Clinical Briefings™ & Clinical Reports from Penn Medicine

Treatment of Idiopathic and De Novo Scoliosis in Adults

noreply@blogger.com (Mark) — Fri, 20 Jan 2012 04:57:00 PST

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

noreply@blogger.com (Mark) — Tue, 17 Jan 2012 06:26:00 PST

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

noreply@blogger.com (Mark) — Mon, 19 Dec 2011 07:42:00 PST

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

noreply@blogger.com (Mark) — Thu, 01 Dec 2011 04:38:00 PST

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

noreply@blogger.com (Mark) — Tue, 29 Nov 2011 07:13:00 PST

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

noreply@blogger.com (Mark) — Mon, 28 Nov 2011 10:20:00 PST

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

noreply@blogger.com (Mark) — Mon, 07 Nov 2011 07:39:00 PST

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

noreply@blogger.com (Mark) — Wed, 26 Oct 2011 08:29:00 PDT

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

noreply@blogger.com (Mark) — Fri, 14 Oct 2011 06:01:00 PDT

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

noreply@blogger.com (Mark) — Fri, 14 Oct 2011 05:39:00 PDT

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

noreply@blogger.com (Mark) — Tue, 04 Oct 2011 11:13:00 PDT

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

noreply@blogger.com (Mark) — Fri, 30 Sep 2011 07:38:00 PDT

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.

Management of Hepatitis C

noreply@blogger.com (Mark) — Wed, 28 Sep 2011 04:48:00 PDT

From the Penn GI News

The Penn Liver Cancer team consists of hepatologists, surgeons, medical oncologists, interventional radiologists, radiologists and radiation oncologists whose primary focus is the care of patients with liver cancer and those at risk for the disease.

Diagnostic and Treatment Options

A variety of liver diseases, including Hepatitis C, can cause inflammation and progressive scar formation in the liver resulting in cirrhosis. Over time, patients with cirrhosis are at risk of developing primary liver cancer (hepatocellular carcinoma or HCC). Consequently, HCC is often the result of a process that started years before the onset of cancer.

Because HCC is present years before its manifestations appear, it is often possible to identify patients at risk of developing HCC at a stage where it is curable. Early diagnosis may be achieved, for example, with screening tests that are used to detect incipient cancer.

The primary challenge in the treatment of liver cancer emanates from the fact that HCC typically occurs in the background of a liver diseased by cirrhosis. Therefore, one has to consider that patients with HCC have two serious health problems: a cancer and a chronic liver disease.

This is important because the severity of liver disease often has a major impact on the choice of treatment options in hepatocellular carcinoma. In all cases, early detection is key, because only early cancer can be cured.

Surgical resection of the tumor can achieve cure of hepatocellular carcinoma, particularly when the tumor is small, but can only be safe and effective if liver function is nearly intact. Liver transplantation, where the entire liver – including the tumor – is removed and replaced with a normal liver from a donor, is a very effective treatment for HCC, as long as the tumor is within specific size limits.

Because the entire liver is replaced, liver transplant circumvents the strict need for a good liver function that surgical resection requires. The other major advantage of transplantation is that it results in removal of the tumor as well as removal of the rest of the liver which, if left behind, will remain at risk of developing additional cancer.

A select group of patients with small favorably located tumors can be cured with minimally invasive treatments such as radiofrequency ablation.

Effective treatment for HCC is also possible in patients with more advanced disease. Transarterial chemoembolization (TACE), in which a chemotherapy mixture is injected directly into the tumor to interrupt its blood supply, results in tumor death and is effective at controlling even larger tumors confined to the liver.

TACE is also useful to prevent tumors from growing while patients with smaller tumors are on the transplant waiting list.

Another effective modality, radioembolization kills tumor cells by injection of radiation-emitting beads into the tumor and is also an effective treatment for larger tumors. Chemotherapy in the form of the oral drug Sorafenib, or clinical trials with new drugs are also a possible effective treatment options.

Navigating the various treatment options in HCC can be complex and requires the expertise of physicians with different areas of specialization.

The Penn Liver Cancer team includes: Rajender Reddy, MD, Director of Hepatology; Thomas W. Faust, MD; Kimberly A. Forde, MD , MHS; Maarouf A. Hoteit, MD;David E. Kaplan, MD, MSc; Karen Krok, MD; and George A. Makar, MD, MSCE.

At Penn, all cases are discussed every week by a multidisciplinary team of specialists in the context of the Penn Liver Tumor Conference. Patients are then evaluated by multiple experts in a single visit to the Penn Liver Tumor Clinic where treatment options are discussed. The Liver Cancer team at Penn has the unique capability of an efficient and expert evaluation of patients, and is committed to offering convenient access to skilled medical care of a complex disease.

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

Download a pdf of the Spring 2011 Penn GI News.

Pancreatic Cancer Research

noreply@blogger.com (Mark) — Thu, 22 Sep 2011 05:26:00 PDT

From the Penn GI News, Summer 2011

Pancreatic cancer is the second most common gastrointestinal malignancy and the fourth leading cause of cancer-related deaths in the United States. Because the majority of patients are diagnosed late in the course of the disease, the prognosis for pancreatic cancer is dismal. More than 95 percent of patients die within five years of diagnosis. There is thus a great need to discover early methods of detection for the disease.

The molecular pathogenesis of pancreatic cancer is being elaborated at Penn and elsewhere, and is known to include mutations of the K-ras oncogene (seen in 90 percent of pancreatic adenocarcinomas), the Hedgehog signaling pathway and the inactivation of the tumor
suppressor genes p53 and p16/Ink4a, among others.

At Penn's Division of Gastroenterology, researchers Andrew Rhim, MD, and Ben Stanger, MD, have been investigating oncogentic mutations to identify biomarkers with the potential to aid in the early diagnosis of pancreatic cancer. Their study is representative of recent research in pancreatic cancer at Penn Medicine.

Epithelial-to-mesenchymal transition and hematogenous dissemination precedes histologic diagnosis of pancreatic cancer
Primary Investigators at Penn: Andrew Rhim, MD, Ben Stanger, MD. Contact: andrew.rhim@uphs.upenn.edu; stanger@exchange.upenn.edu

Background: Metastatic disease is the predominant mode by which cancer, and, particularly pancreatic cancer, kills patients. Indeed, the vast majority of those who are diagnosed with pancreatic cancer also have metastatic disease upon presentation. Of those with limited or small tumors and no radiographic evidence of metastases, many will undergo surgical resection; however, up to 90 percent of all of these patients will eventually succumb to metastatic disease.

These clinical observations thus suggest that the seeds of metastatic disease may be established long before pancreatic tumors are detected, or perhaps, form. The current study tests the hypothesis that pancreatic cell dissemination into the blood stream and colonization of distant organs occur prior to tumor formation.

Objectives: To determine when during cancer progression epithelial-to-
mesenchymal transition (EMT), a molecular reprogramming event thought to be required for the first steps of metastasis; hematogenous dissemination; and distant organ colonization occurs.

Methods: Two unique lineage-labeled mouse models of spontaneous pancreatic ductal adenocarcinoma (PDAC) were created to study the fate of pancreatic epithelial cells during various stages of tumor progression.

Both models relied on the Pdx1-Cre transgenic strain to generate pancreas- specific mutations in Kras and either p53 or P16ink4a/Arf, genes that are mutated with high frequency in human pancreatic cancers.

The Rosa26YFP allele was introduced in both groups to track the fate of pancreatic epithelial cells, resulting in highly specific and efficient fluorescent labeling (>95% of all pancreatic epithelial cells). Pancreas and blood specimens were analyzed from 1) “PanIN” mice with only the precancerous pancreatic intraepithelial neoplasia (PanIN) lesion and no histologic evidence of cancer by hematoxylin and eosin (H&E) staining [aged 2-2.5 mo] and 2) “PDAC” mice harboring pancreatic tumors [aged 3.5-4 mo].

Expression of the markers Zeb1 and Fsp1 (independent predictors of mortality in pancreatic cancer) and the absence of epithelial markers E-cad and CK19 were used to detect EMT in YFP+ pancreatic epithelially derived cells as mesenchymal markers. Fluorescent pancreatic cells in the blood stream and the liver were detected using flow cytometry (FACS) analysis
and immunofluorescent staining of liver sections.

Results: Multicolor immunofluorecent (IF) staining for the YFP epithelial lineage label and the mesenchymal markers Zeb1 and FSP1 revealed double positive (EMT+) cells residing in 2.2% and 17.4% of all PanIN2 and PanIN3 (low- and high-grade dysplasia) lesions, respectively.

Further, individual spindle-shaped YFP+ cells were observed invading into the pancreatic stroma of PanIN mice, despite the absence of a pathologic diagnosis of cancer based on H&E staining. Using FACS, YFP+ pancreatic cells were found in the blood of both tumor-bearing PDAC mice and PanIN mice (94.5 ± 35.4 v. 42.9 ± 20.5 cells/ml blood; p<0.001; n=30) but not in control Pdx-Cre;RosaYFP mice.

