Clinical Briefings™: Clinical Reports from Penn Medicine

Enrolling Clinical Trials: Umbilical Cord Blood Transplantation vs Haploidentical Transplantation for Patients with Hematological Malignancies

noreply@blogger.com (Anonymous) — Thu, 18 Feb 2016 13:36:00 +0000

The Abramson Cancer Center

Researchers at Penn Medicine and the Abramson Cancer Center are participating in a multi-center study to compare double umbilical cord blood (dUCB) transplantation and haploidentical stem cell transplantation (haplo-BM) for the treatment of patients with hematological malignancies.

For persons with blood cancers at risk of relapse, allogeneic hematopoietic stem cell transplantation offers the best chance for a durable response. Related matched donors, typically siblings, are the ideal source of stem cells, but only one in four will be an HLA-identical match. Thus, a significant proportion of patients will not have a sibling donor, and will receive stem cells from other sources.

At the Abramson Cancer Center, the primary source of stem cells outside of related matched donors are HLA-matched unrelated donors, who are accessed through the National Marrow Donor Program (BE THE MATCHTM).

Matched unrelated donors can provide a solid HLA-match, but the time required to identify and accurately pair donor and recipient can exceed the time to disease progression and up to a third of patients won’t find a suitable match (i.e., no more than a mismatch at a single locus).

To address these issues and expand the potential donor pool for hematological stem cell transplantation, the Abramson Center offers access to two alternative sources, double-UCB (dUCB) and half-matched related (HLA-haploidentical) bone marrow donors. The use of two units of umbilical cord blood increases the number of cord blood cells to improve the success of engraftment.

Both UCB and haploidentical SCT are associated with unique advantages and applications, and these are the source of inquiry for an ongoing multicenter comparative clinical trial currently enrolling patients at Penn Medicine. The trial is being conducted under the aegis of the NIH-funded Blood and Marrow Transplant Clinical Trials Network (BMT CTN).

This study follows previous investigations that evaluated the safety and efficacy of related haploidentical and dUCB transplantation after reduced intensity conditioning (RIC), a regimen that uses less chemotherapy and radiation than standard myeloablative conditioning. In these trials, both UCB and haploidentical BMT produced early results similar to that reported for HCT with unrelated donors.

Double Cord Versus Haploidentical (BMT CTN 1101) [NCT01597778]

Objective: This study will test the hypothesis that progression free survival at two years after RIC haplo-BM transplantation is similar to the progression free survival after RIC dUCB transplantation.

Methods: Patients with leukemia or lymphoma will be randomized to receive two units of UCB or haploidentical transplant. Patients in both arms of the study will receive reduced intensity conditioning regimens including total body irradiation, as well as GVHD prophylaxis.

Endpoints: The primary endpoint is progression-free survival (PFS) at 2-years from the date of randomization. PFS is defined as the time interval from date of randomization and time to relapse/progression, to death or to last follow-up. Secondary endpoints will assess the success of donor cell engraftment, platelet and neutrophil recovery and acute and chronic graft-vs-host-disease. Overall survival and treatment-related mortality will also be assessed.

Inclusion/Exclusion: Patients with any of the following conditions may enroll: ALL or AML in first complete remission (CR) not considered favorable-risk; acute leukemias in second or subsequent CR; biphenotypic/undifferentiated/prolymphocyctic leukemias in first or subsequent CR; adult T-cell leukemia/lymphoma in first or subsequent CR; Burkitt’s lymphoma in second or subsequent CR; chemotherapy-sensitive lymphoma.

Patients must have adequate cardiac, hepatic, renal and pulmonary function.

Patients with a suitably matched related or unrelated donor, as defined per institutional practice are ineligible. Patients with chronic lymphocytic leukemia (CLL) are not eligible regardless of disease status.

Interested persons are encouraged to contact Elizabeth Hexner, MD, at elizabeth.hexner@uphs.upenn.edu.

Faculty Team

Investigators with Penn Hematology/Oncology are focused on translating laboratory work into novel therapies and practice-changing discoveries. The scope of Penn’s hematology and medical oncology clinical research enterprise is very broad, spanning all phases of clinical research, including pre-clinical work and discovery, phase 1 and 2 studies and leadership of national phase 3 trials intended to change the standard of care.

Penn clinical investigators regularly publish high profile and important findings in diverse fields, ranging from the most fundamental cellular investigations, to leading edge translational and clinical research.

Conducting Clinical Studies in Hematological Malignancies at Penn Medicine and the Abramson Cancer Center

Adam D. Cohen, MD

Director, Myeloma Immunotherapy

Assistant Professor of Medicine

Noelle Frey, MD

Assistant Professor of Medicine

Alfred Garfall, MD

Assistant Professor of Medicine

Saar I. Gill, MD, PhD

Assistant Professor of Medicine

Elizabeth O. Hexner, MD

Assistant Professor of Medicine

Rebecca L. Hirsh, MD

Assistant Professor of Clinical Medicine

James A. Hoxie, MD

Professor of Medicine

Peter S Klein, MD, PhD

Professor of Medicine

Daniel Landsburg, MD

Assistant Professor of Clinical Medicine

Alison Loren, MD, MSCE

Associate Professor of Medicine

Selina M. Luger, MD

Director, Leukemia Program

Professor of Medicine

James K. Mangan, MD, PhD

Assistant Professor of Clinical Medicine

Anthony R. Mato, MD, MSCE

Assistant Professor of Medicine

Sunita Nasta, MD

Associate Professor of Clinical Medicine

Alexander E. Perl, MD

Assistant Professor of Medicine

David L. Porter, MD

Director, Blood and Marrow Transplantation Jodi Fisher Horowitz Professor in Leukemia Care Excellence

Stephen J. Schuster, MD

Robert and Margarita Louis-Dreyfus Associate Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research

Edward A. Stadtmauer, MD

Section Chief, Hematologic Malignancies

Professor of Medicine

Jakub Svoboda, MD

Assistant Professor of Medicine

Donald Tsai, MD, PhD

Associate Professor of Medicin

Daniel Vogl, MD

Assistant Professor of Medicine

Brendan M. Weiss, MD

Assistant Professor of Medicine

Non-Physician Providers

Sarah J. Del Percio, MSN, CRNP

Bernadette B. Diccion, MSN, CRNP

Heather DiFilippo, MSN, CRNP

Colleen Harker Erb, MSN, CRNP

Danielle Land, MSN, CRNP

Patricia Mangan, MSN, CRNP

Mary Sanchez, MSN, CRNP

Brenda Shelly, MSN, CRNP

Jacqueline Smith, MSN, CRNP

Brandi Swisher, MSN, CRNP

Access

Perelman Center for Advanced Medicine

2 West Pavilion

3400 Civic Center Boulevard

Philadelphia, PA 19104

Cancer Clinical Trials at Penn Medicine

For information regarding cancer clinical trials at Penn Medicine, please visit the Oncolink Clinical Trial Matching and Referral Service.

Physician Liaison, Cancer & Surgery

Donna Fenske Seeger

Cell: 215-410-7472

Enrolling Clinical Trials: Photodynamic Therapy (PDT) for the Treatment of Pleural Mesothelioma and Pleural Malignancies

noreply@blogger.com (Anonymous) — Mon, 18 Jan 2016 20:03:00 +0000

Department of Radiation Oncology • Mesothelioma and Pleural Program

Researchers at Penn Medicine are investigating the addition of photodynamic therapy (PDT) to lung-sparing radical pleurectomy and postoperative chemotherapy for the treatment of mesothelioma and pleural malignancies.

The components of PDT are surprisingly modest: a photosensitizer and a light source of a wavelength sufficient to initiate a reaction in the agent. Injected prior to the procedure, the sensitizer accumulates selectively in tumor cells for 24 to 48 hours, at which time they are exposed to the light source (typically a laser).

The light provokes the generation of an active form of oxygen within the cancer cells, leading to tumor necrosis, DNA fragmentation and membrane damage.

Researchers at Penn Medicine have pioneered the use of a lung-sparing surgery to treatment malignant pleural mesothelioma and have demonstrated that this surgery improves patient quality of life and improves overall survival compared with surgery that removes the entire lung.

These investigators have recently initiated an NIH-supported clinical trial to investigate PDT in combination with radical pleurectomy for the treatment of malignant pleural mesothelioma (MPM). PDT has been an established therapy at Penn Medicine since 1996, and this study will complement ongoing treatment protocols for disseminated cancers of the thoracic cavities and early-stage diseases such as head and neck cancers and anal cancer.

The investigation focuses on the effects of intraoperative PDT on tumors, the surrounding normal tissues, the immune system, and clinical outcomes of patients with MPM.

MPM PDT Phase II Trial
ClinicalTrials.gov Identifier: NCT02153229

Summary: A Phase II randomized study to test whether the addition of photofrin-mediated intra-operative photodynamic therapy (PDT) to radical pleurectomy and post-operative chemotherapy improves overall survival in the treatment of patients with epithelioid MPM, the most common form of the disease.

All patients will have radical pleurectomy with the goal of achieving a macroscopic complete resection followed by four cycles of postoperative chemotherapy, and they will then be randomized to receive
radical pleurectomy with or without intra-operative PDT, followed by chemotherapy. Patients assigned to the PDT arm will be given the photosensitizer prior to surgery and will receive intraoperative light treatment using novel, real-time, isotropic light dosimetry.

Patients assigned to the radical pleurectomy arm will receive chemotherapy alone after surgery, without PDT.

For information about this trial, please contact Sally McNulty, RN, at 215-662-7720 or Keith Cengel, MD, PhD, at 855-216-0098, or write PennCancerTrials@emergingmed.com.

The PDT Program is also performing a prospective outcomes study of all patients who have received PTD therapy for neoplastic diseases at Penn.

Prospective Follow-up of Outcomes in Patients Receiving Photodynamic Therapy for Neoplastic Diseases
ClinicalTrials.gov Identifier: NCT02159742

Summary: This is a prospective study of all patients with malignant pleural mesothelioma or other malignancies with pleural dissemination who are being treated with definitive surgical resection and intraoperative photodynamic therapy (PDT). The study will review treatment parameters (including surgical procedure and photodynamic therapy administration) and treatment outcomes for all organ functions, performance status, tumor recurrence, laboratory values and any other data present in the routinely documented followup visits.

Following de-identification, all data will be added to the existing PDT treatment outcome databases for outcomes analysis, quality improvement and reporting of results in abstract and manuscript forms.

For information about this trial, please contact contact Ashley Feriozzi, BS, at 215-615-3272 or Charles Simone, MD, at 855-216-0098 or write PennCancerTrials@emergingmed.com.

Additional Enrolling Mesothelioma Clinical Studies at the Abramson Cancer Center

Safety and Efficacy of Listeria in Combination With Chemotherapy as Front-line Treatment for Malignant Pleural Mesothelioma
ClinicalTrials.gov Identifier: NCT01675765

Summary: This clinical trial will evaluate the safety and immune response of the sequential administration of cancer vaccine CRS-207 (with or without cyclophosphamide) followed by standard of care chemotherapy (pemetrexed and cisplatin). CRS-207 is a weakened (attenuated) form of Listeria monocytogenes that has been genetically-modified to reduce its capacity to cause disease, while maintaining its ability to stimulate potent immune responses. CRS-207 has been engineered to elicit an immune response against the tumor-associated antigen mesothelin, which has been shown to be present at higher levels on certain tumor cells (such as mesothelioma) than on normal cells.

Pemetrexed and cisplatin are the standard chemotherapy regimen to treat malignant pleural mesothelioma. This trial will evaluate whether giving CRS-207 cancer vaccine with chemotherapy will induce antitumor
immune responses and/or objective tumor response.

For information about this trial, please contact: Mona Jacobs-Small, BS, RRT, CCRC at 215- 662-8632 or mona.jacobs-small@uphs.upenn. edu; or write Evan Alley, MD, PhD at evan.alley@uphs.upenn.edu.

Faculty Team
The Penn Mesothelioma and Pleural Program is comprised of multi-disciplinary investigators across radiation oncology, medical oncology, surgery, pulmonology, radiology, pathology, immunology, radiation biology, and medical physics. Their innovative and practice-changing research has led to numerous clinical advances and research funding.

Performing Clinical Studies in PTD for Mesothelioma and Pleural Disease at Penn Medicine

Evan W. Alley, MD, PhD
Chief, Division of Hematology and Medical Oncology
Co-Director, Penn Mesothelioma and Pleural Program
Penn Presbyterian Medical Center

Keith Cengel, MD, PhD
Associate Professor of Radiation Oncology
Director, Photodynamic Therapy Program

Charles B. Simone, II, MD
Co-Director, Penn Mesothelioma and Pleural Program
Assistant Professor of Radiation Oncology
Chief, Thoracic Oncology Service

Physician Liaison, Cancer & Surgery
Donna Fenske Seeger
215-410-7472
Donna.Fenske@uphs.upenn.edu

ACCESS

Penn Mesothelioma and Pleural Program
Penn Medicine University City
4th Floor
3737 Market Street
Philadelphia, PA 19104

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

Enrolling Clinical Trials: Dose Escalation of Neoadjuvant Proton Radiotherapy in Esophageal Cancer

noreply@blogger.com (Anonymous) — Tue, 05 Jan 2016 16:03:00 +0000

Radiation oncologists at the Roberts Proton Therapy Center and the Abramson Cancer Center are conducting a clinical trial [1] to investigate the use of preoperative carboplatin/paclitaxel in combination with proton therapy followed by surgery for the treatment of locally advanced esophageal cancer.

Esophageal cancer is the third most common gastrointestinal malignancy. There are two histologies––adenocarcinoma and squamous cell carcinoma––with adenocarcinoma prevailing in North America.
The primary treatment at every stage is surgery (transhiatal or transthoracic esophagectomy), often in combination with chemotherapy and radiotherapy. With the publication of the CROSS trial, trimodality therapy comprising preoperative chemoradiotherapy (CRT) followed by surgery became the treatment of choice for locally advanced esophageal cancer.

The CROSS trial found a significant benefit for CRT followed by surgery versus surgery alone, with a median overall survival of 49.4 months in the CRT-surgery group versus 24.0 months in the surgery group. Rates of recurrence were also substantially lower in the CRT-surgery group.

