Bringing Your Idea to the Market: A Primer for Plastic Surgeons.

SUMMARY: The progress of biotechnology, medical instruments, and applied sciences contributes to a rapidly expanding space for the advancement of the medical field. Surgeons experience first-hand the limitations of current medical devices and thus have unique insight into problems that could be solved with new products. The process of turning an idea into a product capable of success in the marketplace, however, is often unfamiliar to surgeons. The authors seek to illuminate this process and provide an ordered list of tasks that can make bringing ideas to market more achievable for surgeons. The first step in this process is the generation and protection of a new idea. Next, the process of making an idea into a product is outlined. This phase involves team assembly, business planning, and product development. Market research and valuation are key to understanding how a product can be applied in the market, and meticulous research during this phase allows for informed decision-making that will help secure funding down the road. Finally, various options for financing are discussed and compared to help surgeon-entrepreneurs find an option that best fits their project, and steps to maximize leverage are described. The development of new products can be a complicated process for surgeons. Organized into four phases, with ordered instructional steps to advance through each phase, the process of bringing an idea to the market is clarified. Facilitating this process will possibly contribute to the continual improvement of medical and surgical abilities through the introduction of new devices and technologies.

Radiation Necrosis of the Lateral Skull Base and Temporal Bone.

Radiation therapy plays a critical role in the treatment of malignancies involving the head and neck. Although the therapeutic effects of ionizing radiation are achieved, normal tissues are also susceptible to injury and significant long-term sequelae. Osteoradionecrosis of the temporal bone (ORNTB) is among the many complications that can arise after therapy. ORNTB is a debilitating and potentially lethal condition that continues to challenge patients and treating physicians. Herein, we review the pathophysiology, presentation, work-up, and management of ORNTB.

Complications in Skull Base Surgery and Subsequent Repair.

Over the past several decades, endoscopic sinus surgery has revolutionized the approach to skull base surgery. Open skull base approaches remain a viable option for advanced skull base tumors. Complications have gone down with increased reliability of vascularized tissue transfer. In this article, the authors explore the various complications that can present following skull base surgery and review the approaches for repair when such issues are encountered.

Management of Skull Fractures and Calvarial Defects.

Scalp and calvarial defects can result from a myriad of causes including but not limited to trauma, infection, congenital malformations, neoplasm, and surgical management of tumors or other pathologies. While some small, nondisplaced fractures with minimal overlying skin injury can be managed conservatively, more extensive wounds will need surgical repair and closure. There are many autologous and alloplastic materials to aid in dural and calvarial reconstruction, but no ideal reconstructive method has yet emerged. Different reconstructive materials and methods are associated with different advantages, disadvantages, and complications that reconstructive surgeons should be aware of. Herein, we discuss different methods and materials for the surgical reconstruction of calvarial defects.

Rare Presentation of Giant Cell Tumor in the Internal Auditory Canal: Case Report and Review of the Literature.

Giant cell tumor (GCT) is a benign but locally aggressive bone tumor that usually involves the end of long bones. It is a relatively common neoplasm in patients, constituting 5 to 10% of all benign bone tumors. Approximately 2% of GCTs occur in the craniofacial skeleton with a predilection for the ethmoid, sphenoid, and temporal bones. The skull base location is unique and not commonly described. Hearing loss, headache, tinnitus, and subcutaneous masses are the most commonly reported symptoms in GCTs of the skull base. In this case report we present the first description of a GCT within the internal auditory canal causing cranial neuropathy and review the recent pertinent literature.

DNA sequence analysis and genotype-phenotype assessment in 71 patients with syndromic hearing loss or auditory neuropathy.

