University of Pennsylvania Health System

Clinical Briefings™: Clinical Reports from Penn Medicine

Tuesday, March 17, 2015

Total Proctocolectomy with J-pouch Reconstruction for Ulcerative Colitis

Division of Colon and Rectal Surgery

Colorectal surgeons at Penn Medicine are performing total proctocolectomy with J-pouch reconstruction/intestinal pouch anal anastomosis (IPAA) for patients with ulcerative colitis (UC).

Since its introduction in the US in the 1980s, this procedure has undergone technical changes that make it much better tolerated, with improved outcomes and faster recovery. In selected individuals, it replaces total proctocolectomy with end ileostomy, and allows for the retention of gastrointestinal continuity—a major concern for all patients.

Emergent indications for surgery in UC include acute flares refractory to medical control, sudden, severe disease manifesting as uncontrolled bleeding in the colon, toxic megacolon, and perforation of the bowel. By contrast to Crohn’s disease, UC is cured by removal of the diseased colon and rectum.

At Penn Medicine, elective total proctocolectomy with J-pouch for UC is offered to patients who have pre-cancerous or dysplastic colonic mucosal changes and to those patients refractory to medical management with intolerable symptoms such as frequency, pain and urgency leading to a progressive decline in quality of life. Because the rate of synchronous or subsequent adenocarcinoma ranges from 10%-50% in this population, both high- and low-grade dysplasia constitute indications for proctocolectomy.

Total proctocolectomy with J-pouch reconstruction is most commonly performed in either two or three stages depending on the condition of the patient. Three-stage procedures are performed for acutely or chronically ill malnourished individuals, patients on high doses of immunosuppressive medications, or those who present emergently with the indications for surgery listed above.

The first stage is a laparoscopic total colectomy with preservation of the rectum and end ileostomy in the right lower quadrant of the abdomen (Figure 1). Sparing the rectum in these circumstances is important. Proctectomy is often the most technically challenging of the procedure. Performing this part of the operation in a well-nourished, healthy, immunocompetent individual reduces morbidity and makes J-pouch creation safer by improving outcomes and reducing septic complications. The second part of the procedure occurs about 3-4 months later depending on the patient’s performance status. This step involves removal of the rectum, creation of the J-pouch from the terminal ileum (about 20 cm) and temporary loop ileostomy to divert the fecal stream proximal to the J-pouch. About two months after J-pouch creation (after the pouch is checked via gastrograffin enema for leaks, sinus tracts or defects) the loop ileostomy is closed through a small peristomal incision (Figure 2).

Two stage procedures are done frequently in well-nourished patients who present electively for proctocolectomy for indications such as dysplasia or failure of medical management. Patients are screened for malnutrition, and are asked to stop anti-TNF therapy about one month in advance of the procedure. Prednisone doses higher than 20mg/day have been associated with J-pouch leaks/complications; thus consideration for a three stage procedure is warranted if higher doses of steroids are required.

Case Study

Mr. V, a 37-year-old with medically refractory ulcerative colitis, was referred to Penn Medicine for evaluation. A review of his medical history indicated that Mr. V’s disease began in his late teens. At this time, his symptoms included bloody diarrhea, bloating, acute pain and cramping.

In the decades since, his UC had responded for varying periods of time to mesalazine, azathioprine, prednisone and finally, infliximab. Each medication brought about a remission followed by a gradual return of symptoms and flare-ups, the most recent of which was attended by 20 to 30 bowel movements a day, dramatic weight loss and hospitalization.

At the time of admission, Mr. V was taking infliximab every two weeks, and was on 30 mg prednisone daily. After a consultation to discuss further medical therapy with other anti TNF-alpha alternatives, it was discovered that Mr. V had considered surgery, but was reluctant because he felt he was too young for an ileostomy.

After counseling, and in consultation with the Division of Gastroenterology, there was agreement that Mr. V would have a total proctocolectomy with J-pouch reconstruction, and that his acute presentation, relative malnutrition and immunosuppression required that the surgery proceed in three stages.

Mr. V returned home two days after the initial step (laparoscopic subtotal colectomy with temporary end ileostomy) in the three-step procedure. In the next four months, he gained almost twenty pounds while gradually weaning himself from prednisone. His sleep improved and for the first time in several years, he was able to begin moderate exercise. Returning for the proctectomy and creation of the J-pouch and temporary loop ileostomy, Mr. V spent another three days in the hospital, then returned home. Two months later his ileostomy was reversed.

Today, at a year post-surgery, he has between four and six bowel movements a day, with perfect control. He is exercising regularly, eating previously forbidden foods and has no activity restrictions or limitations.

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 (Crohn’s disease and ulcerative colitis), diverticular disease and many other diseases of the colon, rectum and anus. The division offers sphincter-preserving colon and rectal surgery for cancer and benign disease, laparoscopic and robotic colorectal surgery, treatment for fecal incontinence and rectal prolapse and both operative and medical therapies for anal diseases.

Performing Total Proctocolectomy and J-Pouch Reconstruction for Ulcerative Colitis at Penn Medicine

Najjia N. Mahmoud, MD
Chief of Colon and Rectal Surgery
Associate Professor of Surgery

Cary B. Aarons, MD
Assistant Professor of Clinical Surgery

Joshua I. S. Bleier, MD
Associate Professor of Clinical Surgery

Skandan Shanmugan, MD
Assistant Professor of Clinical Surgery


Department of Surgery

Perelman Center for Advanced Medicine
3400 Civic Center Blvd
Philadelphia, PA 19104

Penn Medicine University City
3737 Market Street, 4th Floor
Philadelphia, PA 19104

Penn Medicine Washington Square
800 Walnut Street, 20th Floor
Philadelphia, PA 19107

Wednesday, January 28, 2015

Medical and Surgical Management of Myasthenia Gravis and Thymoma

 Department of Thoracic Surgery • Department of Neurology

A multidisciplinary Myasthenia and Thymoma Program at Penn Medicine has been established to coordinate and expedite the management of patients with myasthenia gravis (MG), thymoma and related diseases.

Staffed by neurologists, thoracic surgeons, radiologists, ophthalmologists and many other specialists, the program has the objective of providing accurate diagnoses and medical management for MG and surgical intervention for thymoma and other thymic disorders.

Myasthenia gravis is an autoimmune disorder caused in most patients by antibodies that destroy acetylcholine receptors (AChR) at the neuromuscular junctions of striated muscles. The resulting
loss of AChR manifests in patients with MG as progressive muscle weakness.

The course of MG is variable and symptoms are generally nonspecific, leading frequently to missed or mistaken diagnoses. Treatment for MG can substantially improve the symptoms of the disease. Thus, a missed diagnosis means, at the least, a continued deterioration in quality of life. However, for myasthenia gravis patients with thymoma (an associated disorder that affects up to a third of patients with the disease), or any of a host of comorbidities treated with drugs that inhibit neuromuscular transmission, a missed diagnosis can have profoundly deleterious effects.

At Penn, specialists across the therapeutic spectrum are trained to recognize the early signs of MG so that a confirmatory diagnosis can be made early in the course of the disease. This is typically achieved by blood tests for the presence of antibodies to acetylcholine receptors, electromyography (EMG) and if needed, single-fiber electromyography. Once confirmed, patients have radiographic scans to check for thymoma.

Medical treatment for MG at Penn may include cholinesterase inhibitors (e.g., Mestinon®), steroids and immunosuppressants, which increase the relative amount of acetylcholine by reducing the immune-mediated attack against the AChR. Two procedures are also commonly used to treat MG at Penn. The first, plasmapheresis, removes AChR antibodies from the blood through a process resembling dialysis; the second, intravenous immune globulin (IVIg) therapy, involves infusing pooled gamma globulin to restructure the immune response to AChR. Expanding upon these options, Penn is also a thriving source of clinical trials for patients who are refractory to therapy.