Surgery is a mainstay of curative therapy in esophageal cancer, but is associated with post-operative morbidity and occasional mortality, even in experienced hands. In order to develop a strategy to avoid surgery, improvements in CRT complete response rates (currently 25%-40% at the time of surgery) will need to be substantially improved. Additionally, criteria will need to be developed to determine which patients may benefit from the preclusion of resective therapy.

The Role of Imaging
Bio-imaging molecular markers, such as 18F-FDG (fluorodeoxyglucose) PET, and biomarkers (e.g., circulating tumor cells) may be able to identify patients who respond favorably to treatment. For patients with esophageal cancer, the use of 18F-FDG PET as part of the initial work-up is considered standard for identifying metastatic disease. 18F-FDG PET is also commonly used after chemoradiation to see if metastatic disease has developed prior to surgery. It is possible that interim 18F-FDG PET/CT scans during CRT may help predict responders.

Proton Therapy in Esophageal Cancer
The treatment of esophageal cancer with standard radiation is complicated by the organ’s proximity to a number of critical radiosensitive organs, including the heart and lungs. Proton therapy provides an improvement over standard radiotherapy in its ability to deliver a high dose to tumor targets while maintaining lower doses to surrounding normal tissues. This is possible because proton radiation has a rapid dose fall-off at the distal edge of the target (Bragg-Peak effect), a characteristic that allows for significant reductions in radiation dose to normal organs and the potential for dose escalation.

1. ClinicalTrials.gov Identifier: NCT02213497. Available at: http://1.usa.gov/1H8emls

Investigating Preoperative Proton Radiotherapy in Esophageal Cancer at Penn
Background: A clinical trial of proton therapy in the setting of preoperative radiotherapy for esophageal cancer. This trial seeks to determine the maximally tolerated radiation dose of dose-escalated proton radiotherapy and to assess the utility of bio-imaging molecular markers to identify patients who will respond favorably to treatment.

Objectives: To identify the maximally tolerated radiation dose (MTD) of dose-escalated proton radiotherapy in combination with carboplatin/paclitaxel in the preoperative setting for esophageal cancer; to estimate pathologic response rates by esophagectomy surgical specimens after escalated doses of chemoradiotherapy; to evaluate the utility of mid-treatment 18F-FDG PET imaging at week 4 as a molecular imaging marker to predict treatment response to chemoradiotherapy; and to assess the utility of circulating tumor cells as biomarkers to predict treatment response to chemoradiotherapy.

Methods: Patients will be treated with preoperative chemoradiation followed by surgical resection. Concurrent chemoradiation will consist of weekly carboplatin/paclitaxel for 5 weeks, from start until completion of proton therapy. Radiation therapy dose will be escalated to determine the MTD using a 3+3 phase I study design. Patients will receive once daily proton radiotherapy.

There will be two target volumes: a larger elective volume and a boost volume to include the gross tumor plus additional margin. This boost volume will be treated with the dose escalation schema. Patients will have surgery 4 - 8 weeks after completion of chemoradiotherapy. Ancillary studies include collection of patient serum for analysis of CTCs, as well as 18F-FDG PET imaging at week 4. However, 18F-FDG PET imaging pre-treatment and ~4 weeks after chemoradiation are standard of care and are not research procedures.

Inclusion Criteria: Patients with esophageal cancer to be treated with concurrent preoperative chemoradiation with carboplatin and paclitaxel.

Contact: The principal investigator for this trial is John Plastaras, MD, PhD. For information, prospective patients and/or their clinicians may call 215-615-8078, or email
PennCancerTrials@emergingmed.com

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 Esophageal Cancer at Penn Medicine

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

James M. Metz, MD
Professor and Chair of Radiation Oncology

Edgar Ben-Josef, MD
Vice Chair of Translational Research
Professor of Radiation Oncology

J. Nicholas Lukens, MD
Clinical Instructor of Radiation Oncology

Medical Oncology
Bruce Giantonio, MD
Professor of Medicine

Arturo Loaiza-Bonilla, MD
Assistant Professor of Clinical Medicine

Peter O’Dwyer, MD
Professor of Medicine

Ursina Teitelbaum, MD
Clinical Assistant Professor of Medicine

Paul S. Wissel, MD
Adjunct Professor of Medicine

Surgery
John Kucharczuk, MD
Chief, Division of Thoracic Surgery
Associate Professor of Surgery

Noel N. Williams, MD
Professor of Clinical Surgery

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

Microsurgical Nerve Conduit Neurotization to Restore Sensation after Breast Reconstruction Surgery

noreply@blogger.com (Anonymous) — Mon, 21 Dec 2015 20:06:00 +0000

Penn Plastic Surgery

Plastic surgeons at Penn Medicine are performing microsurgical neurotization to enhance sensation in the reconstructed breast.

The lateral and anterior intercostal nerves that supply the breast are transected during mastectomy, eliminating potential sources of innervation during later reconstruction surgery. In the absence of neurorrhaphy, the reconstructed breast will regain some sensation as a result of nervous migration from surrounding skin and tissue, but this is a gradual and variable process.

A more rapid and predictable restoration of sensation can be achieved by the innervated abdominal flap procedure. This surgery, which involves direct coaptation of the fourth or fifth intercostal nerve to the T10-T12 thoracoabdominal nerve, has generally been associated with superior quality and quantity of sensation vs. natural sensory return.

It has been argued however, that the complexity and added operative time attending neurorrhaphy is unjustified given the possibility of natural nerve regeneration.

Penn plastic surgeons have recently introduced neurotization, a method to simplify and improve upon the efficacy of direct coaptation. This approach involves connecting a cutaneous nerve at the fascia of the abdominal flap to the anterior branch of the third intercostal nerve, which appears at the junction of the sternum and third rib.

This nerve is dissected at the sternum and sutured to an allograft conduit customized to permit minimal traction on the nerve, avoiding tension across the repair. The distal end of the conduit is then sutured to the sensory nerve in the flap. The procedure can be completed in about 15 minutes, and involves less resection and positioning than standard neurorrhaphy.

Sensory perception at two years following neurotization with nerve conduits has been reported to be significantly better than direct coaptation when performed as above described.

At this time, neurotization is performed for abdominal-based free-flap breast reconstruction, including transverse rectus abdominis myocutaneous (TRAM), deep inferior epigastric perforators (DIEP) and superficial inferior epigastric artery (SIEA) flap breast reconstruction.

Case Study

Mrs. M, a 48-year-old woman with left-sided ductal carcinoma in situ (DCIS), came to Penn Medicine for both her mastectomy and breast reconstruction surgery. Following her surgery and radiation therapy, she chose to have a staged breast reconstruction.

During the mastectomy procedure, therefore, Ms. M received a tissue expander beneath the skin and muscles of her chest wall containing a small amount of saline. Four months later, she returned to Penn Plastic Surgery for a deep inferior epigastric perforator (DIEP) flap procedure with nerve conduit neurotization to enhance sensation in the reconstructed breast.

While the recipient site was being prepared in the operating room, a flap of skin and fat was harvested from Mrs. M’s lower abdomen. Microdissection was performed at the abdominal fascia to dissect the largest perforators from the flap.

A cutaneous donor nerve was then defined and dissected out for later neurotization. At the recipient site, the internal mammary artery and vein were prepared at the third intercostals space for anastomosis to the donor perforators.

The anterior branch of the third intercostal nerve was then identified at the third rib and mobilized. Following successful microsurgical anastomosis of the perforator and mammary vessels, a nerve conduit was introduced to coapt the donor and recipient nerves.
Mrs. M recovered for four days in the hospital and was discharged home. At her 6-month, one year and two year follow-up visits, she noted increasing sensation in the reconstructed breast.

Faculty Team

The experienced surgeons in the Division of Plastic Surgery at Penn Medicine offer the most advanced treatment options for patients in need of cosmetic and reconstructive surgery, as well as a comprehensive skin care program. In addition to breast reconstruction, specialty areas include craniofacial reconstruction, congenital anomalies, reconstruction following tumor and trauma, microsurgical techniques, cleft lip and palate surgery, and cosmetic facial and body surgery.

Performing Breast Reconstruction Surgery at Penn

John Fischer, MD
Assistant Professor of Surgery

Josh Fosnot, MD
Assistant Professor of Surgery

Suhail K. Kanchwala, MD
Assistant Professor of Surgery

Stephen J. Kovach III, MD
Assistant Professor of Surgery

David W. Low, MD
Professor of Surgery

Joseph M. Serletti, MD, FACS
Henry Royster–William Maul Measey Professor of Surgery

Liza C. Wu, MD
Associate Professor of Surgery

Micropigmentation Specialist

Mandy Sauler

Access

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

Penn Plastic Surgery Bryn Mawr
23 Morris Avenue, Suite 219
Bryn Mawr, PA 19010

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

Enrolling Clinical Trials: Novel Therapeutics for Chronic Lymphocytic Leukemia

noreply@blogger.com (Anonymous) — Mon, 23 Nov 2015 13:13:00 +0000

Hematology/Oncology • Center for Chronic Lymphocytic Leukemia • Abramson Cancer Center

Researchers with the Division of Hematology/Oncology at Penn Medicine are investigating novel combinations of chemotherapeutic and immunotherapeutic agents for the treatment of chronic lymphocytic leukemia (CLL) under the leadership of Anthony Mato, MD, MSCE, Director of the Center for CLL.

In collaboration with the Abramson Cancer Center, the renowned Penn Division of Hematology/Oncology is expanding the breadth of its investigations to increase treatment accessibility, the number of treatment options available and the inclusiveness of treatment, particularly among under-served and high-risk patient populations.

Currently enrolling clinical trials for the treatment of patients with CLL at Penn are investigating the efficacy and safety of a broad array of agents in front-line and relapsed-refractory settings, including the immunotherapeutics ublituximab and ibrutinib, pembroluzimab/TG-1101/TGR-1202, rituximab and idelalisib and ibrutinib/rituximab, as well as standard chemotherapeutic agents. These trials, performed in collaboration with the National Cancer Institute of the NIH, will encompass patients with previously treated high-risk disease, as well as sub-populations, including Richter’s Transformation.

The primary investigator at Penn Medicine for the following selection of enrolling studies in CLL is Anthony Mato, MD, MSCE. Referring physicians and individuals interested in enrolling in these studies may contact Dr. Mato at anthony.mato@uphs.upenn.edu, or 215-713-7832 (mobile). He and his team are available by email or telephone to discuss clinical cases and will personally facilitate expedited evaluation for clinical trials candidacy.

A Phase 3, Randomized, Study to Assess the Efficacy and Safety of Ublituximab in Combination With Ibrutinib Compared to Ibrutinib Alone, in Patients With Previously Treated High-Risk Chronic Lymphocytic Leukemia (CLL) [NCT02301156]
This study is evaluating the addition of ublituximab, a novel monoclonal antibody, to the tyrosine kinase inhibitor ibrutinib compared to ibrutinib alone in patients with previously treated chronic lymphocytic leukemia (CLL) with high-risk cytogenetic features. Ibrutinib is a selective inhibitor of Bruton tyrosine kinase that is thought to inhibit CLL cell survival and proliferation by blocking some of the enzymes needed for cell growth.

Ibrutinib and Rituximab Compared With Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma [NCT02048813]
A study comparing ibrutinib/rituximab to fludarabine phosphate, cyclophosphamide and rituximab in the treatment of younger patients (younger than 65 yrs) with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma. The primary outcome measure is change in quality of life as measured by the Functional Assessment of Cancer Therapy -Leukemia (FACT-Leu) Trial Outcome Index (TOI).

Brighton: PNT2258 for Treatment of Patients With Richter’s Transformation

[NCT02378038]

A multi-center, single-arm, 2-stage, open-label phase II investigation of PNT2258 to characterize anti-tumor activity and collect safety data on patients with Richter’s Transformation. PNT2258 is a proprietary formulation of a single-stranded 24-base DNAi oligonucleotide that targets the BCL2 protein to restore apoptotic processes leading to the death of cancer cells.

Phase 1/2 “Triple-Therapy” Study With TGR-1202 + TG-1101 + the PD-1 Checkpoint Inhibitor Pembrolizumab in Patients With Advanced Chronic Lymphocytic Leukemia (CLL) at the University of Pennsylvania’s Abramson Cancer Center [NCT02535286]
A Phase 1/2 clinical study in patients with relapsed or refractory CLL that will investigate the use of TGR-1202, an oral PI3K delta inhibitor, and TG-1101 (ublituximab), a glycoengineered anti-CD20 monoclonal antibody, in combination with the anti-PD-1 immune checkpoint inhibitor pembrolizumab. This will be the first clinical trial evaluating the safety, tolerability and effectiveness of the triple combination of a PI3K delta inhibitor with an anti-CD20 mAb and an anti-PD-1 checkpoint inhibitor.

See TG Therapeutics, Inc., news release.

Faculty Team
Investigators with Penn Hematology/Oncology are focused on translating laboratory work into novel therapies and practice-changing discoveries. The scope of Penn’s hematology and medical oncology clinical research enterprise is very broad, spanning all phases of clinical research, including pre-clinical work and discovery, phase 1 and 2 studies and leadership of national phase 3 trials intended to change the standard of care. Penn clinical investigators regularly publish high profile and important findings in diverse fields, ranging from the most fundamental cellular investigations, to leading edge translational and clinical research.

Conducting Clinical Studies in Chemoimmunotherapy for Chronic Lymphocytic Leukemia at Penn Medicine

Principal Investigators
Anthony Mato, MD, MSCE
Assistant Professor of Medicine
Director, Center for CLL

Stephen J. Schuster, MD
Robert and Margarita Louis-Dreyfus Associate Professor in
Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research

David L. Porter, MD
Jodi Fisher Horowitz Professor in Leukemia Care Excellence

Adam Cohen, MD
Assistant Professor of Medicine

Noelle Frey, MD
Assistant Professor of Medicine

Daniel J. Landsburg, MD
Assistant Professor of Clinical Medicine

Alison Loren, MD
Associate Professor of Medicine

Sunita Nasta, MD
Associate Professor of Clinical Medicine

Edward A. Stadtmauer, MD
Professor of Medicine

Jakub Svoboda, MD
Assistant Professor of Medicine

Donald Tsai, MD, PhD
Associate Professor of Medicine

Research Team
Kristy M. Walsh
Research Manager

Elizabeth Chatburn
New Patient Coordinator

Colleen Dorsey, BSN, RN
Research Nurse

Molly J. Fanning
Clinical Research Coordinator

Kaley Piersanti
Administrative Assistant

Allison V. Rago, RN, BSN
Clinical Nurse

Alexandra Vandegrift
Research Assistant

Access
Hospital of the University of Pennsylvania
Perelman Center for Advanced Medicine
2 West Pavilion
3400 Civic Center Boulevard
Philadelphia, PA 19104

Cancer Clinical Trials at Penn Medicine
For information regarding cancer clinical trials at Penn Medicine, please visit the Oncolink Clinical Trial Matching and Referral Service.