These circulating YFP+ cells were devoid of CD45 and Ter-119 (markers of white and red blood cells), expressed YFP, E-cadherin and Pdx-1 transcripts, and formed pancreatospheres in attachment-free cultures, a surrogate test for cancer stem cells. Finally, while rare individual YFP+ cells were found in small hepatic venules of PanIN mice, no metastatic lesions were appreciated, such as those seen in PDAC mice.

Conclusions: Using sensitive genetic tools, this study offers evidence that EMT, invasion, and hematogenous dissemination precede conventional histologic diagnosis of PDAC. These data argue against the classical linear progression model of cancer, whereby dissemination occurs after tumors form. Further, it suggests that current tools that are being used to diagnose carcinoma on biopsy specimens may not be sensitive enough to detect the earliest stages of cancer.

However, it is still unclear if circulating PanIN cells are the source of metastatic lesions. Nevertheless, based on this data, circulating pancreatic cells may be specific biomarkers for advanced PanIN disease and early pancreatic carcinoma. Clinical trials are planned to translate these results to humans.

PANCREATITIS RESEARCH AT PENN

Acute & Chronic Pancreatitis

Chronic pancreatitis (CP) accounts for 80,000 hospital admissions annually in the United States at an estimated annual cost of $2.5 billion.1 Many patients with chronic pancreatitis are disabled from pain and their disease, leading to far greater indirect costs.

Alcohol, smoking and very high triglyceride levels are strong predictors for the development of CP, but the cause of the disease remains unknown in 20 percent of patients even after careful investigation. Among other objectives, clinical research at Penn Gastroenterology is focusing on the race-dependent risk factors for pancreatitis and the identification of biomarkers that will determine the malignant potential of pancreatic cystic neoplasms.

North American Pancreatitis Study 2 (NAPS2): Race-dependent Genotype-phenotype Associations for the Development of Chronic Pancreatitis and Its Subtypes

Primary Investigator: John G. Lieb II, MD. Primary
Contact: Amina A. Wirjosemito, MPH (amina.wirjosemito @uphs.upenn.edu).

Background: In the United States, the rate of chronic and acute pancreatitis among African Americans is about twice that of the white population.2 Only 58 of 1000 patients with CP enrolled in the NAPS2 study were African-American, however, resulting in a sample size insufficient for subset analyses. This study will enroll a cohort of African-American patients with CP of sufficient size to permit comparisons with the NAPS2 dataset.

Objectives: To identify/quantify genetic, epidemiologic, social, medical, surgical, environmental and novel risk factors that lead to the development of nonfamilial CP, especially in African-Americans. To subclassify those risk factors for subtypes of CP (calcific, atrophic, mass-like, minimal-change, and so on) and to make genotype-phenotype associations in CP patients. To quantify pain and quality of life patterns in these CP subtypes in African- Americans and try to correlate those to genotypes.

Methods: This is a multicenter prospective cohort study performed as an ancillary to the North American Pancreatitis Study 2 (NAPS2) using that trial’s parameters, including lifestyle, environmental, clinical and imaging data, to subclassify CP in African-Americans. A linked biorepository (serum and DNA) will also be established. These sporadic patients will be tested for known variations in major susceptibility genes for chronic pancreatitis, as well as for associations with genes hitherto unknown to be related to CP (genome wide association studies). These initial genotyping efforts will support analysis of gene-environment interactions to identify specific risk factors and optimal treatment options in African-Americans and permit comparisons with the NAPS2 dataset.

Pancreatic Cysts
Researchers with the Division of Gastroenterology at Penn Medicine are working with the Department of Pathology to investigate ways to better diagnose and differentiate pancreatic cysts and their progression.

Mesothelin: A Potential Biomarker for the Diagnosis of Mucinous Cystic Lesions of the Pancreas
Principal Investigators: Nuzhat Ahmad, MD; Nirag Jhala, MD. Primary Contact: Pari Shah, MD, — pari.shah@uphs.upenn.edu.

Background: Optimal management of pancreatic cystic neoplasm depends upon accurate diagnosis. Because it can be difficult to differentiate pancreatic cysts without malignant potential, (i.e., pancreatic pseudocysts) from cysts with high malignant potential, such as mucinous cystadenoma, cystadenocarcinoma and intraductal papillary mucinous tumors (IPMTs), pancreatic cystic neoplasms present a diagnostic dilemma. Over-expression of the protein mesothelin has been shown to be associated with invasive intraductal papillary mucinous neoplasia (IPMN) and hence can potentially be used as a marker to predict aggressive behavior of cysts.

Objective: The purpose of this study is to determine if mesothelin expression can be used to differentiate mucinous cystic lesions with low malignancy potential from those with high malignancy potential, as well as predict the malignant potential of mucinous lesions of the pancreas.

Methods: This study will involve developing a database to perform a retrospective review of all patients who underwent resection for cystic lesions of the pancreas between 2001 and 2009 at the Hospital of the University of Pennsylvania. From this cohort, 20 patients will be randomly selected with MCN, IPMN, mucin secreting adenocarcinoma, serous cystadenoma and pseudocysts. Patients may also have prior cytology samples from cyst aspirates.

This selection will be stratified by type of dysplasia (low-grade dysplasia — high-grade dysplasia) and adenocarcinoma. Expression pattern of mesothelin in gastric foveolar, as well as duodenal, mucosal cells will also be determined. Adjacent normal pancreatic tissue will serve as the control for each specimen. Immunohistochemical assays will measure mesothelin expression in each tissue sample.

References: 1. Lowenfels, et al. Curr Gastroenterol Rep. 2005;7:90-95. 2. Yang AL, et al. Arch Intern Med. 2008;168:649-656.

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

Download the Summer 2011 Penn Gastroenterology News.

Management of Treatment-Associated Dry Mouth

noreply@blogger.com (Mark) — Wed, 21 Sep 2011 10:50:00 PDT

Oral Medicine clinicians at Penn Medicine are managing patients who experience dry mouth as a result of treatment for a variety of conditions, including cancer, autoimmune diseases such as Sjogren’s syndrome and lupus, sinus disease and allergic disorders. Side effects from commonly used drugs including antihistamines, antidepressants and tranquilizers are also a major cause of dry mouth.

Dry mouth is a condition marked by the abnormal reduction of saliva, and is the leading treatment-related side effect in the oral cavity. Symptoms of dry mouth include difficulty eating and swallowing, inflammation of the lining of the mouth, mucosal fissures, hoarseness and an increase in tooth decay and gum disease.

Patients with cancer are especially susceptible to dry mouth, because of radiation therapy, radioactive iodine therapy (for thyroid cancer) and chemotherapy, all of which can cause profound, persistent hyposalivation.

In the general population, dry mouth is typically the result of medication use; more than 400 drugs report dry mouth as an adverse event. Mouth breathing, obesity and other physical conditions have also been associated with dry mouth.

Penn oral medicine clinicians approach the management of dry mouth on an individual basis, depending upon the originating condition or circumstance. Patients with salivary glands damaged by radiation therapy, for example, may receive a combination of sialogogues—pharmacologic salivary stimulants—oral moisturizers and salivary substitutes.

Case Study

Mr. G, a 57-year-old man with a history of non-Hodgkin’s lymphoma of the neck, was referred to the Division of Oral Medicine of the Department of Oral and Maxillofacial Surgery for an evaluation after he experienced profound hyposalivation following radiation therapy. In addition to chapped and cracked lips, mucosal fissures
and difficulty swallowing, Mr. G’s tongue became cracked,
swollen and inflamed (Figure 1).

He reported that he had difficulty swallowing and speaking and that the constant perception of dryness was a great source of anxiety and irritation. After an evaluation, Mr. G was prescribed pilocarpine, a sialogogue, and a combination of polyvinylpyrrolidone and hyaluronic acid to hydrate and soothe his oral mucosa. At his follow-up visit, Mr. G reported a substantial improvement in symptoms and improved quality of life.

Faculty Team

The Department of Oral and Maxillofacial Surgery at Penn Medicine includes a group of multidisciplinary specialists who provide medical, surgical and specialty dental services. Penn’s oral and maxillofacial team specializes in non-surgical and surgical treatment of diseases, disorders, injuries and esthetic aspects of the mouth, teeth, jaws and face.

Treating Dry Mouth at Penn Medicine

Thomas P. Sollecito, DMD
Chief, Oral Medicine Division
Professor of Oral Medicine

Martin S. Greenberg, DDS
Professor of Oral Medicine

Eric T. Stoopler, DMD
Director, Oral Medicine Residency Program
Associate Professor of Oral Medicine

Access

Oral and Maxillofacial Surgery
Hospital of the University of Pennsylvania
5 White
3400 Spruce Street
Philadelphia, PA 19104

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

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.