With improvement in MG symptoms, patients with early stage thymoma and selected individuals without thymoma may be candidates for thymectomy. When possible, robotic surgery is preferred as an alternative to sternotomy and transsternal procedures, which are associated with longer hospital stays, increased operative duration and greater blood loss.

Case Study

Mr. D, a 68-year-old man, was referred to a specialist at Penn Otorhinolaryngology-Head and Neck Surgery after a 15-month history of episodic choking and recurrent aspiration pneumonia. Noting mild ptosis that increased in severity upon sustained upward gaze, Mr. D was referred to Penn Neurology, where an anti–acetylcholine receptor (AChR) antibody (Ab) test and electromyography confirmed myasthenia gravis. A chest CT subsequently identified a 4 cm mass in the anterior mediastinum consistent with a thymoma.

Following plasmapheresis and IVIg with concomitant Mestinon® (pyridostigmine bromide) therapy, Mr. D’s symptoms improved sufficiently to permit surgery, and he was scheduled for a robotic thymectomy.

Prior to surgery, an epidural was placed to optimize postoperative pain management; a right chest approach was utilized along with a 3-port technique. Robotic dissection began with the right pericardial fat pad and progressed both cranially and to the left. Both phrenic nerves could be well visualized using the 3-dimensional camera system, and both were preserved during skeletonization, which included all the surrounding fat and tissue (Figure 1). There was no evidence of pericardial involvement as the specimen was dissected free. The brachiocephalic vein was skeletonized and dissection proceeded into the neck to include both upper poles.

On postoperative day 1, Mr. D’s single chest tube was removed and he was discharged home that afternoon on oral narcotics. He required the narcotics for only the first week, resumed his dose of Mestinon, and was able to return to his normal activities after the second week. He continues on Mestinon therapy but at a declining dose two years later.


Penn Neurology
Penn Medicine University City
8th Floor
3737 Market Street
Philadelphia, PA 19104

Thoracic Surgery
Penn Medicine University City
4th Floor
3737 Market Street
Philadelphia, PA 19104

Faculty Team
The Penn Medicine Myasthenia and Thymoma Program is comprised of a multidisciplinary team of thoracic surgeons, neurologists and other specialists dedicated to the comprehensive management
of patients with myasthenia gravis and its associated effects and conditions, including thymoma.

Myasthenia and Thymoma Program Faculty Team

Alan D. Askenase, MD
Clinical Associate Professor of Medicine

Evan W. Alley, MD, PhD
Clinical Associate Professor of Medicine

Sami L. Khella, MD
Chief, Department of Neurology, Penn Presbyterian Medical Center
Professor of Clinical Neurology

Madhura A. Tamhankar, MD
Assistant Professor of Ophthalmology

Joel L. Deitz, MD
Clinical Associate Professor of Medicine

Radiology (Chest)
Warren B. Gefter, MD
Professor of Radiology

Radiation Oncology
Abigail T. Berman, MD

Thoracic Surgery
Taine T.V. Pechet, MD
Interim Chief of Surgery, Penn Presbyterian Medical Center
Associate Professor of Clinical Surgery

Transfusion Medicine
Donald L. Siegel, MD, PhD
Professor of Pathology and Laboratory Medicine

Nicole Aqui, MD
Assistant Professor of Clinical Pathology and Laboratory Medicine

Additional Specialists
Christine H. Hosay, BSN,CMSN
Jeanmarie Salonia, PharmD

Computed Tomography for Thymoma
At Penn Medicine, patients with myasthenia gravis typically undergo computed tomography (CT) imaging to rule out concomitant thymoma. When a thymoma is identified (as in Figure 2), CT is used to characterize the tumor and to investigate the presence and extent of local invasion.

CT scans are also an important source of incidental findings of thymoma in patients assessed for diseases other  than myasthenia gravis.

Tuesday, January 6, 2015

Current Aortic Aneurysm Stent Device Clinical Trials

Vascular Surgery and Endovascular Therapy

Researchers with the Division of Vascular Surgery and Endovascular Therapy at Penn Medicine are conducting clinical trials to evaluate investigational stent grafts for the endovascular repair of abdominal, juxtarenal and pararenal aortic aneurysms.

Three of the studies currently enrolling at Penn are examining devices manufactured by Cook Medical (Bloomington, IN) under the Zenith brand name: the p-Branch stent graft, the Low Profile AAA Endovascular Graft, and the Branch Endovascular Graft-Iliac Bifurcation. Under the direction of principal investigator Ronald M. Fairman, MD, the studies are seeking to ascertain the safety and efficacy of these investigational devices.

The Division of Vascular Surgery and Endovascular Therapy has participated in virtually every stent graft clinical study in the United States since 1996. For information about enrolling in the Zenith studies and other endovascular clinical trials at Penn Medicine, please contact:

Heidi Martin, MS, Clinical Research Coordinator.

Phone: 215-662-4320


Zenith® p-Branch OTS Multicenter Study

This study is investigating the safety and effectiveness of the Zenith p-Branch stent graft as an off-the-shelf option for the treatment of pararenal or juxtarenal abdominal aortic aneurysms. The p-Branch has a unique “off-the-shelf” design with pivoting renal portals that accommodate a
comprehensive range of patients.

Advantages include fenestrations incorporated in the design of the graft to maintain perfusion through the renal arteries and visceral vessels (celiac artery and superior mesenteric artery) and avoidance of open surgery. The study device(s) are inserted through a small incision near each hip and guided into place in the aorta.

Zenith® Low Profile AAA Endovascular Graft Clinical Study

This multi-center, prospective non-randomized clinical investigation is designed to evaluate the safety and effectiveness of the Zenith Low Profile AAA Endovascular Graft in conjunction with the Zenith Spiral-Z AAA Iliac Leg Graft. Study endpoints include freedom from major adverse events at 30 days and (for the treatment cohort) device success at 12 months.

These findings will be compared to performance goals derived from the results of the Zenith AAA Endovascular Graft clinical study. The Zenith Spiral-Z AAA Iliac Leg Graft is indicated for use during a primary or secondary procedure in patients who have iliac/femoral access that is both adequate and compatible with the graft’s Z-Trak® introduction system.

PRESERVE-Zenith® Iliac Branch Clinical Study

The purpose of this study is to evaluate the safety and effectiveness of the Zenith Branch Endovascular Graft-Iliac Bifurcation in combination with the commercially available Atrium* iCAST™ covered stent in patients with an unsuitable distal sealing site for a Zenith iliac leg component proximal to the common iliac bifurcation.

PRESERVE is an extended, multi-center, prospective, non-randomized trial. Patients with anatomy amenable to endovascular repair who meet study criteria will be enrolled. Because the Branch Endovascular Graft-Iliac Bifurcation is intended to maintain blood flow to the internal iliac artery and minimize the risk of associated clinical symptoms with the need for re-intervention, the primary assessment will be based on six-month freedom from patency-related intervention.

The Branch Iliac Endovascular Graft-Iliac Bifurcation was designed to reduce the risks of complications for patients with iliac aneurysms by preserving blood flow to the internal iliac. The Atrium iCAST balloon expandable covered stent offers a low foreshortened design and a one-step deployment technique that enhances placement accuracy.

Faculty Team

The Division of Vascular Surgery and Endovascular Therapy at Penn Medicine is currently the regional leader for carotid, aortic, and peripheral arterial repair surgeries, and is among the handful of research centers nationwide involved in clinical trials to expand the indications for endovascular stent grafts. These new indications will include previously underserved patient populations and complex and complicated aneurysmal disease, including juxtarenal and pararenal aneurysms.