Management of Recurrent Dislocation of the Temporomandibular Joint (TMJ)

noreply@blogger.com (Anonymous) — Fri, 13 Nov 2015 18:00:00 +0000

Department of Oral & Maxillofacial Surgery • Center for Temporomandibular Joint Disease

Oral and Maxillofacial Surgeons at the Penn Center for Temporomandibular Joint Disease are performing procedures both arthroscopically and through open approaches in order to prevent recurrent dislocation of the temporomandibular joint (TMJ).

Temporomandibular joint (TMJ) dislocation occurs when the condyle of the jaw moves forward, out of its functional position within the glenoid fossa and posterior articular eminence, so that the condyle is anterior to the eminence. This stretches the ligaments and muscles, provoking intense local orofacial pain.

TMJ dislocation should not be confused with subluxation, a similar, but self-limiting condition that often resolves spontaneously. There are distinct differences, as well, between acute and recurrent TMJ dislocation.

Acute TMJ dislocation can be caused by factors that range in severity from mild distress (yawning, prolonged dental procedures) to acute trauma and epileptic seizure. Recurrent TMJ dislocations, by comparison, have a much more complicated etiology, and a much greater impact overall on quality of life. The origins of recurrent TMJ dislocation are as often endogenous as they are extracorporeal.

Recurrent dislocation can be attributed to the structure of the TMJ (eg, capsular weakness, internal derangement), facial morphology (diminished articular eminence, ligamentous laxity, uneven jaw growth), habit (prolonged abnormal mastication), disease (osteoporotic bone loss, systemic disorders), and a host of other internal aberrations.

The treatment for acute and recurrent TMJ differs, as well. A standard treatment for acute TMJ dislocation is reduction of the mandible, a technique by which the dislocated jaw is pushed downward and backward into its normal position. TMJ reduction frequently takes place in emergency rooms under sedation or general anesthesia. Studies suggest, however, that reduction and other nonsurgical interventions generally fail to decrease the frequency of dislocation or the rate of repeat ER visits caused by persistent recurrent TMJ dislocation.

Open and arthroscopic interventions, however, have been shown to both diminish the frequency of occurrence and the intensity and duration of orofacial pain associated with chronic TMJ dislocation.

At the Penn Center for Temporomandibular Joint Disease, surgeons are using an open technique, arthroplastic eminoplasty, to treat recurrent TMJ. Eminoplasty of the TMJ involves safely scarring the articular eminence without markedly altering the bony anatomy to allow the condyle to move freely back into its normal position and prevent dislocation.[1]

The technique, which employs a specially designed diamond rasp to minimize bone reduction, has the advantage of avoiding down-fracturing of the eminence. In studies, eminoplasty has been shown to produce clinical outcomes as effective as those obtained with the use of conventional open eminectomy. [2]

References
1. Undt G. Temporomandibular Joint Eminectomy for Recurrent Dislocation. Atlas Oral
Maxillofac Surg. 19:189, 2011.
2. Sato, et al. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:390-395.

Case Study
Mr. F, a 27-year-old male with a history of recent traumatic brain injury, presented following multiple visits to his community hospital emergency room with bilaterally dislocated temporomandibular joints. Following his sixth visit to the ER, Mr. F required reduction of the mandible under sedation.

At the time of his most recent ER visit, the providers were unable to reduce his jaw. Consequently, Mr. F was taken to the OR for muscle paralysis and TMJ reduction under general anesthesia. Following the procedure, he was placed in inter-maxillary fixation (jaw wiring) for several weeks. When he suffered a recurrent dislocation following release from intermaxillary fixation, Mr. F was referred to the Center for Temporomandibular Joint Disease at Penn Medicine.

After a discussion of his options, Mr. F opted to have an open TMJ eminoplasty. During the procedure, Mr. F’s temporomandibular joint was exposed. Then, while the disc and articular cartilage were shielded for protection, a diamond rasp was used to reduce the articular eminence of the glenoid fossa and create a scar along the capsule (Figs. 1 & 2).

The effect of these procedures is to diminish impedance to joint reduction. Mr. F was placed in intermaxillary fixation for one week following the procedure. As of his 1-year follow-up, Mr. F has remained free of TMJ dislocations His jaw function remained within normal limits and he maintains a regular diet. His associated myofascial muscle pain resolved.

Access
Perelman Center for Advanced Medicine
South Pavilion, 4th Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

Penn Presbyterian Medical Center
51 N. 39th Street
Wright-Saunders Building, Suite 565
Philadelphia, PA 19104

Penn Medicine Radnor
250 King of Prussia Road
Radnor, PA 19087
FY-16-9162 11.15

Faculty Team

The faculty at Penn Oral & Maxillofacial Surgery includes internationally known surgeons and pioneers in TMJ surgery. Penn surgeons have extensive experience in treating conditions involving the temporomandibular joint, including complex joint and combined jaw surgeries, and see one of the highest volumes of joint surgery in the country.

The mission of the Penn Center for Temporomandibular Joint Disease at the Department of Oral & Maxillofacial Surgery is to advance the understanding and treatment of temporomandibular joint disease. Finding the source of the pain to define the etiology
of TMJ is one of the Center’s key services.

In addition to practical evaluations, diagnostic tools include Panorex, MRI and CT imaging. Treatment at the Center is directed at the origin of pain. The first-line therapy for TMJ disorders is short-term conservative management. Patients who continue to have symptoms of TMJ disease or progression despite optimal conservative management may benefit from interventional therapy.

Treating Recurrent TMJ Dislocation at Penn Medicine
Center for Temporomandibular Joint Disease

Eric J. Granquist, DMD, MD
Director, The Center for Temporomandibular Joint Disease
Assistant Professor of Oral & Maxillofacial
Surgery/Pharmacology

Lee R. Carrasco, DDS, MD
Associate Professor of Clinical Oral & Maxillofacial
Surgery/Pharmacology

Helen Giannakopoulos, DDS, MD
Associate Professor of Oral & Maxillofacial
Surgery/Pharmacology

Anh D. Le, DDS, PhD
Chair and Norman Vine Endowed Professor of Oral Rehabilitation

Neeraj Panchal, DDS, MD
Clinical Instructor of Oral & Maxillofacial Surgery/Pharmacology

Peter D. Quinn, DMD, MD
Schoenleber Professor of Oral & Maxillofacial
Surgery/Pharmacology

David C. Stanton, DMD, MD, FACS
Associate Professor of Oral & Maxillofacial
Surgery/Pharmacology

Steven Wang, DMD, MD
Clinical Instructor of Oral & Maxillofacial Surgery/Pharmacology

Electrophysiology Research and Publications Update

noreply@blogger.com (Anonymous) — Fri, 23 Oct 2015 13:10:00 +0000

Under the direction of Francis Marchlinski, MD, researchers with the Electrophysiology (EP) Program at Penn Medicine have been at the forefront of clinical research in the treatment of atrial fibrillation and ventricular tachycardia (VT) for almost two decades.
The publications below are representative of the spectrum of past and present clinical investigations at Penn Electrophysiology.

Acute hemodynamic decompensation during catheter ablation of scar-related ventricular tachycardia: incidence, predictors, and impact on mortality.

Methods: The investigators identified univariate predictors of periprocedural AHD in 193 consecutive patients undergoing radiofrequency catheter ablation of scar-related VT. AHD was defined as persistent hypotension despite vasopressors and requiring mechanical support or procedure discontinuation.
Results: AHD occurred in 22 (11%) patients. Compared with the rest of the population, patients with AHD were older (68.5±10.7 versus 61.6±15.0 years; P=0.037); had a higher prevalence of diabetes mellitus (36% versus 18%; P=0.045), ischemic cardiomyopathy (86% versus 52%; P=0.002), chronic obstructive pulmonary disease (41% versus 13%; P=0.001), and VT storm (77% versus 43%; P=0.002); had more severe heart failure (New York Heart Association class III/IV: 55% versus 15%, P less than 0.001; left ventricular ejection fraction: 26±10% versus 36±16%, P=0.003); and more often received periprocedural general anesthesia (59% versus 29%; P=0.004). At 21±7 months follow-up, the mortality rate was higher in the AHD group compared with the rest of the population (50% versus 11%, log-rank P less than 0.001).
Conclusions: AHD occurs in 11% of patients undergoing radiofrequency catheter ablation of scar-related VT and is associated with increased risk of mortality over follow-up. AHD may be predicted by clinical factors, including advanced age, ischemic cardiomyopathy, more severe heart failure status (New York Heart Association class III/IV, lower ejection fraction), associated comorbidities (diabetes mellitus and chronic obstructive pulmonary disease), presentation with VT storm, and use of general anesthesia.
Source: 2015 Feb;8(1):68-75. Full text available here.

Percutaneous epicardial ablation of ventricular arrhythmias arising from the left ventricular summit: outcomes and electrocardiogram correlates of success.

Methods: Between January 2003 and December 2012, a total of 23 consecutive patients (49 ± 14 years; 39% men) with ventricular arrhythmias arising from the left ventricular summit underwent percutaneous epicardial instrumentation for mapping and ablation because of unsuccessful ablation from the coronary venous system and multiple endocardial LV/right ventricular sites.
Results: Successful epicardial ablation was achieved in 5 (22%) patients. In the remaining 18 (78%) cases, ablation was aborted for either close proximity to major coronary arteries or poor energy delivery over epicardial fat. The Q-wave amplitude ratio in aVL/aVR was higher in the successful group, with a ratio of greater than 1.85 present in 4 (80%) patients in the successful group versus 2 (11%) in the unsuccessful group (P = 0.008). The ratio of R/S wave in V1 was greater in the successful group, with 4 (80%) patients in the successful group having a R/S ratio of greater than 2 in V1 versus 5 (28%) in the unsuccessful group (P = 0.056). None of the patients in the successful group had an initial q wave in lead V1, as opposed to 6 (33%) in the unsuccessful group. The presence of at least 2 of the 3 ECG criteria above predicted successful ablation with 100% sensitivity and 72% specificity.
Conclusions: Epicardial instrumentation for mapping and ablation of ventricular arrhythmias arising from the left ventricular summit is successful only in a minority of patients because of close proximity to major coronary arteries and epicardial fat. A Q-wave ratio of greater than 1.85 in aVL/aVR, a R/S ratio of greater than 2 in V1, and absence of q waves in lead V1 help identify appropriate candidates for epicardial ablation.
Source: 2015 Apr;8(2):337-43. Full text available here.

ECG Criteria to Identify Epicardial Ventricular Tachycardia in Nonischemic Cardiomyopathy

The EP team at HUP compared pace maps and VT-generated QRS complexes from endocardial (ENDO) versus epicardial (EPI) origin in patients with NICM. The study findings showed unequivocally that the ECG morphological criteria (presence of a q wave in Lead 1 (QWL1) appears to be the most specific and sensitive criterion for identifying an EPI site of origin. The study identified new interval criteria that would improve the specificity of identifying an EPI VT origin. A simple multi-step ECG algorithm that incorporates both newly identified morphology and defined interval criteria with the potential to further optimize recognition of an EPI VT site of origin was then established (Fig. 1).
Source: Circ Arrhythmia Electrophysiol. 2010;3:62-71. Full text available here.

Epicardial Substrate and Outcome with Epicardial Ablation of Ventricular Tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

Thirteen patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) and previous failed endocardial ablation referred from across the United States underwent epicardial ablation. All patients were experiencing recurrent VT episodes and were being considered for transplant if VT could not be controlled. Percutaneous pericardial access was successfully and safely obtained using a posterior approach to prevent laceration of the dilated RV. In all patients, the low voltage area with electrogram abnormalities (scar) was more extensive on the epicardium than the endocardium and the origin of epicardial VT was frequently opposite normal areas of endocardium (Fig. 2). Twenty-seven VTs were ablated successfully from the epicardium in 12 of the 13 patients. During an average follow-up of over 18 months, ten of 12 patients (84%) with acute VT elimination had no VT, and two patients had only a single VT episode at two and 38 months respectively without subsequent recurrences. Importantly, since this was a young patient population with an average age of 43 years, elimination of VT also obviated the need for amiodarone therapy in all the patients. The excellent outcome at Penn in this drug refractory group of patients supports an earlier role for ablation therapy in this patient population.
Source: Circulation. 2009;120:366-375. Full text available here.

Team of Faculty
The Hospital of the University of Pennsylvania has the largest electrophysiology program on the East Coast and one of the largest hospital-based programs in the US. Comprised of 14 full-time, board-certified electrophysiologists and more than 20 EP specialized nurse practitioners and physician assistants, the team is dedicated exclusively to treating and eliminating serious and potentially life-threatening heart rhythm disturbances. The team’s leadership in ablative and arrhythmia device therapy is evident in their collective contribution to more than 600 articles to scientific journals in the last 10 years.

Hospital of the University of Pennsylvania
Francis E. Marchlinski, MD
Director, Electrophysiology Professor of Medicine
David J. Callans, MD
Associate Director, Electrophysiology Professor of Medicine

Rajat Deo, MD
Assistant Professor of Medicine
Sanjay Dixit, MD
Associate Professor of Medicine
Andrew Epstein, MD, FAHA, FACC, FHRS
Professor of Medicine
Fermin C. Garcia, MD
Assistant Professor of Medicine

Mathew D. Hutchinson, MD
Associate Professor of Medicine
David Lin, MD
Associate Professor of Medicine

Michael P. Riley, MD, PhD
Assistant Professor of Medicine
Ralph J. Verdino, MD
Associate Professor of Medicine

Access

Inpatient Electrophysiology Locations:

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

Outpatient Electrophysiology Locations:

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

Penn Medicine Radnor
250 King of Prussia Road
2nd Floor
Radnor, PA 19087

To refer a patient and/or consult with a physician: Call 800-789-PENN (7366) or visit: PennMedicine.org/referral

To refer or transfer a patient with VT or other urgent arrhythmia problems, call 215-662-3999. You will be immediately placed in contact with a HUP electrophysiologist.