OBJECTIVES: Aetiological assessment of 71 probands whose clinical presentation suggested a genetic syndrome or auditory neuropathy. METHODS: Sanger sequencing was performed on DNA isolated from peripheral blood or lymphoblastoid cell lines. Genes were selected for sequencing based on each patient's clinical presentation and suspected diagnosis. Observed DNA sequence variations were assessed for pathogenicity by review of the scientific literature, and mutation and polymorphism databases, through the use of in silico tools including sorting intolerant from tolerant (SIFT) and polymorphism phenotyping (PolyPhen), and according to the recommendations of the American College of Medical Genetics and Genomics for the interpretation of DNA sequence variations. Novel DNA sequence variations were sought in controls. RESULTS: DNA sequencing of the coding and near-coding regions of genes relevant to each patient's clinical presentation revealed 37 sequence variations of known or uncertain pathogenicity in 9 genes from 25 patients. 14 novel sequence variations were discovered. Assessment of phenotypes revealed notable findings in 9 patients. CONCLUSIONS: DNA sequencing in patients whose clinical presentation suggested a genetic syndrome or auditory neuropathy provided opportunities for aetiological assessment and more precise genetic counselling of patients and families. The failure to identify a genetic aetiology in many patients in this study highlights the extreme heterogeneity of genetic hearing loss, the incompleteness of current knowledge of aetiologies of hearing loss, and the limitations of conventional DNA sequencing strategies that evaluate only coding and near-coding segments of genes.

External auditory canal defect management and reconstruction.

BACKGROUND: The external auditory canal (EAC) is an area commonly involved by skin cancers. Knowledge of the anatomy of this area and proper evaluation and management of patients with these malignancies is essential. OBJECTIVE: The purpose of this article is to provide the reader with an understanding of the anatomy of the EAC, the options available for the treatment of EAC cancers, and repair of the resulting surgical defects. METHODS AND MATERIALS: A review of the current literature was performed to summarize the current literature on this topic. RESULTS: There are a variety of surgical options available for the treatment of these cancers whose use depends on the location and extent of the tumor. It is important to follow a logical reconstructive algorithm after tumor resection to optimize both functional and cosmetic results.

Initial experience with oropharynx-targeted radiation therapy for metastatic squamous cell carcinoma of unknown primary of the head and neck.

AIM: Metastasis of unknown primary (MUP) is commonly treated with radiation therapy (RT) to the entire mucosal surfaces and bilateral neck nodes (LN). We report outcomes of oropharynx-targeted RT, retropharyngeal nodes (RPN) and bilateral LN in this context. PATIENTS AND METHODS: Single-Institution retrospective study of 68 patients. Forty percent were treated with intensity-modulated radiation therapy (IMRT). Fifty-six percent received concurrent chemoradiotherapy (CCRT). The median age was 58 years, 82% were Caucasian, and 75% males. Stage III disease was present in 9%, stage IVA in 75% and IVB in 16%. RESULTS: At a median follow-up of 3.5 years, the actuarial locoregional control was 95.5%. The emergence of primary developed in 1patient (1.5%) and 2patients (3%) failed in the neck. The median time-to-locoregional failure (LRF) was 18 months. Actuarial long-term RT toxicity was grade 1 xerostomia (68%), dysphagia (35%), neck stiffness (15%) and trismus (6%). CONCLUSION: RT to the oropharynx, RPN, and bilateral neck provides excellent oncological and functional outcomes in MUP in non-Asian patients. Sparing the mucosal surfaces of the nasopharynx, hypopharynx, and larynx seems reasonable without impacting on survival and locoregional control.

Five-year outcomes of squamous cell carcinoma of the tonsil treated with radiotherapy.

PURPOSE: To retrospectively review our single institution experience of patients with tonsillar squamous cell carcinoma. MATERIAL AND METHODS: Between 1999 and 2005, a total of 79 patients were identified. Stage distribution was as follows: stages I-II, III, IVA, and IVB were in 6, 14, 43, and 16 patients, respectively. Sixty-three patients (80%) were male. Median age was 55.5 years. Treatment generally consisted of external beam radiation therapy (RT) (median dose, 70 Gy), concomitant chemotherapy (CCRT) (cisplatin 100 mg/m on days 1, 22, and 43), and neck dissection (ND), and was administered as follows: stages I/II, 6 patients received RT alone; stages III/IVA, 20, 5, and 32 patients received RT alone, CCRT, and CCRT followed by ND, respectively; stage IVB, 9 and 7 patients received CCRT and CCRT plus ND, respectively. RESULTS: After a median follow-up of 56 months (range, 12 to 122 mo), the 5-year local control (LC), regional control (RC), distant control (DC), and overall survival (OS) by stage were as follows: stage I-II 100%, 100%, 100%, 100%; stage III-IVA 98%, 96%, 95%, and 88%; stage IVB 100%, 100%, 69%, and 66%, respectively. Among stage IVB patients, DC was significantly lower (P=0.01) and a trend toward lower OS was noted (P=0.08). Long-term percutaneous endoscopic gastrostomy dependence was noted in 3% of them who had received CCRT. The effect of both chemotherapy and ND on treatment outcomes was analyzed; in stage III/IVA patients treated with or without chemotherapy, LC was 97% and 100% (P=0.43); RC was 92% and 100%(P=0.27); and DC was 91% and 94% (P=0.92), respectively. In stage III/IVA, patients treated with CCRT with or without ND, RC was 100% and 88%, respectively (P=0.087). CONCLUSIONS: Primary radiotherapy with or without CCRT followed by ND provides excellent tumor control with acceptable toxicity in treating squamous cell carcinoma of the tonsil.