Performing Endovascular Clinical Trials at Penn Medicine

Scott M. Damrauer, MD
Assistant Professor of Surgery

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

Paul J. Foley, III, MD
Assistant Professor of Clinical Surgery

Michael A. Golden, MD*
Associate Professor of Surgery

Benjamin M. Jackson, MD
Assistant Professor of Surgery J

Venkat R. Kalapatapu, MD
Assistant Professor of Clinical Surgery

Paul L. O’Donnell, DO‡
Clinical Assistant Professor of Surgery

Grace J. Wang, MD, FACS
Assistant Professor of Surgery

*Penn Presbyterian Medical Center
†Penn Medicine University City
‡Cape Regional Medical Center


Patient appointments are available at:

Hospital of the University of Pennsylvania
3400 Spruce Street
4 Silverstein Pavilion
Philadelphia, PA 19104

Perelman Center for Advanced Medicine
Penn Heart and Vascular Center
East Pavilion, 2nd Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

Penn Presbyterian Medical Center
Department of Surgery
266 Wright Saunders Building
39th & Market Streets
Philadelphia, PA 19104

Penn Medicine University City
4th Floor
3737 Market Street
Philadelphia, PA 19104

Penn Medicine Radnor
250 King of Prussia Road
Radnor, PA 19087

Penn Medicine Bucks County
Suite 140
777 Township Line Road
Yardley, PA 19067

Cape Regional Physician Associates
217 North Main St., Suite 104
Cape May Court House, NJ 08210

All images ©Cook Medical (Bloomington, IN), 2014.

Visit Penn Physician VideoLink to view physician-focused videos, Clinical Briefings and more from Penn Medicine.

Friday, December 5, 2014

Paired Kidney Exchange for Kidney Transplantation

The Penn Transplant Institute is a leading center for paired kidney exchange for kidney transplantation, a practice that depends largely upon the benevolence of anonymous, altruistic donors.

Principles and Principals of Paired Kidney Exchange
A common perception of paired kidney exchange is that the process involves single, two-way exchanges between recipients and altruistic donors within their circle of acquaintance or relation. In fact, this is rarely the case.

Almost always, despite friends and family members who were evaluated as live kidney donors, the recipient has failed to find an appropriate match. Incompatibility between donor/recipient pairs can come about not only because of blood type, but because the recipient has been sensitized by previous blood transfusions, previous organ transplants or previous pregnancies.

More often, paired kidney exchanges occur as chains initiated between a “non-directed,” anonymous, altruistic donor and a matched recipient and continued when a friend or relative of this recipient repeats the process by donating to a second matched anonymous recipient. If this person, too, is linked to an unmatched donor, that donor may be enlisted to continue the chain as a donor to another anonymous recipient. Donors in the chain who do not immediately find a matched recipient may choose to begin a separate chain as “bridge” donors from the original chain (see Figure 1).

At Penn, recipients and donors who are willing to participate in paired kidney exchange must undergo a comprehensive medical evaluation. During this stage, the kidney transplant and living donor transplant teams complete a series of evaluations to determine if the procedures are safe and appropriate for the respective recipients and living donors. Only when the team feels it is safe to proceed are the donor and recipient surgeries scheduled.

The benefit of paired kidney exchange is that it offers kidney recipient and donor pairs who aren’t blood and/or tissue-type compatible an alternative to deceased donor transplantation, thus increasing the number of kidney donors while diminishing competition for deceased donor kidneys.

Paired kidney exchanges also play a critical role in expediting transplants and thereby improving outcomes. According to the United States Department of Health and Human Services, the median waiting time among patients aged 18 to 65 in the US for a deceased-donor kidney in 2014 was 4.5 years, versus 185 days for patients participating in paired kidney exchange. The estimated six-month graft survival rate for patients having paired kidney exchange was 98.8%, compared to 95.1% for deceased donor kidney transplants. [1]

Case Study

Upon learning that 32-year-old Mr. B had end-stage kidney disease, his uncle, Mr. C, volunteered to donate a kidney to him. However, tests at the Penn Transplant Institute showed that Mr. C and Mr. B were not a compatible match. Subsequently, Mr. B entered the home dialysis program at Penn and was placed on the waiting list for a deceased kidney.

Several months later, a transplant coordinator at Penn contacted Mr. C and Mr. B to ask if they would be interested in participating in a paired kidney exchange. She explained that an anonymous altruistic donor, Mr. A, had been found compatible with Mr. B and had agreed to donate a kidney to him. The coordinator asked if Mr. C would consider becoming a kidney donor for an anonymous recipient for whom he was compatible.

Mr. C agreed to become a donor, and at Penn, was paired with Mrs. D. The chain would thus involve Mr. A donating a kidney to Mr. B, and Mr. C donating a kidney to Mrs. D. All four participants in the resulting exchange were found to be physically and psychologically prepared for transplant surgery. The four surgeries were scheduled to take place at Penn Medicine on the same day in separate operating rooms.

On the morning of the kidney exchange, Mr. A had surgery first, and his kidney was transplanted into Mr. B. Later that day, a similar exchange took place. This time, Mr. C’s kidney was transplanted into Mrs. D.

All four patients recovered without incident. In the days after surgery, Mr. C and Mr. B decided to meet the pair with whom they had been matched. All donors currently have functioning transplants, due in large part to the initial intervention of Mr. A, the initiating altruistic donor.

Adding to the success of this exchange, Mr. E, the husband of Mrs. D, initiated a second chain of paired exchange kidney transplants two months later by donating a kidney to Mr. F, thus becoming an altruistic “bridge” donor to this new chain.

1. State of the OPTN/UNOS KPD Pilot Program, DHHS 2014]

Faculty Team
The Penn Transplant Institute is home to kidney, liver, lung, heart, pancreas and hand transplantation programs, and is ranked among the top 10 multi-organ transplant centers in the country.

Performing Kidney Transplantation at Penn Medicine

Transplant Surgeons

Ali Naji, MD, PhD
Surgical Director, Kidney and Pancreas Transplant Program
Professor of Surgery

Peter L. Abt, MD
Associate Professor of Surgery

Matthew H. Levine, MD, PhD
Assistant Professor of Surgery

Paige Porrett, MD, PhD
Assistant Professor of Surgery

Transplant Nephrologists

Roy D. Bloom, MD
Medical Director, Kidney and Pancreas Transplant Program
Professor of Medicine

Melissa B. Bleicher, MD
Assistant Professor of Clinical Medicine

Simin Goral, MD
Professor of Medicine

Robert A. Grossman, MD
Professor of Medicine

Mary Ann Lim, MD
Assistant Professor of Clinical Medicine

Peter P. Reese, MD, MSCE*
Assistant Professor of Medicine and Epidemiology

Deirdre L. Sawinski, MD
Assistant Professor of Medicine

Karen Warburton, MD*
Associate Professor of Clinical Medicine

Other Renal Physicians
Meera N. Harhay, MD, MSCE

Attending Physician
Jonathan S. Maltzman, MD, PhD
Assistant Professor of Medicine

Renal Nurse Practitioners
Christina Braun, MSN, CRNP
Carolyn Mylowe, MSN, CRNP
Gail Eastman, MSN, CRNP, CCTC
Jenna Angerstein, MSN, CRNP, CCTN

Transplant Surgery Nurse Practitioners
 Alva Moy-Daley, MSN, CRNP
 Julie Spaulding, MSN, CRNP

*Living Donor Team Nephrologists

Paired Kidney Exchange at Penn Medicine
Penn performed the first successful kidney transplant in 1966, and the Penn Transplant Institute is now a leader in the effort to increase paired kidney exchanges for kidney transplantation.
In partnership with the National Kidney Registry (NKR), a consortium of 72 transplant centers nationwide, the Penn Transplant Institute recently took part in the largest kidney exchange to be concluded in under 40 days and the second largest in history (ultimately involving 28 donors and 28 recipients).

In 2012, the US Department of Health and Human Services awarded the Penn Transplant Institute’s Kidney Transplant program a Silver Level Award. Penn is the only transplant center in the region and one of a select group of programs in the nation to receive this distinction.

In addition to its partnership with the NKR, the largest and most successful kidney transplant matching program in the US, the Penn Transplant Institute is a member of the United Network for Organ Sharing (UNOS). Outside of its participation with these organizations, the Transplant Institute has a large enough waiting list to initiate donor chains within its own programs.


