Faculty Bibliography

Cancer, a local disease at an early stage, systemically evolves as it progresses by triggering alterations in surrounding microenvironment, disturbing immune surveillance and further disseminating its molecular contents into circulation. This pathogenic characteristic of cancer makes the use of biofluids such as blood/serum/plasma, urine, tear and cerebrospinal fluids credible surrogates harboring tumor tissue-derived molecular alterations for the detection of cancer. Most importantly, a number of recent reports have credentialed the clinical validity of saliva for the detection of systemic diseases including cancers. In this review, we discussed the validity of saliva as credible biofluid and clinical sample type for the detection of cancers. We have presented the molecular constituents of saliva that could mirror the systemic status of our body and recent findings of salivaomics associated with cancers. Recently, liquid biopsy to detect cancer-derived circulating tumor DNA has emerged as a credible cancer-detection tool with potential benefits in screening, diagnosis and also risk management of cancers. We have further presented the clinical validity of saliva for liquid biopsy of cancers and a new technology platform based on electrochemical detection of cancer-derived ctDNA in saliva with superior sensitivity and point-of-care potential. The clinical utilities of saliva for the detection of cancers have been evidenced, but biological underpinning on the existence of molecular signatures of cancer-origin in saliva, such as via exosomal distribution, should be addressed in detail.

Previously, we detected circulating tumor DNA that contained two EGFR mutations (p.L858R and exon19 del) in plasma of patients with late-stage non-small-cell lung carcinoma (NSCLC) using the electric field-induced release and measurement (EFIRM) platform. Our aim was to determine whether EFIRM technology can detect these mutations in patients with early-stage NSCLC. Prospectively, 248 patients with radiographically determined pulmonary nodules were recruited. Plasma was collected before biopsy and histologic examination of the nodule. Inclusion criteria were histologic diagnosis of benign nodule (control) and stage I or II adenocarcinoma harboring either p.L858R or exon19 delEGFR mutations. Plasma samples were available from 44 patients: 23 with biopsy-proven benign pulmonary nodules and 21 with stage I or II adenocarcinoma (12 p.L858R and 9 exon19 delEGFR variants). Samples were analyzed for the EGFR mutations using the EFIRM platform. Assay sensitivity was 92% for p.L858R (11 of 12 samples positive) and 77% for exon19 del (7 of 9 samples positive). Specificity was 91% with two false-positive results in 23 patients with EGFR-positive nodules and 95% for the entire 44-patient series. Concordance was 100% with identical mutations discovered in plasma and nodule biopsy. The EFIRM platform is able to noninvasively detect two EGFR mutations in individuals with early-stage NSCLC.

STUDY DESIGN/METHODS:Cross-Sectional Study. OBJECTIVE:The goal of this study is to investigate how surgeons differ in collar and narcotic use, as well as return to driving recommendations following cervical spine surgeries and the associated medico-legal ramifications of these conditions. SUMMARY OF BACKGROUND DATA/BACKGROUND:Restoration of quality of life is one of the main goals of cervical spine surgery. Patients frequently inquire when they may safely resume driving after cervical spine surgery. There is no consensus regarding post-operative driving restrictions. This study addresses how surgeons differ in their recommendations concerning cervical immobilization, narcotic analgesia, and suggested timeline of return to driving following cervical spine surgery. METHODS:Surgeons at the Cervical Spine Research Society annual meeting completed anonymous surveys assessing postoperative patient management following fusion and non-fusion cervical spine surgeries. RESULTS:70% of surgeons returned completed surveys (n = 71). 80.3% were orthopaedic surgeons and 94.2% completed a spine fellowship. Experienced surgeons (>15y in practice) were more likely to let patients return to driving within 2 weeks than less experienced surgeons (47.1% vs 24.3%, p = .013) for multi-level ACDF and laminectomy with fusion procedures. There were no differences between surgeons practicing inside and outside the USA for prescribing collars or return to driving time. Cervical collars were used more for fusions than non-fusions (57.7% vs 31.0%, p = .001). Surgeons reported 75.3% of patients ask when they may resume driving. For cervical fusions, 31.4% of surgeons allowed their patients to resume driving while restricting them with collars for longer durations. Furthermore, 27.5% of surgeons allowed their patients to resume driving while taking narcotics post-operatively. CONCLUSIONS:This survey-based study highlights the lack of consensus regarding patient 'fitness to drive' following cervical spine surgery. The importance of establishing evidence-based guidelines is critical as recommendations for driving in the post-operative period may have significant medical, legal, and financial implications. LEVEL OF EVIDENCE/METHODS:5.

Background/UNASSIGNED:Anterior cervical discectomy and fusion (ACDF) may be performed using an interbody cage or graft with an anterior plate or with a stand-alone (SA) interbody device without the anterior plate. The pros and cons of each vary. This study examined the radiographic outcome of the two techniques with a focus on implant subsidence. Methods/UNASSIGNED:A retrospective review of cases of singe level ACDF by a single surgeon was undertaken. Medical and radiographic records were reviewed to determine subsidence, pre- and post-operative segmental and total lordosis in cohorts of both stand-alone and graft-and-plate constructs. Results/UNASSIGNED:The post-operative radiographs of 35 patients with a SA cage were compared with 41 patients with an allograft block and anterior plate (graft and plate; GP). There was no significant difference in overall subsidence between the two groups although there was a trend toward less clinically significant subsidence (2 mm) in the SA group. For single level ACDF, a SA device appears to be comparable in terms of undesired subsidence. Conclusions/UNASSIGNED:Further studies with different implants and materials may offer further insight.

