Anterior Approach to the Subaxial Cervical Spine: Pearls and Pitfalls.

Since its introduction by Smith and Robinson, the anterior approach to the subaxial cervical spine has become one of the standard procedures for numerous cervical spine pathologies, including, but not limited to degenerative disease, trauma, tumor, deformity, and instability. Along with its increasing popularity and improvements in anterior instrumentation techniques, a comprehensive knowledge of the surgical anatomy during the anterior exposure is critical for trainees and experienced spine surgeons alike to minimize the infrequent but potentially devastating risks associated with this approach. Understanding the anatomy and techniques to minimize damage to relevant structures can reduce the risks of developing notable postoperative complications and morbidity.

Esophageal cancer as initial presentation of Fanconi anemia in patients with a hypomorphic FANCA variant.

Fanconi anemia (FA) is a clinically heterogenous and genetically diverse disease with 22 known complementation groups (FA-A to FA-W), resulting from the inability to repair DNA interstrand cross-links. This rare disorder is characterized by congenital defects, bone marrow failure, and cancer predisposition. FANCA is the most commonly mutated gene in FA and a variety of mostly private mutations have been documented, including small and large indels and point and splicing variants. Genotype-phenotype associations in FA are complex, and a relationship between particular FANCA variants and the observed cellular phenotype or illness severity remains unclear. In this study, we describe two siblings with compound heterozygous FANCA variants (c.3788_3790delTCT and c.4199G > A) who both presented with esophageal squamous cell carcinoma at the age of 51. The proband came to medical attention when he developed pancytopenia after a single cycle of low-dose chemotherapy including platinum-based therapy. Other than a minor thumb abnormality, neither patient had prior findings to suggest FA, including normal blood counts and intact fertility. Patient fibroblasts from both siblings display increased chromosomal breakage and hypersensitivity to interstrand cross-linking agents as seen in typical FA. Based on our functional data demonstrating that the c.4199G > A/p.R1400H variant represents a hypomorphic FANCA allele, we conclude that the residual activity of the Fanconi anemia repair pathway accounts for lack of spontaneous bone marrow failure or infertility with the late presentation of malignancy as the initial disease manifestation. This and similar cases of adult-onset esophageal cancer stress the need for chromosome breakage testing in patients with early onset of aerodigestive tract squamous cell carcinomas before platinum-based therapy is initiated.

Prognostic potential of mid-treatment nodal response in oropharyngeal squamous cell carcinoma.

BACKGROUND: We examine the prognostic implications of mid-course nodal response in oropharyngeal cancer (OPX) to radiation therapy. METHODS: In 44 patients with node-positive OPX undergoing concurrent chemoradiation, nodal volumes were measured on cone beam CTs from days 1, 10, 20, and 35. Nodal decrease (ND) was based on percent shrinkage from day 1. RESULTS: At a median follow-up of 17 months, the 2-year disease-free survival (DFS), locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) were 87%, 92%, 89%, and 92%, respectively. Patients with ND ≥43% at D20 had improved LRC (100% vs 78.4%, P = .03) compared to D20 ND <43%. On multivariate analysis, D20 ≥43% was independently prognostic for LRC (HR 1.17, P = .05). CONCLUSION: Patients with low-risk oropharynx cancer with ND of ≥43% by treatment day 20 had significantly improved LRC. The prognostic benefit of ND may assist in identifying candidates for treatment de-escalation.

Oncogenes overexpressed in metastatic oral cancers from patients with pain: potential pain mediators released in exosomes.

Oral cancer patients experience pain at the site of the primary cancer. Patients with metastatic oral cancers report greater pain. Lack of pain identifies patients at low risk of metastasis with sensitivity = 0.94 and negative predictive value = 0.89. In the same cohort, sensitivity and negative predictive value of depth of invasion, currently the best predictor, were 0.95 and 0.92, respectively. Cancer pain is attributed to cancer-derived mediators that sensitize neurons and is associated with increased neuronal density. We hypothesized that pain mediators would be overexpressed in metastatic cancers from patients reporting high pain. We identified 40 genes overexpressed in metastatic cancers from patients reporting high pain (n = 5) compared to N0 cancers (n = 10) and normal tissue (n = 5). The genes are enriched for functions in extracellular matrix organization and angiogenesis. They have oncogenic and neuronal functions and are reported in exosomes. Hierarchical clustering according to expression of neurotrophic and axon guidance genes also separated cancers according to pain and nodal status. Depletion of exosomes from cancer cell line supernatant reduced nociceptive behavior in a paw withdrawal assay, supporting a role for exosomes in cancer pain. The identified genes and exosomes are potential therapeutic targets for stopping cancer and attenuating pain.

