Treatment of Idiopathic and De Novo Scoliosis in Adults

Surgeons from the departments of orthopaedic surgery and neurosurgery at Penn Medicine have developed a program to provide the full spectrum of treatments for adult patients with scoliosis of the spine.

Generally defined as a curvature of the spine in excess of 30°, scoliosis has two primary classifications in adults: idiopathic disease originating in adolescence, and de novo (or degenerative) scoliosis occurring in middle age and later life. Idiopathic scoliosis affects the thoracic/lumbar spine and has an unknown etiology.

De novo scoliosis affects the lumbar spine and is usually caused by progressive intervertebral disc degeneration. In adults, both types of scoliosis are associated with pain, disfigurement and varying degrees of disability.

Treatment for scoliosis at Penn begins with conservative (non-operative) approaches, with the objective of controlling pain and maintaining function. Typically, conservative therapy involves exercise and conditioning regimens combined with physical therapy and, when warranted, nonsteroidal anti-inflammatory drugs and/or epidural steroid injections.

Surgery has the objective of minimizing pain and ameliorating spinal curvature, and is indicated when pain is unremitting or significant coronal or sagittal decompensation occurs. Chief considerations include the likelihood of successful outcome and the potential for complications given the patient’s age, history and condition.

At Penn, surgery for adult scoliosis involves thorough preoperative evaluation and planning to tailor the procedure to the needs of the individual patient; the primary goal is to minimize complications. Surgeries include posterior and/or anterior spinal fusion and segmental instrumentation; vertebral column resection; pedicle subtraction osteotomy; and spinal reconstructive surgery.

Most patients are ambulatory within 24 to 48 hours of surgery. In many instances the scoliosis surgery will involve the expertise of both the orthopaedic surgeon and neurosurgeon.

Case Study

Mrs. A, a 62-year-old female presented with incapacitating back and leg pain and ambulatory impairment. She could walk only with the aid of a walker and her posture was significantly stooped. Mrs. A’s medical history included four surgeries (among them a lumbar fusion) and failed attempts at conservative treatment, including, physiotherapy, pain medications and epidural steroid injections.

X-rays demonstrated a severe sagittal imbalance and a degree of curvature exceeding 30° (Fig 1). Following a consultation, and after thoroughly understanding what her surgery involved, Mrs. A agreed to have a pedicle subtraction osteotomy and extension of her fusion down to the pelvis. The surgery, which involved the removal of vertebral bone and the placement of pedicle screws and rods, was performed in seven hours.

A year after her surgery, Mrs. A’s pain level has dramatically decreased. Her posture is now upright (Fig. 2) and she can walk without a walker.

Faculty Team

The Spine Service at Penn Medicine involves the expertise of a multidisciplinary team that, in addition to orthopaedic surgeons and neurosurgeons, includes neurologists, rheumatologists, oncologists, physical therapists, physiatrists, radiologists and pain management specialists. This extensive and collaborative team approach to spine care ensures a thorough consideration of both surgical and non-surgical treatment of pain and neurological symptoms.

Performing Scoliosis Surgery at Penn Medicine

Vincent Arlet, MD
Chief, Orthopaedic Spine Surgery

William C. Welch, MD, FAANS, FACS, FICS
Vice Chairman (Clinical), Neurosurgery

Access

Penn Neurosurgery
Pennsylvania Hospital
Washington Square West Building
235 South 8th Street
Philadelphia, PA 19106

Penn Orthopaedics
Penn Presbyterian Medical Center
1 Cupp Pavilion
51 N 39th Street
Philadelphia, PA 19104

Download this Clinical Briefing.

MAGE-A3/6 and NY-ESO-1 immunotherapy administered post-ASCT in patients with advanced myeloma

Researchers in bone marrow transplantation at Penn’s Abramson Cancer Center are currently investigating the application of autologous, genetically modified T cells to the treatment of patients with advanced multiple myeloma. This approach has been likened to vaccine therapy because it involves the introduction of cells that have been altered to prompt an immune response.

Each year, more than 20,000 new cases of multiple myeloma occur in the United States. These cases appear in all facets of the population, with a higher incidence in African-Americans; mean age at diagnosis is 61.5 years. Although myeloma remains incurable, median five-year survival has roughly doubled since the 1970s as a result of the use of novel agents (thalidomide, lenalidomide, bortezomib) in combination with autologous stem cell transplantation (ASCT). ASCT is a standard of care in the United States for patients younger than age 71 with myeloma.

Once the disease relapses and becomes resistant to chemotherapeutic treatment, however, survival is very limited. New approaches are thus needed to further extend survival in myeloma patients.

Penn researchers have pioneered techniques to substantially increase the number of autologous T cells ex vivo and modify their function to have an even greater anti-tumor effect. It has been proposed that the introduction of these autologous T cells can prompt a rapid and vigorous immune response in the aftermath of ASCT.

Retrospective studies suggest that patients who have rapid lymphocyte recovery following ASCT have better clinical outcomes, perhaps because early immune reconstitution confers a protective effect against residual disease progression.

In the current study at Penn,* patients with high-risk multiple myeloma who are otherwise candidates for autologous SCT first undergo autologous T cell collection. This is followed by autologous hematopoietic stem cell collection followed by high-dose melphalan chemotherapy and ASCT. 
Patients are then infused with engineered autologous T cells.

The Penn study seeks to evaluate the safety and efficacy of a peptide vaccine comprised of fragments of the proteins melanoma associated antigen 3 (MAGE-A3) and NY-ESO-1, both of which are frequently found in the plasma cells of patients with myeloma.

MAGE-A3 is among the best characterized and most frequently expressed cancer testis antigens in tumors and is an important target for cancer vaccines; NY-ESO-1 has been shown to elicit spontaneous cellular immune responses in patients with advanced stage cancer. MAGE-A3 is identified with human leukocyte antigen haplotypes -A*0101 and -B*35; NY-ESO-1 is identified with HLA-A*0201. HLA peptide antigens provide cell surface ‘flags’ for expression of intracellular antigens.

The endpoints of the study include degree of response, time to progression and overall survival. In addition, the study will measure the survival of T cells in patients and examine the immune evidence for biological activity of these cells. The incidence of autologous GVHD in patients following infusion of TCR modified autologous T cells will also be assessed. Outcome measures include study-related adverse events and clinical response rates.

*Redirected Auto T Cells for Advanced Myeloma. ClinicalTrials.gov Identifier: NCT01352286. Contact: Edward Stadtmauer: 215-662-2812.


Faculty Team
The Bone Marrow and Stem Cell Transplant program at Penn Medicine and Abramson Cancer Center is the largest transplant center in the region. The program’s vibrant research mission is supported by many clinical trials for both autologous and allogeneic SCT.

Transplant options are available for most patients and are performed with autologous stem cells, matched sibling and unrelated donors and umbilical cord blood. Penn has active programs using both conventional allogeneic SCT and nonmyeloablative allogeneic (“mini”) transplantation. Committed to premier clinical care, Penn physicians strive to work collaboratively with patients’ referring physicians.

