University of Pennsylvania Health System

Clinical Briefings™: Clinical Reports from Penn Medicine

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

Friday, July 10, 2015

Advanced Approaches to the Management of Colorectal Cancer with Liver Metastases

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

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





Monday, June 8, 2015

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

 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

Access

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


Thursday, May 28, 2015

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

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

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


https://drive.google.com/file/d/0B0vaPQ5yI4B3bGRRb09oUWZTWEE/view?usp=sharing

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





Monday, April 20, 2015

Peroral Endoscopic Myotomy (POEM) for Esophageal Achalasia


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


Access
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.




https://drive.google.com/file/d/0B0vaPQ5yI4B3YkpZbGJJWG5XUTg/view?usp=sharing
 




Thursday, April 16, 2015

Surgical Management of Drug-Resistant Epilepsy


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.

Access

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


https://drive.google.com/file/d/0B0vaPQ5yI4B3cl9FR3V5N010QjA/view?usp=sharing

























Tuesday, April 7, 2015

Diagnosis and Treatment of Dry Eye Syndrome

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

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



https://drive.google.com/file/d/0B0vaPQ5yI4B3RVpuZ2c4cGtwSGs/view?usp=sharing





Complex Retrieval of Embedded Inferior Vena Cava Filters

 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

https://drive.google.com/file/d/0B0vaPQ5yI4B3dXBlYzFnay1lZlk/view?usp=sharing
 




Tuesday, March 17, 2015

Total Proctocolectomy with J-pouch Reconstruction for Ulcerative Colitis

Division of Colon and Rectal Surgery

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

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

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

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

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

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

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

Case Study

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

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

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

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

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

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


Faculty Team

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

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

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

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