Long-term outcome of seropositive HIV patients with head and neck squamous cell carcinoma treated with radiation therapy and chemotherapy.

AIM: To report the outcome of radiation therapy (RT) +/- chemotherapy in HIV-seropositive patients with Head and Neck Squamous Cell Carcinoma (HNSCC). PATIENTS AND METHODS: This is the largest single-Institution retrospective study to date, consisting of 73 HIV patients with HNSCC treated from January 1997-2010. The median age at RT, HIV diagnosis and the duration of patients being HIV seropositive were 51, 34, and 11 years, respectively. Seventy patients had SCC and one had submandibular salivary duct carcinoma. Stages I-II, III and IVA/B were: 22%, 27% and 51%, respectively. Primary cancer sites comprised the larynx (37%), oropharynx (32%), oral cavity (13%), hypopharynx (7%), nasopharynx (4%), unknown primary (MUP) (4%), nasal cavity (3%), and submandibular salivary duct (1%). All patients had an ECOG performance scale of ≤1 and were treated with RT +/- chemotherapy. Fifty patients (70%) were on highly active anti-retroviral therapy (HAART) during treatment, and the median CD4 count was 290 (range: 203-1142). Median dose of 70, 63, and 54 Gy were delivered to the gross disease, high-risk neck, and low-risk neck respectively. Median duration of treatment was 52 (range: 49-64) days. Twelve patients (17%) underwent neck dissection for N3 disease. RESULTS: After a median follow-up of 47 months (range: 7-140), the 4-year locoregional control (LRC) and overall survival (OS) were 69% and 55% respectively. Seven patients (10%) developed second primary sites within the first 5 years of completing RT (2 anal SCCs and 5 HNSCCs). The LRC for Stages III/IV larynx and oropharynx SCC (which represent the majority of the cohort) were 76% and 70%, respectively. Chemo/RT-related late toxicities were dysphagia of grade≤2, 3, and 4 found in 74%, 15% and 11% of patients, respectively. Hoarseness (grade 1) was reported in 10% of patients; no patient experienced grade ≥2. Xerostomia grade ≤2, and 3 was found in 77% and 23% of patients, respectively. A Chi-square test and univariate analysis showed statistically significant relationships between LRC and duration of RT (p<0.001), as well as positive trends for weight loss (<10%) and absence of second malignancy. CONCLUSION: Definitive RT +/- chemotherapy for HIV-seropositive patients with HNSCC appears to be less effective compared to the observed rates of LRC and OS of other HNSCC without HIV. Due to advances in the HAART which prolongs HIV patients' survival, it is extremely important to establish better treatment strategies to improve therapeutic ratio in this growing patient population.

An evolving paradigm for the workup and management of high-risk cutaneous squamous cell carcinoma.

BACKGROUND: No established standard of care exists for aggressive cutaneous squamous cell carcinoma (CSCC). OBJECTIVE: We sought to establish an aggressive CSCC management protocol by reviewing high-risk CSCC (HCSCC) and very high-risk CSCC (VCSCC) cases at our institution. METHODS: This was a retrospective review of all CSCC cases treated at our institution. RESULTS: A total of 27 patients were identified of 1591 cases treated between 2000 and 2011. Four patients with HCSCC received surgery alone and 1 received surgery and radiation. All remain disease free (median follow-up 5 years). Among patients with VCSCC, 4 received surgery alone: 1 (25%) showing a complete response and 3 (75%) showing disease progression. Eleven received surgery and radiation: 4 (36.4%) with complete response (median follow-up 3 years) and 7 (63.6%) with disease progression (median time to recurrence 6 months). Six received surgery and cetuximab: 3 (50%) had a complete response (median follow-up 3 years), 2 (33%) had disease progression, and 1 (14%) could not be assessed because of inability to tolerate infusions. One patient received surgery, cetuximab, and radiation, and remains disease-free after 4 years. LIMITATIONS: Lack of randomization, blinding, a true control arm, or standardization of treatment protocols are limitations. CONCLUSIONS: Patients with very HCSCC may have improved outcomes with surgery and adjuvant cetuximab.

