OMICS and 21st Century Brain Surgery from Education to Practice: James Rutka of the University of Toronto Interviewed by Joseph B. Martin (Boston) and Türker Kılıç (İstanbul)

Interview

L et's start with a brief overview of your professional background to date. Table 1 already provides your biography. But, we are interested in knowing other nuances and how you developed your current interests in surgical research, brain tumors, state-of-the-art surgeon education, and omics biomarker driven personalized medicine?

I began my interests in research as a neurosurgery resident when I went to University of California at San Francisco (UCSF) to work in the Brain Tumour Research Centre under the tutelage of Dr. Charles Wilson. There, I began my research studies on astrocytoma invasion and proliferation. I received my PhD with Dr. Stephen DeArmond and Dr. Mark Rosenblum on the role of transforming growth factors in human glioblastoma multiforme (GBM). The 3 years I spent in San Francisco were pivotal in my becoming an academic neurosurgeon with an interest in human brain tumours. At that time, 1984–1987, I published several peer-reviewed articles, and I met countless influential and esteemed researchers in the field of neuro-oncology. My peers there set the stage for me to advance my career in both experimental and clinical neuro-oncology once my residency was completed.

Malignant brain tumors are often fatal, and yet personalized medicine via OMICS systems diagnostics are offering renewed hope for diagnosis and targeted, safer, and more efficacious treatments. Our readers would benefit from learning the ways in which genomics, proteomics, metabolomics, or other systems diagnostics might guide current and future surgery practices? To what extent is this happening already? What are the anticipated broader impacts on surgeon education, healthcare access, and economics?

The field of neuro-oncology is changing rapidly. We now know there are numerous molecular biomarkers that can be used to establish the diagnosis of different human brain tumors. These simply were not available, or known as recently as 20 years ago. Some of these findings include the loss of the INI1 gene for atypical teratoid rhabdoid tumor, the loss of chromosomes 1p/19q to indicate the diagnosis of anaplastic oligodendroglioma, MGMT promoter methylation in human GBM, nuclear beta catenin to signify medulloblastoma, and the ACVR1 gene in diffuse intrinsic pontine glioma, to name just a few. These days, all neurosurgeons and treating physicians will need to know these and other molecular markers so that their patients will receive the very best treatment possible. Of course, molecular tests such as these can be expensive to perform, and so the various health care authorities will need to make this a priority if patients with human brain tumors will be diagnosed effectively and appropriately.

What do you think has been the most important development in the field of brain surgery broadly (not limited to malignant brain tumors) in the last 5 years (e.g., intractable epilepsy, other), with a view to omics diagnostics and personalized medicine? This could include advances in early diagnosis and/or improved treatments.

There have been several major advances in brain surgery in the past 20 years, and they include the use of neuronavigation, a type of global position sensor technique that enables a neurosurgeon to stay on target when operating in the depths of the brain. Neuronavigation has clearly changed the ability for neurosurgeons to perform complex neurosurgical procedures while maintaining neurological function. Another major advance has come from the use of neuromonitoring throughout brain surgery. In this situation, neuromonitoring can be performed continuously during surgery to ensure the integrity of critical neuroanatomical pathways during the removal of lesions in the brain that may be in proximity to fiber pathways that are important to preserve. If resections are performed too close to these pathways, then the neurophysiologist can detect an alteration in the integrity of the pathway before a permanent neurological deficit is sustained. The final development that has made a difference in brain surgery is the move towards more minimally invasive surgical procedures such as endovascular neurosurgery, endoscopic endonasal neurosurgery, and tubular surgery performed through burr holes and using neuronavigation strategies.

You have done a lot of work on the use of simulation in neurosurgeon training. Do you foresee that genomics, proteomics, or other omics biomarkers being used as part of the new generation simulation programs so as to train the surgery residents and as part of the continuing medical education programs? It is tempting to imagine that stratified surgery via omics diagnostics might help to apply different surgical procedures that can be first wetted through simulations? Is this happening, can it happen or will it happen?