High-Risk Retrieval of Embedded Inferior Vena Cava Filters

noreply@blogger.com (Mark) — Wed, 21 Sep 2011 06:34:00 PDT

Interventional radiologists at Penn Medicine have developed a minimally invasive technique to effectively retrieve inferior vena cava (IVC) filters embedded in the vessel wall.

Although the safety record for both permanent and retrievable IVC filters is very good, because of potential long-term problems, it is recommended that the devices be removed as soon as protection from pulmonary embolism is no longer needed.

These concerns include an increased risk of recurrent deep vein thrombosis when a filter is in place, rare but potentially harmful fracture of the devices and symptomatic penetration of the filter struts.

In most series, roughly five to ten percent of IVC filters are found to be embedded when retrieval attempts are made and are thus refractory to standard retrieval methods. Tip embedding is one of the major causes of failed retrieval attempts. This occurs when the filter has tilted, allowing the tip to become impacted within the wall of the IVC.

Embedding prevents access to the top of the filter (used to recover the devices) and thus precludes standard retrieval with snares or proprietary devices such as retrieval cones.

Penn interventional radiologists perform complex high-risk retrievals of tip-embedded IVC filters using rigid endobronchial forceps. The approach employs a sheath placed into the IVC from the right internal jugular through which the forceps are maneuvered to dissect away entrapping tissue and grasp the filter tip. In a recent study performed at Penn, this approach was successful in 95 percent of retrieval attempts (20 of 21 patients) without complication.

Case Study

Mr. W, a 37-year-old man, presented to Penn Interventional Radiology with a filter embedded in the wall of his inferior vena cava. According to his medical history, Mr. W had a history of deep vein thrombosis, for which he had been taking coumadin for some years. Recently, however, he had a bleeding ulcer, requiring temporary cessation of anticoagulation.

To protect him from pulmonary emboli during this time, a retrievable filter was placed in his inferior vena cava at his community hospital.

After Mr. W’s ulcer had healed and he had re-started coumadin, an unsuccessful attempt was made to retrieve the IVC filter. At this time, an inferior vena cavagram showed the tip of the filter embedded in the vessel wall (Figure 1). Mr. W was then referred to Penn for an office consultation with an interventional radiologist.

At Penn, Mr. W had CT venography of the abdomen to evaluate the IVC and rule out the presence of clots trapped in the filter. After discussing the risks and benefits of leaving the filter in place versus removing it, he was scheduled for complex IVC filter retrieval.

To ensure continued protection from pulmonary embolism, anticoagulation was not interrupted during the one-hour outpatient procedure, for which Mr. W received light sedation.

Using a right internal jugular vein approach and under fluoroscopic guidance in an IR operating room, rigid endobronchial forceps were placed through a sheath and used to dissect away the embedding tissue.

The filter was then grasped (Figure 2) and pulled out directly through the sheath. A follow-up venogram was performed to evaluate the IVC for damage or thrombus. After his procedure, Mr. W was observed for two hours, and went home the same day. He had no adverse effects from the procedure and remains under the care of his family physician.

Faculty Team

The specialists with the Interventional Radiology Division at Penn Medicine offer the diagnosis and treatment of a variety of diseases using minimally invasive techniques. The Division is situated in six interventional radiology suites at the Hospital of the University of Pennsylvania, and has an active outpatient clinic and consulting service.

Performing Complex IVC Retrievals at Penn Medicine

Scott O. Trerotola, MD
Stanley Baum Professor of Radiology

S. William Stavropoulos, MD
Associate Professor of Radiology

Jeffrey I. Mondschein, MD
Assistant Professor of Clinical Radiology

Richard Shlansky-Goldberg, MD
Associate Professor of Radiology

Penn Interventional Radiology

Scott O. Trerotola, MD
Stanley Baum Professor of Radiology

Timothy W. I. Clark, MD
Associate Professor of Clinical Radiology

Mandeep S. Dagli, MD
Assistant Professor of Radiology

Cormac T. Farrelly, MD
Assistant Professor of Radiology

Maxim Itkin, MD
Adjunct Assistant Professor of Radiology

Jeffrey I. Mondschein, MD
Assistant Professor of Clinical Radiology

Richard Shlansky-Goldberg, MD
Associate Professor of Radiology

Michael C. Soulen, MD
Professor of Radiology

S. William Stavropoulos, MD
Associate Professor of Radiology

Deepak Sudheendra, MD
Assistant Professor of Clinical Radiology

Access

Penn Interventional Radiology
Hospital of the University of Pennsylvania
1 Silverstein
3400 Spruce Street
Philadelphia, PA 19104

Penn Presbyterian Medical Center
4 Wright-Saunders Building
51 N. 39th Street
Philadelphia, PA 19104

Penn Radiology
Hospital of the University of Pennsylvania
Ground Dulles
3400 Spruce Street
Philadelphia, PA 19104

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.

Umbilical Cord Blood (UCB) Transplantation for Patients with Hematologic Malignancies

noreply@blogger.com (Mark) — Tue, 13 Sep 2011 04:35:00 PDT

Researchers with the Bone Marrow and Stem Cell Transplant program at the Abramson Cancer Center of the University of Pennsylvania are seeking to hasten immune system reconstitution and hematopoietic recovery in patients with hematologic malignancies receiving umbilical cord blood (UCB) transplantation.

UCB represents a promising source of stem cells for patients with advanced hematologic diseases for whom hematopoietic stem cell transplantation (HSCT) may be life saving.

The benefits of UCB transplantation after HSCT are well established. Cryopreserved UCB grafts offer a rich source of hematopoietic stem cells (HSCs) and naïve donor T cells. The grafts are immediately available from a rapidly growing list of national and international cord blood banks.

Since a lower incidence of graft-versus-host disease exists after HSCT with UCB than that seen after transplantation of unrelated blood or bone marrow stem cells, the requirement for HLA matching is less stringent. The major limitation of UCB HSCT is delayed hematopoietic and immune reconstitution.

To address these limitations, researchers at Penn are completing a Phase I clinical trial. Building upon an earlier trial at Penn that established the safety of delayed infusion of costimulated allogeneic T cells in patients with advanced hematologic malignancies, this trial assesses the safety (in terms of graft versus host disease) of UCB-derived T cells expanded ex vivo via CD3/CD28 costimulation and reinfused at the time of UCB HSCT.

A secondary endpoint of the trial will be to study time to engraftment and immune reconstitution in recipients of this therapy. Patients with hematological malignancies who are eligible and appropriate for UCB transplantation were enrolled if they did not have a suitable related or unrelated donor available, and had a suitable umbilical cord blood graft identified.

Cord blood units are selected if they are frozen in two aliquots with sufficient cell numbers to support a transplant.This protocol adds another option for patients who require allogeneic SCT but who do not have a suitable matched sibling or unrelated donor.

This trial, A Phase 1 Dose Escalation Study of Infusion of ex Vivo cd3/cd28 Costimulated Umbilical Cord Blood-derived t Cells in Adults Undergoing Transplantation for Advanced Hematologic Malignancies (NCT00891592), is currently active, but no longer recruiting.

Case Study

Ms. B, a 42 year old woman with high risk acute myelogenous leukemia in first remission, first presented at Penn in December 2008 with a white blood count of 60,000 composed primarily of myeloblasts. Cytogenetic studies showed deletion of chromosome 7 and multiple other abnormal clonal rearrangements. Her cells also expressed an internal tandem duplication of FLT3. She received standard induction chemotherapy with idarubicin and cytarabine.

A biopsy on day 14 showed residual disease and she received retreatment. At 28 days after her second course of induction chemotherapy, her white blood count was 2000/μL with a normal differential, her hemoglobin was 10 g/dL and her platelet count 70,000/μL.

A bone marrow biopsy showed less than five percent blasts and one of 20 cells still had deletion of chromosome 7 and multiple cytogenetic abnormalities. She was in a minimal disease state but considered incurable with standard chemotherapy. For Ms. B, allogeneic stem cell transplantation offered the only chance of long-term cure.

However, HLA typing of two siblings did not identify a match, nor were any well matched donors identified through a preliminary search of the National Marrow Donor Program registry. A subsequent search for potential cord blood units identified a unit comprised of a 5 x 107 total nucleated cells/kg, matched at 5 of 6 HLA antigens tested and frozen in two aliquots.

The cord blood was requested and delivered within one week of the search. The identification and rapid delivery of a well matched cord blood unit allowed Ms. B, a patient with very high-risk disease, to proceed from search to transplant within one month. She is currently undergoing cord blood transplantation.

The addition of activated T cells to the traditional cord blood graft may speed graft recovery and immune reconstitution; this hypothesis will continue to be tested during this and subsequent clinical trials.

Faculty Team

The Bone Marrow and Stem Cell Transplant program at the University of Pennsylvania and Abramson Cancer Center is the largest transplant center in the region. Our 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. We have active programs using both conventional allogeneic SCT and for nonmyeloablative allogeneic (“mini”) transplantation. We are committed to premier clinical care and strive to work collaboratively with patients’ referring physicians.