Endovascular Revascularization for Wound Care in Critical Limb Ischemia

noreply@blogger.com (Anonymous) — Thu, 22 Oct 2015 17:00:00 +0000

Department of Interventional Radiology

Interventional radiologists at Penn Medicine are performing endovascular revascularization procedures to advance wound care in patients with critical limb ischemia (CLI).

CLI, an end-manifestation of peripheral arterial disease, is defined as occlusion of the peripheral arteries with the manifestation of “rest pain” and tissue loss. Untreated CLI is invariably progressive, leading to diffuse limb ulceration, necrosis and gangrene, and to correspondingly high rates of amputation, morbidity and mortality. Rates of mortality for CLI at five years approach 50%. [1]

For patients with symptomatic CLI, as demonstrated by angiogram, the goals of management include timely resolution of pain, wound healing, limb preservation, maintenance of limb function and ambulatory status, and survival.

At Penn Interventional Radiology, the standard of care for patients with CLI includes surgical and interventional revascularization. Recent reports suggest no difference between these modalities in overall mortality, rates of amputation or amputation-free survival at ≥2 years. [2]

Patency and vascularization of the pedal arch is associated with improved wound healing and limb salvage in patients with CLI, and for this reason, interventional angioplasty is often a preferred strategy for patients requiring wound management for partial amputation (i.e., transmetatarsal amputation).

Case Study

Mr. M, a 60-year-old male with diagnosed critical limb ischemia, had a transmetatarsal amputation (TMA) for non-healing ulcers of the foot at a community hospital near his home. Unfortunately, even with a negative pressure wound therapy device in place, the stump of the TMA failed to heal, preventing closure of the wound.

Two days after the procedure, an angiogram at the hospital demonstrated no flow in the anterior tibialis and peroneal arteries, with minimal flow to the foot through the distally occluded posterior tibialis (Fig. 1). Concerned that the lack of wound healing would lead to necrosis and the possibility of full amputation, Mr. M’s vascular surgeon referred him to Penn Interventional Radiology for a consultation.

After a discussion of his options, Mr. M agreed to have an angioplasty procedure to open the blockage in the posterior tibialis artery. This procedure was successful, and blood flow was restored to the foot. However, the most distal aspect of the posterior tibialis artery remained blocked, and subsequent attempts to close the TMA flap failed due to lack of perfusion. Following further discussion, Mr. M opted for a distal pedal angioplasty revascularization.

During the procedure, a microcatheter was introduced into the foot and advanced under x-ray guidance through the posterior tibialis into the lateral plantar, pedal arch and dorsalis pedis arteries. A long-segment angioplasty revascularization of the posterior tibialis artery was then performed which included the pedal arch (Fig. 2).

Marked improvement in blood flow was seen post-angioplasty (Fig. 3), and Mr. M was discharged the next day to home. In the weeks following the procedure, his TMA stump healed completely.

References
1. Nehler, MR, Peyton, BD. Is revascularization and limb salvage always the treatment for critical limb ischemia? J Cardiovasc Surg. 2004;45:177–184.
2. Schuyler Jones W, Dolor RJ, Hasselblad V, Vemulapalli S, Subherwal S, Schmit K, Heidenfelder B, Patel MR. Comparative effectiveness of endovascular and surgical revascularization for patients with peripheral artery disease and critical limb ischemia. Am Heart J. 2014;167:489-498.e7.

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. In addition to dedicated IR suites, the Division has an active outpatient clinic, as well as admitting and consulting services.

Performing Endovascular Revascularization for Wound Care in CLI
at Penn Medicine

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

Jonas Redmond, MD
Assistant Professor of Clinical Radiology

Micah Watts, MD
Assistant Professor of Radiology

Hospital of the University of Pennsylvania
Scott O. Trerotola, MD
Stanley Baum Professor of Radiology

Deepak Sudheendra, MD
Assistant Professor of Clinical Radiology

Mandeep S. Dagli, MD
Assistant Professor of Radiology

S. William Stavropoulos, MD
Professor of Radiology

Maxim Itkin, MD
Adjunct Associate Professor of Radiology

Jeffrey I. Mondschein, MD
Associate Professor of Clinical Radiology

Richard Shlansky-Goldberg, MD
Professor of Radiology

Michael C. Soulen, MD
Professor of Radiology

Gregory Nadolski, MD
Assistant Professor of Radiology

Micah M. Watts, MD
Assistant Professor of Radiology

Penn Presbyterian Medical Center
Timothy W. I. Clark, MD
Associate Professor of Clinical Radiology

Jonas Redmond, MD
Assistant Professor of Clinical Radiology

Pennsylvania Hospital
Raymond Fabrizio, MD
Assistant Professor of Clinical Radiology

Benjamin D. Hammelman, 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 North 39th Street
Philadelphia, PA 19104

Pennsylvania Hospital
800 Spruce Street
Philadelphia, PA 19107

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

Surgical and Medical Management of Osteosarcoma

noreply@blogger.com (Anonymous) — Mon, 19 Oct 2015 15:25:00 +0000

The Orthopaedic Oncology Service at Penn Medicine is devoted to the management of patients with benign and malignant tumors of bone and soft tissues. The most common bone lesions include osteosarcoma, chondrosarcoma, Ewing sarcoma and giant cell tumor, among others. Primary bone sarcomas are rare (~1% of all adult cancers) and occur from infancy through late adulthood. The majority of patients with these tumors have pain at the bony site in addition to swelling or a stiff adjacent joint. Treatment varies depending on the tumor type/grade, age of the patient and location of the tumor.

The management of patients with osteosarcoma by the Orthopaedic Oncology Service at Penn Medicine involves an individualized interdisciplinary and multi-modal approach beginning with accurate diagnosis. Radiologists, pathologists, medical/pediatric oncologists and orthopaedic oncology surgeons review sophisticated imaging studies and minimally invasive image-guided needle biopsies. MRI scans with specific tumor sequences allow Penn orthopaedic oncologists to better plan surgical procedures by accurately determining the tumor characteristics and extent.

The objectives of osteosarcoma treatment include preservation of limb function and prevention of disease recurrence, progression, or metastasis. Limb preservation techniques for malignant tumors of bone and soft tissue are a specialty at Penn Medicine, and are personalized to the patient, taking into account their age, location of the tumor, and coordination with other treatments. Patients with osteosarcoma require chemotherapy in addition to surgery to remove the primary bone cancer.

Great advances in limb salvage techniques have emerged over the last 20 years. Although amputation of the limb remains necessary for 5-10% of patients, every effort is made to perform limb salvage in order to maintain the function of the extremity and minimize the risk of local recurrence.

Surgical management of osteosarcoma at Penn has benefited from advances in the technology of internal fixation, soft tissue attachments to prostheses, and biologic options to recreate living bone. Metal prosthetic joints have become the most common method of reconstruction for patients when an osteosarcoma is near a joint. Improvements in biomechanics, metallurgy and engineering have allowed for the development of advanced, modular prostheses that will provide a more durable, long-lasting reconstruction for patients who are candidates for limb salvage surgery.

Finally, future advances in the treatment of patients with osteosarcoma will come from the laboratory in the form of new drugs or biologic agents that can specifically target the tumor cells to prevent metastasis.

Case Study
Mr. K, an 18-year-old soccer player, began having right hip pain in June 2014. The pain gradually worsened, requiring increasing doses of pain medication. Imaging studies at an outside institution initially suggested a benign synovial condition called pigmented villonodular synovitis (PVNS). With the development of worsening symptoms and a limp, repeat imaging studies were ordered, and these showed a destructive bone-producing lesion in the proximal femur with a surrounding soft tissue mass (Figs. 1, 2).

Referred to the Orthopaedic Oncology service at Penn, Mr. K had a CT-guided needle biopsy of the right proximal femur lesion that revealed a high-grade osteosarcoma. Staging studies showed no evidence of metastasis.

Mr. K began systemic chemotherapy and was scheduled for removal of the primary tumor in January 2015. Because his osteosarcoma was located in the proximal femur and extended into the hip joint, his surgical options included a hindquarter amputation or an extra-articular wide resection and complex acetabular reconstruction. Mr. K opted for limb salvage, and a team of hip reconstruction and orthopaedic oncology surgeons was assembled.

A successful extra-articular resection of the right hip joint and proximal femur was performed with negative margins and 70% necrosis of the tumor. Reconstruction involved a proximal femoral megaprosthesis with reconstruction of the abductor and iliopsoas tendons and a complex acetabular reconstruction with a tantalum uncemented component and multiple augments (Figs. 3, 4).

Mr. K was in a hip abduction brace for 6 weeks and protected weight bearing for 3 months to allow bony ingrowth into the tantalum acetabular component. Having completed chemotherapy, he remains cancer free, and is now walking with a cane and working to regain right leg strength in physical therapy. He will be followed closely for signs of local or systemic recurrence of osteosarcoma.

Faculty Team
The comprehensive Penn Orthopaedic Oncology Service is a multi-disciplinary program that includes specialists in orthopaedic oncology, medical oncology, surgical oncology, reconstructive plastic surgery, radiation therapy, interventional and diagnostic radiology and musculoskeletal pathology.

Treating Sarcoma at Penn Medicine
Orthopaedic Oncology Service
Kristy L. Weber, MD
Director, Penn Sarcoma Program
Chief, Orthopaedic Oncology
Abramson Family Professor in Sarcoma Care Excellence

Surgical Oncology
Giorgos C. Karakousis, MD
Assistant Professor of Surgery
Medical Oncology

Arthur P. Staddon, MD
Director of Medical Oncology, Bone or Soft Tissue Sarcoma Program
Clinical Professor of Medicine

Lee Hartner, MD
Clinical Associate Professor of Medicine

Radiation Oncology
William Levin, MD
Clinical Assistant Professor of Radiation Oncology

James D. Kolker, MD
Clinical Assistant Professor of Radiation Oncology

Suneel N. Nagda, MD
Assistant Professor of Clinical Radiation Oncology

Neurosurgery
James M. Schuster, MD, PhD
Associate Professor of Neurosurgery
Associate Professor of Orthopaedic Surgery

Neil Malhotra, MD
Assistant Professor of Neurosurgery

Plastic/Microvascular Surgery
Stephen J. Kovach, III, MD
Assistant Professor of Surgery

L. Scott Levin, MD
Chair, Department of Orthopaedic Surgery
Paul D. Magnuson Professor of Bone and Joint Surgery
Professor of Surgery (Division of Plastic Surgery)

Musculoskeletal Radiology
Ronnie Sebro, MD, PhD
Assistant Professor of Radiology

Musculoskeletal Pathology
Kumarasen Cooper, MBChB, PhD
Professor, Anatomic Pathology

Paul J. Zhang, MD
Director, Immunohistochemistry Laboratory

John J. Brooks, MD
Professor of Pathology & Laboratory Medicine

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

Pennsylvania Hospital
Penn Orthopaedics
Garfield Duncan Building, Suite 2C 301
South 8th Street
Philadelphia, PA 19106

Pharmacomechanical Thrombolysis of Symptomatic Deep Vein Thrombosis

noreply@blogger.com (Anonymous) — Tue, 25 Aug 2015 16:25:00 +0000

Division of Interventional Radiology

Interventional radiologists at Penn Medicine are performing pharmacomechanical thrombolysis in conjunction with catheter-directed thrombolytic therapy to manage symptomatic acute and subacute deep vein thrombosis (DVT). The goal of the therapy is to remove the majority of the clot burden with significantly less thrombolytic medication than conventional catheter-directed thrombolysis alone, thereby decreasing the risk of bleeding and more importantly, helping to minimize damage to the veins that can subsequently lead to life-long complications known as post-thrombotic syndrome (PTS).

The etiologies for DVT include several prothrombotic factors such as recent surgery, cancer, trauma, prolonged periods of inactivity (i.e., air travel), central venous catheters, hormone therapy, genetic hypercoaguable syndromes, and superficial thrombophlebitis.

DVTs generally begin as occlusive clots at the valve cusps in the veins of the calf. Half will resolve spontaneously, but about 25% of symptomatic DVT will progress by extension into the proximal (iliofemoral) veins. In addition to causing symptoms of pain and swelling, the presence of iliofemoral DVT accounts for the highest risk of recurrent DVT and more importantly, the highest risk of pulmonary embolism.

Of patients with symptomatic ileofemoral DVT, 25-60% will go on to develop (PTS), a condition caused by damage to valves in the deep veins. PTS is characterized by chronic lower extremity swelling, pain, skin changes, and venous ulceration secondary to chronic venous hypertension.

The standard of care for acute and subacute DVT is anticoagulation, a therapy that prompts endogenous clot lysis and prevents further clot formation and propagation. However, anticoagulation works slowly and studies suggest that fewer than 50% of ileofemoral DVT will dissolve completely within six months. Unfortunately, valvular damage can occur during this time frame.

To hasten the resolution of DVT and preempt PTS, interventional radiologists at Penn Medicine are performing pharmacomechanical thrombolysis in combination with catheter-directed thrombolysis. Pharmacomechanical thrombolysis involves infusing a small amount of potent thrombolytic directly into the clot, fragmenting the clot, and then suctioning the clot fragments from the vein. This technique allows for a 40-50% reduction in thrombolytic dose, greatly diminishing the risk of bleeding that may be associated with thrombolytic therapy.

Case Study

Ms. G, a 44-year-old woman, presented to the Penn Medicine Trauma Center with pain and swelling of her entire lower left leg. She reported having had severe cramping in the leg for two days previously, but that the pain had been relieved by NSAIDs. With the exception of oral contraceptive use for the past year, her medical history was unremarkable.

At Penn, a Doppler ultrasound and CT identified extensive thrombus in the left popliteal, femoral, and iliac veins extending to the inferior vena cava (Fig. 1). No evidence of pulmonary embolism was found, however. Ms. G was started on IV heparin and transferred to the inpatient medical service.

Penn Interventional Radiologists were consulted to discuss treatment options. After learning about standard of care treatment and more aggressive treatment options, Mrs. G opted for pharmacomechanical thrombolysis versus conservative standard of care with anticoagulation and compression stockings. The following morning, she went to the Interventional Radiology suite, where she was placed under conscious sedation in the prone position, and venous access was obtained near the ankle in the left posterior tibial vein. Given the extent and acuity of the clot burden, pharmacomechanical thrombolysis alone was performed resulting in removal of the majority of the thrombus.