Hematologic Malignancies Physicians

Edward A. Stadtmauer, MD
Director, Hematologic Malignancies Program
Professor of Medicine

Selina M. Luger, MD
Director, Leukemia Program
Professor of Medicine

David L. Porter, MD
Director, Allogeneic Stem Cell Transplantation
Professor of Medicine

Stephen J. Schuster, MD
Director, Lymphoma Program
Associate Professor of Medicine

Noelle V. Frey, MD
Assistant Professor of Medicine

Elizabeth O. Hexner, MD
Assistant Professor of Medicine

Alison Loren, MD, MS
Assistant Professor of Medicine

Sunita D. Nasta, MD
Assistant Professor of Medicine

Jakub Svoboda, MD
Assistant Professor of Medicine

Donald Tsai, MD, PhD
Assistant Professor of Medicine

Dan Vogl, MD
Assistant Professor of Medicine

Brendan M. Weiss, MD
Assistant Professor of Medicine

Access
Abramson Cancer Center
Perelman Center for Advanced Medicine,
West Pavilion, 2nd Floor
3400 Civic Center Boulevard

Download a pdf of this Clinical Briefing:

Emergent Treatment of Complex Blunt Multisystem Trauma

Surgeons with Penn’s Division of Traumatology, Surgical Critical Care and Emergency Surgery are implementing a systematic approach to the emergent treatment and management of patients with complex blunt multisytem trauma that integrates and incorporates specialists and treatments commensurate with the severity and difficulty of these injuries.

The optimal outcome of blunt multisystem injuries requires the careful orchestration of several disciplines. Blunt thoracic aortic injury is an especially life-threatening injury that rarely occurs in isolation. Associated injuries include other chest injuries (hemopneumothorax, rib fractures, pulmonary contusion), head injuries, pelvis and extremity fractures and dislocations, and abdominopelvic injuries.

Advances in the diagnosis and management of blunt thoracic aortic injury include CT angiography, intense heart rate and blood pressure control with short acting intravenous beta blockade, and thoracic endovascular stent grafting. These advances have markedly decreased the hospital morbidity and mortality of this injury.1

Patients have better outcomes when treated at designated trauma centers.2 At the Hospital of the University of Pennsylvania (HUP), a state-accredited Level I Trauma Center, a fellowship-trained attending trauma surgeon is present in-house 24 hours a day. The surgical intensive care unit is staffed with a dedicated surgical critical care service, led by a board-certified surgical intensivist. The intensivist model is associated with better outcomes.3

Regarding specialty care, HUP is a regional referral center for complex thoracic aortic surgery, including endovascular techniques. Orthopaedic injuries are managed by the region’s only dedicated trauma orthopaedics service.

Case Study

Mrs. R, a 51-year-old female, was involved in a head-on motor vehicle collision and taken initially to a community hospital emergency room. Her workup there demonstrated the following injuries: traumatic transection of the proximal descending thoracic aorta (Figure 1), fractures of bilateral ribs (seven total), comminuted intraarticular fracture of the distal left femur, fracture of left tibial plateau, and fracture of right patella (Figure 2).

Mrs. R was transferred emergently to the trauma service at HUP for further management, including consideration for thoracic endovascular stent grafting of her aortic injury.

At HUP, her hemodynamics and pain were managed by the surgical critical care service and consultations were arranged with cardiac surgery, vascular surgery and orthopaedic surgery. The aortic injury remained stable. Imaging revealed that endovascular repair would require occlusion of the origin of the left subclavian artery.

However, because her pulmonary status was tenuous, Mrs. R was not a candidate for open aortic repair. Subsequently, she had a left carotid-subclavian artery bypass to debranch the thoracic aorta, followed by a thoracic endovascular stent graft for her aortic injury. She then underwent open reduction and internal fixation of her left femur and right patellar fractures and was eventually discharged to rehabilitation.

References - 1. Demetriades D, Velmahos GC, Scalea TM, et al. J Trauma.
2008;64:1414-1419; 2. Mackenzie EJ, Rivara FP, Jurkovich GJ, et al. New
Engl J Med. 2006;354:366-378; 3. Fuchs RJ, Berenholtz SM and Dorman T.
Best Pract Res Clin Anaesthesiol. 2005;19:125-135.

Faculty Team
The Division of Traumatology, Surgical Critical Care and Emergency Surgery at Penn Medicine operates a Level 1, regional resource trauma center accredited by the Pennsylvania Trauma Systems Foundation and a 24-bed dedicated surgical intensive care unit (SICU) with in-house trauma attendings 24/7/365.

The trauma center is nationally and internationally recognized as a model program for other hospitals. The SICU provides care for injured and critically ill patients by a multidisciplinary team comprised of a dual board-certified attending surgeon/ intensivist, board-certified physician intensivists, acute care nurse practitioners, surgical critical care fellows, resident physicians, critical care registered nurses, respiratory therapists, nutritionists and critical care pharmacists. Among the most technologically advanced in the region, the SICU also includes a telemedicine ICU.

Managing Complex Multisystem Trauma at Penn Medicine

Patrick M. Reilly, MD
Chief, Division of Traumatology, Surgical Critical Care
and Emergency Surgery
Professor of Surgery

Steven R. Allen, MD
Assistant Professor of Surgery

Benjamin Braslow, MD
Associate Professor of Surgery

Forrest Fernandez, MD
Assistant Professor of Clinical Surgery

Daniel N. Holena, MD
Assistant Professor of Surgery

Patrick K. Kim, MD
Assistant Professor of Surgery
Trauma Program Medical Director

Jose L. Pascual, MD
Assistant Professor of Surgery

C. William Schwab, MD
Professor of Surgery

Carrie A. Sims, MD
Assistant Professor of Surgery

Access
Hospital of the University of Pennsylvania
Traumatology, Surgical Critical Care and Emergency Surgery
Dulles 2
3400 Spruce Street
Philadelphia, PA 19104

To contact a member of the Division of Traumatology, Surgical Critical Care, or Emergency Surgery for a clinical question or patient transfer, please call 877-937-7366.


Download a pdf of this Clinical Briefing.

Transanal Endoscopic Microsurgery for Lesions of the Mid to Upper Rectum

Penn colon and rectal surgeons are now using transanal endoscopic microsurgery (TEM) to excise advanced polyps and selected early cancers (ultrasound T1) in the mid to upper rectum.

A minimally invasive approach, TEM permits surgeons to reach lesions up to 10-15 cm from the anal verge and to remove whole tumors while sparing the function of the rectum. The procedure employs an operating proctoscope through which instruments are introduced to perform excision and other functions under direct three-dimensional magnified visualization of the operating field.

The objectives of rectal cancer surgery include sphincter preservation, prevention of disease recurrence and long-term survival. Oncologic surgical principles require removal of the tumor-bearing organ, along with all nodal tissue. These operations may involve significant morbidity in terms of recovery from surgery, the possible need for temporary or permanent stomas and in post-operative function.