Factors in Successful Elimination of Elective Tracheotomy in Mandibular Reconstruction With Microvascular Tissue.

IMPORTANCE: Limited data exist on performing major oral cavity resections and reconstructions without elective tracheotomy. OBJECTIVES: To describe a group of patients who successfully underwent major microvascular mandibular reconstruction without an elective tracheotomy and to perform a literature review to identify commonalities between our group and the available literature to identify potential common factors that might contribute to the success of this approach. DESIGN, SETTING, AND PARTICIPANTS: Case series with retrospective medical chart review of 15 patients who underwent fibula microvascular free flap reconstruction of mandibular defects without tracheotomy between 2000 and 2014 (the most common indication was osteoradionecrosis) conducted at a tertiary referral hospital center. EXPOSURES: Mandibular reconstruction with fibula free flap without elective tracheotomy. MAIN OUTCOMES AND MEASURES: Perioperative morbidity and mortality with a focus on airway management and perioperative complications. RESULTS: The median age of 15 patients (11 males and 4 females) at the time of reconstruction was 42 years (range, 10-64 years). The indication for surgery was nonmalignant pathologic abnormalities in 8 patients (53%), osteosarcoma in 4 patients (27%), and oral cavity squamous cell carcinoma in 3 patients (20%). All patients were intubated endonasally and, excepting 1 pediatric case, were extubated the day following surgery. The fibula spanned the parasymphysis and/or symphysis in 2 patients, and was limited to the mandibular body in others (mean length, 7.6 cm [range, 4.0-15.0 cm]). The flap design was osteocutaneous in 3 patients and osseous in the rest. No patient required reintubation or tracheotomy. No complications due to endonasal intubation occurred. The average hospital length of stay was 11 days. CONCLUSIONS AND RELEVANCE: Major oral cavity resection and reconstruction with microvascular free flaps can be performed safely without elective tracheotomy in a select group of patients. Limited data exist on patient selection criteria. Further studies are needed to identify favorable factors and develop protocols for safe patient selection.

Changes in abundance of oral microbiota associated with oral cancer.

Individual bacteria and shifts in the composition of the microbiome have been associated with human diseases including cancer. To investigate changes in the microbiome associated with oral cancers, we profiled cancers and anatomically matched contralateral normal tissue from the same patient by sequencing 16S rDNA hypervariable region amplicons. In cancer samples from both a discovery and a subsequent confirmation cohort, abundance of Firmicutes (especially Streptococcus) and Actinobacteria (especially Rothia) was significantly decreased relative to contralateral normal samples from the same patient. Significant decreases in abundance of these phyla were observed for pre-cancers, but not when comparing samples from contralateral sites (tongue and floor of mouth) from healthy individuals. Weighted UniFrac principal coordinates analysis based on 12 taxa separated most cancers from other samples with greatest separation of node positive cases. These studies begin to develop a framework for exploiting the oral microbiome for monitoring oral cancer development, progression and recurrence.

Primary mucosal melanoma arising from the eustachian tube with CTLA-4, IL-17A, IL-17C, and IL-17E upregulation.

Primary malignant melanoma arising from the eustachian tube is extremely rare. We report the case of a 63-year-old white man who presented with a 1-month history of left-sided hearing loss and aural fullness. Flexible fiberoptic laryngoscopy detected a blue-purple mass that appeared to arise from the left lateral nasopharynx. Computed tomography demonstrated an enhancing mass arising from an orifice of the left eustachian tube. The tumor was debulked endoscopically and was confirmed to have originated in the left eustachian tube. Histologically, the tumor was made up of heavily pigmented pleomorphic spindle cells with frequent mitoses. The tumor cells were immunohistochemically positive for S-100 protein, HMB-45, Melan-A, and PNL-2. The final diagnosis was a mucosal malignant melanoma. We also performed a nested polymerase chain reaction assay for several genes of interest, including CTLA-4, IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, IL-17F, PLZF, Foxp3, RORγt, CD27, and CD70. These genes have been studied mainly in cutaneous melanomas, especially for the development of immunotherapy, but only very limited studies have been done on mucosal melanomas. Our investigation found upregulation of CTLA-4, IL-17A, IL-17C, and IL-17E. Based on our finding of CTLA-4 upregulation, it may be suggested that our patient might have had low antitumor immunity and that he might have benefited from CTLA-4 blockade. On the other hand, upregulation of IL-17A and IL-17E might reflect increased antitumor immunity, which could suggest that patients with a mucosal melanoma might benefit from immunomodulators associated with the effect of Th17. These genes also have great potential to help melanoma patients obtain tailored treatment, and they can be used as biomarkers for predicting prognosis.