Hematologic Malignancy Physicians

Edward A. Stadtmauer, MD
Director, Bone Marrow & Stem Cell Transplant Program
Professor of Medicine

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

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

Sunita 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

Access

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

For more information about cancer services at Penn Medicine, please visit the Abramson Cancer Center.

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

Patients with hematologic malignancies may be referred to any member of our transplant group and will be considered for umbilical cord blood transplant if a suitable family member or well matched unrelated donor cannot be identified in a timely manner.

Digital Breast Tomosynthesis for Breast Cancer Screening

noreply@blogger.com (Mark) — Wed, 03 Aug 2011 09:52:00 PDT

Breast imagers at Penn Medicine are now using digital breast tomosynthesis, or DBT, to perform three-dimensional mammography for breast cancer screening and diagnosis.

The DBT system employs a digital X-ray that records a series of low-dose, high-resolution images of the breast while traversing a small (15°) arc around the compressed breast. As the projection angle changes, images are recorded at slightly different depths and thicknesses, from one surface of the breast to the other.

The compression time of approximately four seconds needed for DBT is similar to that used for standard two-dimensional digital mammography. Following the procedure, reconstruction algorithms are used to create a 3-D rendering of the interior breast architecture.

This rendering is presented to the breast imager as a stack of images of the breast that, in total, represent the area from one skin surface to the other. Each DBT image can be magnified or manipulated to better reveal minute detail. These processes can reduce the superimposition of overlapping tissue shadows seen in two-dimensional mammograms, allowing more accurate interpretations of breast changes.

Among the greatest advantages of DBT for radiologists at Penn is that it offers images with a clarity and degree of detail substantial enough to reduce some of the false-positives and false-negatives associated with 2-D mammographic imaging. In small series studies, researchers have reported reducing the false-positive callback rate by as much as 30 to 40 percent.

Like most newer technologies, however, DBT has a few minor drawbacks:

The approved indications for DBT state that it must be used as an adjunct to standard digital mammography. This means that the radiation dose for women having DBT is slightly higher than it would be with standard digital mammography. Even with the addition of DBT, however, the dose remains lower than the maximum allowed with older, analog mammography.
Because DBT is a new platform, techniques for best use are still evolving. Studies at Penn are evaluating whether the dose of DBT can be reduced without losing image integrity.
To date, no substantial trials of 3-D tomosynthesis have been performed in the U.S., though a large trial is currently being planned. A large-scale population- based study is ongoing in Europe. These trials are very hard to do, and must involve many thousands of women to show a significant benefit in cancer detection of tomosynthesis over routine mammography.

Case Study

Ms. G, a 49-year-old woman, had a routine
annual mammogram that was interpreted as “normal” (Figure 1).

After learning of the breast tomosynthesis clinical trial at Penn, however, Ms. G enrolled and had a bilateral DBT study.

In this study, the tomosynthesis view of her right breast revealed an irregular, suspicious mass that was not visible on the standard 2-D mammographic view. A magnified view provided further definition of the mass, which on biopsy was found to be an invasive ductal carcinoma (Figure 2, arrow).

Faculty Team

The Department of Radiology at Penn Medicine is a highly specialized, full-service department which strives to meet all patient and clinician needs in diagnostic imaging and image-guided therapies. The Breast Imaging Division, accredited by the American College of Radiology, provides screening and problem-solving mammography for outpatients at the Ruth and Raymond Perelman Center for Advanced Medicine.

The basic examination utilizes state-of-the-art, low-dose film screen equipment with the capability for supplemental clarification with magnification, spot compression, and special projects.

Performing Digital Breast Tomosynthesis at Penn Medicine

Julia A. Birnbaum, MD
Clinical Assistant Professor of Radiology

Emily F. Conant, MD
Professor of Radiology

Sara C. Gavenonis, MD
Assistant Professor of Radiology

Susan Roth, MD
Professor of Radiology

Jennifer D. Tobey, MD
Clinical Assistant Professor of Radiology

Susan P. Weinstein, MD
Associate Professor of Radiology

Access

Penn Radiology
Perelman Center for Advanced Medicine
Atrium, Ground Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

To refer a patient and/or consult with a doctor:
Please call 877-937-PENN (7366) or visit:
PennMedicine.org/PhysicianLink.

Clinical Research in Radiology at Penn Medicine

Comparison of Full-Field Digital Mammography with Digital Breast Tomosynthesis Image Acquisition in Relation to Screening Call-Back Rate Protocol-ACRIN PA 4006 (PI E.F. Conant)

Objective: To evaluate the specificity of 2-D full-filed digital mammography versus a combination of 2-D and 3-D tomosynthesis imaging in breast cancer screening. This study will measure specificity by participant call-back rate per modality. Varying combinations of 2-D mammography and tomosynthesis projections will be evaluated to optimize the screening paradigm and limit radiation exposure when tomosynthesis is incorporated. Prospective and retrospective imaging data will be assessed.

Study Design: A total of 550 participants will be recruited for this trial; 500 will be recruited at time of screening mammography to join Group A (asymptomatic women 25 years and older with no history of breast cancer recruited from a prospective population of patient scheduled for screening mammography) and 50 will be recruited from women called back from screening for abnormalities detected on 2-D full-field digital mammography will be recruited to provide an enriched population of true-positive and false-positive digital mammography and tomosynthesis cases, where tomosynthesis is added to the diagnostic work-up for these participants (Group B). Accrual will be accomplished in 12 months at two institutions in Pennsylvania.

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.

Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy for Advanced Abdominal Cancers

noreply@blogger.com (Mark) — Wed, 03 Aug 2011 09:52:00 PDT

Endocrine and oncologic surgeons at Penn Medicine are performing open cytoreduction surgery (CRS) in conjunction with hyperthermic intraperitoneal chemotherapy (HIPEC) to treat advanced peritoneal carcinomatosis. Penn Medicine is among a small number of academic medical centers in the region performing the HIPEC procedure.

The goal of open cytoreductive surgery is complete removal of all visible tumor (generally to a size of 2.5 mm or less) in the abdominal cavity. Cytoreductive procedures are aggressive and thorough, and have an average duration of about seven hours.

Following removal of all visible tumor, heated chemotherapeutics (HIPEC) are administered directly into the abdominal cavity to eradicate any microscopic or small volume disease. HIPEC works by increasing the direct tumor toxicity of chemotherapeutic drugs, as well as their distribution and penetration. Delivery of chemotherapy directly into the peritoneum has been shown to substantially increase drug exposure to the peritoneal surface.

At Penn, procedures involving CRS with HIPEC are multidisciplinary, involving surgical and medical oncologists, anesthesiologists experienced in performing extended surgeries and critical care specialists who provide aftercare. CRS with HIPEC therapy is used for the treatment of patients with pseudomyxoma peritonei, primary peritoneal mesothelioma, and select patients with carcinomatosis from appendiceal, colorectal, gastric and ovarian primary cancers with disease confined to the abdominal cavity. Patients with these advanced cancers have frequently been previously treated with other therapies and have limited options beyond CRS with HIPEC.

Case Study*

Mrs. S, a 68-year-old woman, was referred to the Department of Endocrine and Oncologic Surgery with a history of mucinous colon adenocarcinoma for which she had undergone a partial colectomy two years prior with subsequent chemotherapy.

During follow-up for her surgery, Mrs. S was noted to have a rising level of carcinoembryonic antigen (CEA), a tumor marker for cancers of the gastrointestinal tract. A CT examination at this time demonstrated a new cystic mass in her right ovary with questionable other smaller masses in her abdomen (Figure 1).

Subsequently, a needle aspiration biopsy confirmed a recurrence of colon cancer with no evidence of spread beyond the abdomen. After a consultation, Mrs. S agreed to cytoreduction surgery followed by HIPEC.

Her debulking surgery included resection of both ovaries (which were involved by tumor) and resection of smaller tumor nodules in the retroperitoneum. Following the surgical removal of the tumors, Mrs. S had inflow and outflow catheters placed in her abdominal cavity with temperature probes,
and her abdomen was temporarily closed.

A perfusion pump then infused a chemotherapeutic solution heated to 42° C into the peritoneal cavity where it circulated continuously for 90 minutes. The chemotherapy solution was then washed out, the catheters were removed and the abdomen was closed.

Mrs. S remained in the ICU for two days for close observation following her surgery, and another eight days in the hospital prior to discharge. A CT scan at her most recent follow-up visit found no evidence of recurrence.

*Case Study profiles are based upon actual patients; non-clinical information has been altered to protect individual privacy.

Faculty Team

The Endocrine and Oncologic Surgery (EOS) program at PENN offers surgical expertise and multidisciplinary care for patients with a wide variety of benign and malignant tumors of the endocrine system and with gastrointestinal, skin and soft tissue malignancies. The EOS program is committed to achieving outstanding patient outcomes and to improving the future of care through basic science and clinical research efforts.