During the procedure, a high grade stenosis of the left common iliac vein was identified as the culprit lesion, suggesting a diagnosis of May Thurner syndrome, an often under-diagnosed and overlooked cause of extensive left iliofemoral DVT. May Thurner, which is more commonly seen in women, is due to compression of the left common iliac vein by the overlying right common iliac artery and the spine posteriorly.

May Thurner is managed with angioplasty and stenting to treat the underlying mechanical compression and prevent recurrent DVT. Because patients with the syndrome receive anticoagulation therapy for only 3-6 months (vs. potentially lifelong treatment for acute unprovoked DVT), accurate diagnosis of May Thurner is of critical importance.

Angioplasty of the left common iliac vein was performed for Ms. G, resulting in improvement, but continuing compression of the vessel. To resolve this issue, a stent was placed to buttress the left common iliac vein resulting in excellent venous outflow (Fig. 2). Ms. G remained in the hospital overnight for observation and was released to home the next day. She has since made a full recovery.

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. In addition to dedicated IR suites, the Division has an active outpatient clinic, admitting and consulting services.

Performing Pharmacomechanical Thrombolysis for DVT at Penn Medicine

Interventional Radiology

Hospital of the University of Pennsylvania

Scott O. Trerotola, MD
Chief, Interventional Radiology
Stanley Baum Professor of Radiology

Mandeep S. Dagli, MD
Assistant Professor of Radiology

Terence Gade, MD, PhD
Assistant Professor of Radiology

Stephen J. Hunt, MD, PhD, DABR
Instructor of Medicine

Maxim Itkin, MD
Associate Professor of Radiology

Jeffrey I. Mondschein, MD
Associate Professor of Clinical Radiology

Gregory Nadolski, MD
Assistant Professor of Radiology

Richard Shlansky-Goldberg, MD
Professor of Radiology

Michael C. Soulen, MD
Professor of Radiology

S. William Stavropoulos, MD
Professor of Radiology

Deepak Sudheendra, MD
Assistant Professor of Clinical Radiology

Micah Watts, MD
Adjunct Assistant Professor of Radiology

Penn Presbyterian Hospital

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

Jonas Redmond, MD
Assistant Professor of Clinical Radiology

Pennsylvania Hospital

Raymond Fabrizio, MD
Assistant Professor of Clinical Radiology

Benjamin D. Hammelman, MD
Assistant Professor of Clinical Radiology

Total Pancreatectomy with Islet Auto-Transplantation for Treatment of Refractory Chronic Pancreatitis

noreply@blogger.com (Anonymous) — Fri, 24 Jul 2015 16:02:00 +0000

Division of Gastroenterology • Division of Endocrinology, Diabetes & Metabolism

Gastrointestinal and transplant surgeons, gastroenterologists, and endocrinologists at Penn Medicine are performing total pancreatectomy with islet auto-transplantation (TPIAT) for treatment of refractory chronic pancreatitis.

Chronic pancreatitis (CP) is defined by severe and irreversible pancreatic parenchymal damage attended by progressive interstitial fibrosis and varying degrees of exocrine and endocrine dysfunction. The disease is provoked when inflammation or obstruction of the pancreatic duct prevents the escape of pancreatic enzymes into the gastrointestinal tract, leading essentially to self-digestion.

Complications include intractable pain, nutrient maldigestion, pancreatogenic diabetes, steatorrhea, necrosis and an increased likelihood for pancreatic ductal adenocarcinoma. Concurrent complications in adjacent organs, including stenoses of the duodenum, bile duct and portal vein, are not unusual.

Treatment: Currently, there is no durable medical treatment for the inflammation or fibrosis associated with CP. Treatment is thus largely palliative, consisting of enzyme supplementation, somatostatin analogues and antioxidants with opioids supplemented, when necessary, by nerve blocks for potential pain management. The efficacy of these treatments generally diminishes over time.

Patients who are refractory to medical treatment for progressive chronic pancreatitis with pseudocysts are candidates for endoscopic decompression, and beyond this, for strategic partial resection of the pancreas or total pancreatectomy. The latter is identified with complete loss of exocrine and endocrine function resulting in pancreatic exocrine insufficiency and brittle surgical diabetes.

Outside of these impositions, improvement in quality of life is typically quite good following total pancreatectomy, with the majority of patients reporting substantial resolution of pain, and cancer risk is eliminated. Efforts to further enhance the post-surgical experience for patients having pancreatectomy have thus focused on sustaining pancreatic endocrine function through isolation of the islet cells from the diseased pancreas for auto-transplantation back in the patient’s liver.

TPIAT is performed at Penn Medicine by a multidisciplinary team comprising endocrinologists, gastroenterologists, surgeons and pain specialists. By infusing the patient’s own islet cells, TPIAT avoids the need for immunosuppression. In 5-year prospective studies, patients having TPIAT have consistently reported improvement in quality of life, with the majority (about two-thirds) reporting narcotic independence within one year; insulin independence occurred in a minority of patients (about one-third) and waned over time in these studies, but glycemic control was substantially improved. [1]

[1.] Bellin MD, Freeman ML, Gelrud A, Slivka A, Clavel A, Humar A, Schwarzenberg SJ, Lowe ME, Rickels MR, et al. Pancreatology. 2014;14:27-35.

Case Study

Mr. G, a 39-year-old gentleman, was referred to the Divisions of Gastrointestinal Surgery and Transplant Surgery at Penn Medicine for evaluation of chronic pancreatitis. Mr. G’s medical history included tobacco and alcohol abuse, cholelithiasis treated by cholecystectomy and recurrent episodes of pancreatitis requiring six hospitalizations in the past year and leading to a dependence on opioids. An endoscopic decompression of the pancreas shortly after his 37th birthday provided a transient improvement in pain, which he described as unremitting and particularly excruciating during exacerbations of pancreatitis. He has been on medical leave from work for the past year and is deeply concerned about his future job security.

Mr. G’s lab workup revealed elevated serum pancreatic enzyme levels during episodes of pancreatitis and normal fasting glucose and HbA1c. A fecal elastase was consistent with pancreatic exocrine insufficiency, and an oral glucose tolerance test excluded diabetes. An abdominal CT scan demonstrated pancreatic fibrosis and ductal stenosis.

At this point, Mr. G began pancreatic enzyme replacement to treat his exocrine insufficiency. Because his endoscopic decompression had been ineffective, and with no significant dilation of the main pancreatic duct that might be amenable to surgical decompression, he consented to have a TPIAT procedure to alleviate his pain and improve his quality of life. He was counseled, in addition, that total pancreatectomy would produce surgical diabetes and that the hoped-for goal of islet auto-transplantation was to prevent or significantly ameliorate this problem.

Mr. G was instructed in the use of a multi-dose insulin injection regimen that would be required for at least a few months post-operatively. Because splenectomy is required as part of a total pancreatectomy due to its shared blood supply, Mr. G also received vaccination against pneumococcus, H. influenza, and meningococcus. He was admitted to the hospital in the morning for surgery. Under general anesthesia, an open total pancreaticoduodenectomy was performed with splenectomy, and the pancreas was immediately separated and brought to the islet isolation facility in the adjacent building.

While Mr. G underwent choledochojejunostomy and gastrojejunostomy, the pancreas was collagenase digested and the islet cells separated from the acinar and ductal tissue by centrifuge purification. The isolated islets cells were brought back to the operating room and using the splenic vein stump were infused in the portal circulation for delivery throughout the liver parenchyma. Medial management included prophylactic antibiotics, cautious anticoagulation, and insulin to maintain normoglycemia during the period of islet engraftment.

Following surgery, Mr. G was monitored in the intensive care unit for three days until his anticoagulation and insulin was transitioned to subcutaneous administration. His diet was advanced, and he remained under observation in a routine hospital room until discharge on the tenth day post-operatively. The pain service managed his post-operative comfort and prepared Mr. G for post-discharge weaning from narcotics.

By the third post-operative month, Mr. G had healed from surgery, had been tapered off narcotics, was tolerating his diet while taking his prescribed pancreatic enzymes, and was maintaining normal glucose levels and HbA1c while taking only once daily long-acting insulin. By the sixth post-operative month, Mr. G had tapered off his insulin and continued to maintain normal glucose control.

Faculty Team

Penn Medicine is among a handful of medical centers nationwide with an FDA-compliant current Good Manufacturing Processes (cGMP) facility for the isolation and transplantation of islet cells and the combination of services, specialties and experience required to perform TPIAT. Home to both the Penn Transplant Institute and the Institute for Diabetes, Obesity and Metabolism (IDOM), Penn receives support from the National Institute for Diabetes and Digestive and Kidney Diseases for its Diabetes Research Center and Center for Molecular Studies on Digestive and Liver Diseases.

Penn is also a member of the Clinical Islet Transplantation (CIT) Consortium, a network of NIH-supported clinical centers conducting pivotal studies of islet transplantation for patients with type 1 diabetes.

Performing TPIAT at Penn Medicine

Department of Surgery

Division of Transplantation Surgery
Ali Naji, MD, PhD
Surgical Director, Kidney and Pancreas Transplant Program
J. William White Professor of Surgical Research

Division of Gastrointestinal Surgery
Jeffrey A. Drebin, MD, PhD, FACS
Chairman, Department of Surgery
John Rhea Barton Professor of Surgery

Department of Medicine
Division of Endocrinology, Diabetes & Metabolism
Michael R. Rickels, MD, MS
Medical Director, Pancreatic Islet Cell Transplant Program
Associate Professor of Medicine

Division of Gastroenterology

Nuzhat Ahmad, MD
Associate Professor of Medicine

Vinay Chandrasekhara, MD
Assistant Professor of Medicine

Gregory G. Ginsberg, MD
Director, Endoscopic Services
Professor of Medicine

Immanuel Ho, MD
Clinical Professor of Medicine

David L. Jaffe, MD
Professor of Clinical Medicine

Michael L. Kochman, MD
Vice Chair of Clinical Affairs, Department of Medicine
Wilmott Family Professor of Medicine

Kashyap Panganamamula, MD
Clinical Associate Professor of Medicine

Michael Rajala, MD, PhD
Assistant Professor of Clinical Medicine

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Penn Transplant Institute
Hospital of the University of Pennsylvania
1 Founders Building
3400 Spruce Street
Philadelphia, PA 19104

Administrative Coordinator
Division of Transplant Surgery

Diane McLaughlin, BS, CRCC
Telephone: 215-662-2037
FAX: 215-615-4900
diane.mclaughlin@uphs.upenn.edu

Advanced Approaches to the Management of Colorectal Cancer with Liver Metastases

noreply@blogger.com (Anonymous) — Fri, 10 Jul 2015 15:14:00 +0000

Colorectal surgeons and surgical oncologists at Penn Medicine are now performing staged or combined laparoscopic resections of colorectal cancers with liver metastases (CLM).
Many patients with colorectal cancer develop metastases, often confined to the liver. Of these metastases, about half are present at the time of initial diagnosis.

The remainder manifest as metachronous disease. At presentation, patients with more limited disease may be resectable; however, many individuals have more advanced disease at presentation and require systemic chemotherapy. A subset of these patients will become candidates for resection through downstaging.

Technical advances and improvements in perioperative care have enhanced the safety of liver surgery, and major hepatectomy in particular. Surgery is associated with improved long-term survival in patients with CLM. Criteria for hepatic metastasectomy include the ability to completely resect metastatic disease with preservation of a sufficient remnant liver.

At Penn Medicine, specialists in colorectal surgery, endocrine and oncologic surgery and interventional radiology have developed a collaboration that, despite its practical and intuitive character, remains uncommon in the region. Together, the Penn team has developed a variety of laparoscopic and open approaches to CLM that allow resection of all disease and rapid recovery with an eye on completion of multimodality therapy.

Patients with limited CLM disease may be candidates for single stage combined laparoscopic resection of the colorectal primary tumor and metastases. Those with bilobar synchronous CLM may benefit from laparoscopic resection of colorectal primary and left sided liver metastases. Second stage right hepatectomy can then be performed at a later date. If the left liver remnant is not sufficient to support right hepatectomy based on volume measurements, right portal vein embolization (PVE) may be performed to allow for left liver hypertrophy prior to the second stage operation (Fig. 1).

Case Study 1
Mrs. E, age 68, was referred to Penn Medicine with a two-month history of anemia. With the exception of mild arthritis, she was otherwise healthy. A colonoscopy at Penn revealed a large (>3 cm) cecal cancer. A biopsy confirmed a diagnosis of adenocarcinoma; subsequently, a CT scan identified a single 3 cm lesion in the left lobe of the liver (Fig. 2).

After two months of systemic therapy with radiographic response in the liver, a combined laparoscopic resection of the isolated metastases was performed, aided by intraoperative ultrasound and laparoscopic right colectomy. Mrs. E was discharged from the hospital on postoperative day six and started adjuvant chemotherapy seven weeks after surgery. She completed an additional four months of chemotherapy and is now on surveillance. She remains disease free 11 months after surgery.

Case Study 2
Mr. H, a 73-year-old with a diagnosis of synchronous rectosigmoid cancer and bilobar CLM (two peripheral lesions in the left liver and three lesions in the right liver) came to Penn Medicine for management.

A first stage laparoscopic colectomy and partial left hepatectomy was performed. He then received two months of systemic therapy with radiographic response in the residual right-sided liver lesions. Restaging CT scan revealed a small left future liver remnant (21% of calculated total liver volume). Mr. H then underwent PVE; hypertrophy of the liver remnant was confirmed on repeat CT scan.

Subsequently, Mr. H had a right hepatectomy through an open abdominal incision. He was discharged on the sixth postoperative day and is currently receiving adjuvant chemotherapy as planned preoperatively.

Faculty Team
Colorectal liver metastases are managed at Penn Medicine by a collaborative team drawn from the Divisions of Endocrine and Oncologic Surgery, Colon and Rectal Surgery and Interventional Radiology. The Division of Endocrine and Oncologic Surgery offers comprehensive management of malignant diseases of the breast, gastrointestinal tract, liver, and endocrine organs such as the thyroid and adrenal gland. The Division of Colon and Rectal Surgery offers diagnosis and treatment of diseases arising in the anus, rectum, and large bowel, including colon, rectal, and anal cancer and inflammatory bowel disease. Penn Interventional Radiology is devoted to the minimally invasive, image-guided procedures for the treatment of vascular and lymphatic disorders, regional and local cancers and women’s health conditions.