Squamous cell carcinoma of the oral cavity in nonsmoking women: a new and unusual complication of chemotherapy for recurrent ovarian cancer?

PURPOSE: To describe occurrences of oral squamous cell carcinoma (SCC) in patients who had received long-term pegylated liposomal doxorubicin (PLD) for ovarian cancer. PATIENTS AND METHODS: In our cohort of patients on maintenance PLD for ovarian and related mullerian epithelial malignancies, we encountered two patients with invasive SCC of the oral cavity (one of them multifocal) and one with high-grade squamous dysplasia. Review of patients at our institution receiving PLD for recurrent ovarian cancer identified three additional patients. The duration of treatment, cumulative PLD dose, human papillomavirus (HPV) positivity, BRCA status, stage at diagnosis, outcome, and other characteristics are reviewed. RESULTS: All five cases were nonsmokers with no known risk factors for HPV and four were negative for p16 expression. Four of the patients had known BRCA mutations whereas one tested negative. Cumulative doses of PLD were >1,600 mg/m2 given over 30-132 months. Three had SCCs staged as T1N0 oral tongue, alveolar ridge (gingival), and multifocal oral mucosa; one had a T2N0 oral tongue; and one had dysplasia. After excision, two were given radiation but recurred shortly thereafter; the others remain well and have had no further exposure to cytotoxic drugs, including PLD. CONCLUSION: Awareness of this possible long-term complication during PLD treatment should enhance the likelihood of early detection of oral lesions in these patients. Decisions to continue maintenance PLD after complete response of the original cancer should perhaps consider the benefits of delaying ovarian cancer recurrence versus the possible risk for a secondary cancer.

Head and neck radiotherapy compliance in an underserved patient population.

OBJECTIVES/HYPOTHESIS: Compliance to intensive multiweek radiation therapy (RT) regimens in head and neck cancer (HNC) patients is challenging, particularly among medically underserved patients with fewer financial and social resources. Treatment prolongation reduces local control and overall survival rates, making adherence to treatment a key factor in optimal outcome. We evaluated factors affecting compliance in medically underserved patients who received RT for HNC in a large municipal hospital setting in New York City. STUDY DESIGN: Retrospective review. METHODS: Treatment records of patients treated between July 2004 and August 2008 were reviewed. Number of and reasons for missed treatments were identified. Several demographic, toxicity, and treatment variables were analyzed for impact on compliance. RESULTS: Eighty consecutive HNC patients who underwent RT with a 5- to 7-week regimen were identified. Thirty-two patients (40%) missed no treatments, 36 (45%) missed one to six treatments, six (8%) missed seven to 14 treatments, two (3%) missed more than 14 treatments, and four (5%) did not complete treatment. Reasons for missed treatments were hospitalization (31% of events) and toxicity (20%). Patients with percutaneous endoscopic gastrostomy tube were more likely to miss treatments (P = .01, chi(2) test). No other variable showed a significant association with missed treatments (chi(2) test). CONCLUSIONS: Intensive RT for HNC can be delivered with very good adherence within a medically underserved population. Eighty-five percent of patients completed treatment with 0 to 6 days of interruption. Efforts to further improve adherence in this population are ongoing.

Validation of the histologic risk model in a new cohort of patients with head and neck squamous cell carcinoma.

BACKGROUND: Half of the patients with head and neck squamous cell carcinoma (HNSCC) can be expected to fail therapy, indicating that more aggressive treatment is warranted for this group. We have developed a novel risk model that can become a basis for developing new treatment paradigms. Here we report on the performance of our model in a new multicenter cohort. DESIGN: Eligible patients from 3 institutions (Montefiore Medical Center, University of Manitoba, and New York University Medical Center) were identified and pathology slides from their resection specimens were reviewed by Margaret Brandwein-Gensler; risk category was assigned as previously published. Kaplan-Meier analysis was performed for disease progression and survival. Cox proportional hazards regression was performed, adjusted for potential confounders. A teaching module was also developed; attending pathologists were asked to score coded slides after a lecture and multiheaded microscope teaching session. Agreement was assessed by calculating Cohen unweighted kappa coefficients. RESULT: The validation cohort consisted of 305 patients, from the above institutions, with 311 primary HNSCC of the oral cavity, oropharynx, and larynx. The median follow-up period for all patients was 27 months. Risk category predicts time to disease progression (P=0.0005), locoregional recurrence (P=0.013), and overall survival (P=0.0000) by Kaplan-Meier analysis. High-risk status is significantly associated with decreased time to disease progression, adjusted for clinical confounders (P=0.015, hazard ratio 2.32, 95% confidence interval 1.18-4.58) compared with collapsed intermediate and low-risk groups. We also demonstrate substantial interrater agreement (kappa=0.64), and very good rater agreement when compared with the standard (kappa=0.87). CONCLUSIONS: We demonstrate significant predictive performance of the risk model in a new cohort of patients with primary HNSCC, adjusted for confounders. Our training experience also supports the feasibility of adapting the risk model in clinical practice.