Performing HIPEC at Penn Medicine

Endocrine and Oncologic Surgery

Douglas L. Fraker, MD
Jonathan E. Rhoads Professor of Surgical Science

Giorgios C. Karakousis, MD
Assistant Professor of Surgery

Anesthesiology and Critical Care

Eric P. Greenblatt, MD
Clinical Associate Professor of Anesthesiology and Critical Care

Benjamin A. Kohl, MD
Assistant Professor of Anesthesiology and Critical Care

Perfusionists

Doreen Cowie, CCP
Katherine Gray, CCP

Access

Abramson Cancer Center
Perelman Center for Advanced Medicine,
West Pavilion, 4th Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

Penn PhysicianLink®:
An Exclusive Program for Referring Physicians

Penn PhysicianLink® simplifies the lines of communication between referring physicians and Penn Medicine. A single, dedicated physician-only telephone line offers direct access to a special Call Center reserved for medical professionals to facilitate a comprehensive collection of support services to expedite and facilitate referrals, transfers, consults and appointments for patients.

By calling just one number, physicians and their staff will have access to any Penn Medicine physician and/or location. The physician-to-physician phone line is available 24-hours-a-day, seven-days-a-week.

To refer a patient and/or consult with a doctor, call the exclusive PhysicianLink telephone line at 877-937-PENN (7366) or visit http://www.pennmedicine.org/PhysicianLink/.

Clinical Research in Ovarian Cancer Immunotherapy

noreply@blogger.com (Mark) — Wed, 13 Jul 2011 07:07:00 PDT

Researchers at the Penn Ovarian Cancer Research Center (OCRC) are expanding their immunotherapy program to offer state-of-the-art personalized therapy to patients with recurrent ovarian, primary peritoneal and fallopian tube cancers.

Patients with these malignancies may be eligible to enter advanced clinical trials in immunotherapy to investigate the use of vaccines manufactured from the patient’s own tumor followed by T cells expanded in culture from peripheral blood.

Despite intense efforts to improve chemotherapy for ovarian cancer, no significant progress has been made over the past 30 years;survival rates have not changed in the past decade. Novel therapeutic approaches are direly needed.

Stimulating the immune system to attack tumors is not a new concept. What is new, however, is combining personalized vaccines based on autologous tumor with potent immune stimulators and post vaccine lymphocyte reinfusion. The underlying notion is that tumors are different enough from the normal body, such that they can be recognized and attacked as “foreign” or “non-self ” by the host’s immune system, once the latter is properly educated and activated.

Researchers at the Penn OCRC are currently conducting three phase I/II clinical trials for patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer using autologous vaccines developed from patients’ autologous tumor.

One vaccine protocol administers intranodally autologous dendritic cells loaded with autologous tumor lysate, in combination with bevacizumab (UPCC-19809). Patients must have a tumor lesion of >2 cm.

Another protocol administers tumor lysate intradermally in combination with an immunomodulatory drug, Toll-like receptor 3 (Ampligen) (UPCC-29810). Patients must be HLA-A2+ with a largest tumor lesion of <2 cm. Patients with recurrent disease are eligible, although tumor from primary debulkings can be banked for future use.

The third clinical trial works on the hypothesis that antitumor immune response generated by a vaccine can be significantly augmented by infusion of autologous activated lymphocytes. Accelerated recovery of CD4+ and CD8+Tcell counts would occur in the setting of lymphopenia in the wake of the adoptive transfer of in vivo vaccine-primed T cells in combination with bevacizumab (UPCC 26810). This trial is a sequential trial following the above vaccine studies. Eligible patients are those vaccinated with autologous vaccine.

In a pilot study that was completed in 2010, patients with recurrent progressive stage III and IV ovarian cancer with available tumor lysate from secondary debulking surgery underwent priming with intravenous bevacizumab and oral metronomic cyclophosphamide (bev/cy x 2 doses), followed by vaccination with an autologous DC preparation pulsed with autologous tumor lysate (5-10x10e6 DC per dose, 3 doses) plus bevacizumab (two doses).

This was followed by lymphodepletion using high-dose outpatient cyclophosphamide and fludarabine (cy/flu, 300 and 30 mg/m2/day, respectively, x 3 days) and transfer of 5x10 e9 autologous vaccineprimed, ex vivo CD3/CD28-costimulated peripheral blood T cells, in combination with vaccination.

Feasibility, safety, and biological and clinical efficacy were evaluated. Three subjects have completed vaccination and T cell transfer, while three additional subjects completed vaccination only. Therapy was feasible and well tolerated as an outpatient regimen. Vaccination following bevacizumab and metronomic cyclophosphamide preconditioning elicited vaccine-specific T cell response in four patients. Clinical benefit was seen in four out of six patients after vaccination where two subjects had partial response, two had stable diseases.

Following outpatient cy/flu lymphodepletion, adoptive transfer of vaccine-primed, CD3/CD28-costimulated autologous T cells resulted in clinical response in two of three patients, with one patient achieving CR. No toxicities were seen.

Case Study

Mrs. T, a 46-year-old woman, was diagnosed with stage 2C ovarian cancer and had her first debulking surgery in October 2007. She was then placed on carboplatinum/taxol standard of care chemotherapy. In December 2008, she recurred and underwent a secondary debulking surgery. She then received radiation followed by bevacizumab and cyclophosphamide.

Mrs. T recurred again in June 2009 and was debulked for the third time a month later. At this time, her tumor tissue (which would normally have been discarded) was used to create a personalized autologous vaccine. Mrs. T enrolled in a pilot vaccine study at Penn in November 2009.

She underwent priming with intravenous bevacizumab and oral metronomic cyclophosphamide (bev/cy x 2 doses), followed by vaccination with an autologous DC preparation pulsed with autologous tumor lysate plus bevacizumab. After completing this trial, she went on to receive additional maintenance vaccines, then reenrolled in the current vaccine trial (UPCC19809) in September 2010 and completed this trial in January 2011.

Mrs. T continued to receive maintenance vaccine until May 2011. She is currently disease-free, and has had no evidence of disease since entering the immunotherapy program at Penn in November 2009.

Penn Ovarian Cancer Research Center Now Storing Tumor Tissue
for Non-Penn Medicine Patients

Originally, the Penn Ovarian Cancer Research Center (OCRC) had restricted its immunotherapy program to patients who completed surgery at Penn Medicine. Now, Penn is accepting tumor tissue even when the surgery is performed at outside institutions. A patient who has surgery at her local hospital can have her tumor tissue shipped to the OCRC, where it is processed and stored live for future immunotherapy.

For more information, please contact us at 215-615-6727 or via email at lknd@mail.med.upenn.edu.

Faculty Team

The Penn Ovarian Cancer Research Center (OCRC) is a joint effort of the research and clinical facilities of the Perelman School of Medicine at the University of Pennsylvania, the Abramson
Cancer Center and the Department of Obstetrics and Gynecology.

The goal of the OCRC is to identify new methods to detect, prevent and treat ovarian cancer and to improve the quality of life for women with the disease. The Faculty of the Penn Ovarian Cancer Research Center includes world-renowned clinicians and researchers with a commitment to the investigation of novel, advanced approaches to the diagnosis and treatment of ovarian cancer.

Performing Research in Ovarian Cancer at the Penn Ovarian Cancer Research Center

George Coukos, MD, PhD
Celso Ramon Garcia Professor of Reproductive Biology

Christina S. Chu, MD
Assistant Professor of Obstetrics and Gynecology

Sarah F. Adams, MD
Assistant Professor of Obstetrics and Gynecology

Stephen C. Rubin, MD
Franklin Payne Professor of Gynecologic Oncology

Thomas C. Randall, MD
Associate Professor of Clinical Obstetrics and Gynecology

Janos L. Tanyi, MD
Assistant Professor of Obstetrics and Gynecology

Lana E. Kandalaft, PharmD, PhD
Director of Translational Research and Clinical Development

Daniel J. Powell, Jr., PhD
Research Assistant Professor of Pathology and Laboratory Medicine

Access

Jordan Center for Gynecologic Cancer
Abramson Cancer Center
Perelman Center for Advanced Medicine,
West Pavilion, 3rd Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

To find more information about clinical trials at the
Penn Ovarian Cancer Research Center, visit:
http://www.uphs.upenn.edu/obgyn/research/ovarian.htm

Download a pdf of this Clinical Briefing.

Multidisciplinary Management of Non-Small Cell Lung Cancer

noreply@blogger.com (Mark) — Wed, 13 Jul 2011 05:07:00 PDT

Cancer specialists at Penn Medicine are treating non-small cell lung cancers (NSCLC) with a stage-specific, multimodality and multidisciplinary approach. For patients with early stage cancer without lymph node involvement, surgical intervention is the standard treatment at Penn.

Most patients with Stage II lung cancer (e.g., lymph node involvement) are offered a combination of surgery and adjuvant post-operative chemotherapy.