Common cavity and custom-made electrodes: speech perception and audiological performance of children with common cavity implanted with a custom-made MED-EL electrode.

OBJECTIVE: Few studies exist on children with common cavity, fewer still on their long-term audiological development after having received a cochlear implant. Our goal was to observe and report the long-term audiological progress of children with common cavity who were implanted with a custom-made electrode. METHODS: In this longitudinal, multi-center study, 19 children were implanted with a MED-EL custom-made electrode via either single slit cochleostomy or double posterior labyrinthotomy. We observed their audiological development with a test battery consisting of Categories of Auditory Performance (CAP), Speech Intelligibility Rating (SIR), and Ling 6-Sounds tests. We tested the children 1 month prior to the surgery; at first fitting; at 1, 3, 6, 12, and 18 months post first-fitting; at 2 years after first-fitting; and, whenever possible, at 3, 4, and 5 years after first-fitting. RESULTS: Children with common cavity tend to steadily and significantly improve their audiological skills over time. This development may, however, be highly individual; probably in part due to relatively high levels of additional needs. Parents should be counseled to establish realistic post-implantation expectations. Surgically, contrary to our expectations, we cannot confirm that double posterior labyrinthotomy reduces intracochlear electrode movement or that the MED-EL custom electrode leads to fewer incidences of intra- or post-implantation complications. CONCLUSIONS: Cochlear implantation is a safe and effective treatment option in children with common cavity. The majority of children with CC derive significant audiological benefit from implantation. Intra- and post-surgical complications, while serious, and be dealt with effectively in most cases.

Chondromyxoid fibroma of the mastoid portion of the temporal bone: MRI and PET/CT findings and their correlation with histology.

We report a very rare case of a chondromyxoid fibroma of the mastoid portion of the temporal bone in a 38-year-old woman who presented with left-sided hearing loss. Magnetic resonance imaging identified an expansile mass in the left mastoid bone with a heterogeneous hyperintense signal on T2-weighted imaging and peripheral enhancement. Subsequent positron emission tomography/computed tomography identified erosive bony changes associated with hypermetabolism. The patient underwent an infratemporal fossa resection with a suboccipital craniectomy/cranioplasty. We briefly review the aspects of this case, including a discussion of the differential diagnosis and the correlation between histologic and imaging findings.

Clinical validation and applications for CT-based atlas for contouring the lower cranial nerves for head and neck cancer radiation therapy.

OBJECTIVES: Radiation induced cranial nerve palsy (RICNP) involving the lower cranial nerves (CNs) is a serious complication of head and neck radiotherapy (RT). Recommendations for delineating the lower CNs on RT planning studies do not exist. The aim of the current study is to develop a standardized methodology for contouring CNs IX-XII, which would help in establishing RT limiting doses for organs at risk (OAR). METHODS: Using anatomic texts, radiologic data, and guidance from experts in head and neck anatomy, we developed step-by-step instructions for delineating CNs IX-XII on computed tomography (CT) imaging. These structures were then contoured on five consecutive patients who underwent definitive RT for locally-advanced head and neck cancer (LAHNC). RT doses delivered to the lower CNs were calculated. RESULTS: We successfully developed a contouring atlas for CNs IX-XII. The median total dose to the planning target volume (PTV) was 70Gy (range: 66-70Gy). The median CN (IX-XI) and (XII) volumes were 10c.c (range: 8-12c.c) and 8c.c (range: 7-10c.c), respectively. The median V50, V60, V66, and V70 of the CN (IX-XI) and (XII) volumes were (85, 77, 71, 65) and (88, 80, 74, 64) respectively. The median maximal dose to the CN (IX-XI) and (XII) were 72Gy (range: 66-77) and 71Gy (range: 64-78), respectively. CONCLUSIONS: We have generated simple instructions for delineating the lower CNs on RT planning imaging. Further analyses to explore the relationship between lower CN dosing and the risk of RICNP are recommended in order to establish limiting doses for these OARs.