Penn Transplant Institute Kidney Transplant Program

The Perelman Center for Advanced Medicine
2 West Pavilion
3400 Civic Center Boulevard
Philadelphia, PA 19104

Renal Electrolyte and Hypertension
Perelman Center for Advanced Medicine
South Pavilion, 1st Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

Patients also evaluated at:

Penn Medicine Radnor*
250 King of Prussia Road
Radnor, PA 19087
* A facility of the Hospital of the University of Pennsylvania

Penn Medicine Bucks County
777 Township Line Road
Yardley, PA 19067

Penn Medicine—1400 East Route 70
1400 East Route 70
 Cherry Hill, NJ 08034

Penn Medicine Woodbury Heights
1006 Mantua Pike
Woodbury Heights, NJ 08097

The contact number for recipients and donors is 215.662.6200.

Visit Penn Physician VideoLink to view physician-focused videos, Clinical Briefings and more from Penn Medicine.

Thursday, November 20, 2014

Periacetabular Osteotomy for Complex Structural Hip Deformity

Department of Orthopaedic Surgery  •  Center for Hip Preservation

Orthopaedic surgeons at Penn Medicine are performing periacetabular osteotomy (PAO) surgeries for native hip preservation in adolescents, young adults and adults (generally up to 45 years of age) with dysplasia and other structural hip deformities.

Structural hip deformities affect a large proportion of younger adults who present with symptomatic hip pain in the United States. These conditions are often of congenital, developmental, or traumatic origin, and typically involve morphologic abnormalities of the acetabulum or femur leading to instability and/or impingement, a pathological conflict between the two bones during movement.

The mechanical aberrations identified with structural hip deformity commonly involve dysplasia and femoroacetabular impingement (FAI) and their associated pathologies. Hip pathology can also involve malalignment or rotational deformities of the femur (e.g., issues with femoral torsion), among other anomalies.

Impingement occurs when the proximal femur contacts the acetabulum during range of motion, such as flexion and internal rotation. Impingement is often caused by asphericity of the femoral head (cam type) or over-coverage of the acetabulum (pincer type). With dysplasia, insufficient coverage of the femoral head by the acetabulum can lead to symptomatic instability and early labral and cartilage degeneration. This continuum—from impingement to instability—is an important concept in evaluating younger patients with hip pain.

The tantamount consideration in younger patients with dysplasia and/or FAI is to preserve the native hip by addressing underlying structural abnormalities. Accordingly, orthopaedic surgeons at Penn Medicine employ a spectrum of corrective hip preservation surgeries for this population, including both arthroscopic and open techniques such as re-orientation of the acetabulum.

Periacetabular osteotomy (PAO), for example, addresses the underlying structural deficiencies of a shallow or poorly oriented acetabulum. In PAO, a series of osteotomy cuts encompass the acetabulum, preserving the hip abductors and the posterior, weight-bearing column of the pelvis. The socket is then freed from the pelvis and reoriented in a position of better coverage of the femoral head. This offers the opportunity to restore more normal hip joint mechanics and ideal loading of the articular cartilage. The goal is long-term durability of the native joint in adolescent and young adult patients with dysplasia.

PAO is not a “standard” surgery, and patient selection is important. The procedure is demanding, in that osteotomy and precise reorientation are required, and each step requires a certain level of experience and training. However, the potential advantages of PAO, which include greater long-term joint stability and durability of the cartilage, may help younger patients to avoid or delay joint-replacement surgery, such as total hip arthroplasty.

Case Study

Mr. J, a 25-year-old man, was referred to the Center for Hip Preservation at Penn Medicine with structural deformity of the right hip, the result of a segmental fracture of the proximal femur at age four. His hip and leg were placed in a cast, and his fracture healed in a malaligned position.

As a young adult, Mr. J had chronic, progressive and disabling pain (especially in the setting of his high-demand work as a manual laborer) that he managed with daily opioid medications. In the months prior to evaluation at Penn, he had extensive physical therapy and an intra-articular injection for pain control. He was unemployed for much of this time.

At Penn, Mr. J was deemed a candidate for hip preservation. Imaging determined that he had severe acetabular dysplasia, a tear of his acetabular labrum, a torsional deformity of the femur (45 degrees of retrotorsion) and FAI due to a cam lesion of the femoral head-neck junction (Fig. 1).

Despite these abnormalities, however, there was no evidence of overt osteoarthritis at his hip. After discussion of the risks, benefits and treatment alternatives, Mr. J elected to have corrective surgery. Pre-procedural imaging and modeling were completed to ensure proper intra-operative alignment targets of the reoriented hip and femur.

At PAO was performed to correct the acetabular dysplasia. Nerve monitoring and fluoroscopic imaging were used to ensure safe and accurate surgery. Bone grafting was completed at the acetabular osteotomy sites, with autograft harvested from the pelvic osteotomy mobile fragment. A surgical hip dislocation was also performed, with careful preservation of the critical blood supply to the femoral head. A labral repair and femoral head-neck osteochondroplasty were completed to address the intra-articular sequelae of FAI.

Although Mr. J’s intra-articular causes of FAI were optimized, the extra-articular rotational deformity of the femur did not allow for adequate impingement-free range of motion. Therefore, a subtrochanteric derotational osteotomy with internal fixation was performed to bring the femur into normal rotational alignment. Bone autograft harvested from the greater trochanteric bed was used to supplement the osteotomy fixation (Fig. 2).

Mr. J was on crutches the day after his procedure and was in the hospital for three days, where he received physical therapy, as well as a continuous passive motion machine. Partial weight-bearing was permitted on discharge. He was weaned from all pain medications by several months post-operatively. At six months, he was walking with no gait aids, and by seven months he had found full-time work.

Faculty Team

The Penn Medicine Center for Hip Preservation is comprised of a multi-disciplinary team dedicated to the diagnosis and treatment of hip pain in adolescent, young adult and adult patients. Patients evaluated for hip pain at Penn also have access to the region’s first integrated Musculoskeletal Center, which includes state-of-the-art motion analysis, neuromuscular testing, and advanced metabolic measurements through the Center for Human Performance.

The exceptional procedures offered at the Penn Center for Hip Preservation include hip arthroscopy with labral repair, arthroscopic and open treatment of focal cartilage injury, management of avascular necrosis of the femoral head with stem-cell therapy, treatment of sequelae of childhood disease like Perthes disease and slipped capital femoral epiphysis (SCFE), complex femoral osteotomy and limb deformity correction, repair of abductor and hamstring tendon injury, microsurgery and vascularized fibular grafting, surgical hip dislocation, and periacetabular (Ganz/ Bernese) osteotomy, among other advanced treatments.

Performing Periacetabular Osteotomy for Hip Preservation at Penn Medicine

Atul F. Kamath, MD
Director, Center for Hip Preservation
Assistant Professor of Orthopaedic Surgery
Consultants to the Penn Center for Hip Preservation

L. Scott Levin, MD, FACS
Paul B. Magnuson Professor of Bone and Joint Surgery
Chair, Department of Orthopaedic Surgery
Professor of Surgery, Division of Plastic Surgery

Charles L. Nelson, MD
Chief, Adult Reconstruction Section
Associate Professor of Orthopaedic Surgery

John D. Kelly, IV, MD
Associate Professor of Clinical Orthopaedic Surgery

J. Bruce Kneeland, MD
Section Chief, Musculoskeletal Imaging Division
Professor of Radiology

To hear Dr. Kamath discuss hip preservation for younger patients, visit the ReachMD(TM) series Medical Breakthroughs from Penn Medicine.

Tuesday, October 14, 2014

Sialendoscopic Management of Salivary Stones and other Salivary Duct Pathologies

Surgeons with Penn Otorhinolaryngology-Head and Neck Surgery are performing novel high-tech diagnostic and interventional sialendoscopy procedures to treat patients with diseases of the parotid and submandibular salivary glands.

At Penn, the primary objective for patients with sialolithiasis (stone disease) and inflammation of the salivary gland (sialadenitis) is to make a diagnosis, clear the duct and preserve the native salivary gland, if possible, and to achieve these ends using the safest, least invasive and most appropriate therapy.