Select patients with regionally advanced cancer are offered a tri-modality treatment strategy, beginning with chemotherapy and radiation followed by re-evaluation and surgical intervention consolidated with chemotherapy in the postoperative period.

The team treating patients with lung cancer at Penn includes surgical and medical oncologists, thoracic surgeons, radiation oncologists, radiologists, pulmonary specialists, clinical research coordinators and a host of support services professionals.

The goals of this team include providing the highest standard of care to patients with lung cancer at every stage––including access to clinical trials––as well as a strategy for personalized treatment informed by the latest research, clinical experience, patient need and interaction with referring physicians.

Case Study*

Mr. V, a 73-year-old man with a 55-year history of smoking, was referred to Penn Medicine with a history of back pain and chronic cough unresponsive to antibiotics. Following an inconclusive chest x-ray at a community hospital, Mr V.’s physician referred him to the Penn Lung Center.

Bronchoscopy, including an endobronchial ultrasound (EBUS) examination of Mr. V’s mediastinal lymph nodes, revealed an adenocarcinoma in the upper lobe of his left lung. A week later, staging mediastinoscopy was performed, which revealed no active nodal involvement.

At this time, a resection was planned, but surgery was delayed when Mr. V was found to have purulent secretions consistent with active pneumonia. A second bronchoscopy was performed to clear Mr. V’s pneumonia and he was placed on antibiotics.

Several weeks later, after adequate recovery, he underwent a left extended posterior lateral thoracotomy, left upper lobectomy with en bloc resection of the chest wall including ribs two through five, mediastinal nodal dissection, and complex prosthetic chest wall reconstruction. Final pathology showed complete resection with clean margins.

Mr. V was discharged from the hospital on postoperative day five, and received four cycles of postoperative adjuvant chemotherapy over the next 12 weeks. At the end of this time, a consult in radiation therapy determined that there was no indication for the addition of radiation.

Mr. V is now participating in the MAGARIT clinical vaccine trial, a Phase III Study evaluating the clinical efficacy of recMAGE-A3 + AS15 versus placebo in non-small cell lung cancer after complete resection in two co-primary objective populations: the overall population and the population of patients who did not receive adjunct chemotherapy.

*Case Study profiles are based upon actual patients; non-clinical information has been altered to protect individual privacy.

Clinical Research in Cancer at Penn

All patients with lung cancer at Penn Medicine are offered access to clinical trials through the efforts of the Abramson Cancer Center of the University of Pennsylvania.

Patients meet with a clinical research coordinator during their initial visit to Penn, and are offered a wide array of clinical trials in which to participate. Many of these studies involve treatments individualized to target proteins, antigens or receptors within a patient’s personal tumor profile.

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 benefi t from the newest and best therapies available.

Penn 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 Radiation Oncology

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

Smith (Jim) Apisarnthanarax, MD
Assistant 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 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 Oncology Pulmonology

Andrew R. 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

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

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

Pennsylvania Hospital
700 Spruce Street
Philadelphia, PA 19107

Penn Medicine Cherry Hill
409 Route 70 East
Cherry Hill, NJ 08034

Shore Memorial Hospital
One East New York Avenue
Somers Point, NJ 08244

To refer a patient and/or consult with a Penn lung cancer specialist please call
215-615-LUNG (5864) or contact Penn PhysicianLink® here or at 877-937-7366.

Download a pdf of this Clinical Briefing.

Rapid Diagnosis and Treatment of Necrotizing Soft-Tissue Infection

noreply@blogger.com (Mark) — Wed, 13 Jul 2011 04:10:00 PDT

Surgeons with the Division of Traumatology, Surgical Critical Care, and Emergency Surgery have developed an algorithm for the management of rare, necrotizing soft tissue infections (NSTIs) based upon accurate and timely diagnosis, early, aggressive intervention and intensive follow-up
care. [1]

The hallmarks of NSTI are rapid subcutaneous microbial infiltration and extensive necrosis of soft tissue and fascia. Spread of the infection from the site of origin and consequent tissue necrosis may occur in as little as an hour.

Initiating events may include external trauma or direct spread from a perforated viscus or urogenital organ. Bacterial invasion is attended by production of endo- and exotoxins that provoke tissue ischemia, liquefactive necrosis and systemic illness.

The bacteria linked to NSTI include the group A streptococci Streptococcus pyogenes, Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). Patients with diabetes and imunosuppression are particularly at risk for NSTI.

NSTI is highly lethal if not rapidly and correctly diagnosed and treated. Diagnosis may be complicated by the rarity of the condition (<1000 cases/year in the United States) and the nonspecific character of symptoms at the site of injury in the early stages, which include pain, redness and swelling.

To address these properties when diagnosing NSTI, surgeons with the Division of Traumatology, Surgical Critical Care and Emergency Surgery at Penn combine empirical judgment with a high degree of clinical suspicion.

When necessary, diagnosis may be confirmed by CT scan, which can show inflammatory changes, such as fascial edema and thickening or abscesses, as well as laboratory and microbiology investigations. Treatment, coordinated between surgeons and intensivists, involves a combination of serial debridement, antibiotics and hyperbaric oxygen therapy.

Case Study*

Mr. L, a 32-year-old man, visited the emergency room of his community hospital with an inflamed insect bite on his left forearm. A brief, visual examination of the wound in the ER found evidence of inflammation and mild infection.

Mr. L received a prescription for oral antibiotics and went home. The next day, however, he returned to the hospital. At this time, his arm was swollen and discolored, and a small ulcer had developed near the wound. Mr. L was immediately hospitalized and started on IV antibiotics.

Despite these efforts, his pain increased and erythema continued to spread up his arm. Pus from the ulcer tested positive for group A streptococci and staphylococci.

Presuming a diagnosis of necrotizing soft tissue infection, Mr. L was transferred to the Division of Traumatology, Surgical Critical Care and Emergency Surgery at Penn Medicine.

Upon arrival, he was operated on to debride the necrotic tissue, which was found throughout the subcutaneous tissue of his forearm. A complete blood count at this time demonstrated pronounced leukocytosis (>30,000 cells/mm3).

Hyperbaric therapy was initiated immediately after the debridement surgery, and was repeated at intervals eight times during the next four days. Subsequently, Mr. L developed septic shock and required vasopressor support. During this time, he underwent serial examinations under anesthesia and further wound debridements.

Mr. L remained on mechanical ventilation for a total of eight days. An antibiotic regimen, including daptomycin and penicillin G, was tailored for him to prevent further infection. Twelve days after entering the hospital, Mr. L was discharged to home. Ultimately, he required skin grafting as a result of the extensive debridement of his arm (Figure 1).

*Case Study profiles are based upon actual patients; non-clinical information has been altered to protect individual privacy.

1. Sarani B, Strong M, Pascual J, Schwab CW. Necrotizing Fasciitis: Current Concepts and Review of the Literature. J Am Col Surg. 2009;208:279-288.

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 with in-house faculty from the division 24/7/365.

The trauma center is nationally and internationally recognized as a model program for other hospitals. The SICU provides in-house 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 Necrotizing Soft-Tissue Infections at Penn Medicine

C. William Schwab, MD
Chief, Division of Traumatology, Surgical Critical Care
and Emergency Surgery
Professor of Surgery

Patrick M. Reilly, MD
Vice 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

Daniel N. Holena, MD
Assistant Professor of Surgery

Patrick K. Kim, MD
Assistant Professor of Surgery

Jose L. Pascual, MD
Assistant Professor of Surgery

Babak Sarani, MD
Assistant Professor of Surgery

Carrie A. Sims, MD
Assistant Professor of Surgery

Access

Traumatology, Surgical Critical Care and Emergency Surgery
Perelman Center for Advanced Medicine
West Pavilion, 2nd Floor & 4th Floor
3400 Civic Center Boulevard
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.

To refer a patient and/or consult with a physician:
Call 877-937-PENN (7366) or visit PennMedicine.org/PhysicianLink.

Download a pdf of this Clinical Briefing.

TransOral Robotic Surgery for Young Adults with Oropharyngeal Cancers Resulting from Human Papillomavirus Infection

noreply@blogger.com (Mark) — Mon, 06 Jun 2011 10:01:00 PDT

Surgeons with the Department of Otorhinolaryngology-Head and Neck Surgery at Penn Medicine are performing TransOral^TM Robotic Surgery (TORS) to treat young adults with oropharyngeal cancers caused by the human papillomavirus (HPV).

A virus that thrives in the epithelium of the skin and mucous membranes, HPV (and particularly HPV type 16) is now associated with 25 percent of cancers of the mouth and throat.

The presence of HPV as a factor in oropharyngeal cancers has brought about a redefinition of the “typical” patient profile for these malignancies. Formerly, the typical patient with oropharyngeal cancer was a male in late middle age with a history of alcohol and tobacco abuse.