Providing Surgery for Colorectal Cancer with Liver Metastases at Penn Medicine

Endocrine and Oncologic Surgery
Robert E. Roses, MD
Assistant Professor of Surgery
robert.roses@uphs.upenn.edu
215-662-2068

Division of Colon and Rectal Surgery
Najjia N. Mahmoud, MD
Chief of the Division of Colon and Rectal Surgery
Associate Professor of Surgery
najjia.mahmoud@uphs.upenn.edu
215-662-6746

Interventional Radiology
Michael C. Soulen, MD, FSIR
Director of Interventional Oncology
michael.soulen@uphs.upenn.edu
215-615-3591

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

Enrolling Clinical Trials: Proton Beam Radiation for WHO Grade I-III Meningiomas and Hemangiopericytomas

noreply@blogger.com (Anonymous) — Mon, 08 Jun 2015 15:07:00 +0000

Penn Radiation Oncology • Roberts Proton Therapy Center

Radiation oncologists at the Roberts Proton Therapy Center are conducting a Phase II clinical trial to ascertain the feasibility of proton therapy as an adjunct to surgery for WHO Grade I-III meningiomas and hemangiopericytomas.

This study seeks to assess the effect of proton therapy on rates of acute toxicity, fatigue and quality of life in the same population. The frequency of recurrence and long term toxicity will also be evaluated.

Surgery is the first-line therapy for the meningiomas, but the complexity of the lesions often precludes total resection, contributing to recurrence. The Simpson Criteria establish guidelines to measure the extent of surgery to predict probability of recurrence in meningeal tumors.

Simpson Grade I assigns a 9% risk of recurrence at 10 years to lesions having macroscopic gross total resection (GTR) with excision of the dura, sinus and bone. Simpson Grade IV, or subtotal resection, is associated with a 40% risk of recurrence at 10 years.

When GTR cannot be achieved, radiotherapy is often recommended. Retrospective reports suggest that post-operative radiation results in enhanced local control and substantial improvement in overall survival for patients with incomplete surgery and inoperable lesions.

However, standard photon radiotherapy (external beam radiation therapy or stereotactic radiosurgery) can expose significant normal brain tissue to the cumulative effects of radiation— and thus, increased risk of neurocognitive impairment. Higher doses of radiation to Grade II and III meningiomas are being investigated in an attempt to improve control rates.

At the Roberts Proton Therapy Center, radiation oncologists are assessing the application of proton radiotherapy to the treatment of meningiomas and brain cancers in a Phase II clinical trial. The objective of this trial is to assess the effect of proton therapy on quality of life and acute toxicity.

Proton radiotherapy is distinguished from standard photon therapy by its capacity to deliver high-dose-volume within an anatomical site while maintaining lower doses to surrounding normal tissues. Penn Medicine also offers pencil beam scanning for proton therapy. Pencil beam scanning allows for enhanced conformal dose around critical structures through modulation of dose in depth, while retaining the rapid dose fall-off from the Bragg-Peak effect.

Phase II Study
The phase II study will collect longitudinal data on fatigue and quality of life after proton therapy and gather toxicity data. Local control rates will also be evaluated.

Design: Thirty-eight patients will be enrolled in the phase II study. Patients from both the feasibility and phase II stages will be pooled for data analysis (a total of 50 patients), as the intended treatment is the same for both groups. Patients will be treated and followed for a minimum of 90 days from start of radiotherapy to determine acute toxicity. Patients will continue to be followed beyond 90 days for the late toxicity, fatigue, quality of life and progression-free and overall survival.

Objectives: Proton therapy at standard doses is not expected to improve clinical outcome but will likely reduce rates of acute toxicity, fatigue and poor quality of life. Most reports of fatigue and quality of life have been retrospective cross-sectional studies. Thus, fatigue and quality of life are not well understood for these patients.

Following radiotherapy, it is expected that fatigue will be most severe at 6 to 9 months and will gradually improve at 12 to 24 months. Quality of life outcomes may follow a similar pattern. Higher than standard doses of radiation may improve local control rates of Grade II and III meningiomas.

Endpoints: The endpoints for the Phase II study will include acute toxicity, late toxicity, fatigue, quality of life, cumulative total dose to normal brain tissue, progression-free survival and overall survival.

Detection of Vascular and Neuronal Changes and their Correlation to Neurocognitive Changes Following Proton and Photon Radiotherapy in Patients Receiving Skull Base and Brain Radiation

In addition to the Phase II study, a prospective neurocognitive trial is currently enrolling at Penn to study the use of proton therapy in patients treated with brain tumors and compare this to historical group of patients treated with photons. Patients receiving radiation therapy to the brain are eligible (as are a select group of family members not receiving radiation) to determine any neurocognitive effects of radiation and attempt to find imaging correlates to assist in radiation treatment planning in the future.

This study will collect longitudinal data on a series of neurocognitive tests as well as obtain magnetic resonance imaging (MRI) studies to estimate the degree of cognitive loss, if any, following radiotherapy using a prospective, longitudinal design beginning prior to radiotherapy (approximately baseline), and then approximately 1.5, 6, 12, and 24 months post completion of radiotherapy.

Design: Seventy patients will be enrolled and treated with radiation therapy to the brain or base of skull. They will then be followed over two years and obtain neurocognitive testing and MRI scans at specific time points over the course of 2 years. This will be done in conjunction to obtaining information regarding late toxicity.

Objectives: To determine if the decrease in overall low dose radiation with proton therapy to the brain has a meaningful impact on neurocognition and compare this to historical group of patients that received photon therapy as well as compared to normal control patients. In addition, we will attempt to correlate the changes noted with imaging correlates to assist in treatment planning for the future.

Endpoints: These include changes in neurocognition with an attempt to determine clinical and imaging correlates for memory decline.

Contact Information:
Prospective participants and/or their physicians may contact Ellen Rash at 215-614-1786 for information about enrolling in these trials.

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 Proton Therapy for Meningiomas and Hemagiopericytomas at Penn Medicine

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

Goldie A. Kurtz, MD
Instructor of Radiation Oncology

Robert Lustig, MD
Professor of Clinical Radiation Oncology
Chief of Clinical Operations

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

Continent Urinary Diversion and Orthotopic Neobladder Surgery After Cystectomy for Invasive Bladder Cancer

noreply@blogger.com (Anonymous) — Thu, 28 May 2015 18:39:00 +0000

Surgeons at Penn Medicine are performing continent urinary diversion and orthotopic neobladder procedures following cystectomy for invasive bladder cancer.

Surgery for high risk bladder cancer (>T2 disease or high grade non-invasive disease refractory to other treatment) is complex and combines the removal of the bladder (cystectomy) with some form of urinary tract reconstruction. Cystectomy generally involves a prostatectomy in men and a hysterectomy and partial vaginectomy in women. In both cases, a meticulous, extended pelvic lymphadenectomy is also performed.

Neoadjuvant chemotherapy is usually performed in the presence of muscle invasive disease, but adjuvant chemotherapy may also be used in appropriate situations. Chemotherapy, offered by the Division of Hematology/Oncology at Penn, can improve survival outcomes in patients with bladder cancer.

Urinary diversion, performed after the cystectomy, is required since the function of urine storage and emptying has been lost after the removal of the bladder. In the United States, the procedure is most often accomplished with a simple ileal loop diversion in which a short portion of small intestine is attached to the ureters from the kidneys and then brought to the skin. This is covered by an external stoma bag where urine is stored and emptied by the patient.

Since the mid 1980’s Penn surgeons have improved upon cystectomy with urinary diversion by constructing a continent neobladder that eliminates the need for a stoma bag. Neobladder reconstruction allows the patient to retain a normal body appearance and maintain urinary function while treating the cancer. Approximately 80 to 90 percent of patients nationwide receive a simple ileal loop; nearly half of Penn patients undergo continent reconstruction.

Orthotopic neobladder surgery involves the creation of a pouch in the pelvis constructed from a portion of the small bowel and anastomosed to the urethra. (Figure 1). After such surgery, patients can void through the urethra. A separate procedure, cutaneous continent diversion, involves an intra-abdominal pouch constructed from detubularized bowel and accessed from a small, flat, catheterizable stoma at the skin no wider than the head of pencil eraser. These more sophisticated forms of reconstruction do not interfere with either neoadjuvant or adjuvant administration of chemotherapy.

The general goals of orthotopic neobladder surgery and cutaneous continent diversion include the creation of a reservoir with adequate capacity, urinary continence during normal activity and volitional emptying. The majority of patients (approximately 98%) regain daytime continence. Some patients may have urinary seepage in the evening (10-15%) which is correctable with pelvic floor training and evening fluid intake.

Case Study
Mr. Y, a 62 yr old male, was referred to Penn Urology following an episode of gross hematuria, after which a cystoscopic exam demonstrated a sessile lesion in the posterior wall of the bladder. On final pathology, Mr. Y was noted to have tumor invasion in the muscularis propria of the bladder. A metastatic evaluation consisting of a chest and abdominal CT revealed no sign of metastases or lymphadenopathy. Mr. Y reported a 30-pack/year smoking history, but no family history of cancer. His medical history included two cardiac stents placed within the past five years for cardiovascular disease.

After a thorough consideration of his options, Mr. Y chose to have a cysto-prostatectomy with a neobladder and lymph node dissection. He was scheduled for surgery within six weeks. Because his clinically displayed disease was low volume, Mr. Y chose not to have chemotherapy prior to surgery.

Mr. Y’s surgery was initiated with a lower midline incision and exposure of the pelvic organs, during which the ureters were identified and mobilized and an extensive pelvic lymph node dissection was performed. A cystectomy and prostatectomy were then performed with attention to preservation of nerves and continence mechanisms and without compromise to the oncologic principle of obtaining negative margins.

Once these procedures were accomplished, an appropriate segment of bowel was selected and demarcated and separated from the GI tract, but maintained on its vascular supply. A bowel anastomosis was then performed, and the bowel segment opened to provide maximal surface area and optimal volume for the neobladder (Figure 1). The pouch was then constructed and the ureters anastomosed to it to bring the kidneys and pouch into continuity.

After the construction of the pouch, it was reanstomosed to the urethra, which was determined to be healthy by a negative frozen margin. Mr. Y was hospitalized for five to eight days and returned for X-ray studies two weeks later to assess healing of the pouch.

At this point, all additional drains were removed and Mr. Y was scheduled for continence training with experts in pelvic floor rehabilitation at Penn Urology. His final pathology was pT2a N 0/48 M0. He did not have post-operative chemotherapy. At five years post-surgery, he showed no evidence of cancer recurrence.

Faculty Team
Penn urologists bring a wealth of knowledge to the care of patients with urologic problems and are known for their expertise in cancer, voiding dysfunction, urinary incontinence, stone disease, interstitial cystitis and male sexual dysfunction. Penn urologists perform an average of 50 cystectomy surgeries each year for bladder cancer. Orthotopic neobladder surgery and cutaneous continent diversion surgeries have been performed at Penn for more than two decades.

Performing Continent Urinary Diversion and Neobladder Surgery at Penn Medicine

Urology
S. Bruce Malkowicz, MD
Professor of Urology

Thomas J. Guzzo, MD, MPH
Assistant Professor of Urology in Surgery

Medical Oncology
David J. Vaughn, MD
Professor of Medicine
Vice Chief for Clinical Affairs, Division of Hematology/Oncology,
Hospital of the University of Pennsylvania

Ronac Mamtani, MD, MSCE
Assistant Professor of Medicine

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

Peroral Endoscopic Myotomy (POEM) for Esophageal Achalasia

noreply@blogger.com (Anonymous) — Mon, 20 Apr 2015 19:14:00 +0000

Gastroenterological endoscopists at Penn Medicine are now performing incisionless Peroral Endoscopic Myotomy (POEM) to treat esophageal achalasia.

Achalasia is a rare idiopathic motility disorder that manifests as hypertension and incomplete relaxation of the lower esophageal sphincter (LES) and aperistalsis of the esophageal body. The disorder is a result of impairment of the smooth muscle fibers, leading to failure of bolus transit through the esophagus. Symptoms include dysphagia, regurgitation, heartburn and chronic chest pain, with the consequent potential for weight loss, malnutrition and pulmonary sequelae.

Following diagnosis of esophageal achalasia by esophageal manometry and barium swallow esophagram, the standard surgical treatment is the Heller myotomy. First performed in 1914, Heller myotomy involves cutting the muscles of the LES to open the valve and permit food and liquids to pass into the stomach. Laparoscopic multi-port Heller myotomies are now the preferred approach. Post-operative complications may include infection, bleeding and rarely, esophageal or gastric perforation. The Heller procedure is often combined with fundoplication to prevent gastroesophageal reflux.

Alternatives to surgery for the treatment of achalasia include balloon dilation to expand the constricted sphincter and injections of botulinum directly into the esophagus to relax spastic muscle contractions. Both treatments are effective in the short term, but may require repeated administration to improve the symptoms of achalasia.

A more recent innovation, Peroral Endoscopic Myotomy (POEM) has been developed in Japan by Haruhiro Inoue, MD, PhD, who guided the introduction of the procedure at Penn Medicine. POEM involves the use of endoscopic tools to perform an intramural myotomy (as opposed to the extramural Heller procedure). A full description of the procedure can be found in the Case Study below.

In Dr. Inoue’s original series of 70 cases at Showa University Hospital, Yokohama, Japan, [1] POEM resulted in significant reductions in LES pressure (elevated in most patients with achalasia) and subjective symptom score. Marked improvement was noted in endoscopic appearance and esophageal emptying on barium swallow. Symptomatic post-POEM gastroesophageal reflux disease was observed in 11.4% of patients, but all were successfully treated with standard proton pump inhibitors.

Reference
1. Minami H, Inoue H, Haji A, et al. Per-oral endoscopic myotomy: Emerging indications and evolving techniques. Digestive Endoscopy 2015; 27: 175–181.

Case Study

Mr. Y, age 43 years, was referred to Penn Gastroenterology eight months after a botulinum toxin injection procedure for diagnosed achalasia at a hospital near his home in New Jersey.

Mr. Y’s symptoms at this time included protracted post-prandial pain, dysphagia to both solids and liquids and occasional vomiting.