Local excision may be appropriate for advanced polyps and certain early cancers given the very low likelihood of nodal involvement (<10 percent in many early cancers) and has traditionally been employed for the purposes of polyp removal in low rectal polyps and for diagnosis in indeterminate lesions that are otherwise not amenable to colonoscopic removal.

However, most lesions of the mid to upper rectum are inaccessible to local excision using standard instruments. In patients having standard transanal excision, incomplete removal or fragmentation of excised lesions accounts for recurrence rates as high as 30 percent.

The advantages of TEM relative to standard cancer operations include rectal preservation, less blood loss, less pain, fewer complications and a faster recovery time. When compared to standard transanal excision, TEM results in superior visualization and less tissue fragmentation. This results in a significantly decreased recurrence rate for both adenomas and selected early
cancers.


Case Study

Mrs. M, a 58-year-old woman, was referred to the division of Colon and Rectal Surgery at Penn following two months of diarrhea and acute pain when a sigmoidoscopy revealed a large villous adenoma on the right wall of the mid rectum. At Penn, an ultrasound of the lesion found no evidence of invasion; a subsequent biopsy suggested that the lesion was benign.

Although all villous adenomas are considered premalignant and should be removed, the lesion was not amenable to removal by conventional colonoscopy. A transanal endoscopic microsurgery
was scheduled to remove the lesion.

The procedure was performed in approximately 90 minutes under general anesthesia with no complications. Intraoperative biopsies revealed clear surgical margins and no invasive disease. Mrs. M was mobile on the day of surgery and was discharged the next day. At her one year follow-up, no evidence of disease was present.

Faculty Team

The Division of Colon and Rectal Surgery at Penn Medicine provides the highest quality diagnostic and surgical options for patients with colon, rectal and anal cancer, inflammatory bowel disease (Crohns disease and ulcerative colitis), diverticular disease and many other diseases and disorders of the colon, rectum and anus.

The division offers (anal) sphincter-preserving colon and rectal surgery for cancer and benign disease, laparoscopic colon surgery, surgery for anal incontinence and rectal prolapse and both operative and medical therapies for anal diseases and complaints.

Performing Transanal Endoscopic Microsurgery at Penn Medicine

Joshua I.S. Bleier, MD, FACS, FASCRS
Assistant Professor of Surgery

Colon & Rectal Surgeons

Robert D. Fry, MD, FACS, FASCRS
Chairman, Department of Surgery, Pennsylvania Hospital
Chief, Division of Colon and Rectal Surgery
Emilie & Roland de Hellebranth Professor of Surgery

Cary Aarons, MD
Assistant Professor of Surgery

Brian R. Kann, MD, FACS, FASCRS
Assistant Professor of Surgery

Najjia N. Mahmoud, MD, FACS, FASCRS
Associate Professor of Surgery

Access
Department of Surgery
Hospital of the University of Pennsylvania
4 Silverstein
3400 Spruce Street
Philadelphia, PA 19104

Department of Surgery
Penn Presbyterian Medical Center
Wright Saunders
Suite 266
51 N 39th Street
Philadelphia, PA 19104

Department of Surgery
Pennsylvania Hospital
Garfield Duncan Building
Suite 305
700 Spruce Street
Philadelphia, PA 19106

Download a pdf of this Clinical Briefing.

Proton Radiotherapy for Recurrent Cancers

Radiation oncologists at Penn Medicine are conducting a clinical trial to determine the feasibility of proton radiotherapy (PRT) as a modality for the treatment of previously radiated patients with histologically confirmed, non-CNS solid malignancies and tumor recurrence in or near prior radiation fields. The study (ClinicalTrials.gov Identifier: NCT01126476) includes five cohorts: recurrent cancers of the head and neck, thorax, abdomen, pelvis and extremities.

The challenge when considering curative or aggressive local control of previously irradiated recurrent tumors is that photon beam radiotherapy (including intensity-modulated  radiation therapy or IMRT), carries significant risk for organs at risk from the cumulative effects of radiation.

Unlike photon beam radiotherapy, protons deposit the bulk of their energy only at the end of their path. Thus, proton radiotherapy may offer potential dosimetric and clinical advantages compared to photon radiation in patients experiencing recurrent cancers.

The first phase of the current study at Penn studies the feasibility of re-irradiation in each of the cohorts. In cohorts where feasibility has been verified, patients can then be enrolled in the second registration phase of the study. The study evaluates patients for both acute and late toxicity.

For more information about this study, contact: John Plastaras, MD, PhD at 215-615-3714 or admin@ctsrmc.org.

The initial findings from a prospective dosimetric analysis of PRT versus IMRT in pelvic tumors were presented at the 53rd annual meeting of the American Society for Therapeutic Radiology and Oncology in October 2011.


Prospective Trial of Proton Re-Irradiation of Recurrent Pelvic Tumors: Dosimetric Analysis*

Objectives: To provide an initial dosimetric analysis of PRT versus IMRT in pelvic tumors and an acute adverse effects profile for these patients. The primary endpoints were feasibility and acute toxicity.

Methods: All patients (N=10) were adults with solid tumor recurrences in or near prior radiation fields treated at least three months prior to entering the study. Malignancies included rectal adenocarcinoma, sarcoma and cervical carcinoma. Patients were further stratified by treatment volume as either low volume CTV (<250 cc, n=6) or high volume CTV (>250 cc, n=4). Fifty percent of patients received concurrent chemotherapy as 5-FU-based treatment (N=4) or cisplatin (N=1). IMRT plans were generated for backup purposes, and were optimized to deliver the same biologically equivalent dose as the PRT plans. IMRT and PRT plans were compared.

Results: Early findings suggest that in the prospective setting, PRT for the re-irradiation of recurrent pelvic malignancies reduces dose to many critical OARs when compared with intensity-modulated radiotherapy (IMRT) including bowel dose.

 *Abigail Berman Milby MD, Stefan Both PhD, Tiffany Sharkoski BA, James M. Metz MD,
   Smith Apisarnthanarax MD, Zelig Tochner MD, John P. Plastaras MD, PhD. Department of
   Radiation Oncology, University of Pennsylvania, Philadelphia, PA.


Faculty Team
Among the largest and most respected programs in the world, Penn Radiation Oncology offers a variety of innovative treatment options to patients with cancer. In addition, as a national leader in basic science, translational research and clinical trials, Penn Radiation Oncology offers patients access to the latest treatment options––including proton therapy––before they are widely available elsewhere.

Performing Clinical Research in Proton Therapy for Recurrent Cancers at Penn Medicine

Smith Apisarnthanarax, MD
Assistant Professor of Radiation Oncology

Curtiland Deville, MD
Assistant Professor of Radiation Oncology

James M. Metz, MD
Clinical Director, Department of Radiation Oncology
Associate Professor of Radiation Oncology

John P. Plastaras, MD, PhD
Assistant Professor of Radiation Oncology

Ramesh Rengan, MD, PhD
Assistant Professor of Radiation Oncology

Zelig A. Tochner, MD
Professor of Radiation Oncology

Access
Penn Radiation Oncology
Perelman Center for Advanced Medicine
Concourse Level
3400 Civic Center Boulevard
Philadelphia, PA 19104

Abramson Cancer Center
Penn Presbyterian Medical Center
Medical Arts Building, Suite 103A
51 N 39th Street
Philadelphia, PA 19104


Download a pdf of this Clinical Briefing.