Patients with HPV-associated oropharyngeal cancers, by contrast, are usually between 20 and 40 years of age and are less likely to smoke and drink than older patients.1 Moreover, sexual activity is the primary risk factor identified with HPV-associated oropharyngeal cancers.

Outcomes are significantly improved when oropharyngeal cancer is caught early. For this reason, Penn otorhinolaryngologists now urge heightened awareness for the signs and symptoms of oropharyngeal cancer in younger, high-risk patients who might otherwise not be suspected of having cancer.

The symptoms identified with oropharyngeal cancers in younger people are similar to those commonly found in such benign conditions as viral sore throat––including persistent pharyngitis, voice changes and dysphagia. While masses or lesions that fail to heal are suspicious, even these symptoms fall within the indications for a wide variety of pre-cancerous and benign lesions that affect the wider population.

In addition to TORS, the treatments for oropharyngeal cancer at Penn include transoral laser surgery, radiation therapy and photodynamic therapy, depending upon the stage and extent of the cancer. Penn is currently evaluating tests for gene receptors in HPV, and clinical research in this area is ongoing.

1. Andrews E, Seaman WT, Webster-Cyriaque J. Oropharyngeal carcinoma in non-smokers and non-drinkers: a role for HPV. Oral Oncol. 2009;45:486-491.

Case Study

Mrs. G, a 44-year-old woman, presented to her personal physician with an enlarged lymph node in her right neck. The lump was not painful but she noticed that it was getting bigger, even after her primary physician placed her on antibiotics. Mrs. G had no significant medical history and did not smoke or drink.

Following a seven-day course of antibiotics that brought no improvement, she was referred to the Penn Department of Otorhinolaryngology-Head and Neck Surgery for an evaluation.

At Penn, Mrs. G had a thorough head and neck examination followed by a CT scan and office endoscopy. The CT identified a 2 cm mass involving the right tonsil region (Figure 1). A subsequent needle aspiration biopsy of the neck mass determined that it was a P16-positive squamous cell cancer.

Immunohistochemical expression of P16 protein has been found to be a reliable diagnostic surrogate marker for human papillomavirus. Based upon the clinical and pathologic data and on the recommendation of her surgeons, Mrs. G agreed to have TORS to remove the oropharyngeal cancer, followed by a neck dissection to remove high risk lymph nodes.

The TORS was completed in 45 minutes. Mrs. G went home several days after the surgery without complication. Final results showed complete removal of the cancer and no expansion of the cancer beyond the single lymph node in her neck. There were no other high risk features and no further treatment was recommended. After two weeks of mild swallowing difficulties, Mrs. G was speaking and eating normally.

*Case Study profiles are based upon actual patients; non-clinical information has been altered to protect individual privacy.

Faculty Team

The board-certified otorhinolaryngologists with the Department of Otorhinolaryngology-Head and Neck Surgery at Penn Medicine specialize in the evaluation, diagnosis and treatment of a full spectrum of disorders of the ears, nose and throat, including rare benign and malignant lesions, thyroid disease and skull base tumors.

The management of HPV-associated oropharyngeal cancer at Penn is a multidisciplinary effort involving otorhinolaryngologists and specialists trained in oncology and radiation oncology, as well as an extensive network of support services.

Diagnosing and Treating HPV-Associated Oropharyngeal Cancers at Penn Medicine

Otorhinolaryngology-Head and Neck Surgery

Bert W. O’Malley, Jr., MD
Gabriel Tucker Professor and Chair,
Department of Otorhinolaryngology-Head and Neck Surgery

Gregory S. Weinstein, MD, FACS
Vice Chairman,
Department of Otorhinolaryngology-Head and Neck Surgery
Professor of Otorhinolaryngology-Head and Neck Surgery

Ara Chalian, MD
Associate Professor of Otorhinolaryngology-Head and Neck Surgery

Kelly M. Malloy, MD
Assistant Professor of Otorhinolaryngology-Head and Neck Surgery

Jason G. Newman, MD
Assistant Professor of Otorhinolaryngology-Head and Neck Surgery

Access

Department of Otorhinolaryngology-Head and Neck Surgery

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

Penn Presbyterian Medical Center
Market & 38th Streets
Philadelphia, PA 19104

Pennsylvania Hospital
811 Spruce Street
Philadelphia, PA 19107

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

To refer a patient and/or consult with a doctor:
Call 877-937-PENN (7366) or visit
PennMedicine.org/PhysicianLink.

Download a pdf of this Clinical Briefing:

Mohs Micrographic Surgery and Rapid Immunostaining for the Treatment of Malignant Melanomas of the Head and Neck

noreply@blogger.com (Mark) — Mon, 06 Jun 2011 08:22:00 PDT

Surgeons in Dermatologic Surgery and Cutaneous Oncology at Penn Medicine are combining advanced Mohs micrographic surgery with rapid immunostaining to improve their ability to treat melanomas of the head and neck.

By combining Mohs micrographic surgery with rapid immunostaining in the operating room, surgeons at Penn are better able to detect and remove melanomas. In addition, using rapid immunostaining with Mohs, fewer than 2 percent of melanomas recur at the site of surgery following resection (mean 58 months).[1] Traditional methods of surgery are identified with rates of recurrence higher than 10 percent in studies with a follow-up of three years or more.[2]

The fellowship-trained Mohs surgeons and certified histotechnologists at Penn Medicine have developed careful protocols for rapid immunostaining. By permitting surgeons to highlight and detect cancer cells under the microscope during surgery, rapid immunostaining reduces the risk of performing multiple surgeries for incompletely excised melanomas. Because rapid immunostains are as accurate as slower methods of tissue processing,[3] moreover, surgeons can perform multiple stages of surgery on the same day.

In addition to immunostaining for melanoma, Penn offers a full spectrum of immunostains to track high-risk squamous cell cancers, as well as less common tumors, such as dermatofibrosarcoma protuberans and extramammary Paget’s disease.

During Mohs micrographic surgery, all visible melanoma and a margin of clinically normal skin are first excised. The excised skin is then immediately frozen, immunostained and examined under the microscope. If cancer cells are detected at the margin, the Mohs surgeon performs another targeted excision to remove the precise areas where cancer still remains.

This process of targeted cancer removal and microscopic examination continues until all the cancer has been excised. Typically, Mohs surgeons at Penn reconstruct the wound on the same day of surgery. Mohs surgery is performed under local anesthesia, which is widely regarded as the safest method of anesthesia available.

1. Bricca GM, et al. J Am Acad Dermatol. 2005;52:92-100.
2. Dawn ME, et al. Dermatol Surg. 2010;33:395-402.
3. Cherpelis BS, et al. Dermatol Surg. 2009;25:207-213.

Case Study*

Mrs. K, a 68-year-old, fair skinned female, was referred to Dermatologic Surgery and Cutaneous Oncology at Penn for an evaluation following a recurrence of melanoma on her right cheek.

Mrs. K had an extensive history of sun exposure and damage to her skin. Ten years before presenting at Penn, she had a non-Mohs procedure at an outside hospital to remove a superficial melanoma from her cheek. This surgery required three consecutive excisions before it appeared that all the cancer had been eliminated.

A decade later, Mrs. K developed a subtle pink and tan spot around the scar from the previous surgery that, when biopsied, showed a recurrence of the melanoma. Wishing to avoid the risk of multiple excisions and the chance that the cancer would grow back again, Mrs. K’s dermatologist referred her to Penn for definitive excision of her tumor with Mohs surgery and same-day reconstructive surgery after obtaining clear microscopic margins.

Mrs. K was seen in consultation in the Mohs surgery suite at the Ruth and Raymond Perelman Center for Advanced Medicine. A large amount of background sun-damage was present on her face and at the scar on her cheek from the prior excision. The pink and tan areas at the site of the melanoma were very indistinct and hard to distinguish from the pink and tan spots on much of the rest of her cheek.

Mohs micrographic surgery was recommended to clear the incompletely excised melanoma. The Mohs surgeons first carefully outlined all areas suspicious for melanoma. Then, the previous scar was removed and examined with frozen sections stained with MART-1 immunostain and traditional hematoxylin and eosin to evaluate the microscopic residual disease. These procedures found clear evidence of residual melanoma in Mrs. K’s skin (see figure 1).

A peripheral and deep margin of normal skin beyond the edge of the cancer was then excised and examined under the microscope. Twenty-five percent of the margin still contained melanoma in situ. Immediately, Mrs. K had another margin of skin excised around the residual cancer. Examination of the microscopic edge of this specimen was free of cancer (Figure 2).

The Mohs surgeon then reconstructed Mrs. K’s wound with a local tissue flap. She returned home the same day. Currently, she is seen on a frequent basis for total skin and lymph node examinations to evaluate for melanoma recurrence and to monitor for newly arising skin cancers. Today, five years after her Mohs surgery, she remains free of any evidence of cancer.

*Case Study profiles are based upon actual patients; non-clinical information has been altered to protect individual privacy.