In many cases, diagnosis is aided by radiography, usually after the onset of classic symptoms. Sialoliths of small to moderate size may be treated by sialendoscopy, a relatively recent innovation that is used at Penn Medicine for both diagnosis and treatment.

About Sialendoscopy
Sialendoscopy is a minimally invasive technique that has the potential to avoid nerve injury and the facial and oral scarring associated with traditional open surgery. The sialendoscope combines a delicate, semi-rigid (1.3 mm) fiber-optic endoscope, an irrigation port and a working channel in a single instrument. The endoscope broadcasts high definition images to a monitor. (See Fig 1).
Irrigation is used to dilate the ducts, permitting exploration of the branches of the salivary duct system. The working channel is the conduit for the instruments used to remove obstructions such as salivary duct stones, including custom-designed baskets, micro-burrs and guidewires.

The approach to larger salivary stones during sialoendoscopy sometimes employs hybrid treatments such as laser fragmentation. In these cases, otorhinolaryngologists at Penn collaborate with urologists, who use similar techniques to treat kidney stones. If accessible, larger stones can thus be broken up into smaller fragments, permitting them to be eliminated by irrigation or basket retrieval.
Multiple or deeply placed stones may require a combined approach or a more limited open approach where the sialendoscope is used to transilluminate the duct.

In addition to sialolithiasis, the indications for sialendoscopy at Penn Medicine include ductal injuries, duct stenoses, radioactive-iodine induced sialadenitis and autoimmune sialadenitis, including Sjogren’s Syndrome.

Case Study
JG, a 23-year-old male, came to Penn Medicine for suspected parotitis after experiencing repeated episodes of post-prandial facial swelling over a three month period. A CT scan at Penn found a 3mm density in JG’s left parotid duct deemed highly suspicious for a salivary stone (see Fig. 2).
After a consultation to review his treatment options, JG opted for sialendoscopy.

At the start of the procedure, the left parotid duct papilla was dilated to permit irrigation of the duct. A 1.3 mm scope was then advanced and navigated within the duct to the obstruction, a compact sialolith, lodged at a bifurcation distal to the parotid gland.

With further irrigation to dilate the duct, a six-wire basket was placed over a guide wire and extended until it grasped the stone. At this point, the stone was gently drawn beyond the bifurcation, but floated into the opposite duct. A micro-sialendoscopic burr was then introduced, freeing the stone, which was grasped by a 3-wire basket and extracted by rotating past the muscle to the papilla. JG’s recovery from surgery was unremarkable, and he was discharged the same day. At his one-year follow-up visit, there was no evidence of evolving sialoliths in the cleared duct or elsewhere.

Faculty Team
The faculty of Penn Otorhinolaryngology-Head and Neck Surgery are leaders in the field in patient care, surgical innovation and clinical and laboratory research. The Department logs more than 86,000 patient visits each year—the highest volume in the nation of any center or program performing otorhinolaryngology-head and neck surgery—and offers comprehensive and multidisciplinary programs to manage every disease or disorder affecting the organs and tissues of the nose, ears, throat, face and skull base.

Performing Sialendoscopic Procedures at Penn Medicine

Christopher H. Rassekh, MD, FACS
Associate Professor of Otorhinolaryngology-Head and Neck Surgery
Director, Penn Medicine Sialendoscopy Program

Erica R. Thaler, MD
Professor of Otorhinolaryngology-Head and Neck Surgery

Assisting with Laser Lithotripsy
Keith N. Van Arsdalen, MD
Director, Lithortriptor Center
Professor of Urology in Surgery

Key Team Members
Joshua H. Atkins, MD, PhD
Assistant Professor of Anesthesiology and Critical Care

Laurie A. Loevner, MD
Professor of Radiology

Rita Glenn-West, BSN, RN, CNOR
Coordinator, Operating Room Sialendoscopy Procedures

Tashara Nicholson
Clinical Administrative Assistant
Assistant to Dr. Rassekh in Sialendoscopy Clinic

Hospital of the University of Pennsylvania
5 Silverstein
3400 Spruce Street
Philadelphia, PA 19104

Sialendoscopy Clinical Briefing

Tuesday, July 22, 2014

Living Donor Liver Transplantation at Penn Medicine

Penn Transplant Institute

Transplant surgeons and hepatologists at Penn Medicine are performing living donor liver transplantation for patients with end-stage liver disease.

In the United States, the number of patients currently on the waiting list for liver transplantation is approximately three times that of available donor livers. Living donor liver transplantation (LDLT) allows for increased access to a lifesaving transplant and has become a very successful and accepted standard of care for many patients with end-stage liver disease. Post-transplant outcomes with LDLT are comparable to, or better than, deceased donor transplants.

Adult-to-adult LDLT involves removing 40% to
60% of the liver from a healthy donor (typically a family member or friend of the recipient) and transplanting it into a patient who has been deemed appropriate for liver transplantation. While LDLT is major surgery, donors return to normal activity soon after the procedure. Because the liver has the remarkable capacity to regenerate, the donor’s liver is restored to nearly normal size within a few months after donation.

One of the greatest benefits of living donation is that it can be made available to patients with a lower Model for End Stage Liver Disease (MELD) score, eliminating the long wait for a deceased donor, and reducing the risk of a patient dying while waiting for a transplant.

The Penn Transplant Institute performs LDLT in patients with mean MELD scores of 15±5, depending upon blood type (Figure 1), which is a great benefit in our region, where the mean MELD at transplant for deceased donors since 2008 has been in the range of 27±7.

Transplanting at a lower MELD score means patients don’t have to wait until they are critically ill to obtain a liver. The Penn Transplant Institute has been performing pediatric living donor transplantation since 1996, and adult living donor transplants since 1999, with an established track record of superb patient and graft survival. Since 2002, our adult 1- and 3-year patient survival rates are 98% and 91%, respectively, compared to national rates of 90% and 82% at 1 and 3 years
(Figure 2).

Case Study

JD, a 28 year-woman with cirrhosis secondary to biliary atresia, has been followed by the hepatology program at Penn Medicine since the age of 18.  In 2013, following the development of bleeding esophageal varices, hepatic encephalopathy, and ascites, her case was referred to the Penn Liver Transplant team.

After considering the internal waitlist criteria and reviewing JD’s MELD score of 18 and other factors, the Committee concluded that her symptoms and medical status were appropriate to place her on the United Network for Organ Sharing (UNOS) liver transplant wait list.  However, because she was blood type A, her standing on the list was unlikely to result in any offers of deceased donors.

Despite optimal medical management, JD’s condition continued to deteriorate, with multiple hospitalizations for complications of her liver disease, included repeated bouts of encephalopathy, ascites and spontaneous bacterial peritonitis. Even with her worsening condition, however, her MELD score never rose above 23. This meant that she was below the threshold needed to be at the top of the list for an optimal organ given her blood type and the regional organ scarcity.

As a result of her declining condition, JD stopped working and married her boyfriend in a rapidly planned wedding, because she wasn’t sure she would live long enough to plan a formal wedding. After speaking with the liver transplant team about the possibility of a living donor transplant, JD consulted with her family and close friends.

Several weeks later, a longtime friend, AJ, decided that he wished to be evaluated as a living donor. At age 24, AJ was within the donor age parameters, his physical condition was excellent, and he had no history of past or current serious disease.

Following a very thorough medical and surgical evaluation, extensive imaging, and laboratory testing, as well as private meetings with a social worker, psychiatrist, and independent donor advocate, AJ was found to be a suitable living donor candidate.

Having determined that AJ arrived at the decision of his own volition, he was cleared to complete his evaluation, and donate a portion of his liver to his friend.

Two weeks later, AJ donated the right lobe of his liver to JD, with both donor and recipient back at home a little over a week later.  Six months after the surgery, JD and AJ are even closer friends than before.  JD is back to working full time, and enjoying life as a newlywed.  AJ returned to work after three months, and now is a full-time grad student, and  while returning to his previous level of physical activity, has been coaching a high school crew team.