Spinal cord compression due to synovial facet cyst in thoracolumbar spine is rare. Several etiologies of juxtafacet cysts (JFCs) in this location have been discussed, particularly overload of the arthritic facet joints. Due to the narrow caliber of the thoracic spine, JFC in this location can present with radicular pain or progressive myelopathy. We report an interesting case of a 67 year-old woman who presented with the signs and symptoms of thoracic myelopathy. A left-sided T11/12 JFC was identified on MRI and CT scans correlating with her myelopathy. She experienced a substantial improvement in her myelopathic symptoms after surgical excision of the JFC. The presentation, etiology, and therapeutic aspects of JFC are discussed in detail.

Degenerative spondylolisthesis is a common presentation, yet the best surgical treatment continues to be a matter of debate. Interbody fusion is one of a number of options, but its exact role remains ill defined. The aim of this study was to provide a contemporary review of the literature to help determine the role, if any, of interbody fusion in the surgical treatment of degenerative spondylolisthesis. A systematic review of the literature since 2005 was performed. Details on study size, patient age, surgical treatments, levels of slip, patient reported outcome measures, radiographic outcomes, complications and selected utility measures were recorded. Studies that compared a cohort treated with interbody fusion and at least one other surgical intervention for comparison were included for review. Only studies examining the effect in degenerative spondylolisthesis were included. Two authors independently reviewed the manuscripts and extracted key data. Thirteen studies were included in the final analysis. A total of 565 underwent interbody fusion and 761 underwent other procedures including decompression alone, interspinous stabilisation and posterolateral fusion with or without instrumentation. Most studies were graded Level III evidence. Heterogeneous reporting of outcomes prevented formal statistical analysis. However, in general, studies reviewed concluded no significant clinical or radiographic difference in outcome between interbody fusion and other treatments. Two small studies suggested interbody fusion is a better option in cases of definite instability. Interbody fusion only provided outcomes as good as instrumented posterolateral fusion. However, most studies were Level III, and hence, we remain limited in defining the exact role of interbody fusion-cases with clear instability appear to be most appropriate. Future work should use agreed-upon common outcome measures and definitions.

BACKGROUND CONTEXT: Adjacent segment degeneration (ASD) has been described after anterior cervical fusion surgeries though ASD is not always clinically relevant. Hilibrand et al described a grading system for ASD after anterior cervical fusion. We expand the ASD definition with an analysis of radiographic adjacent segment pathology (RASP) by also assessing the progression of kyphotic alignment, and spondylolisthesis at adjacent segments in patients following cervical laminoplasty (LP) and posterior cervical decompression and fusion (CDF). PURPOSE: To assess radiographic adjacent segment pathology by analyzing adjacent segment degeneration, and the progression of kyphotic alignment and spondylolisthesis at segments adjacent to operated levels for LP and CDF surgery. STUDY DESIGN/SETTING: Retrospective analysis of cervical radiographs in patients undergoing prior LP and CDF surgery. PATIENT SAMPLE: 64 patients undergoing prior LP and CDF surgery. OUTCOME MEASURES: NDI and mJOA. METHODS: Preoperative and postoperative radiographs were analyzed for ASD, progression of adjacent level kyphosis and spondylolisthesis at proximal, distal or any other segments. The RASP was determined by combining proximal and distal ASD, and the adjacent level kyphosis and spondylolisthesis into one spectrum of disease. The presence and rate of development of adjacent segment pathology was compared for LP and CDF. HRQOLs included NDI and mJOA. RESULTS: 64 patients were included (24 LP and 40 CDF) with mean age 59.9 years (46.9% female) and 30.2 months mean follow-up. Spondylolisthesis at the adjacent segment was more prevalent in CDF (29.2% vs 4.5%). Both LP and CDF demonstrated a similar rate of RASP (LP 40.9%, CDF 44%). NDI correlated with proximal adjacent level degeneration (r = 0.34, p = 0.024) and kyphosis (r = 0.36 p = 0.017). CONCLUSIONS: Both cervical laminoplasty and posterior cervical decompression and fusion are associated with adjacent level degeneration. However, there is a higher rate of adjacent segment spondylolisthesis after CDF. Motion preservation procedures may have less of a role in preventing adjacent level degeneration than previously thought. Adjacent segment degeneration correlated with NDI disability in these patients

There has been a rapid increase in the number of lumbar fusion procedures performed in the last 10 years. Many of these procedures involve the use of bone grafts and specifically bone graft extenders and substitutes. Fusion depends on host and surgical factors including the selection of an appropriate graft. Bone grafts have osteoconductive, osteoinductive, and osteogenic properties. Iliac crest autograft has long been considered the gold standard for bone graft procedures as it inherently imparts all three. However, its use is associated with significant disadvantages including donor site pain, increased operative time, and insufficient availability. Allograft has been used to avoid the complications of donor site morbidity but has increased risks of rejection, disease transmission, and slower incorporation into the host bone. The use of alternative bone grafting options, such as demineralized bone matrix, synthetics (ceramics), bone morphogenetic proteins, collagen-based matrices, autogenous growth factors, and bone marrow aspirate, have become routine in some institutions. This review paper highlights the different bone grafting options currently available, discusses their pros and cons, and briefly reviews the relevant literature.