The botulinum toxin injection procedure provided some immediate relief, but within three to six weeks, his symptoms began a slow and progressive return. Mr. Y was in otherwise good health.

At Penn, a barium esophagram revealed esophageal dilatation and stenosis of the cardiac region of the esophagus with delayed evacuation of the barium meal (Fig. 1) . After a consultation to discuss his options, it was agreed that Mr. Y would have a POEM procedure. Mr. Y’s POEM was initiated by creating a 2 cm entry site into the mid-esophageal wall and then a tunnel in the submucosal space extending immediately beyond the esophagogastric junction to the lesser curve of the gastric cardia (Fig. 2).

Next, an inner circular muscle myotomy was performed by grasping and dividing the fibers. Following the myotomy, the endoscope was withdrawn from the submucosal tunnel and reinserted into the lumen to inspect the mucosa, ensure mucosal integrity and confirm easy passage of the endoscope through the LES consistent with an adequate myotomy. The mucosal entry site was then closed with endoscopic clips (Fig. 3).

Mr. Y was observed overnight in the Second-Stage Recovery Unit following his procedure. He received IV-hydration until post-operative day 1, when a barium esophagram was obtained. Noting no loss of mucosal integrity or leakage, Mr. Y was started on a liquid diet and discharged home. Two days later, he began a solid diet, and his recovery thereafter was unremarkable. At his six-month follow-up,
he reported a complete resolution of symptoms.

Faculty Team
The Division of Gastroenterology at Penn Medicine is comprised of a multidisciplinary team of clinician specialists who treat a variety of digestive, liver and pancreatic disorders. Many Penn gastroenterologists are actively involved in clinical research, as well, pioneering advances within their fields to bring more options to the detection and management of inflammatory bowel disease, Crohn’s disease, celiac disease and gastroesophageal reflux disease and other gastrointestinal disorders. The genetics of gastroenterological disease are a particular focus of research at Penn, as are the effects of comorbid disease and other risk factors.

Performing Peroral Endoscopic Myotomy at Penn Medicine

Gregory G. Ginsberg, MD
Director of Endoscopic Services
Professor of Medicine
Professor of Surgery in Medicine

Vinay Chandrasekhara, MD
Assistant Professor of Medicine

Other collaborators include:

Daniel T. Dempsey, MD
Professor of Surgery

Kristoffel R. Dumon, MD
Assistant Professor of Surgery

Gary W. Falk, MD, MS
Professor of Medicine

David Metz, MD
Clinical Chief of Gastroenterology
Professor of Medicine

Michael L. Kochman, MD
Wilmott Family Professor of Medicine
Professor of Surgery in Medicine

Noel N. Williams, MD
Professor of Clinical Surgery

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Penn Gastroenterology
Perelman Center for Advanced Medicine
South Pavilion, 4th Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

Enrolling Clinical Trials at Penn Gastroenterology

Expanding the Clinical Applications of Functional Luminal Imaging (EndoFLIP) in Esophageal Stenoses
The purpose of this study is to investigate the use of a functional luminal imaging probe to characterize benign esophageal luminal strictures before and after dilation and identify predictors of response to therapy. Patients will be evaluated during endoscopy using functional luminal imaging (EndoFLIP; Crospon Medical Devices, Galway, Ireland) to characterize the geometry of benign luminal esophageal narrowing before and after dilation. Contact Maureen DeMarshall, BSN, RN, at demarshm@mail.med.upenn.edu.

Preliminary Evaluation of Septin9 in Patients With Hereditary Colon Cancer Syndromes
This is an observational, case-control study evaluating the quantitative level of Septin9 in plasma pre- and post-colectomy in patients with hereditary colorectal cancer (CRC) syndrome, Familial Adenomatous Polyposis (FAP), Lynch syndrome (also known as HNPCC), and Multiple Adenomatous Polyposis (MAP, also known as MYK/MYH), with genetically related FAP-family members as controls and references. Contact Julie Starr at (215) 349 – 8527, or jstarr@mail.med.upenn.edu.

Familial Barrett’s Esophagus (FBE)
This is a multi-center study whose aim is to define the epidemiology and genetics of Barrett’s esophagus and adenocarcinoma. The researchers have studied families affected with Barrett’s esophagus and esophageal adenocarcinoma. They have found that Barrett’s and esophageal cancer occur at a younger age in these families, suggesting that familial Barrett’s esophagus is a genetically inherited disease. Contact Maureen Demarshall, RN, at demarchm@mail.upenn.edu.

Surgical Management of Drug-Resistant Epilepsy

noreply@blogger.com (Anonymous) — Thu, 16 Apr 2015 12:17:00 +0000

Penn Epilepsy Center

Epileptologists from the departments of Neurosurgery and Neurology at Penn Medicine have recently introduced a collection of innovative technologies to better treat patients with drug-resistant epilepsy (defined as having seizures refractory to two or more seizure medications).

Medications can control seizures in about two-thirds of persons with epilepsy. The approximate one-third of patients with drug-resistant epilepsy experience a significant impact on quality of life, elevated risk of injury and increased risk of sudden unexpected death.

For patients with drug-resistant epilepsy, the options available at Penn Medicine include resective surgery and vagus nerve stimulation (VNS), as well as newer approaches. Surgery has the potential to cure or decrease seizure frequency when an epileptogenic focus can be identified. Intracranial EEG evaluations are often performed to identify seizure foci prior to resection. Vagus nerve stimulation is an option for patients who are not resective surgical candidates. VNS reduces the frequency and intensity of seizures, but is not curative.

The new technologies available to treat patients with refractory epilepsy at Penn Medicine include Visualase® MRI-Guided Laser Ablation and the NeuroPace RNS® System. Penn neurosurgeons and neurologists have collaborated to introduce these advanced modalities, which can better identify the source of seizures and treat or prevent seizures in patients with drug-resistant epilepsy.

Visualase MRI-Guided Laser Ablation Technology

Visualase laser ablation is a technology that combines a saline-cooled 15 watt, 980-diode laser probe (less than 2 mm diameter) with real-time MRI-guidance to induce interstitial thermal ablation of targeted lesions in the brain (Fig. 1).

Pre-treatment images are acquired for target planning and an intraoperative temperature map is used to minimize damage to healthy tissue. Open surgery is not required. Patients may be awake during therapy and are usually discharged the next day.

NeuroPace RNS System

The NeuroPace RNS System is a programmable responsive neurostimulation system designed to detect and treat abnormal electrical activity in the brain. The System employs brief bursts of electrostimulation from an RNS neurostimulator implanted in the cranium to abort pre-seizure EEG patterns programmed by physicians.

Intracranial EEG (iEEG)
Structural MRI, fdg-PET and ictal scalp EEG recordings cannot identify the epileptic network in many refractory epilepsy patients having pre-surgical evaluation. For these patients, intracranial EEG (iEEG) hybrid depth and subdural grid and strip electrodes (Fig. 3) are required for long-term, high-resolution monitoring and mapping of the cortical surface. iEEG allows Penn clinicians to map the epileptic network and cortical function, making safe resective surgery with a goal of cure possible for many drug-resistant epilepsy patients.

Visualase®; 2015 Medtronic, Inc. Minneapolis, Minnesota.
NeuroPace RNS® System; 2015 NeuroPace, Inc. Mountain View, CA.

Faculty Team

The Penn Epilepsy Center (PEC) is comprised of an interdisciplinary team of clinicians dedicated to advancing the fields of invasive neurophysiology, neuroimaging and neurosurgery for patients with epilepsy in all of its forms. The PEC offers state-of-the-art diagnostic techniques, medical treatments, surgery and support to patients
with epilepsy.

Treating Epilepsy at Penn Medicine

Brian Litt, MD
Director, Penn Epilepsy Center
Professor of Neurology, Bioengineering and Neurosurgery

Gordon H. Baltuch, MD, PhD
Director, Center for Functional and Restorative Neurosurgery
Professor of Neurosurgery

Kathryn Davis, MD, MTR
Medical Director, Epilepsy Monitoring Unit
Assistant Professor of Neurology

Timothy H. Lucas II, MD, PhD
Director, Translational Neuromodulation Laboratory
Assistant Professor of Neurosurgery

John R. Pollard, MD
Associate Professor of Clinical Neurology

Sarah Schmitt, MD
Director, EEG Laboratory
Assistant Professor of Clinical Neurology

Danielle Becker, MD, MSc
Assistant Professor of Clinical Neurology

Doug Maus, MD, PhD
Assistant Professor of Clinical Neurology

The Penn Epilepsy Center

The Penn Epilepsy Center offers a comprehensive, individualized evaluation and a wide variety of surgical treatments for patients whose epilepsy is difficult to manage. As a Level 4 epilepsy center, we have the expertise and facilities to provide the highest-level of medical and surgical evaluation and treatment for patients with epilepsy.

The Center offers comprehensive evaluation for people who have experienced:

Long-standing seizures that are not adequately controlled
One or more seizures
Unacceptable side effects from epilepsy treatments
Unusual events that a physician believes may have been seizures

Epilepsy Monitoring Unit

The Epilepsy Monitoring Unit features a modern eight-bed unit with video EEG for the evaluation of individuals who are candidates for surgery and for differential diagnosis of “spells.” Epilepsy patients are admitted for long-term monitoring (anywhere from 3 to 7 days) and are typically weaned from medications to determine the cause and origin of seizures. Some patients undergoing this treatment require intracranial electrode monitoring. A number of other diagnostic tools may also be used to locate the origin of the seizures, including MRI, MEG, EEG, SPECT and PET.

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Penn Neuroscience Center
Perelman Center for Advanced Medicine
South Pavilion, 2nd Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

Pennsylvania Hospital
330 South 9th Street
Philadelphia, PA 19107

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

Diagnosis and Treatment of Dry Eye Syndrome

noreply@blogger.com (Anonymous) — Tue, 07 Apr 2015 17:00:00 +0000

Penn Dry Eye & Ocular Surface Center

Ophthalmologists at the Penn Dry Eye & Ocular Surface Center are applying recent advances in diagnostic technology to diagnose the primary causes of keratoconjunctivitis sicca (or dry eye syndrome) in order to optimize treatment for the condition.

Traditionally, dry eye syndrome (DES) has been thought of as a deficiency of tears at the ocular surface. Symptoms include blurred vision, scratchiness, irritation, redness or tiredness of the eyes. Recent investigations have shown, however, that DES is much more complex than previously thought, and that “tear film dysfunction syndrome” might more accurately describe the condition.

Tear film dysfunction can be broken down into two basic etiologic classifications: insufficient tear production or increased evaporation of tears from the eye surface. The tear film is made up of lipid, aqueous and mucin components. Individuals with dry eye syndrome can be deficient in any of these basic factors.

Lipid tear deficiency is most commonly caused by blepharitis or meibomian (oil producing) gland dysfunction. This leads to abnormally increased evaporation of the tears from the surface of the eye.
Mucin deficiency can be caused by conditions such as vitamin A deficiency, chemical injury, and Stevens-Johnson syndrome. Mucin is produced by goblet cells, and promotes even distribution of the aqueous tears over the surface of the eye.

Aqueous tear deficiency is associated with insufficient tear production. Congenital causes include conditions such as Riley-Day syndrome or familial dysautonomia. Acquired causes of aqueous tear deficiency include contact lens wear, increasing age, hormonal changes, medications, and Sjogren’s Syndrome and other autoimmune diseases.

DES is often misdiagnosed, and accurate assessment of the underlying causes of a patient’s ocular surface disease is critical. Misdiagnosis and the resulting delay in appropriate treatment can permit the continuation of destructive disease processes and can lead to eventual permanent scarring of the ocular surface.

Diagnosis
The Penn Dry Eye & Ocular Surface Center has developed a multidisciplinary approach to identify the cause of a patient’s tear film dysfunction or ocular surface disease. Ophthalmologists collaborate with specialists in other departments to provide care for any medical problems or conditions that may be contributing to the patient’s eye problems.

In the office, specially-trained ophthalmologists perform thorough evaluations of the ocular surface. These assessments may include analysis of the tear film for specific proteins, cytokines and osmolarity. Schirmer testing is used to measure tear production, while optical coherence tomography (OCT) allows quantification of tear meniscus height.

Special stains and impression cytology are used to evaluate the cornea and conjunctiva. Keratographs utilizing trans-illumination and infrared light capture detailed images of the meibomian glands in the upper and lower eyelid and lid margin. The oil or lipid layer is also measured with sophisticated surface interferometers.

Treatment Options
Management of tear film dysfunction and ocular surface disease at the Penn Dry Eye & Ocular Surface Center is tailored to the individual patient and has the objective of promoting the health of the ocular surface. Lifestyle changes, artificial tears and topical eye ointments may help patients with mild DES.

Patients with moderate to severe DES may benefit from medical treatment with immunomodulators, anti-inflammatory agents, omega-3 fatty acid supplements, autologous serum, mucolytic agents or surgical interventions such as punctal occlusion, cautery or various lid surgeries.

The specialists at the Penn Dry Eye & Ocular Surface Center also perform amniotic membrane transplantation, artificial cornea transplants (keratoprosthesis surgery) and other advanced ocular reconstructive surgeries. Therapeutic options for eyelid diseases include intense pulsed light (IPL) therapy (Fig. 2), Lipiflow, Blephex, lid debridement and meibomian gland probing (Fig. 3).

Patients may also be fitted for specialized contact lenses including various types of scleral lenses. In addition, supplemental treatments including drops, gels, ointments, vitamins, lid scrubs, warming and cooling gel packs, goggles, specialized sunglasses, etc. are offered on site for patients to purchase.

Research at the Dry Eye & Ocular Surface Center

Dry Eye Assessment and Management Study (DREAM)

The objective of the DREAM study is to evaluate the effectiveness and safety of supplementation with omega-3 fatty acids in relieving the symptoms of moderate to severe dry eye disease. The study is designed to test the hypothesis that omega-3 supplementation is an effective treatment for dry eye disease (DED). Please see http://1.usa.gov/13JncIl for inclusion criteria.