Clinical Trials Examine Proton Therapy for Resected Non-Small Cell Lung Cancer

Radiation oncologists at Penn Medicine are conducting clinical trials to better understand the full potential and capabilities of proton therapy for the treatment of patients with non-small cell lung cancer (NSCLC).

While research has shown that the biologic effect on exposed tissues is essentially the same for standard radiotherapy and proton therapy (PT), the distinction between the two with regard to radiation exposure in the critical organs of cancer patients remains largely unresolved.

To address this issue, researchers at the Roberts Proton Therapy Center at Penn Medicine recently compared passive scattering proton therapy (PSPT) and intensity modulated proton therapy (IMPT) to intensity modulated photon beam radiotherapy (IMRT) in patients with completely resected
non-small cell lung cancer (NSCLC).

Proton Beam versus IMRT for Post-Operative Radiotherapy in Completely Resected IIIA Non-Small Cell Lung Cancer

Objectives: The aim of this study was to determine whether proton therapy provides relative dosimetric sparing of critical organs at risk (OARs) during the post-operative period. IMRT has been shown to reduce lung, heart and esophagus dose over 3D-conformal radiotherapy in the definitive treatment of advanced stage NSCLC and other thoracic malignancies. However, the detrimental effects of post-operative radiotherapy on OARs is thought to negate potential improvements in outcome in these patients.

Methods: The computed tomography treatment planning scans of patients with completely-resected IIIA NSCLC treated with IMRT post-operative radiotherapy were used for this study. The following critical normal structures were delineated on each planning CT scan: body, spinal cord, heart, esophagus, contralateral lung, ipsilateral lung, and total lung minus the planning target volume. The IMRT, PSPT, and IMPT plans were analyzed for dosimetric endpoints. The proton plans were constructed with two or three beams. IMRT plans were optimized to deliver 50.4 Gy all in 1.8 Gy fractions. The proton plans were optimized to deliver the same biologically equivalent dose as was originally delivered in the IMRT plans. Dose volume histograms were analyzed for all OARs.

Results: The decrease in dose to all OARs with IMPT was large and statistically significant compared with IMRT and PSPT (Fig. 1). PSPT reduced the volume of lung receiving a higher dose, but increased the low-dose lung bath. Reductions by IMPT were seen in dosimetric parameters to normal lung predictive of radiation pneumonitis and to heart doses predictive of morbidity and mortality. This reduction may correlate with a decrease in the incidence of this dose limiting toxicity and thus improve the therapeutic ratio.

Faculty Team
Among the largest and most respected programs in the world, Penn Radiation Oncology offers a variety of innovative treatment options to patients with cancer. In addition, as a national leader in basic science, translational research and clinical trials, Penn Radiation Oncology offers patients access to the latest treatment options––including proton therapy––before they are widely available elsewhere in the region.

Performing Clinical Research in Proton Therapy at Penn Medicine

Michelle Alonso-Basanta, MD, PhD
Assistant Professor of Radiation Oncology

Justin E. Bekelman, MD
Assistant Professor of Radiation Oncology

John Christodouleas, MD, MPH
Assistant Professor of Radiation Oncology

Curtiland Deville Jr., MD
Assistant Professor of Radiation Oncology

Stephen M. Hahn, MD
Chair, Department of Radiation Oncology
Professor of Radiation Oncology

Ramesh Rengan, MD, PhD
Chief, Thoracic Service
Assistant Professor of Radiation Oncology

Zelig A. Tochner, MD
Vice Chair of Proton Therapy
Professor of Radiation Oncology

Neha Vapiwala, MD
Chief, Genitourinary Service
Assistant Professor of Radiation Oncology

Access

Roberts Proton Therapy Center
Penn Radiation Oncology
Perelman Center for Advanced Medicine
Concourse Level
3400 Civic Center Boulevard
Philadelphia, PA 19104

Proton Therapy Research at Penn
Penn researchers are advancing and refining proton therapy (PT) for patients with cancer and other serious diseases. Current clinical trials seek to determine which cancers are most appropriately treated with proton therapy and ways in which PT may best be combined with standard chemotherapy and radiotherapy to improve surgical outcomes and reduce radiation exposure. Penn Radiation Oncology research programs are funded by the National Institutes of Health (NIH). For a full list of currently enrolling clinical trials in proton therapy, visit this site.

Download a pdf of this Clinical Briefing.

Advances in Enteral Feeding at Penn Medicine

From the Penn GI News, Fall 2011

Gastroenterologists at Penn Medicine are partnering with a variety of specialists throughout the health system to introduce new enteral feeding tube (ETF) techniques and devices for patients with conditions that prevent normal swallowing and feeding. The indications for ETF include impaired swallowing as a result of brain injury or trauma, gastrointestinal obstruction, pancreatitis, motility disorders and cystic fibrosis and other hypercatabolic states, including burn injuries and Crohn’s disease.

In these critically ill patients, enteral feeding has been shown to complement nutrition by modulating the metabolic reaction to stress and enhancing the immunological function of the bowel. Moreover, ETF is superior to total parenteral nutrition (TPN) in cost and adverse events (catheter and blood infections and venous thromboses).

“Enteral nutrition is an important facet of health care in patients with digestive and related disorders at Penn,” explains Gregory Ginsberg, MD, director of endoscopy at Penn and current president of the American Society for Gastrointestinal Endoscopy. “Enteral feeding employs the functional gut and as such preserves aspects of gut flora and function. This facilitates retention of the immunological function of the gut and is associated with decreased risk for bacterial translocation and lowered infection risk.”

Endoscopic means of enteral access to facilitate nutritional support can assume many forms. Short-term nutritional support is typically accomplished via nasoenteric feeding tubes (NETs). Longer-term feeding arrangements generally involve percutaneous endoscopic gastrostomy (PEG) tubes or direct-percutaneous endoscopic jejunal (DPEJ) tubes, a specialty of gastroenterologists at Penn Medicine.

Used when the proximal-most portion of the digestive tract must be bypassed and feeding must be delivered beyond the ligament of Treitz, the DPEJ technique is technically challenging, Dr. Ginsberg says.

“We’ve worked to develop tools and techniques to best ensure success in selected patients. In preclinical work, for example, we incorporate magnetic attraction forces to help localize and transiently fix the small intestine to the anterior abdominal wall to facilitate the placement of DPEJ tubes.”

Appropriate indications for the DPEJ procedure include post-operative anatomy, pancreatitis and entero-respiratory reflux.

Low-profile PEG Button Tubes Improve Enteral Feedings for Young Patients
Penn gastroenterologists have recently introduced low-profile percutaneous endoscopic gastrostomy (PEG) button tubes designed for single-step application in young patients and those with pre-existing tubes.
“The concern with conventional PEG tubes is that they can come loose as a result of forces placed on the exterior tubing,” says Octavia Pickett-Blakely, MD, MHS. “The button design places the bolster at the abdominal wall, which decreases the risk of pull-out and irritation at the wound site in young, active patients.”
In studies of pediatric patients, those with low-profile PEG tubes were likely to have fewer tube dislodgments and briefer hospital stays than patients with standard PEG tubes.


