First-In-Human Study in Cancer Patients Establishing the Feasibility of Oxygen Measurements in Tumors Using Electron Paramagnetic Resonance With the OxyChip.

OBJECTIVE: The overall objective of this clinical study was to validate an implantable oxygen sensor, called the 'OxyChip', as a clinically feasible technology that would allow individualized tumor-oxygen assessments in cancer patients prior to and during hypoxia-modification interventions such as hyperoxygen breathing. METHODS: Patients with any solid tumor at ≤3-cm depth from the skin-surface scheduled to undergo surgical resection (with or without neoadjuvant therapy) were considered eligible for the study. The OxyChip was implanted in the tumor and subsequently removed during standard-of-care surgery. Partial pressure of oxygen (pO2) at the implant location was assessed using electron paramagnetic resonance (EPR) oximetry. RESULTS: Twenty-three cancer patients underwent OxyChip implantation in their tumors. Six patients received neoadjuvant therapy while the OxyChip was implanted. Median implant duration was 30 days (range 4-128 days). Forty-five successful oxygen measurements were made in 15 patients. Baseline pO2 values were variable with overall median 15.7 mmHg (range 0.6-73.1 mmHg); 33% of the values were below 10 mmHg. After hyperoxygenation, the overall median pO2 was 31.8 mmHg (range 1.5-144.6 mmHg). In 83% of the measurements, there was a statistically significant (p ≤ 0.05) response to hyperoxygenation. CONCLUSIONS: Measurement of baseline pO2 and response to hyperoxygenation using EPR oximetry with the OxyChip is clinically feasible in a variety of tumor types. Tumor oxygen at baseline differed significantly among patients. Although most tumors responded to a hyperoxygenation intervention, some were non-responders. These data demonstrated the need for individualized assessment of tumor oxygenation in the context of planned hyperoxygenation interventions to optimize clinical outcomes.

Orbital Floor Reconstruction: A Comparison of Outcomes between Absorbable and Permanent Implant Systems.

There are distinct advantages and disadvantages between bioresorbable and permanent implants in orbital floor reconstruction. Our aim was to compare the outcomes and complications of resorbable implants and permanent implants in orbital floor fracture repair. A retrospective chart review was performed on all patients who underwent orbital floor fracture repair at a rural, tertiary care center from 2011 through 2016. Main outcome measures included improvement in diplopia, ocular motility, enophthalmos, hypoglobus, and infraorbital nerve sensation. A total of 87 patients underwent orbital floor reconstruction. After exclusion criteria were applied, 22 patients were included in the absorbable implant cohort, and 20 patients in the nonabsorbable implant cohort. All absorbable implants were composed of poly L-lactide/poly glycolide/poly D-lactide (PLL/PG/PDL), and nonabsorbable implants included both titanium/porous polyethylene (Ti/PPE) composite and titanium (Ti) mesh. Mean fracture surface area was 2.1 cm 2 (standard deviation [SD]: ± 0.9 cm 2 , range: 0.4-3.6 cm 2 ) for the absorbable implant group and 2.3 cm 2 (SD: ± 1.1 cm 2 , range: 0.6-4.4 cm 2 ) for the nonabsorbable implant group ( p = 0.58). There were no significant differences in diplopia, ocular motility, enophthalmos, hypoglobus, and infraorbital nerve sensation between absorbable and nonabsorbable implant groups. The mean follow-up time for absorbable and nonabsorbable implant groups was 622 (SD ± 313) and 578 (SD ± 151) days respectively ( p = 0.57). For moderate-size orbital floor fracture repairs, there is no difference in outcomes between absorbable implants consisting of PLL/PG/PDL and nonabsorbable implants consisting of Ti mesh or Ti/PPE combination.

Diagnostic Value of Lingual Tonsillectomy in Unknown Primary Head and Neck Carcinoma Identification After a Negative Clinical Workup and Positron Emission Tomography-Computed Tomography.