Toxicity of head-and-neck radiation therapy in human immunodeficiency virus-positive patients.

PURPOSE: To examine the acute morbidity of high dose head and neck RT and CRT in patients with infected with HIV. METHODS AND MATERIALS: All HIV-positive patients who underwent radiation therapy for head and neck cancer in our department between 2004 and 2008 were reviewed. Treatment related data were examined. All treatments were delivered with megavoltage photon beams or electron beams. Patients were evaluated by an attending radiation oncologist for toxicity and response on a weekly basis during therapy and monthly after treatment in a multidisciplinary clinic. Acute toxicities were recorded using the Radiation Therapy and Oncology Group (RTOG) common toxicity criteria. Response to treatment was based on both physical exam as well as post-treatment imaging as indicated. RESULTS: Thirteen patients who underwent RT with a diagnosis of HIV were identified. Median age was 53 years and median follow-up was 22 months. Twelve had squamous cell carcinoma and one had lymphoproliferative parotiditis. Median radiation dose was 66.4 Gy and median duration of treatment was 51 days. The median number of scheduled radiotherapy days missed was zero (range 0 to 7). One patient (8%) developed Grade 4 confluent moist desquamation. Eight patients (61%) developed Grade 3 toxicity. CONCLUSION: Based on our results, HIV-positive individuals appear to tolerate treatment for head and neck cancer, with toxicity similar to that in HIV-negative individuals.

Incidental trichinellosis of strap muscle identified after thyroglossal duct cyst excision.

OBJECTIVES: (1) Present a unique case of a thyroglossal duct cyst (TGDC) excised for recurrent infections with Trichinella spiralis in adjacent strap muscle; (2) review the literature regarding the diagnosis and treatment of subclinical trichinellosis of the head and neck. STUDY DESIGN: Case report and literature review. METHODS: Case report and literature review. RESULTS: We present the case of a male immigrant who suffered from recurrent midline neck infections due to aTGDC. The patient underwent an uneventful Sistrunk procedure. Histological examination of the surgical specimen revealed a chronically infected TGDC as well as remnants of skeletal muscle adjacent to the cyst containing nematode larvae, positively identified as Trichinella spiralis. The patient was subsequently evaluated by an infectious disease specialist and required no further treatment for his parasitic infection. DISCUSSION: The presence of nematode infections in developed countries is rare today given improved hygiene practices and control of meat quality. We present a unique case of incidentally noted Trichinella spiralis infection of the head and neck. To our knowledge, this is the first described case of trichinellosis of strap muscle adjacent to an excised TGDC and furthermore highlights the rarity of Trichinella spiralis infections of the head and neck. CONCLUSIONS: Trichinella spiralis may exist subclinically in a variety of human tissues including neck muscles.

Functional reconstruction of glossectomy defects: the vertical rectus abdominus myocutaneous neotongue.

The vertical rectus abdominus myocutaneous (VRAM) flap is a valuable option for tongue reconstruction. However, the traditional inset (skin to remaining oral mucosa) obviates a more anatomic reconstruction. Eight patients underwent total or subtotal glossectomy with VRAM reconstruction. The muscle inset was supported at the inferior mandibular border attached to the remaining lingual mucosa or gingiva. The neotongue, consisting of skin and subcutaneous fat, was sutured posteriorly to the remaining tongue base, and the other surfaces were trimmed and left unsutured. Reconstruction was successful in all patients. The neotongue assumed palatal configuration, and within 2 weeks uniform granulation tissue followed by mucosalization occurred. One year postoperatively, all patients tolerated ad lib diets, spoke intelligibly, were gastrostomy tube and tracheotomy free and had no evidence of aspiration. This neotongue sits on the mandible under voluntary control, permitting effective obturation against the hard palate and providing successful speech and swallowing.