Download a pdf of the Penn GI News for Fall 2011.

Total Ankle Replacement with the STARTM Ankle System

Orthopaedic surgeons at Penn Medicine are implanting the Scandinavian Total Ankle Replacement (STAR™ Ankle*) system for the treatment of end-stage tibiotalar arthritis as a result of trauma or rheumatoid disease. Penn Medicine is currently the only place in the Philadelphia region offering the STAR system for total ankle replacement.

Total ankle replacement was originally developed in the 1970s as an alternative to tibiotalar arthrodesis (ankle fusion). Early implant designs led to high failure rates, however, and thereafter, ankle fusion became the established gold standard for the treatment of end-stage ankle arthritis.

Renewed interest in total ankle replacement occurred when long-term studies determined that ankle fusion contributes to the development of advanced symptomatic hindfoot arthritis and increasing functional limitations. Improvements in design, materials and surgical technique followed, and total ankle replacement is today a viable alternative to ankle fusion for the treatment of ankle arthritis.

The STAR ankle system in use at Penn is designed to maintain a normal range of motion for the ankle. It is currently the only three piece, mobile bearing, non-constrained, uncemented device approved by the Food and Drug Administration for total ankle replacement for the treatment of ankle arthritis.

The system is comprised of two cobalt chromium alloy interfaces coated with titanium. The upper interface is attached to the tibia and is a flat planar surface, permitting internal and external rotation and translation in the antero-posterior and mediallateral directions. The second interface is attached to the talus and is shaped like a cylinder, allowing plantarflexion-dorsiflexion motion.

A polyethylene mobile bearing is situated between the metal parts. An advantage of the mobile bearing is that the flat upper surface allows some rotation, thus reducing stress at the prosthesis–bone interface.

Case Study
Mr. R, a 62-year-old patient, was referred to the Department of Orthopaedic Surgery at Penn for evaluation of degenerative osteoarthritis in his left ankle. Mr. R had pain of increasing severity even at rest and was using a cane at presentation. His medical history included NSAIDs and cortisone treatment. Following a consultation, Mr. R opted to have total ankle replacement surgery in the hope that he could retain some mobility in his ankle.

The STAR arthroplasty procedure was conducted through an anterior 15 cm to 20 cm approach to the ankle joint through the extensor retinaculum above the extensor hallucis longus tendon. Following the removal of 5 to 8 mm of the distal articular surface at the dome of the tibial plafond and 4 to 6 mm of the superior dome of the talus, 2 to 3 mm was resected from the medial and lateral talus.

Anterior and posterior chamfer cuts were then made to create a truncated pyramidal shaped surface for seating of the talar component. A vertical slot was created in the central aspect of the talus to receive the fin of the talar prosthesis and a prosthesis placed and impacted onto the prepared talar surface.

To accommodate the barrels of the tibial component, two holes were drilled from anterior to posterior at the edge of the prepared distal tibial surface. A gouge was then used to connect the holes with the prepared flat surface of the distal tibia and a tibial component inserted. A polyethylene trial spacer of appropriate size was then selected and inserted. Mr. R’s lower leg and ankle were then immobilized in a below knee cast.

Mr. R recovered well from his surgery and was discharged on post-operative day four. During the next two weeks, he was permitted minimal weightbearing on his left ankle. This was followed by two weeks of 50% weightbearing and two weeks of full weightbearing in the cast, after which the cast was removed. At one year post-surgery, Mr. R has regained full mobility.

Reference
Saltzman CL, Mann RA, Ahrens JE, et al. Prospective Controlled Trial of STAR Total Ankle Replacement Versus Ankle Fusion: Initial Results. Foot Ankle Int. 2009;30:579-596.
*The StarTM Ankle System is a trademark of Small Bone Innovations, Inc., Morrisville, PA.

Faculty Team

Penn Orthopaedics Foot and Ankle Service offers comprehensive, state-of-the-art surgical and non-surgical treatment for all routine foot and ankle disorders including bunions, hammertoes, and the most complex reconstructive procedures for deformities secondary to trauma, tendon injury, rheumatoid disease, and diabetes. Penn’s foot and ankle team is the only practice in the area performing the STAR total ankle replacement for ankle arthritis.

Performing Total Ankle Replacement at Penn Medicine
Keith L. Wapner, MD
Chief, Foot and Ankle Service
Clinical Professor of Orthopaedic Surgery

Keith L. Wapner, MD, specializes in total ankle replacement surgery and the treatment of tendon injuries, rheumatoid arthritis, bunions, and diabetes. He completed a residency in orthopaedic surgery at the University of Pennsylvania School of Medicine, and fellowships in joint replacement surgery at the Ohio State University, and foot and ankle reconstruction at the University of California, San Francisco. A past president of the American Orthopaedic Foot & Ankle Society, Dr. Wapner is a paid consultant to Small Bone Innovations, Wright Medical Technology and MemoMetal Technologies. He receives institutional support from EBI and Hanger Orthopedic Group.

Penn Foot and Ankle Service
Wen Chao, MD
Clinical Associate of Orthopaedic Surgery

Andrew M. Steiner, MD

Keith L. Wapner, MD
Clinical Professor of Orthopaedic Surgery

To refer a patient to Penn Medicine, please call Penn PhysicianLink® at 877-937-7366 or visit pennmedicine.org/physicianlink.

Download a pdf of this Clinical Briefing.

Surgical Correction of Uterus Didelphys with Obstructed Hemivagina

Surgeons with the Department of Obstetrics and Gynecology at Penn Medicine are performing minimally invasive laparoscopic surgery to correct rare congenital anomalies in adolescents and young women, including uterus didelphys with obstructed hemivagina, a condition characterized by the duplication of the uterus, cervix and vagina and congenital absence of the ipsilateral kidney (see Figure 1).

Uterus didelphys is the result of a developmental anomaly of the urogenital septum and is linked etiologically with fetal renal development. In between 15 percent to 30 percent of females with uterus didelphys, one of the vaginal openings is obstructed by the transverse position of the septa (often the right side), resulting in a “blind,” hemivagina. This anomaly is often present in women with ipsilateral renal agenesis and other renal abnormalities.

The rarity and complexity of uterus didelphys with blind hemivagina make its diagnosis uniquely dependent upon the experience of the provider. Diagnosis rarely occurs prior to menarche, when acute symptoms resulting from menstrual fluids trapped in the obstructed vagina occur. Symptoms and findings may include dysmenorrhea, acute lower abdominal or pelvic pain, recurrent pain and/or a paravaginal mass. Endometriosis is not uncommon in these patients.

Specialists with the Penn Center for Advanced Gynecologic Surgery at Penn Fertility Care have extensive experience in the treatment of congenital anomalies, including uterus didelphys. At Penn, ultrasound and/or pelvic MRI confirms the diagnosis of uterus didelphys with blind hemivagina. The standard of care for this condition involves minimally invasive surgical techniques that optimize preservation of reproductive potential and evacuate the trapped contents of the obstructed vagina.