The National Institutes of Health Adult-to-Adult Living Donor Liver Transplant study (A2ALL)

The Penn Transplant Institute is among a consortium of nine centers of excellence participating in the multicenter National Institutes of Health-sponsored Adult-to-Adult Living Donor Liver Transplant study (A2ALL), which explores both long-term outcomes in donors and recipients.

Reports from A2ALL have shed light on the principal conditions for optimal graft survival in ALDLT recipients. Among these are the experience of the transplant center, recipient age, and cold ischemia time. A significantly lower risk of graft failure exists among centers that have performed more than 15 ALDLTs, and both older recipient age and cold ischemia >4.5 hours have been linked to higher rates of graft failure. [1]

A2ALL has also shown that there is significant benefit for living donor transplant patients with symptomatic liver disease and relatively low MELD scores as a result of decreased death on the wait list. [2] Data from the UNOS database shows that post-transplant graft and patient survival is better with living donors at three and five years than for deceased donor liver transplants. [3]


1. Olthoff KM, Abecassis MM, Emond JC, et al. Outcomes of adult living donor liver
    transplantation: comparison of the Adult-to-adult Living Donor Liver Transplantation Cohort
    Study and the national experience. Liver Transpl. 2011;17(7):789-797.
2. Berg CL, Merion RM, Shearon TH, Olthoff KM, et al. Liver transplant recipient survival benefit
    with living donation in the model for endstage liver disease allocation era. Hepatology. 2011;
3. Goldberg DS, Abt PL, Olthoff KM, Shaked A. Superior Survival Using Living Donors and
    Donor-Recipient Matching Using a Novel Living Donor Risk Index. Hepatology. 2014.


Faculty Team

The Penn Transplant Institute offers a comprehensive liver transplant program for patients suffering with end-stage liver disease, liver cancer, and metabolic liver disease. Physicians at Penn have performed more than 1,500 liver transplants and have extensive experience in treating patients with Hepatitis B and C, autoimmune and cholestatic liver disease, alcoholic cirrhosis, liver cancer, and
metabolic disease.

Performing Living Donor Liver Transplantation at Penn Medicine

Liver Transplant Surgeons

Kim M. Olthoff, MD
Chief, Division of Transplant Surgery
Donald Guthrie Professor in Surgery

Abraham Shaked, MD, PhD
Director, Penn Transplant Institute
Eldridge L. Eliason Professor of Surgery

Peter L. Abt, MD
Associate Professor of Surgery


David S. Goldberg, MD, MSCE
Medical Director, Living donor liver transplantation

George A. Makar, MD, MSCE
Medical Director of Liver Transplantation

Living Donor Coordinator

Linda Wood, BSN, RN


Perelman Center for Advanced Medicine
3400 Civic Center Boulevard,
Philadelphia, PA 19104

Monday, June 2, 2014

Intraoperative Molecular Imaging Detects Residual Tumor Cells During Lung Cancer Surgery

Abramson Cancer Center • Penn Lung Center • Division of Thoracic Surgery

At Penn Medicine, surgeons are using molecular imaging technology to prevent cancer recurrence by improving the detection of residual cancer cells during surgery.

Surgery is 8 to 10 fold more effective than chemotherapy or radiation therapy for almost all solid tumors, and is the most important predictor of long-term survival in cancer patients in the United States. However, the overall success of cancer surgery is diminished by local recurrence in up to a third of patients.

Recurrence is typically due to malignant cells that remain in the surgical field even when the algorithm for their eradication involves meticulous resection at the surgical margins, excision of involved lymph nodes and satellite lesions and the use of intraoperative frozen sectioning by pathologists to ensure the complete eradication of cancer during surgery. That these efforts so often fail demonstrates the challenge of identifying invasive and occult cancer cells through observation and palpation during surgery.

To improve the long-term efficacy of cancer surgery, thoracic surgeons and radiation oncologists at Penn Medicine are using investigational intraoperative imaging systems that visually enhance residual cancer cells and the abnormal tissue densities typical of malignant lesions. These systems use fluorescent contrast agents that have an organic tropism for cancer cells, and that once absorbed, glow under certain lighting conditions, permitting lesions and cancerous cells to be identified and readily removed.

Using these systems in separate applications during surgery, the team at Penn Medicine has identified nodules as deep as 1.3 cm from the surface of solid organs and as small as 0.2 cm in size, as well as nodules in organs other than that of the primary tumor. In addition, cancer cells that are invisible to optical observation have been identified at the margins of surgery in lung cancer patients.

Case Study

Mrs. M, a 64-year-old woman, was referred to Penn Thoracic Surgery for evaluation following six-months of persistent cough and bronchial irritation. Mrs. M had never smoked, and with the exception of hypertension, her medical history was unremarkable. A chest x-ray at Penn revealed a mass (>3.5 cm) in the upper lobe of her left lung in ` Figure 1: A small lesion (0.7 cm) appears under near-infrared light in the lower left lobe of a patient thought to have Stage IA pulmonary adenoma. The lesion was undetected by PET/CT scan and visual examination; this patient was subsequently re-staged to stage IIIA. close proximity to the pleura.

A PET/CT scan found no evidence of spread to nearby lymph nodes or metastases. A transthoracic needle aspiration biopsy of the mass revealed malignant cells, and a histological analysis identified a moderately-differentiated cancer with clear cell features consistent with a primary pulmonary adenocarcinoma. Cytogenetic analysis was negative for EGFR/Kras mutations and ALK rearrangement.

There was no evidence of metastases. Mrs. M’s cancer was classified as a surgically resectable Stage IA pulmonary adenocarcinoma. After a discussion during which Mrs. M expressed apprehensions about cancer recurrence based on personal experience, she provided her informed consent to take part in the fluorescent image-guided investigation.

Prior to surgery, Mrs. M underwent CT scanning. The scan was reviewed by a radiologist to confirm the presence of a solitary pulmonary nodule. Twenty-four hours before her surgery, an intravenous contrast agent was administered.

During her surgery, surgeons located the primary nodule using visual inspection and manual palpation. Following an inspection of the ipsilateral lung by both surgeons that found no other lesions, the operating room lights were removed, and the near-infrared spectroscopy (NIR) imaging system was sterilely draped and positioned above the chest.

The primary nodule was imaged and photo-documented by white light and fluorescence. The imaging system was then used to search for additional nodules in her lung, subsequently identifying a single small (0.7 cm) lesion in the lower lobe of her left lung (Figure 1) close to the pleural surface, and two lymph nodes near the original primary tumor. Both lesions and the lymph nodes were removed and re-imaged for confirmation in the operating room before being submitted to pathology. Mrs. M’s cancer was then re-staged to stage IIIA.

Mrs. M remained in the hospital for two days following her surgery and was discharged home. Her recovery was unremarkable. She received adjuvant chemotherapy and radiaton therapy without significant morbidity. At her six-month and one-year follow-up visits, x-rays and CT/PET scans found no evidence of recurrent cancer.

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

John C. Kucharczuk, MD
Associate Professor of Surgery

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

Sunil Singhal, MD
Assistant Professor of Surgery
Thoracic Medical Oncology

Corey J. Langer, MD
Professor of Medicine

Kenneth M. Algazy, MD
Clinical Professor of Medicine

Tracey Evans, MD
Assistant Professor of Medicine

Thoracic Radiation Oncology

John Christodouleas, MD
Assistant Professor of Radiation Oncology

Keith Cengel, MD, PhD
Assistant Professor of Radiation Oncology

Thoracic Oncology Pulmonology

Andrew Haas, MD, PhD
Assistant Professor of Medicine

Morris Swartz, MD
Associate Professor of Medicine

Anil Vachani, MD
Assistant Professor of Medicine


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

Wednesday, April 30, 2014

Personalized Diagnostics for Hematologic and Solid Tumor Cancers

Pathologists and specialists in laboratory medicine at the Penn Center for Personalized Diagnostics (CPD) are performing genomic testing—including large-scale, massively parallel DNA sequencing and chromosomal analysis for identification of large structural rearrangements—to define genomic alterations in hematologic and solid tumor cancers for cancer patients at Penn Medicine.