Faculty Team

The Division of Dermatologic Surgery and Cutaneous Oncology at Penn Medicine is dedicated to delivering the most current and precise treatments for common and rare malignancies of the skin.

Mohs micrographic surgery and reconstructive surgery are performed in modern, comfortable outpatient facilities staffed by fellowship-trained Mohs surgeons, certified histotechnicians, and an expert support staff. A personalized skin care maintenance program is developed for each patient according to his or her individual risk of skin cancer. Preventive treatments and non-surgical treatments for precancerous and early cancerous lesions are also available.

Performing Mohs Micrographic Surgery for Melanoma at the Ruth and Raymond Perelman Center for Advanced Medicine

Christopher J. Miller, MD
Assistant Professor of Dermatology

Joseph F. Sobanko, MD
Assistant Professor of Dermatology

Access

Perelman Center for Advanced Medicine
Suite 1-330S
3400 Civic Center Boulevard
Philadelphia, PA 19104

Focus on Melanoma Conference

In May 2011, Penn Medicine hosted its Eighth Annual Focus on Melanoma Conference, a full-day program designed to address the personal and medical issues facing patients with melanoma, their loved ones and caregivers.

The conference provided information on the latest advances in melanoma risk, prevention, diagnosis, treatment, symptom management and psychosocial issues, as well as the opportunity to network and gain support from other melanoma survivors.

Conference presentations, including recent advances in clinical research in melanoma, immunotherapy, surgery and dermatology are available online here.

Penn PhysicianLink®

Penn PhysicianLink® is an exclusive program that helps all referring physicians connect with Penn Medicine. This comprehensive package of support services expedites and facilitates direct physician communication for patient consults, referrals and transfers.

Penn’s dedicated physician-only telephone line, 877-937-PENN (7366), offers direct access to a special call center reserved for medical professionals to facilitate patient consults, appointments, referrals, and transfers to Penn Medicine hospitals. The physician-to-physician phone line is available 24 hours a day, 7 days a week.

To refer a patient and/or consult with a physician:
Call 877-937-PENN (7366) or visit
PennMedicine.org/PhysicianLink.

Download a pdf of this Clinical Briefing:

Management of Hepatocellular Carcinoma

noreply@blogger.com (Mark) — Mon, 02 May 2011 11:34:00 PDT

Hepatologists, surgeons, medical oncologists, interventional radiologists, radiologists and radiation oncologists at Penn Medicine are treating patients with hepatocellular carcinoma and those at risk for the disease.

Hepatocellular carcinoma (HCC) is an increasingly prevalent problem in the United States. Hepatitis C-associated HCC is likely the major culprit for a dramatic increase in HCC incidence and mortality in the past two decades.¹

There are many treatment options for patients with hepatocellular carcinoma.² Since early detection offers the best opportunity for cure, screening for HCC in patients with cirrhosis is of utmost importance and is often a key determinant of outcome.

Surgical resection of the tumor can achieve cure of HCC, particularly when the tumor is small and liver function is preserved. With partial hepatectomy, there is always concern for development of another HCC in the remaining diseased liver, which can happen in up to 50-70 percent of cases. Liver transplantation is often the most effective treatment for HCC, if the tumor is within a certain stage.

Because the entire liver is replaced, liver transplant circumvents the strict need for good liver function that surgical resection requires. The other major advantage of transplantation is that it results in removal of the tumor as well as removal of the rest of the liver which, if left behind, will remain at risk of developing additional tumors. The result is that the recurrence rate of HCC after transplantation is 10-20%, much lower than after resection. A select group of patients with small, favorably located tumors can be cured with ablative therapies, such as percutaneous or laparoscopic radiofrequency ablation.

Effective treatment for HCC is possible also in patients with more advanced disease. Trans-arterial chemoembolization (TACE), in which a chemotherapy mixture is injected directly into the tumor and its blood supply is interrupted, results in tumor death and is effective at controlling even larger tumors.

TACE is also useful to prevent tumors from growing while patients with smaller tumors are on the liver transplant waiting list. Radioembolization involves the injection of radiation-emitting beads into the tumor and is often an alternative option to TACE. Systemic chemotherapy in the form of the oral drug Sorafenib or clinical trials with newer drugs are also effective treatment options in advanced disease.

Navigating the various treatment options in HCC can be complex and requires the expertise of physicians with different areas of specialization. At Penn, patients presenting with liver tumors are discussed every week by a multidisciplinary team of specialists in the context of a conference. Patients are then evaluated by multiple physicians and surgeons with expertise in liver cancer and liver disease in a single visit to the Penn Liver Tumor Clinic where treatment options are discussed.

The liver tumor team at Penn has the unique capability of an efficient and expert evaluation of patients, and is committed to offering convenient access to skilled medical and surgical care of a complex disease.

Case Study*
Mr. A is a 53-year-old teacher with chronic hepatitis C-related cirrhosis who recently failed standard therapy for hepatitis C. He has no symptoms of liver disease, and has only small varices on an upper screening endoscopy. He has no other medical history and works full time. On an ultrasound of the liver obtained for screening, a 2.5 cm mass was found. AFP was normal. An MRI of the liver was performed (Figure 1).

Mr. A’s case was discussed in the Penn Multidisciplinary Liver Tumor Conference. Review of the films confirmed a diagnosis of hepatocellular carcinoma by imaging characteristics; no biopsy for confirmation was warranted. Treatment options were discussed. Since the location of the lesion would require a right hepatectomy and the presence of varices indicated portal hypertension, it was felt that resection would carry a high risk of liver failure.

The potential for the less invasive treatment option of radiofrequency ablation was discussed, but it was felt that this would be a suboptimal treatment in his case because he would be an excellent transplant surgical candidate.

Mr. A was seen in consultation in liver tumor clinic concurrently by a hepatologist, a transplant/hepatobiliary surgeon and an interventional radiologist. The risks, benefits and alternatives of the different treatment options were discussed. After reviewing his options, the patient elected to pursue liver transplantation. He completed a liver transplant evaluation and was listed for transplantation.

To prevent the tumor from growing while waiting for transplantation, TACE was performed. Partial tumor necrosis was achieved and the lesion remained stable in size until he received a transplant, about 9 months after being listed.

Pathology of the explanted liver showed moderately differentiated HCC in the right lobe, 2.8 cm in size; about 70% of the nodule was necrotic and there was no evidence of vascular invasion. The patient was enrolled in a surveillance program for recurrent disease, with serial imaging of the chest and abdomen. At 18 months post transplant, there is no evidence of recurrent HCC and the patient is asymptomatic.

*Case Study profiles are based upon actual patients; non-clinical information has been altered to protect individual privacy.

References
1. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and
molecular carcinogenesis. Gastroenterology. 2007;132:2557-2576.
2. Mendizabal M, Reddy KR. Current management of hepatocellular carcinoma.
Med Clin Nor Am. 2009;93:885-900.

Team of Faculty
The Penn Liver Tumor Clinic brings together a multidisciplinary team of physicians, nurse specialists and hospital support staff who provide coordinated care throughout the treatment process. The goal is to meet the unique physical and emotional needs of each patient in a caring, professional environment.

Hepatologists

K. Rajender Reddy, MD,
Director of Hepatology
Medical Director of Liver Transplantation

Thomas W. Faust, MD, MBE

Kimberly A Forde, MD, MHS

Maarouf A. Hoteit, MD

David E. Kaplan, MD, MSc

Karen Krok, MD

George A. Makar, MD , MSCE

Hepatology Physician Extenders

Brenda Appolo, BS, MHS, PA-C

Ashley Reiter, CRNP

Transplant and Hepatobiliary Surgeons

Abraham Shaked, MD, PhD
Director, Penn Transplant Institute

Kim Olthoff, MD
Director, Liver Transplant Program

Peter L. Abt, MD

Matthew H. Levine, MD, PhD

Medical Oncologists

Weijing Sun, MD
Medical Director, GI Oncology

Bruce Giantonio, MD

Nevena Damjanov, MD

Ursina R. Teitelbaum, MD

Radiologists

Mark A. Rosen, MD, PhD

Evan S. Siegelman, MD

Interventional Radiologists

Michael Soulen, MD

S. William Stavropoulos, MD

Jeff Mondschein, MD

Mandeep S. Dagli, MD

Radiation Oncologists

Robert Lustig, MD

John P Plastaras, MD, PhD

Smith Apisarnthanarax, MD

Liver Tumor Clinic Coordinator

Dawn Drazek, RN, BSN, CCTC

Access
The Penn Transplant Institute
Liver Tumor Clinic
Perelman Center for Advanced Medicine
West Tower, 2nd Floor
Philadelphia, PA 19104

Download a pdf of this Clinical Briefing.

To refer a patient and/or consult with a doctor:
Contact Dawn Drazek, RN, BSN, CCTC,
Liver Tumor Coordinator, or
Call 877-937-PENN (7366) or visit
PennMedicine.org/PhysicianLink.