Tolerance and toxicity of primary radiation therapy in the management of seropositive HIV patients with squamous cell carcinoma of the head and neck.

OBJECTIVES/HYPOTHESIS: To report tolerance and toxicity of radiotherapy (RT) with or without chemotherapy in HIV seropositive patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: This is a single institution retrospective study of 73 HIV seropositive patients with SCCHN treated from January 1997 through 2010. Stages I, II, III, and IV were 8%, 10%, 24%, and 58%, respectively. The median age at RT, HIV diagnosis. and the duration of HIV seropositive were 51 (32-72), 34 (25-50), and 11 (6-20) years, respectively. Patients were treated definitively with RT alone (35%) or concurrent chemo-RT (65%). Median dose of 70 Gy (66-70) was delivered to the gross disease. Median duration of treatment was 52 (49-64) days. Fifty patients (70%) were on HAART. RESULTS: RT± chemotherapy induced acute toxicity was: median weight loss 20 pounds (6-40), 100% developed dysgeusia and xerostomia (grades 1-3). Acute mucositis and dysphagia/odynophagia grades ≤ 2 and 3 were 83% and 17%, respectively. Treatment breaks in excess of 10, 7, and 3 days were found in 5%, 13%, and 15% of patients, respectively. With a median follow-up of 4 years (2-12) the RT ±chemotherapy induced late dysphagia and xerostomia grades >2 were 26% and 23% of patients, respectively. CONCLUSION: Our data show that primary RT ±chemotherapy for HIV seropositive SCCHN is less tolerated compared to the historical data for SCCHN without HIV. LEVEL OF EVIDENCE: 2b.

Trimodality management of sinonasal undifferentiated carcinoma and review of the literature.

OBJECTIVE: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive malignancy with optimal management remains unclear. We performed a review of the impact of trimodality approach on SNUC outcome. METHODS: This is a single-institution retrospective study of 18 patients, who were managed between 1997 and 2009. The median age at presentation was 52 years (28 to 82). Nine patients (50%) were female. Three patients had stage II disease and underwent surgery alone, 12 had stages III and IVa and underwent surgery combined with chemoradiation, and 3 had stage IVb and underwent definitive chemoradiation. Patients who underwent preoperative, postoperative, and definitive chemoradiation received 60, 66, and 70 Gy of radiation, respectively. In all patients receiving concurrent chemoradiation, cisplatin was used, at a dose of 100 mg/m every 3 weeks for 3 cycles. Neoadjuvant chemotherapy included docetaxel, cisplatin, and 5-fluorouracil (TPF) every 3 weeks for 2 to 3 cycles. RESULTS: After a median follow-up of 26 months (16 to 120), a total of 8 patients (44%) have experienced the following: 1 persistent disease (5.5%), 4 local failure (22%), and 3 distant metastases (DM, 16.5%). Five of the 8 patients had preexisting cranial nerve deficits or gross cranial invasion. The 2-, 3-, and 4-year local control (LC), disease-free survival (DFS), and overall survival (OS) were 78%, 72%, and 56%; 75%, 65%, and 52%; and 75%, 50%, and 48%, respectively. Trimodality approach provided 83% LC and 92% DM-free survival, whereas other modalities provided 50% LC and 33% DM-free survival. The causes of death for the entire cohort were DM and local invasion. Acute chemoradiotherapy toxicity was 100% grades 1 and 2 dermatitis, mucositis, and fatigue, 55% developed grades 1 and 2 dysphagia, and 6% had grade 3 mucositis. Long-term toxicity was 28% grade 1 xerostomia, 11% retinopathy and optic neuropathy, and 6% orbital exenteration and grade 3 peripheral neuropathy. CONCLUSIONS: SNUC is an aggressive neoplasm that frequently presents at an advanced stage. Our data show that trimodality approach in the form of surgery combined with chemoradiation seems to offer better LC and lower DM compared with other modalities.

