University of Pennsylvania Health System

Clinical Briefings™: Clinical Reports from Penn Medicine

Monday, January 18, 2016

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

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

Tuesday, January 5, 2016

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



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



https://drive.google.com/file/d/0B0vaPQ5yI4B3ZUpLZ3JINXVWck0/view?usp=sharing




http://clinicalresearch.itmat.upenn.edu/participant/




Monday, December 21, 2015

Microsurgical Nerve Conduit Neurotization to Restore Sensation after Breast Reconstruction Surgery

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

https://drive.google.com/file/d/0B0vaPQ5yI4B3R2NXWDFKTlVmcTQ/view?usp=sharing

Monday, November 23, 2015

Enrolling Clinical Trials: Novel Therapeutics for Chronic Lymphocytic Leukemia

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
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.

https://drive.google.com/file/d/0B0vaPQ5yI4B3MTZvQlZXeFl4MjQ/view?usp=sharing




http://clinicalresearch.itmat.upenn.edu/participant/

Friday, November 13, 2015

Management of Recurrent Dislocation of the Temporomandibular Joint (TMJ)

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

https://drive.google.com/file/d/0B0vaPQ5yI4B3anBlV3JweERKNUU/view?usp=sharing

https://www.pennmedicine.org/s-landing/refer-patient.html





Friday, October 23, 2015

Electrophysiology Research and Publications Update

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: Circ Arrhythm Electrophysiol. 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: Circ Arrhythm Electrophysiol. 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

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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.

Thursday, October 22, 2015

Endovascular Revascularization for Wound Care in Critical Limb Ischemia

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

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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


https://drive.google.com/file/d/0B0vaPQ5yI4B3eUxhMF9qWUU4SWM/view?usp=sharing





https://www.pennmedicine.org/s-landing/request-appointment.html












Monday, October 19, 2015

Surgical and Medical Management of Osteosarcoma

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
  
https://www.pennmedicine.org/s-landing/request-appointment.html

https://drive.google.com/file/d/0B0vaPQ5yI4B3YVdIRUJURUw2SDQ/view?usp=sharing








Tuesday, August 25, 2015

Pharmacomechanical Thrombolysis of Symptomatic Deep Vein Thrombosis

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

https://drive.google.com/file/d/0B0vaPQ5yI4B3eTVPVTVDYzczMjg/view?usp=sharing

Friday, July 24, 2015

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

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 


Access
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


https://drive.google.com/file/d/0B0vaPQ5yI4B3SV9CdjJNUkhzSG8/view?usp=sharing