Primary investigator: Vatinee Bunya, MD
Contact: 215.662.8191

Evaluation of Efficacy of 20 µg/ml rhNGF New Formulation (With Anti-oxidant) in Patients With Stage 2 and 3 Neurotrophic Keratitis

The primary objective of this study is to evaluate the efficacy of 20 µg/ml 6 times a day of recombinant nerve-growth factor (rhNGF) eye drop solution containing anti-oxidant compared to vehicle (formulation containing anti-oxidant) given 6 times a day. The evaluation of efficacy is intended as complete healing of stage 2 (persistent epithelial defect) and 3 (corneal ulcer) neurotrophic keratitis (NK) as measured by the central reading center using corneal fluorescein staining; assessing the duration of complete healing; improvement in visual acuity and improvement in corneal sensitivity. Please see http://1.usa.gov/1B43BQr for additional information.

Primary investigator: Mina Massaro Giordano, MD
Contact: 215.662.8100

Faculty Team
Tear film dysfunction and other ocular surface diseases are treated at the Penn Dry Eye & Ocular Surface Center by specially trained ophthalmologists who have a particular interest in caring for patients with dry eye and other types of ocular surface disease. The Center involves collaboration with specialists in cornea and external disease, oculoplastics, contact lens, rheumatology, dermatology and endocrinology.

Ophthalmology
Mina Massaro-Giordano, MD
Associate Professor, Comprehensive Ophthalmology
Co-Director, Penn Dry Eye & Ocular Surface Center

Vatinee Y. Bunya, MD
Assistant Professor, Cornea & External Disease
Co-Director, Penn Dry Eye & Ocular Surface Center

Stephen E. Orlin, MD
Associate Professor, Cornea & External Disease
Director, Cornea Service

Michael E. Sulewski, MD
Clinical Associate of Ophthalmology
Chief of Ophthalmology, VA Hospital
Co-director, Cornea Service

Oculoplastics
Sonul Mehta MD
Assistant Professor of Ophthalmology

Rheumatology
Frederick B. Vivino, MD
Professor of Clinical Medicine
Director, Sjogren’s Syndrome Center
Chief of Rheumatology, Penn Presbyterian Medical Center

Chadwick R. Johr, MD
Assistant Professor of Clinical Medicine
Co-Director of Sjogren’s Syndrome Center

Dermatology
Catherine M. Quirk, MD
Clinical Associate of Dermatology

Endocrinology
David M. Finkel, MD
Physician

Contact Lens
Diane Heistand-Talecki, COT, NCLC, FNAO
Kathy McNelis, COA, NCLC
Cynthia Silvestri, NCLC

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

Complex Retrieval of Embedded Inferior Vena Cava Filters

noreply@blogger.com (Anonymous) — Tue, 07 Apr 2015 16:16:00 +0000

Department of Radiology • Division of Interventional Radiology

Interventional radiologists at Penn Medicine are performing retrieval of tip-embedded inferior vena cava (IVC) filters using rigid endobronchial forceps, a technique developed by Penn Interventional Radiology. The efficacy and safety of the technique has recently been confirmed in a clinical study published in the journal Radiology. [1]

The largest venous trunk in the body, the IVC is a conduit for thromboemboli originating in the legs.
Among hypercoagulable individuals, particularly those with contraindications for anticoagulant therapy, caval blood clots are a primary cause of catastrophic pulmonary embolism. Percutaneous placement of permanent or retrievable IVC filters is an effective way to trap these clots before they reach the lungs.

Although the FDA recommends that IVC filters be removed when no longer needed, it is estimated that fewer than half of retrievable devices are taken out each year. This number includes the 5 to 10 percent of retrieval attempts that fail because the filter tip is embedded in the vessel wall.

Tip-embedded filters must be removed because they present a substantial risk for vessel occlusion, fracture, and further penetration through the IVC into bowel, bone, arteries and other structures. Standard retrieval of IVC filters involves capturing the devices with snares or cones. Neither technique is effective, however, when the filter tip is embedded in the vessel wall (see Fig. 1).

Every tip-embedded filter retrieval is considered a high-risk procedure. Incomplete, failed or overly aggressive removal of the filter can result in vessel damage and/or further distortion/fracture of the filter.

IVC Filter Retrieval at Penn

For more than a decade, interventional radiologists at Penn Medicine have been developing methods to improve the results of IVC filter retrieval and to optimize retrieval of tip-embedded caval filters.

The approach to these complex retrievals involves the use of rigid endobronchial forceps placed into the IVC from the right internal jugular vein through a sheath and dissecting away engulfing tissue, grasping the filter tip and removing the device (Fig. 2). The technique incorporates several imaging modalities, including rotational venography, spot radiography, and CT venography.

In a recent retrospective study at Penn (see back page), the endobronchial forceps approach was used successfully to retrieve 109 of 114 (96%) tip-embedded IVC filters. Three minor complications and one major complication occurred (the latter involved a patient in whom the struts as well as the tip were embedded), but these resulted in no permanent sequelae.

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 records, he had a history of deep vein thrombosis, for which he’d been taking warfarin for some years. Recently, however, he’d experienced a bleeding ulcer, requiring him to temporarily cease taking the drug.

To protect Mr. W from pulmonary emboli in this interim, a retrievable filter was placed in his inferior vena cava at his community hospital. After Mr. W’s ulcer had healed and he re-started warfarin, he returned to the hospital to have the IVC filter removed. An inferior vena cavagram at this time showed the tip of the filter embedded in the vessel wall, however, and the retrieval attempt was abandoned.

Mr. W was then referred to Penn Interventional Radiology, where he was scheduled for a complex IVC filter retrieval after an office consultation. His anticoagulation was not interrupted for the one-hour procedure, which was performed in an outpatient setting. Following access at the right internal jugular, endobronchial forceps were used to cut away the tissue surrounding the embedded tip, allowing the filter to be grasped and removed.

Following the procedure, Mr. W was observed for two hours; he 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, admitting and consulting service.

Performing Complex IVC Retrievals at Penn Medicine

Scott O. Trerotola, MD
Stanley Baum Professor of Radiology
S. William Stavropoulos, MD
Professor of Radiology

Hospital of the University of Pennsylvania
Mandeep S. Dagli, MD
Assistant Professor of Clinical Radiology
Stephen Hunt, MD
Instructor in Radiology
Maxim Itkin, MD
Adjunct Associate Professor of Radiology
Jeffrey I. Mondschein, MD
Associate Professor of Clinical Radiology
Gregory Nadolski, MD
Assistant Professor of Radiology
Richard Shlansky-Goldberg, MD
Professor of Radiology
Michael C. Soulen, MD
Professor of Radiology
Deepak Sudheendra, MD
Assistant Professor of Clinical Radiology
Micah Watts, MD
Adjunct Assistant Professor of Radiology

Penn Presbyterian Medical Center
Timothy W.I. Clark, MD
Associate Professor of Clinical Radiology
Jonas Redmond, MD
Assistant Professor of Clinical Radiology

Pennsylvania Hospital
Raymond Fabrizio, MD
Assistant Professor of Clinical Radiology
Benjamin D. Hammelman, 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 North 39th Street
Philadelphia, PA 19104

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

Total Proctocolectomy with J-pouch Reconstruction for Ulcerative Colitis

noreply@blogger.com (Anonymous) — Tue, 17 Mar 2015 16:34:00 +0000

Division of Colon and Rectal Surgery

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

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

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

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

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

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

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

Case Study

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

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

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

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

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

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

Faculty Team

The Division of Colon and Rectal Surgery at Penn Medicine provides the highest quality diagnostic and surgical options for patients with colon, rectal and anal cancer, inflammatory bowel disease (Crohn’s disease and ulcerative colitis), diverticular disease and many other diseases of the colon, rectum and anus. The division offers sphincter-preserving colon and rectal surgery for cancer and benign disease, laparoscopic and robotic colorectal surgery, treatment for fecal incontinence and rectal prolapse and both operative and medical therapies for anal diseases.

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

Najjia N. Mahmoud, MD
Chief of Colon and Rectal Surgery
Associate Professor of Surgery
najjia.mahmoud@uphs.upenn.edu

Cary B. Aarons, MD
Assistant Professor of Clinical Surgery
cary.aarons@uphs.upenn.edu

Joshua I. S. Bleier, MD
Associate Professor of Clinical Surgery
joshua.bleier@uphs.upenn.edu

Skandan Shanmugan, MD
Assistant Professor of Clinical Surgery
skandan.shanmugan@uphs.upenn.edu

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Department of Surgery

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

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

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

Medical and Surgical Management of Myasthenia Gravis and Thymoma

noreply@blogger.com (Anonymous) — Wed, 28 Jan 2015 19:46:00 +0000

Department of Thoracic Surgery • Department of Neurology

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

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

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

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

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

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

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

Case Study

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

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

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

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

Access

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

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

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

Myasthenia and Thymoma Program Faculty Team

Cardiology
Alan D. Askenase, MD
Clinical Associate Professor of Medicine

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

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

Neuro-Ophthalmology
Madhura A. Tamhankar, MD
Assistant Professor of Ophthalmology

Pulmonology
Joel L. Deitz, MD
Clinical Associate Professor of Medicine

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

Radiation Oncology
Abigail T. Berman, MD

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

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

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

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

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

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

Current Aortic Aneurysm Stent Device Clinical Trials

noreply@blogger.com (Anonymous) — Tue, 06 Jan 2015 13:38:00 +0000

Vascular Surgery and Endovascular Therapy

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

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

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

Heidi Martin, MS, Clinical Research Coordinator.

Phone: 215-662-4320

Email: Heidi.Martin@uphs.upenn.edu

Zenith® p-Branch OTS Multicenter Study

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

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

Zenith® Low Profile AAA Endovascular Graft Clinical Study

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

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

PRESERVE-Zenith® Iliac Branch Clinical Study

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

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

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

Faculty Team

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

Performing Endovascular Clinical Trials at Penn Medicine

Scott M. Damrauer, MD
Assistant Professor of Surgery

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

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

Michael A. Golden, MD*
Associate Professor of Surgery

Benjamin M. Jackson, MD
Assistant Professor of Surgery J

Venkat R. Kalapatapu, MD†
Assistant Professor of Clinical Surgery

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

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

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

Access

Patient appointments are available at:

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

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

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

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

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

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

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

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

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

Paired Kidney Exchange for Kidney Transplantation

noreply@blogger.com (Anonymous) — Fri, 05 Dec 2014 20:00:00 +0000

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

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

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

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

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

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

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

Case Study

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

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

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

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

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

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

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

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

Performing Kidney Transplantation at Penn Medicine

Transplant Surgeons

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

Peter L. Abt, MD
Associate Professor of Surgery

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

Paige Porrett, MD, PhD
Assistant Professor of Surgery

Susanna M. Nazarian, MD, PHD

Assistant Professor of Surgery

Transplant Nephrologists

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

Melissa B. Bleicher, MD
Assistant Professor of Clinical Medicine

Simin Goral, MD
Professor of Medicine

Robert A. Grossman, MD
Professor of Medicine

Mary Ann Lim, MD
Assistant Professor of Clinical Medicine

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

Deirdre L. Sawinski, MD
Assistant Professor of Medicine

Karen Warburton, MD*
Associate Professor of Clinical Medicine

Renal Nurse Practitioners
Jenna Angerstein, MSN, CRNP, CCTN
Naomi Barton, MSN, CRNP
Gail Eastman, MSN, CRNP
Transplant Surgery Nurse Practitioners
Alva Moy-Daley, MSN, CRNP
Julie Spaulding, MSN, CRNP

Manager, Transplant Outreach and Communication
Denny DuPont
215-873-7983
denise.dupont@uphs.upenn.edu

*Living Donor Team Nephrologists

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

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

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

Access

Penn Transplant Institute Kidney Transplant Program

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

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

Patients also evaluated at:

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

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

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

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

The contact number for recipients and donors is 215.662.6200.

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

Periacetabular Osteotomy for Complex Structural Hip Deformity

noreply@blogger.com (Anonymous) — Thu, 20 Nov 2014 17:50:00 +0000

Department of Orthopaedic Surgery • Center for Hip Preservation

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

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

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

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

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

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

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

Case Study

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

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

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

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

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

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

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

Faculty Team

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

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

Performing Periacetabular Osteotomy for Hip Preservation at Penn Medicine

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

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

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

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

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

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

Sialendoscopic Management of Salivary Stones and other Salivary Duct Pathologies

noreply@blogger.com (Anonymous) — Tue, 14 Oct 2014 16:09:00 +0000

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

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

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

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

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

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

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

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

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

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

Performing Sialendoscopic Procedures at Penn Medicine

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

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

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

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

Laurie A. Loevner, MD
Professor of Radiology

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

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

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

Living Donor Liver Transplantation at Penn Medicine

noreply@blogger.com (Anonymous) — Tue, 22 Jul 2014 17:44:00 +0000

Penn Transplant Institute

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

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

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

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

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

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

Case Study

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

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

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

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

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

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

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

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

___________________________________________________________________________________

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

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

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

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

References

1. Olthoff KM, Abecassis MM, Emond JC, et al. Outcomes of adult living donor liver
    transplantation: comparison of the Adult-to-adult Living Donor Liver Transplantation
    Cohort Study and the national experience. Liver Transpl. 2011;17(7):789-797.
2. Berg CL, Merion RM, Shearon TH, Olthoff KM, et al. Liver transplant recipient
    survival benefit with living donation in the model for endstage liver disease allocation
    era. Hepatology. 2011;54(4):1313-1321.
3. Goldberg DS, Abt PL, Olthoff KM, Shaked A. Superior Survival Using Living Donors
    and Donor-Recipient Matching Using a Novel Living Donor Risk Index. Hepatology.
    2014.

___________________________________________________________________________________

Faculty Team

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

Performing Living Donor Liver Transplantation at Penn Medicine

Liver Transplant Surgeons

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

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

Peter L. Abt, MD
Associate Professor of Surgery

Hepatology

Rajender Reddy, MD
Director, Hepatology; Medical Director, Liver Transplantation

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

Maarouf A. Hoteit, MD
Assistant Professor of Clinical Medicine

Ranjeeta Bahirwani, MD
Assistant Professor of Clinical Medicine

Vandana Khungar, MD, MSc
Assistant Professor of Medicine

Christine Hsu, MD
Assistant Professor of Clinical Medicine

Kimberly A. Forde-McLean, MD, MHS
Assistant Professor of Medicine

Rotonya Carr, MD
Assistant Professor of Medicine

Living Donor Coordinator
Linda Wood, BSN, RN

Transplant Outreach & Communication
Denny DuPont
215-873-7983
denise.dupont@uphs.upenn.edu

Access

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