Quantitative evaluation of transtemporal and facial translocation approaches to infratemporal fossa.

OBJECTIVE: To compare the extent of exposure and surgical maneuverability provided by facial translocation and transtemporal approaches for access to the infratemporal fossa and anterolateral skull base. MATERIALS AND METHODS: Surgical procedures were performed on five fresh frozen adult cadavers (ten sides) with no known pathology. Facial transfacial approaches with and without a mandibulotomy and transtemporal approaches were evaluated. OBJECTIVE measures were (1) the distance from the surgical plane to designated anatomic landmarks and (2) the surgical angle of exposure. RESULTS: Distances from the surgical plane to the anatomic reference points were comparable for most of the access procedures (3 to 6 cm). The extended midfacial translocation and bilateral facial translocation approaches did, however, provide a shorter operative distance (1 to 3 cm) for access to the infratemporal fossa and contralateral structures, respectively. The transtemporal approaches facilitate a better angle of exposure (74 to 84 degrees) to the petrotemporal region, while the transfacial approaches were superior for access to the infratemporal structures. CONCLUSIONS: Based on the results, we propose a clinical algorithm for selecting a surgical approach based on the position and extent of an infratemporal or petrotemporal lesion.

Oropharyngeal kaposi sarcoma in related persons negative for human immunodeficiency virus.

OBJECTIVES: Kaposi sarcoma (KS) is a vascular tumor that can affect the mucosa of the upper aerodigestive tract. Although KS is the most common malignancy in patients with acquired immunodeficiency syndrome, it is rare in immunocompetent persons. We describe an unusual presentation of KS in 2 related individuals and describe our attempts to determine whether oropharyngeal KS is associated with human herpesvirus 8 (HHV-8). METHODS: All relevant clinical and surgical information, including information on tumor histopathologic and human immunodeficiency virus (HIV) serologic tests, was abstracted from the patient charts and electronic databases. HHV-8 immunohistochemistry was performed on paraffin-fixed specimens. RESULTS: Both patient 1 and patient 2 (the nephew of patient 1) were referred for workup of a tonsillar mass that was pathologically confirmed to be KS. In each case, HIV serologic testing was negative, and a screening immunologic workup, including a quantitative natural killer cell count, a B- and T-lymphocyte count, and immunoglobulin analysis, also yielded findings that were within normal limits. Immunohistochemistry performed on 1 pathological specimen showed positive staining for the presence of HHV-8, the etiologic agent of KS. CONCLUSIONS: The presence of oropharyngeal KS in 2 related HIV-negative individuals supports a role for genetic factors in susceptibility to KS, a common exposure to an infectious agent such as HHV-8, or both. Whereas most KS cases in industrialized countries are associated with immunodeficiency, clinical and laboratory data do not suggest that either of the patients described in this report are immunodeficient. Their susceptibility to KS may be secondary to a subtle inherited defect in host resistance to HHV-8, or another unknown factor.

The basis of racial differences in the incidence of thyroid cancer.

BACKGROUND: The incidence of thyroid cancer in black Americans is half that in white Americans. It is unknown whether this gap represents a population difference in disease or is attributable to inferior cancer screening in the black population. METHODS: A population-based cohort study of 53,990 patients (1973-2003) was performed using the National Cancer Institute's Surveillance Epidemiology End Results database. Socioeconomic variables were explored using the Healthcare Cost and Utilization Project database and macroeconomic data. RESULTS: Since 1973, thyroid cancer incidence among whites has increased 150.2% (4.0 to 9.9 of 100,000), while incidence among blacks has increased 73.2% (3.0 to 5.1 of 100,000). Across 17 regions, the incidence correlated with the percentage of the population with health insurance (r = 0.56, P = .02). Regression analysis suggested that half of the black-white incidence gap might be attributable to differences in health insurance status. Patients with thyroid cancer were more likely to be insured or reside in wealthier ZIP codes. Black patients were more likely to present at advanced age (RR 1.08, P < .0001) and with tumors >4 cm in size (RR 1.13, P <.0001). Black patients were slightly less likely to present with advanced disease (RR 0.96, P = .0008). Cancer-specific mortality was identical in the two populations. DISCUSSION: Sociodemographic data and differences at presentation support a small detection disparity in thyroid cancer, which may contribute to part of the incidence gap. However, this effect is not sufficiently strong to fully explain the incidence gap. A population difference in the incidence of disease may be coexistent.