Typically, this procedure is done vaginally by removing a portion of the vaginal septum to allow the accumulated menstrual blood to be released and to connect the two sides to make a single vagina. Sometimes laparoscopy is performed at the same time to evaluate and treat co-existing endometriosis and adhesions caused by the flow of menstrual blood backwards through the fallopian tubes due to the vaginal obstruction.

Case Study

CJ, a 14-year-old female, was referred to Penn Medicine by her primary care provider with acute lower abdominal pain. At Penn, CJ was noted to be very uncomfortable and had difficulty walking. She reported that she had first menstruated at age 12 and that she had experienced cyclic pelvic pain of increasing severity for the last year. CJ’s mother, who was present, reported that she was born with a single left kidney.

Abdominal exam revealed a tender large mass in the lower abdomen extending half way up to the umbilicus. A pelvic ultrasound was ordered; this revealed a duplex uterus and a substantial right-sided mass in the lower abdomen. An MRI of CJ’s pelvis was then performed to permit further evaluation. These images revealed a dilated, fluid filled mass in the lower pelvis within a right-sided hemivagina, and confirmed the uterus didelphys (Figure 1).

In the operating room at Penn CJ had drainage of the right hemivagina and removal of the vaginal septum on the right. Laparoscopy revealed a uterus didelphys with the right side slightly larger than the left due to the distended hemivagina, and normal ovaries and fallopian tubes. There was extensive endometriosis throughout the abdomen but no adhesions.

She was discharged to home the same day. At her postoperative visit she looked happy, and reported that she had no pain or abdominal distention for the first time in many months and was able to participate in her school activities again.

Faculty Team

Specialists in adolescent gynecology at Penn Fertility Care offer evaluation and medical and surgical treatment for a wide variety of disorders that affect menstrual and reproductive function in young women. In addition to amenorrhea and delayed puberty, these disorders include ovarian cysts, polycystic ovary syndrome (PCOS) and congenital reproductive tract disorders (müllerian anomalies) or uterine anomalies.

For adolescents undergoing cancer therapy and cancer survivors, Penn physicians offer counseling regarding fertility preservation and treatment of the long-term reproductive and endocrine complications associated with cancer treatments. Our team collaborates with oncologists at the Children’s Hospital of Philadelphia and the Abramson Cancer Center and a consortium of researchers developing improved and effective fertility preservation options.

Performing Surgery for Uterus Didelphys at Penn Medicine

Hospital of the University of Pennsylvania

Samantha M. Pfeifer, MD
Associate Professor of Obstetrics and Gynecology
Director, Reproductive Surgery Program

Clarisa R. Gracia, MD, MSCE
Assistant Professor of Obstetrics and Gynecology
Director, Fertility Preservation Program

Pennsylvania Hospital

Scott E. Edwards, MD
Assistant Professor of Clinical Obstetrics and Gynecology

Adolescent Reproductive Health

Samantha M. Pfeifer, MD
Associate Professor of Obstetrics and Gynecology

Clarisa R. Gracia, MD, MSCE
Assistant Professor of Obstetrics and Gynecology

Scott E. Edwards, MD
Assistant Professor of Clinical Obstetrics and Gynecology

Suleena Kansal Kalra, MD, MSCE
Assistant Professor of Obstetrics and Gynecology

Access
Penn Fertility Care
3701 Market Street
5th Floor
Philadelphia, PA 19014

Penn Fertility Care
Spruce Building, 7th Floor
801 Spruce Street
Philadelphia, PA 19107

Penn Medicine Radnor
Penn Health for Women
250 King of Prussia Road
Radnor, PA 19087

Reproductive Surgery at the Penn Center forAdvanced Gynecologic Surgery

The Penn Center for Advanced Gynecologic Surgery at Penn Fertility Care is comprised of reproductive surgeons with expertise in the conservation of fertility and the correction of anatomical disorders that affect reproductive function. These specialists are experienced in the care of adolescents with müllerian anomalies and other conditions requiring surgical invervention, and often work in collaboration with pediatric urologists at the Children’s Hospital of Philadelphia.

To refer a patient to Penn Medicine, please contact Penn PhysicianLink^TM here or at 877-937-7366.


Download a pdf of this Clinical Briefing.

Clinical Research in Immunotherapeutic Therapies for Resectable Non-Small Cell Lung Cancer

Penn Medicine is a participating site for the MAGE-A3 as Adjuvant, Non-Small Cell Lung Cancer Immunotherapy (MAGRIT) trial, the largest trial to date in the adjuvant treatment of non-small cell lung cancer (NSCLC).

With surgery alone, patients with resectable NSCLC have a five-year survival ranging from 23% for stage IIIA to 67% for stage IA disease. Patient mortality is typically associated with cancer recurrence at sites other than the lung, suggesting the presence of systemic disease at diagnosis.

To address this concern, patients with completely resected stage II – IIIA NSCLC (and selected patients with stage IV disease) typically receive preoperative and adjuvant cisplatin-based chemotherapy. However, even with chemotherapy, only 14% of patients with NSCLC survive for five years.

The limited success of chemotherapy has prompted researchers with the Division of Thoracic Surgery at Penn Medicine and elsewhere to investigate antigen-specific vaccinations for non-small cell lung cancer. These agents have been shown to have the potential to improve patient survival.

Details and participant information for the MAGRIT trial at Penn may be found at http://1.usa.gov/oLTydN.

Proposed Mechanism of Action of Antigen-Specific Cancer Immunotherapeutics

Clinical Trials

MAGRIT – Phase 3

A Randomized Double-Blind, Placebo-Controlled Phase 3 Study to Assess the Efficacy of recMAGE-A3 + AS15 Antigen-Specific Cancer Immunotherapeutic as Adjuvant Therapy in Patients with Resectable MAGE-A3-positive Non-Small Cell Lung Cancer (NSCLC)
ClinicalTrials.gov Identifier NCT00480025 (NCT00638105)

Description: A phase 3, randomized, double-blind, controlled clinical trial of the immunotherapeutic investigational agent recMAGE-A3 + AS15 in patients with tumor antigen-positive non-small cell lung cancer. The trial involves 13 injections over a period of 27 months.

Objectives: The primary objective of this study is to demonstrate the clinical efficacy of recMAGE-A3 + AS15 versus placebo in patients with NSCLC after complete surgical resection. The primary outcome measure is disease-free survival. Secondary outcome measures include overall survival, seropositivity and occurrence of adverse events at predefined endpoints.

PRAME – Phase 1
Evaluation of a New Anti-cancer Vaccine for Patients With Non-small Cell Lung Cancer, After Tumor Removal by Surgery
ClinicalTrials.gov Identifier: NCT01159964
 
Description: An open-label, phase 1 dose-escalation study of the recPRAME + AS15 ASCI agent when given to patients with PRAME-positive NSCLC after tumor resection. The population will include patients with completely resected, stage IB, II or IIIA NSCLC. The surgical technique for resection must involve at least a lobectomy or sleeve lobectomy. The tumor must be tested for PRAME expression and must be PRAME-positive for enrollment in the vaccine trial. Patients must have adequate bone marrow reserves and renal and hepatic function.

