Clinical anatomy leading the way for solutions: An important paradigm for translational research (2016)

The term “translational research” has rightfully gained popularity over the last decade. It classically refers to the application of basic science discoveries to meaningful improvement in patient outcomes, i.e., from “bench to bedside,” and implies the novel discovery of treatment principles to positively affect the health of its intended medical population (Woolf, 2008). It is also widely recognized to involve a continuous cycle of feedback between a clinical question, discovery, translation, and application, leading to point of care treatment (i.e., from “bedside to bench to bedside”). While the emphasis has largely been on basic science, such as genomics and molecular or cancer biology for medical advances, we propose that it can and should also be on anatomy and surgical advances as well: the bench where discovery begins, does not have to be in a laboratory surrounded by test tubes and pipettes, but rather, can happen in the anatomy laboratory through dissection. The “bedside to bench and back” model can be applied in clinical anatomy by answering clinical problems with anatomic explanations, and translating the discoveries to targeted treatments in patients (Fig. 1). The bedside to bench to bedside model is depicted for clinical anatomy as a continuous cycle: answering clinical problems with anatomic explanations and applying targeted treatments (with permission, Mayo Foundation, 2016). As an example, for two centuries, intraneural ganglion cysts—a collection of gelatinous material within the connective tissue of a nerve—remained a curiosity and baffled and frustrated surgeons and patients alike. Early attempts were made to define the disease process from a biochemical, microscopic, or embryological perspective. Over the last decade, our group has established the pathogenesis of intraneural ganglion cysts based on a simple observation of a joint derived intraneural cyst, generating a hypothesis which we subsequently tested at the most common sites—that these cysts were consistently derived from a synovial joint. We then proposed a unifying articular theory by applying articular branch anatomy and analyzing (i.e., interpreting and reinterpreting) high resolution imaging studies and operative findings). We then challenged it by testing apparent outliers and generalizing it to unusual locations, and proved it (Spinner et al., 2013, 2016). While we searched for an animal model, we fortuitously discovered an anatomic model and examined the first known surgical specimen (Spinner et al., 2008): a common pattern of an articular connection could be demonstrated. Subsequent experience both within our institution and from the international literature (Desy et al., 2016) has reinforced the central role of a pathological joint in the pathogenesis of intraneural ganglion cysts. In the past, surgeons targeted the cyst itself for treatment (involving resection of the cyst cavity or the nerve or aspiration/decompression of the cyst). These approaches had suboptimal results and high recurrence rates. By understanding the pathogenesis of intraneural cysts a surgeon can offer a different treatment: indeed the practice paradigm is shifting. The gold standard has become an open surgical procedure disconnecting the articular branch near the pathological joint or resecting the joint's synovial surfaces, when possible. Outcomes have improved and recurrences have largely been eliminated. Is there a platinum standard? Can we design a better intervention? If one believes and applies the underlying anatomy and science, advances can be anticipated by incorporating new techniques and technologies to address the causative problem: a joint-based minimally invasive (endoscopic or arthroscopic) procedure to repair the capsular defect, or even a non-invasive image-guided (percutaneous or transcutaneous [focused ultrasound]) approach to disconnect the articular branch from the joint. These types of innovative solutions are in development for the treatment of intraneural ganglion cysts (Hwang et al., 2010; Prasad et al., 2015) based on their initial and encouraging success for the management of extraneural cysts (He et al., 2013). Future treatment will be aimed at addressing the cause (joint pathology) and the conduit (an articular branch) and searching for a cure. As new questions arise, we must seek to answer them. Taking the lessons learnt at the bedside to bench and back, it was possible to apply our solution to an analogous clinical problem—cystic adventitial disease—that is, cyst within a vessel wall: after all, vessels run near nerves as part of neurovascular bundle, so it seemed logical to hypothesize that the same principles would apply. This entity has also been unexplained and problematic for over half a century. We have demonstrated that these adventitial cysts are similarly joint-related (Spinner et al., 2003) and in doing so, we are shifting attention from the effect (cyst) to the cause (the joint) and its conduit (a capsular branch). Therapy will therefore need to focus on the cause (joint pathology and its vascular conduit). Classically speaking, we believe that all roads lead to the joint; in other words, the joint has become the alpha and the omega. The solution to clinical problems sometimes requires a “re-adjusting of the lens”—shifting focus from the microscopic to the macroscopic and back. Complex problems can often be solved by elegantly simple solutions. Improving patient experience and outcomes requires a systematic, targeted, anatomic approach. The translation of anatomic research in improved clinical outcomes is an iterative process that requires a constant cycle of feedback between bedside and bench. For surgeons, the anatomy lab represents our “bench,” and where we conduct our “basic research” and has been instrumental in creating this new “translational” paradigm. Conducting research in clinical anatomy is essential not only to focus on the cause of a clinical problem but also to understand downstream implications. The road to surgical discovery starts in and centers around the anatomy lab: for surgeons not only to practice but to find anatomic solutions which can be translated to patients. Ideas catalyze advances. Indeed, the time has come to shift the lens of the term translational research to include an anatomical basis for targeted treatment: a new manifesto perhaps.