At this stage, simulation training for surgeons is rather inexact, but it is improving. Some of the models being developed will enhance the feel, touch, and look of actual neurosurgical procedures. At the moment, the best simulation training may still be achieved on cadaver models. But some of the upcoming virtual models using computer simulation for endoscopic third ventriculostomy, and brain tumor removal are looking rather promising. It is perhaps a bit early for the information from omics diagnostics to be used directly in simulation training, but there is no doubt that this could be achieved once the actual simulation models are improved upon.

What are the barriers to this?

The barriers relate to the artificial nature of several of the simulation models at present. It is extremely difficult from a physics, computer graphics, and virtual network standpoint to create a simulation model that precisely mimics the human condition. Something as seemingly simple as “haptics,” the science of applying touch (tactile) sensation and control to interaction with computer applications, actually turns out to be extraordinarily complex in terms of trying to model to feel real. However, progress is being made, and haptics are likely to be made better and more realistic in the future.

Please can you tell us the extent to which modern surgical advances such as personalized brain surgery is feasible in resource-limited settings, be they in developing or developed world? For one thing, omics systems science has now broad appeal around the world.

Newer generation (e.g., omics) system diagnostics are rapidly emerging as a facet of postgenomics medicine. However, many challenges do remain, including the need to address the knowledge deficits among the stakeholder communities, patients, and scholarly readers of the medical literature. It is therefore difficult to say how these advances can be readily transferable to resource-limited settings. Many of these postgenomics advances we have discussed relating to brain surgery require the use of technologies that are still very expensive, and unavailable to neurosurgeons working in underserviced areas. However, there are great opportunities to ensure that curriculum development and transfer of state-of-the-art information continues globally across countries, be they achieved through the internet, social media, and other electronic means.

What do you think should be the role for surgeons in engaging with personalized medicine collaboratively with nonsurgeons such as internists? Looking further, what are the ways in which surgery, as a profession, can contribute to university-society integration that is happening in some other fields of postgenomics medicine such as breast cancer screening via new generation omics diagnostics.

There is no question that clinical collaboration is the key. Neurosurgeons cannot work in isolation in the field of personalized medicine. They will need the expertise and assistance of internists, neuropathologists, neurologists, neuropsychologists, neuroradiologists, neuroradiation oncologists, medical oncologists, social workers, advanced care practitioners, and many other professionals. This is the current interdisciplinary team of individuals required to engage in strategies grounded in personalized medicine informed by emerging knowledge from omics diagnostics. Additionally, there is a need to collaborate across the disciplinary and stakeholder knowledge silos, for example, the attendant stakeholders within the broader industry, governments, and citizen group stakeholders so as to ensure that the latest drug and diagnostics combinations can be designed and assessed, and so they remain relevant to the user community (e.g., patients, citizens, hospital administrators, health economists, policymakers, etc.) needs.

What do you plan to work on next in regards to prognostication of malignant brain tumors?

I plan to work with my colleagues at Sick Kids Hospital in Toronto to study patients with diffuse intrinsic pontine glioma, medulloblastoma, and ependymoma for the latest molecular changes, many of which we have characterized, that will help prognosticate how patients do following treatments. This will require the accumulation of numerous patients for each tumor type, and may take 1 to 2 years to complete.

What is the role for global collaborations in the field of omics diagnostics, simulation, and personalized medicine in brain surgery and surgeon education?

It is critical that centers that are unable to perform molecular diagnostics locally be encouraged to send portions of their specimens to other centers that are able to complete these tests. In this way, large collections of different tumor types can be isolated in a few centers where molecular diagnostics are performed. Then, using “Big-Data” analyses and large bioinformatics platforms, we will be able to find trends in gene expression analyses that will help us identify further targets for human brain tumors.

Is there anything else you would like to add pertaining to surgery practice and/or education in 21^st century in the age of omics diagnostics, simulation, and personalized medicine?

Nothing additional comes to mind except that I encourage the young and senior scholars around the world, be they in neurosurgery, internal medicine, or allied health fields, to consider learning the emerging interface of postgenomics medicine and 21^st century brain surgery where novel diagnostics and therapeutic innovations might likely materialize in the coming decades. We live in exciting times for 21^st century surgery where much research and teaching are waiting to be carried out across the world for the current and the next generation of surgeons that will benefit many citizens and patients.