Inroads toward robot-assisted cochlear implant surgery using steerable electrode arrays.

HYPOTHESIS: Robotic insertions of actively steerable perimodiolar electrode arrays can substantially reduce insertion forces and prevent electrode buckling. BACKGROUND: Perimodiolar electrodes have been proven to be effective in reducing insertion forces. However, the dedicated techniques of atraumatic electrode insertion require intensive surgeon training. Although some specialized medical robots have been developed to help surgeons in certain minimally invasive surgeries, none are applicable to electrode insertions. METHODS: A robot prototype capable of automatically inserting novel steerable electrode array and adjusting its approach angle toward the scala tympani has been constructed and tested. Comparisons of insertion forces using robotically assisted steerable and straight electrodes on scala tympani models are presented. Simulations and experiments are conducted to compare the robotic insertion outcomes and insertion forces. RESULTS: The use of robotically assisted steerable electrodes for insertions significantly reduces the insertion forces compared with straight electrodes. Based on the results from the experiments, a second-generation robot with insertion force-sensing capability and haptic control to be used in the operating room has been designed for cochlear implant surgery. CONCLUSION: Preliminary experimental results using robot-assisted steerable electrode prototype show that it is effective in reducing insertion forces and preventing electrode buckling. A second-generation robot has been designed and constructed for cochlear implant surgery under operating room conditions.

Basal cell carcinoma with intracranial invasion.

The risk of invasion and destruction of cranium, underlying dura, and cranial nerves by basal cell carcinoma (BCC) is extremely low, with an estimated incidence of 0.03%. Intracranial BCC invasion by direct extension is rare, and orbital spread from a nasal lesion has not been reported in the literature. We describe a case of intracranial invasion of a multiply recurrent nasal BCC, which caused progressive bilateral blindness from optic nerve compression, with spinal canal involvement causing subsequent lower extremity weakness and paralysis. This case underscores the importance of early and appropriate treatment of high risk BCC, and aggressive treatment of recurrent lesions as early as possible.

Intra-operative monitoring of cochlear function during cochlear implantation.

The objective of this study was to determine if intra-operative auditory monitoring is feasible during cochlear implantation and whether this can be used as feedback to the surgeon to improve the preservation of residual hearing. This prospective non-randomised study was set in a paediatric tertiary referral hospital. Thirty eight consecutive paediatric patients undergoing cochlear implantation who had measurable auditory thresholds pre-operatively were divided into two cohorts. The unmonitored cohort included the first 22 patients and the monitored cohort included the last 16 patients. The main outcome measure(s) were pre-operative, intra-operative and more than one month post-operative average auditory thresholds at 500, 1000 and 2000 Hz measured using auditory steady-state response audiometry. The average pre-operative thresholds were 103.5 dB HL and 99.7 dB HL in the unmonitored and monitored cohorts, respectively. These were not statistically different (p > 0.3). In the monitored cohort, we measured auditory thresholds to assess cochlear function at multiple time points during the operation. Compared to baseline, thresholds were increased 0.7 dB after drilling the mastoidectomy and well, 0.2 dB after opening the cochlea and 4.6 dB after inserting the electrode array. One month post-operatively, the average thresholds were 114.0 dB HL in the unmonitored cohort but only 98.8 dB HL in the monitored cohort (p < 0.001). Both the use of intra-operative auditory monitoring and higher pre-operative thresholds were associated with improved preservation of residual hearing (p

Path planning and workspace determination for robot-assisted insertion of steerable electrode arrays for cochlear implant surgery.

In previous works, the authors showed that using robot-assisted steerable electrode array insertions can significantly reduce the insertion forces compared to non-steerable electrode arrays. In addition to steering the electrode array, it is possible to change its angle of approach with respect to the scala tympani. This paper focuses on determining the relevance of changing the angle of approach of the electrode array by comparing steerable electrode array insertions using a two Degrees-of-Freedom (DoF) robot versus a four DoF robot. Optimal insertion path planning strategies are presented for both two and four DoF insertions. Simulation results and experiments show that the four DoF insertions can improve over two DoF insertions. Moreover, changing the angle of approach can further reduce the insertion forces. The simulation results also provide the workspace requirements for designing a custom parallel robot for robot-assisted cochlear implant surgery.