Massively parallel DNA sequencing (sometimes known as next-generation sequencing or NGS) can recognize abnormalities in tumor cells that are not readily apparent to pathologists at a microscopic level. When applied to the DNA of an individual’s cancer cells, the process can yield a complete profile of the tumor genome, including personal mutation signatures for distinct tumor subtypes, that is as distinct as a fingerprint.

In addition, the testing for genomic rearrangements can detect tumor susceptibility to some targeted therapies.  Together these analyses are powerful detectors of signatures that can be used to identify individualized treatment options and to gauge the extent to which a patient will respond to treatment.

At the CPD, a joint initiative between the Department of Pathology and Laboratory Medicine and the Abramson Cancer Center at Penn Medicine, approximately 75% of patients tested have received genomic testing results that altered prognosis or empowered the treating oncologists to alter the patients’ treatment therapy, or both.

The Penn CPD is a CAP/CLIA certified laboratory. The equipment and instrumentation at the CPD currently include an Illumina HiSeq 2500, two Illumina MiSeq sequencers and an ION® Personal Genome Machine, all of which are capable of detecting low-level mutation loads and are instrumental in the sequencing of genomic DNA in tumor specimens.

The CPD offers two cancer gene-sequencing panels (below), a custom hematologic malignancy panel, focused primarily on AML, MDS and CLL, and a more comprehensive solid tumor panel, containing 47 genes known to be mutated in a wide range of tumor types.

Case Study
Mr. M, a 43-year-old policeman, was referred to the Abramson Cancer Center by his personal physician after a chest CT scan revealed a massive lesion in his right lung (Figure 1). The x-ray was preceded by several months of declining health attended by weight loss, severe headache, back pain and chronic low-grade fever.

A sputum analysis and fine needle aspiration biopsy at the Abramson Cancer Center confirmed the presence of stage IV non-small cell lung cancer (NSCLC). Soon thereafter, a full-body MRI found lesions at Mr. M’s spine and brain, as well. 

Mr. M was young and had never smoked, characteristics more likely to be associated with the presence of mutations in targetable genes, including the epidermal growth factor receptor (EGFR), and the tyrosine kinase mutation EML4-ALK, both potent oncogenic drivers linked to lung tumorigenesis.

EGRF mutations are identified in 15% to 20% of lung adenocarcinomas and ALK gene rearrangements are found in 3% to 5% of NSCLCs.  Both gene mutations are seen predominately in younger patients who never smoked, a unique subset of the NSCLC population, and are rarely seen in older individuals and those with a smoking history.

In recent years, very efficacious tyrosine kinase inhibitors have been developed to treat patients with EGFR and EML4-ALK mutations. However, because each agent is designed to target a specific mutation, it was critical to initiate a complete profile of Mr. M’s tumor genome.

At the Penn Center for Personalized Diagnostics, a comprehensive solid tumor panel and cytogenetic analysis was subsequently performed on tissue derived from Mr. M’s tumor. The report delivered to his oncologist two weeks later confirmed an EML4-ALK translocation (Figure 2).

 Mr. M immediately began therapy with crizotinib, an oral, small molecule tyrosine kinase inhibitor that targets ALK. Crizotinib has been shown in clinical trials to offer sustained progression-free survival in NSCLC patients with brain metastases, and is associated with much lower rates of adverse effects than many other cancer therapies.

Mr. M responded well to treatment. A CT scan taken at eight weeks post-diagnosis demonstrated an 80% reduction in the dimension of his lung tumor (Figure 3), near eradication of brain metastases and a significant reduction of spinal lesions. At one year post-diagnosis, Mr. M has returned to work and his disease is stable.

Faculty Team

A joint initiative between the Department of Pathology and Laboratory Medicine and the Abramson Cancer Center at Penn Medicine, the Center for Personalized Diagnostics (CPD) integrates molecular genetics, pathology informatics and genomic pathology to develop personalized diagnostic profiles for individuals with cancer. Using customized computational methods, including large-scale, massively parallel DNA sequencing and chromosomal analysis, the CPD identifies personal mutation signatures for distinct tumor subtypes. This information may then be used to determine whether a tumor is susceptible to targeted therapies and to elucidate potential cancer treatment options.

The Penn Center for Personalized Diagnostics

Faculty and Staff

David B. Roth, MD, PhD, FCAP
Acting Director, Center for Personalized Diagnostics

Jennifer Morrissette, PhD, FACMG
Clinical Director

David B. Lieberman, MS, CGC
Genetic Counselor


Center for Personalized Diagnostics
3020 Market Street, Suite 220A
Philadelphia, PA 19104

Visit to hear an interview with David D. Roth, MD, of the Center for Personalized Diagnostics at Penn Medicine. Dr. Roth discusses the CPD and the ways it can help physicians and oncologists create customized treatment plans for patients with cancer. 

Thursday, April 17, 2014

Enrolling Clinical Trials: Biomarker Identification in Orthopaedic and Oral Maxillofacial Surgery Subjects to Identify Risks of Bisphosphonate Use

Department of Orthopaedics • Trauma and Fracture Service • Department of Oral & Maxillofacial Surgery

Surgeons and researchers with the Penn Orthopaedic Trauma and Fracture Service and Oral and Maxillofacial Surgery have initiated a clinical study to identify the factors that cause some individuals to experience severe adverse events as a result of prolonged bisphosphonate therapy.

Bisphosphonates block the activity of cells that resorb bone, and are commonly prescribed for the treatment of osteoporosis and other conditions that deplete or compromise bone.

Most patients taking bisphosphonates experience few ill effects during the course of treatment. However, a minority of patients taking the drugs experience severe adverse effects, including atypical femur fractures in the context of low-energy trauma, changes in cortical thickening of bone, and osteonecrosis of the jaws. 
The pathophysiology of bisphosphonate-related events in this population is thought to involve suppressed bone turnover leading to accumulating microdamage and increased susceptibility to fractures. The fractured bones are characterized by a thickened and brittle cortex, delayed healing and altered bone metabolism.

Although the link between prolonged bisphosphonate therapy and subtrochanteric femur fractures and osteonecrosis of the jaw is well known, no adequate retrospective or meta-analysis of the affected patient population exists. Precise determination of risk factors for drug-related adverse events has been complicated by the number of bisphosphonate drugs, varying dose regimens, inter-individual genetics, comorbidities, treatment compliance and other factors.

To address these issues, surgeons and researchers at Penn Medicine are conducting a study that will attempt to identify genomic and RNA biomarkers that may play a role in differential metabolism of bisphosphonates or indicate tendency toward the severe adverse events associated with these drugs.

Biomarker Identification in Orthopaedic and Oral Maxillofacial Subjects
Methods: This is a nested case-control study with matched and counter-matched controls and a reference group of healthy volunteers, with age and sex matching, if possible. The study population will include individuals with a current or past history of bisphosphonate use with bisphosphonate-related osteonecrosis of the jaw (BRONJ) or atypical fracture of the femur, and a control population comprised of non-bisphosphonate using orthopaedic patients with typical fractures and oral-maxillofacial patients without osteonecrosis of the jaw. Patients will provide blood samples for profiling of DNA and miRNA biomarkers.

Objectives: This study will consolidate the many confounding variables associated with bisphosphonate exposure to evaluate local and/or systemic biomarkers of bone health and bisphosphonate treatment in healthy individuals or in those experiencing clinical events (i.e., atypical fractures or BRONJ, as appropriate).

Primary outcome variable(s): absorption, distribution, metabolism, excretion (ADME) profiling of DNA from all sample types and of miRNA biomarkers in circulating blood.

