Clinical Science: Thoracic Oncology

At UCLA, I remain Director of the Mesothelioma Program which is recognized as one of the world's leading centers for lung-sparing surgery for malignant pleural mesothelioma. My pioneering approach to this asbestos-related cancer is now being increasingly adopted and shown to be superior to other treatments including the former prevailing radical surgery (ie, extrapleural pneumonectomy or EPP) that removes the lung. I wrote a seminal  invited paper on the “con” side of EPP published in the Annals of Surgical Oncology and remains one  of the most widely cited paper on the issue. Over the last 3 years, I have collaborated with Dr. Fereidoun Abtin, one of UCLA’s interventional radiologists to develop a program in percutaneous cyroablation for recurrent mesothelioma in the chest. This work showing a local control rate of over 95% was presented (along with 3 other abstracts on chemotherapy timing, hospital resource utilization, and type of chemotherapy regimen for a rare type of mesothelioma, sarcomatoid type) at the most recent meeting of the International Mesothelioma Interest Group in Boston, MA in September, 2012 and was noted by Dr. Sugarbaker at the end of the conference to be one of the “highlights” of the conference and one of the most important advances of the last two years.

Another major annual event that I initiated in 2011 was to have an International Symposium at UCLA on Lung-Sparing Therapies for Malignant Pleural Mesothelioma. I have worked on this (currently our 4th year) with Dr. Joyce Fried in the Dean’s office as part of the continuing medical education program. This Symposium invites national and international experts to LA for a all-day Symposium which highlights rational therapy to preserve lung function but treat cancer. We have had a variety of experts and this Symposium alone has raised the visibility of our program tremendously. (see enclosed Symposia programs). I have been the chair and organizer of all these meetings. Furthermore, the feedback from the participants and the running of the program has been cited by the Dean’s office as perhaps the most successful CME course at UCLA.

The incredible success of cyroablation in this context led us to explore its use in a similar clinical scenario; that is metastatic and recurrent thymoma. We recently presented our data at the annual meeting of the International Thymic Malignancies Interest Group in Washington, DC and have submitted a paper with this data for publication. I have also obtained IRB approval to participate in an international thymic malignancy registry in an international attempt to increase “big data” on patients with thymic neoplasms, and I will be entering al the information from UCLA to make sure that UCLA is a vital center for future thymic cancer research.

I also serve as the principle investigator for the American College of Surgeons Oncology Group for UCLA and have been the only UCLA surgeon to participate in prior trials, including a study utilizing radiofrequency ablation as an alternative to surgery for high risk stage I lung cancer patients, an important but as yet unanswered clinical question. Currently, I am part of a surgeon representative on a small national planning committee for the VALOR (Veterans Administration Lung cancer surgery Or stereotactic ablative Radiotherapy) trial which is a proposed national phase III VA Co-op study that is currently being planned with a goal to open in 2015. In the past I have been one of the co-investigators in the UCLA Lung SPORE.

Clinical Science: Thoracic Surgery

I am director of the UCLA lung volume reduction surgery program At UCLA after participating in the National Emphysema Treatment Trial (NETT) study and have been the only thoracic surgeon to actively do lung volume reduction surgery. I also have actively participated in an implantable endobronchial program, which places devices that obviates the need for surgery in some selected patients and am the only participating surgeon. For nearly the past 10 years, I have been the only general thoracic surgeon at UCLA to use the da Vinci surgical robot and am recognized nationally for this expertise. I have developed advanced minimally-invasive robotic-assisted procedure for thymic tumors and myasthenia which allow patients to have surgery without chest tubes or major incision and to go home in 24 hrs saving thousands of healthcare dollars. I also have developed a minimally-invasive robotic-assisted transhiatal esophagectomy protocol that dramatically reduces morbidity, practically eliminates the use of ICU care, and again decreases the cost of care by thousands of dollars.

Finally, I am developing a similar minimally-invasive robotic-assisted thoracic outlet procedure as well as diaphragm plication for eventration. Finally, I also am chief of the division of thoracic surgery at the West Los Angeles VA Medical Center where case loads have increased to 100-125 cases/year, enough to justify our recent recruitment of a second surgeon for that institution, Dr. Svetlana Kotova, whom I mentor, and have developed a similar minimally-invasive robotic-assisted program there as well. Finally together with Majid Sarrafzadeh, Professor of Computer Science and Electrical Engineering and Co-Director of the UCLA Wireless Health Institute, I am exploring the possibility of developing advanced wireless monitoring technology to continuously monitor patients with lung diseases in a manner similar to continuous EKG monitoring and cardioversion monitoring of patients with heart problems. 

Basic Science: Thoracic Oncology

Previously I established the “Punch” Worthington research laboratory funded by a generous donation from one of my patients. This laboratory seeks to investigate two asbestos related cancers: lung cancer and mesothelioma. We have received multiple small grants  to evaluate the roles of hyperthermia, interferon, chemotherapy, and anti-angiogenic therapies in tissue culture models and have published the initial report about the use of hyperthermia (despite its popularity in clinical centers) which suggests that the clinical use of this unproven therapy is not justified. This has made a big impact on the field. We also are preparing papers on the use of cryotherapy in vitro based on our clinical success and we also have investigated the effects of betadine and water which have been used for years in a number of instances by surgeons without data. Interestingly, we have shown that there is some antitumor effect from all three of these “therapies” which exceeds any prior believed benefit of heated chemotherapy! Our data will likely lead to a dramatic change in the approach to intraoperative adjunctive therapy for mesothelioma. Furthermore, because of our basic science research findings, I am now working with Dr. Warren Grundfest in the School of Engineering to develop a novel therapy device to apply cryotherapy to the inside of the chest during surgery. An SBIR grant is now being prepared to help explore this therapy.  I also worked to participate in a national mesothelioma virtual bank but with the national debt crisis, funding for this (originally through the CDC) has been cut; so I am working now with the Pacific Heart, Lung, & Blood Institute to essentially move this bank functionally to that Institute to continue to collect tumor and tissue specimens as well as to work on software to collect correlative clinical information. Previously, we showed that IL-4 receptors were up-regulated on mesothelioma cells and these cells were very sensitive to an IL-4 based immunotoxin, results of which were published in 2004. This molecule was recently licensed through the NIH to a small drug company and we are now working to create a sustained release form and to complete additional testing to allow for an initial FDA-approve phase I/II human trial within the next year or two. Additional molecular as well as cellular techniques are being investigated including a novel 3-D multicellular culture system that I am working on with collaborators at the Pacific Heart, Lung, & Blood Institute. This culture system will obviate the need for most preclinical animal testing and can serve to understand the immune system interactions that occur in the tumor microenvironment and what manipulation will help make immunotherapy a more effective reality in the future. Assays evaluate cell proliferation, invasion, and apoptosis in several thoracic malignancies, including lung cancer, mesothelioma, and esophageal cancer.