Objectives: The primary objective of this study is to assess the safety and immunogenicity of the recPRAME + AS15 ASCI. The primary outcome measure is the occurrence of dose-limiting toxicities during study treatment and follow-up and anti-PRAME humoral immune response at predefined endpoints.

Contact Information: PI: John Kucharczuk, MD. For more information contact: Marie Kromplewski, RN, BSN,CCRC at 215-615-4117 or Janet Riggs MSN, RN, DrNP(c) at 215-615-4368.


About MAGRIT

MAGRIT is an international, randomized, double-blind phase 3 clinical trial evaluating an investigational antigen-specific cancer immunotherapeutic (ASCI) agent based upon the melanoma associated A3 antigen (MAGE-A3) for the treatment of NSCLC.

MAGE-A3 is a tumor-specific antigen detected in between 35% and 50% of patients with NSCLC. The MAGE-A3 ASCI employs a recombinant protein with the potential to activate a variety of T cell responses.

The goal of MAGRIT is to determine the capacity of the MAGE-A3 ASCI to control NSCLC in patients who have had surgery to resect the tumor. Initiated in 2007, the MAGRIT trial has enrolled more than 3200 patients to date.

Faculty Team

The lung cancer team at Penn Medicine is leading an effort to revolutionize the early diagnosis, prevention and treatment of lung cancer. Penn is a major center for lung cancer clinical trials, allowing patients to benefit from the newest and best therapies available.

Thoracic Surgery

Joel D. Cooper, MD
Professor of Surgery

Joseph S. Friedberg, MD
Associate Professor of Surgery

John C. Kucharczuk, MD
Associate Professor of Surgery

Vincent E. Lotano, MD
Assistant Professor of Surgery

Taine T.V. Pechet, MD
Associate Professor of Surgery

Sunil Singhal, MD
Assistant Professor of Surgery

Stacey Su, MD
Assistant Professor of Surgery

Thoracic Medical Oncology

Corey J. Langer, MD
Professor of Medicine

Ken Algazy, MD
Clinical Professor of Medicine

Tracey Evans, MD
Assistant Professor of Medicine

James P. Stevenson, MD
Associate Professor of Medicine

Thoracic Radiation Oncology

Stephen M. Hahn, MD
Chairman, Department of
Radiation Oncology
Professor of Radiation Oncology

Smith (Jim) Apisarnthanarax, MD
Assisstant Professor of Radiation Oncology

John Christodouleas, MD
Assistant Professor of Radiation Oncology

Keith Cengel, MD, PhD
Assistant Professor of Radiation Oncology

Ramesh Rengan, MD
Assistant Professor of Radiation Oncology

Thoracic Oncology Pulmonology

Andrew Haas, MD, PhD
Assistant Professor of Medicine

Dan Sterman, MD
Associate Professor of Medicine

Morris Swartz, MD
Associate Professor of Medicine

Anil Vachani, MD
Assistant Professor of Medicine

Access

Penn Lung Center
Perelman Center for Advanced Medicine
West Pavilion, 1st Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

Abramson Cancer Center
Perelman Center for Advanced Medicine
West Pavilion, 2nd Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

Penn Presbyterian Medical Center
51 N 39th Street
Philadelphia, PA 19104

Pennsylvania Hospital
700 Spruce Street
Philadelphia, PA 19107

To refer a patient to Penn Medicine, contact Penn PhysicianLink® here or at 877-937-7366.

Download a pdf of this Clinical Briefing.

Clinical Diagnosis and Surgical Treatment of Pheochromocytomas

From the Penn GI News

The Penn NET Treatment Program is a major regional source of referrals for patients with pheochromocytomas. The elevated catecholamines induced by these tumors can cause a variety of diverse (and often confusing) symptoms, including (but not limited to) the classic triad of headache, palpitations and sweating. Many patients will have hypertension, which can be labile.

Patients with pheochromocytoma entering the Penn NET Treatment Program are diagnosed and treated by an interdisciplinary team of clinicians within the Renal-Electrolyte and Hypertension Division and the Division of Endocrine and Oncologic Surgery. Typically, initial therapy focuses upon relief of the symptoms caused by hormone over-secretion.

Coordinating Treatment for GEP-NETs and PETs

A nurse coordinator at the Abramson Cancer Center provides an important element of both patient care and confidence, overseeing diagnostics and treatment plans, coordinating visits and follow-up and administering central scheduling for all patients. The nurse coordinator also serves as the liaison for research should appropriate clinical trials become available to patients. According to Dr. Metz, the dedicated nurse coordinator is at the core of the process, ensuring cohesion in the treatment plan, involving the patient at every step and providing updates to the treatment team about important developments. Octreotide, MIBG and other necessary medications are administered through the divisions of Gastroenterology, Hematology-Oncology, Renal Electrolyte and Hypertension, Interventional Radiology and Nuclear Medicine and Medical Genetics.

Case Study 1

Mrs. G, a 49-year-old female, was referred to the Penn Neuroendocrine Tumor Treatment Program for carcinoid tumor surgery. Several months before presenting at Penn, she had developed lower leg edema, flushing and diarrhea.

These symptoms led her to visit her ob/gyn, who ordered an abdominal CT scan that found widely dispersed tumors in her liver. At Penn, a 24-hour urine test for 5-hydroxyindolacetic acid (5-HIAA), the main urinary metabolite of serotonin,measured >150 mg/day (normal=<6 mg/day); an assessment of chromogranin A (CgA), a NET marker, found levels >100 u/L (normal range = 2-18 u/L). An octreoscan identified a primary tumor in the terminal ileum and an extensive tumor burden in the right lobes of her liver but no metastases beyond the liver.

Mrs. G was diagnosed with widely metastatic carcinoid tumors in her liver and carcinoid syndrome and began octreotide LAR, 20 mg/month, which improved, but did not resolve her symptoms. Her dose was increased to 30mg/month and following an interdisciplinary review of her tests and scans, it was recommended that Mrs. G have chemoembolization of the tumors in her right liver followed by debulking surgery.

Following two visits to interventional radiology for chemoembolization, she had liver resection surgery in the division of gastroenterological surgery. She recovered from these procedures without incident. At this time, her 5-HIAA and CgA levels were within normal levels. Six months post-surgery, a CT scan revealed no new hepatic lesions and no new metastases. At one year, Mrs. G’s status remains stable on octreotide maintenance therapy.

Case Study 2

Mr. R presented at age 12 with headaches and diarrhea; he was diagnosed with a right adrenal pheochromocytoma and underwent right adrenalectomy.

At age 37, Mr. R was seen at the Penn Center for Complex Hypertension with recurrence of diarrhea and headaches. His BP was 132/80 mm Hg and he was not on any antihypertensive medications. He was found to have a left adrenal mass consistent with pheochromocytoma and was scheduled for a second adrenalectomy.