Secondary outcome variable(s): RNA (miRNA and mRNA) biomarkers as assessed by microarray profiling and/or Taqman assays; protein biomarkers from all sample types; histomorphometric or basic histologic differences within or between bone samples from each group; results of metagenomic testing of skin, wound, oral cavity or surgical site; Incidence of osteonecrosis of the jaw or other diagnosis requiring treatment intervention; incidence of fractures or progression to arthroscopy; demographic and medical history of bisphosphonate exposure and/or adverse events in the study population.

For more information, visit #NCT01875458.

Faculty Team

An integrated team of surgeons, nurses, social workers, therapists, interventional radiologists, rehabilitation specialists and researchers, the Penn Orthopaedic Trauma and Fracture Service provides comprehensive orthopaedic care to patients with traumatic injuries or fractures. The Service is committed to pre-eminent orthopaedic surgery and clinical research and excellence in the education of orthopaedic trauma surgeons.

The Penn Department of Oral and Maxillofacial Surgery is composed of dental/medical specialists whose expertise encompasses non-surgical and surgical treatment of oral and maxillofacial disorders, traumatic injuries, congenital defects, oral lesions and temporomandibular joint dysfunction.

Study Team Surgeons

Samir Mehta, MD
Chief, Orthopaedic Trauma and Fracture Service
Assistant Professor of Orthopaedic Surgery

Jaimo Ahn, MD, PhD
Assistant Professor of Orthopaedic Surgery

Derek Donegan, MD
Assistant Professor of Orthopaedic Surgery

John L. Esterhai, Jr., MD
Professor of Orthopaedic Surgery

David C. Stanton, MD, DMD
Associate Professor, Oral & Maxillofacial Surgery

Clinical Research Team

Kelly McGinnis, MPA, CRA
Program Manager

Annamarie D. Horan, MPA, PhD
Director of Clinical Research


Penn Orthopaedics
Hospital of the University of Pennsylvania
2 Silverstein
3400 Spruce Street
Philadelphia, PA 19104

Penn Oral & Maxillofacial Surgery
Hospital of the University of Pennsylvania
5th Floor, White Building
3400 Spruce Street
Philadelphia, PA 19104

Tuesday, April 15, 2014

Enrolling Clinical Trials: Liver Cancer Treatment and Research at Penn Medicine

From the Spring 2014 Newsletter of the Penn Medicine Division of Gastroenterology

Edgar Ben-Josef, MD, Maarouf Hoteit, MD, David Kaplan, MD, Kim Olthoff, MD, Michael C Soulen, MD

Penn Medicine is a leading medical center in the nation in providing advanced clinical care and innovative investigational treatments to patients with liver cancer at every stage of the disease.

The liver cancer treatment program at Penn Medicine involves the integration of five national leading centers of treatment and research: The Abramson Cancer Center, the Penn Transplant Institute, the Roberts Proton Center, the Penn Center for Viral Hepatitis and the Division of Gastroenterology and Hepatology.

Every patient with liver cancer at Penn benefits from the expertise of specialists in each section of the program. Cancer treatment is a collaborative process, as each decision is complicated by the need to consider different aspects of the disease. What the Penn liver cancer program does—and does well—is function as a team whose various medical and surgical disciplines are focused on state of the art care for patients with liver cancer.

The anchor of the Penn liver cancer treatment program is the weekly Liver Tumor Conference. Here, clinicians with expertise in hepatology, hepatobiliary and transplant surgery, interventional radiology medical oncology, radiation-oncology, diagnostic radiology, and pathology contribute to the deliberative decisions necessary for the treatment of each patient with liver cancer. Each case is reviewed on the basis of the type and extent of cancer, health status, prior treatments and physical condition. Options are then considered and recommendations made.


The standard curative therapies for HCC at Penn include surgical resection, radiofrequency ablation and liver transplantation. All curative treatments depend on confirmation that the cancer is contained within the liver, has not invaded the major liver vessels and that the number and size of the tumors are within the parameters for cure.

Surgical resection is typically performed in patients with intact liver function. Patients with impaired liver function are candidates for transplantation. Patients with small tumors who are not healthy enough for surgery are candidates for radiofrequency ablation.
The treatments at Penn for advanced HCC include chemoembolization, radioembolization or external radiation for cancers contained to the liver in patients with good liver function.

Patients also have access to systemic therapy in the form of sorafenib or a variety of investigational treatments in the setting of clinical trials, including biological therapies, targeted immunotherapies, and proton therapy.

Clinical Research

Penn Medicine prides itself in being a national leader in advancing the science of cancer medicine and in the development of innovative cancer treatments in the setting of clinical trials. There are a number of clinical trial options available to patients with Liver Cancer at Penn.

A Phase II study of proton beam irradiation of unresectable primary liver tumors [ Identifier: NCT00976898] 

Penn Medicine is part of a multi-center study to evaluate the efficacy and safety of proton therapy in patients with unresectable liver cancer. A recent addition to the armamentarium for HCC at Penn, proton therapy is available at the Roberts Proton Therapy Center - one of only five proton centers on the East coast.

Proton therapy is expected to have advantages in liver cancer because the liver is particularly  sensitive to the effects of radiation. Proton dose distributions can be designed to conform closely to the tumor volume with a marked reduction in radiation exposure to the non involved liver, allowing delivery of higher doses to tumors within the liver with minimal effects on the surrounding liver.

The objective of this trial is to demonstrate local control (an important endpoint in abdominal cancers) in greater than 80% of patients at two years with proton beam irradiation for unresectable hepatocellular cancer.

Secondary objectives include a determination of the safety and tolerance of the treatment program, an evaluation of tumor response, patterns of failure and five-year overall survival, among other goals.

Patients will receive proton beam irradiation in 15 fractions over 3 weeks. Acute toxicity evaluations will occur weekly during study treatment, and at 3 month follow up. Thereafter, evaluation for tumor response will be conducted using Response Evaluation Criteria In Solid Tumors (RECIST) criteria and for acute and late toxicity per Common Terminology Criteria for Adverse Events (CTCAE ) v. 3.0.


The primary investigator at Penn is Edgar Ben-Josef, MD. Please contact Kristi Varillo
at 215.615.3273 for more information.

A Phase II randomized multi-center placebo-controlled blinded study of sorafenib adjuvant therapy in high risk orthotopic liver transplant (OLT) recipients with hepatocellular carcinoma (HCC)

Patients with evidence of a high risk liver cancer following liver transplantation form a group for whom limited options exist to reduce the risk of cancer recurrence.

These patients are currently the subject of a randomized, blinded, placebo-controlled clinical trial at Penn Medicine to investigate the efficacy and safety of the protein kinase inhibitor sorafenib in the adjuvant setting after liver transplant. This study is under the direction of Kim Olthoff, MD, of Penn Transplant Surgery, Maarouf Hoteit, MD, of Penn Gastroenterology and Nevena Damjanov, MD, of Penn Oncology.

The primary endpoint of the trial will be two-year recurrence-free survival. Other study endpoints include one-year recurrence free survival; overall survival; safety; impact of drug-drug interactions (i.e. immunosuppression agents); impact of biomarkers (alpha-fetoprotein [AFP], protein-induced by vitamin K absence or antagonist II [PIVKA II]); the effects of therapy on wound healing; and the impact on hepatitis C viral recurrence.

The trial will include patients who had hepatocellular carcinoma (HCC) with one of the following at the time of the pathological analysis of the transplant: microvascular/macrovascular invasion, tumor outside of Milan criteria, or poor tumor differentiation.

Patients with elevated surrogate markers (AFP greater than 500 or PIVKA greater than 400) pre transplant and with biopsy proven HCC prior to liver transplantation or at the time of transplant will also be included.

Patients will be randomized to one of two treatment arms: ARM I patients will receive sorafenib tosylate orally (PO) twice daily (BID). ARM II patients will receive placebo PO BID. Treatment will continue in both arms for 24 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients will be followed up every six months for two years.


The contact for referrals and participants is Mary Shaw, at 215.614.0528.