
  3. Grossman SR*, Lyle S, Resnick MB, Sabo E, Lis RT, Rosinha E, Liu Q, Hsieh CC, Bhat G, Frackelton AR Jr, Hafer LJ. p66 Shc Tumor Levels Show a Strong Prognostic Correlation with Disease Outcome in Stage IIA Colon Cancer. Clin Cancer Res 2007; 13:5798-5804. [*corresponding author]
  4. Paliwal S, Pande S, Kovi R, Sharpless NE, Bardeesy N, Grossman SR. Targeting of C-terminal Binding Protein (CtBP) by ARF results in p53-independent apoptosis. Mol Cell Biol 2006; 26:2360-2372.

COLORECTAL SURGERY DIVISION

Justin Maykel MD, Karim Alavi MD, Brian Sweeney MD, Paul Sturrock MD, Janet McDade NP, Andres Cervera MD

Anal Cancer Database.

    • Previous records review of all patients with anal cancer (Retrospective Collection of data)
    • Prospectively reviewed and maintained.
    • Evaluation of trends, predictive factors as well as treatment response and follow up of patients treated in UMass.
    • Outcomes Comparison with national standards.
    • Adequate follow up and evaluation of these results will provide a better understanding of this disease’s behavior and clinical response. Further research and treatment options will be evaluated and developed using this database.

Colon and Rectal Database – Under development.

Translational Research

    • Foster collaborative research, seeking clinical application of newly developed technology in the Colorectal Cancer area.
    • Evaluation of injection of a substance developed at UMass intratumorally in patients with recurrent or persistent Anal Cancer.

Evaluate Impact of Diversity on the Treatment of Colon and Rectal Cancer Patients

    • Patients with diverse characteristics (ethnicity, gender, religion, insurance status, socioeconomic status) receive equal care by the UMASS Colorectal Surgery Service.
    • To evaluate and ensure that patients with colorectal cancer at UMass are receiving the same quality of care regardless of their ethnicity, gender, religion, socioeconomic or insurance status).

Retrospective study to evaluate the utility of repeat CT scan in Restaging of Rectal Cancer after neoadjuvant chemotherapy and radiation.

    • Restaging CT Scan after neoadjuvant therapy for Rectal Cancer is routinely used in UMass.
    • With this retrospective study we seek to evaluate the usefulness and overall impact on decision making of this CT, as well as the clinical scenarios where it is necessary.
    • Pending results, a significant reduction in cost could be demonstrated in the management of Rectal Cancer patients.

UMass Employee Colorectal Cancer Screening Program

    • For promoting awareness, removing financial and time-off barriers, generating a healthy competition will result in increased rates of colorectal cancer screening.
    • Launched March 2009 100 employees screened
      • **1 colon cancer identified in an asymptomatic patient

Outpatient Colectomy

    • A select group of patients can safely recover at home starting the first day following colon resection.
    • Prospective study to evaluate and demonstrate the feasibility of performing colon resections in an outpatient basis.
    • If demonstrated this will allow to decrease the cost of Cancer treatment, and allow patients to recover in a faster more comfortable setting at Home.

Incorporation of Simulation into Colorectal Surgery Curriculum for Medical Students and Residents

    • Thorough understanding and simulation practice in detecting clinical and endoscopic findings related to Colorectal Cancer will provide undergraduate Medical students and postgraduate Residents with a higher capability of Early Detection of Cancer with increased patient safety.

Influence of coffee in prevention of post-operative ileus

    • IRB approved, soon to be launched study to evaluate coffee as a promoter of bowel activity after colon surgery. Pending Grant.
    • Decrease in rate of postoperative ileus will allow faster recovery, shorter length of stay in hospitals and decrease overall cost in Colorectal cancer patients