He was treated with dibenzylene for preoperative alpha blockade and alpha methyl-tyrosine. A left-sided adrenalectomy was performed; now unable to produce endogenous steroids, Mr. R began a regimen of hydrocortisone and fludrocortisone. Because certain genetic mutations are associated with bilateral adrenal pheochromocytoma, Mr. R was referred for genetic testing.

Genotyping studies were positive for Von Hippel Lindau V84L mutation, an autosomal dominant trait with a 50 percent risk of inheritance. Mr. R’s 18-year-old son, JW, was also found to be carrying the vHL mutation. JW had no symptoms; supine and sitting BP were 120/78 mm Hg and 118/82 mm Hg. Standing blood pressure was 96/74 mm Hg with a heart rate of 120 beats/minute.

Urine studies show elevated normetanephrine levels. MRI of the abdomen showed a left adrenal mass and laparoscopic adrenocortical sparing surgery was performed. While his BP remained normal with home BP monitoring, JW’s plasma and urine metanephrines never “normalized.”

A repeat MRI performed a year later revealed a new tumor in the right adrenal gland and a second adrenal cortex sparing surgery for his second pheochromocytoma was performed. Both Mr. R and JW remain disease-free several years later with yearly surveillance with blood tests and imaging for recurrent pheochromocytoma.

Treating Pheochromocytomas at Penn Medicine

Debbie Cohen, MD
Associate Professor of Medicine

David Metz, MD
Professor of Medicine

To refer a patient to Penn Medicine, please contact Penn PhysicianLink^TM here or at 877-937-7366.

Download a pdf of the Winter 2011 Penn GI News.

Biomechanical Modeling to Determine Risk of Aortic Dilatation, Dissection and Rupture

In collaboration with the Gorman Cardiovascular Research Laboratory at the University of Pennsylvania, surgeons from the Division of Vascular Surgery and Endovascular Therapy, led by Benjamin M. Jackson, MD, are using computational biomechanical models to study the role that mechanical wall stress plays in a variety of aortic pathologies.

Electrocardiogram-gated computed tomography angiography (ECG-gated CTA) scan data were used to create the three dimensional models. Finite element analysis (FEA – a numerical method that subdivides complex structures into small elements with defined material properties to predict the distribution of wall stress in these structures under physiological loading) was then applied to the three dimensional mesh to determine the wall stress distribution of the aorta.

The researchers examined the etiology of thoracic aortic dissection and evaluated the rupture risk of aneurysms of the thoracic aorta. Their findings, which were presented at the 2010 meetings of the American Heart Association, the American College of Surgeons and the Society for Vascular Surgery, are reviewed below.

Clinical Study Review

Increased Ascending Aortic Wall Stress in Patients with Bicuspid Aortic Valves[1]
Objective: This study sought to determine why patients with bicuspid aortic valves (BAV) are at increased risk of ascending aortic dilatation, dissection, and rupture compared to patients with normal tricuspid aortic valves (TAV). BAV is a defect of the aortic valve that results in the formation of two leaflets or cusps instead of the normal three.
Methods: The investigators hypothesized that ascending aortic wall stress may be increased in BAV compared to TAV. Biomechanical models of the aorta were created using BAV/TAV pairs matched for diameter. Finite element analysis was then performed to predict wall stress in the ascending aorta using a systolic pressure load of 120 mm Hg and a uniform aortic wall thickness of 1.7 mm.
Results: When normalized by radius, the wall stress was greater in the ascending aorta of patients in the BAV group [0.31 ± 0.06 MPa/cm] than in those of the TAV group [0.27 ± 0.03 MPa/cm, P=0.013] (Figure 1). Thus, increased ascending aortic wall stress may account in part for the increased propensity to aortic dilatation, rupture and dissection in patients with BAV.
[1] Ann Thorac Surg. 2011;92:1384-1389.

Rupture Risk of Saccular Descending Thoracic Aortic Aneurysms by Stress Modeling
Objective: To investigate the rupture risk of saccular descending thoracic aortic aneurysms (DTA) by comparing wall stress in patients with saccular DTAs to that found in patients with fusiform DTA.
Methods: Three-dimensional meshes of the aorta were created from computed tomography angiography scan data of subjects with fusiform and saccular DTAs. Finite element analysis was then performed to determine wall stress using a systolic pressure load of 120 mm Hg and a uniform aortic
wall thickness of 3.2 mm.
Results: The normalized wall stress for saccular DTA was found to be greater than that for fusiform DTA (Figure 2), indicating that geometric factors (such as aneurysm shape) influence wall stress and rupture risk. The finding that saccular aneurysms have a higher wall stress than fusiform aneurysms of similar diameter provides a rationale for the repair of saccular DTA at a smaller diameter and suggests a role for biomechanical modeling
in surgical decision-making.

Pathogenesis of Acute Aortic Dissection: A Finite Element Stress Analysis[2]
Objectives: This study was performed to determine whether type A and B aortic wall dissections are caused by elevated pressure-induced regional wall stress.
Methods: The researchers created a three-dimensional mesh of the aorta. Finite element analysis using a systolic pressure load of 120 mm Hg was then performed to predict regional thoracic aortic wall stress.
Results: The researchers identified local maxima of wall stress above the sinotubular junction in the ascending aorta and distal to the left subclavian artery. No local maximum of wall stress was found in the remainder of the descending thoracic aorta. This stress distribution may contribute to the pathogenesis of aortic dissections, given their co-localization. Future investigations to determine the utility of image-derived biomechanical calculations in predicting aortic dissection are warranted, and therapies designed to reduce the pressure load-induced wall stress in the thoracic aorta are rational.
[2] Ann Thorac Surg. 2011;91:458-463.
Faculty Team
The Division of Vascular Surgery and Endovascular Therapy at Penn provides comprehensive therapy for arterial vascular disorders and Paget-Schroetter syndrome, including treatment of cerebrovascular disease, aneurysmal disease of the aorta, iliac, and peripheral arteries and treatment of occlusive disease of the aorta and its branches. The Division is also among a select group of research centers involved in FDA trials investigating new, advanced ways to treat thoracoabdominal aortic aneurysms.

Division of Vascular Surgery and Endovascular Therapy

Ronald M. Fairman, MD
Chief, Division of Vascular Surgery and Endovascular Therapy
Clyde F. Barker-William Maul Measey Professor of Surgery

Edward Y. Woo, MD
Associate Professor of Surgery

Benjamin M. Jackson, MD
Assistant Professor of Surgery

Grace J. Wang, MD
Assistant Professor of Surgery

Gorman Cardiovascular Research Group

Joseph H. Gorman, III, MD
Professor of Surgery

Robert C. Gorman, MD
Professor of Surgery

Access
Perelman Center for Advanced Medicine
Penn Heart and Vascular Center
East Pavilion, 2nd Floor
3400 Civic Center Boulevard

To refer a patient to Penn Medicine, please contact Penn PhysicianLink^TM here or at 877-937-7366.

Download a pdf of this Clinical Briefing.