OBJECTIVE: Diagnostic rates of unknown primary head and neck carcinoma (UPHNC) using lingual tonsillectomy (LT) are highly variable. This study sought to determine the diagnostic value of LT in UPHNC identification using strict inclusion criteria and definitions to produce a more accurate estimate of diagnosis rate. METHODS: In this retrospective chart review, records of patients who underwent LT for UPHNC were reviewed. Inclusion criteria included absence of suspicious findings on physical exam and positron emission tomography-computed tomography as well as negative biopsies after panendoscopy and palatine tonsillectomy. Following inclusion criteria, 16 patients were reviewed. A systematic literature review on LT for the workup of CUP was also performed. RESULTS: LT was performed using transoral robotic surgery (TORS), transoral laser microsurgery (TLM), or transoral microsurgery with cautery (TMC). Following LT, primary tumor was identified in 4 patients out of 16. Detection rate by technique was 1/6, 2/7, and 1/3 for TORS, TLM, and TMC respectively. Postoperative bleeding occurred in three patients (19%); however, this was not related to the LT. Following literature review, 12 studies were identified; however, only 3 had enough data to compare against. All three studies had a cohort with suspicious findings on clinical exam. A total of 34 patients had a negative workup, with no suspicious findings on clinical exam and subsequently received an LT. CONCLUSION: This study suggests that LT should be considered initially in the diagnostic algorithm for UPHNC. This study can increase the patient size in this cohort by approximately 47%.

Parotidectomy using the Harmonic scalpel: ten years of experience at a rural academic health center.

BACKGROUND: Parotidectomy is one of the most commonly performed procedures by otorhinolaryngologists. Traditionally dissection is performed with a combination of a steel scalpel and bipolar cautery; however, starting in the early 2000s, the Harmonic scalpel has provided an alternative method for dissection and hemostasis. The purpose of this study is to compare operative time, blood loss, complications, and cost between the Harmonic scalpel and steel scalpel plus bipolar cautery for superficial and total parotidectomy. METHODS: Retrospective cohort of patients who underwent superficial or total parotidectomy with the Harmonic or cold steel between 2000 and 2015. Across 255 patients, comparison between operative time, blood loss, complications, and cost was performed. RESULTS: Superficial parotidectomy was performed on 120 patients with the Harmonic and 54 with steel scalpel. Total parotidectomy was performed on 59 patients using the Harmonic and 22 patients with cold steel. For superficial parotidectomy, the Harmonic reduced operative time (216 ± 42 vs. 234 ± 54 min, p = 0.03) and decreased blood loss (28 ± 19 vs. 76 ± 52 mls, p < 0.05). With total parotidectomy the Harmonic decreased operative time (240 ± 42 vs. 288 ± 78 min, p = 0.01) and reduced blood loss (38 ± 21 mls vs. 85 ± 55 mls, p < 0.05). There were no differences in complication rates between groups. Harmonic use was associated with surgical cost reduction secondary to reduced operative times. CONCLUSIONS: The Harmonic scalpel decreases blood loss and operating time for superficial and total parotidectomy. Shorter operative times may decrease the overall cost of parotidectomy.

Improving Access to Head and Neck Cancer Surgical Services through the Incorporation of Associate Providers.

OBJECTIVE: The urgent nature of head and neck cancer referrals often results in overbooked schedules, access delays, and patient, physician, and staff dissatisfaction. The goal of this study is to examine how incorporation of associate providers (APs) into a head and neck tumor clinic (HNTC) can improve access. METHODS: Scheduling data for the Dartmouth-Hitchcock HNTC 2 years prior (January 2011 to December 2012) and 2 years subsequent (January 2013 to December 2014) to program initiation were abstracted, including number of new patients seen per month, third available for new and established patients, overbooked hours, surgeon productivity, and patient satisfaction scores. RESULTS: New patients seen per month increased from 44 ± 4 to 60 ± 5 (P < .001). Third available for new patients decreased from 56 ± 4 to 27 ± 2 days and from 43 ± 3 to 35 ± 2 days for follow-ups (P < .001). Overbooked hours decreased from 14.7 ± 3.1 to 8.6 ± 1.7 hours (P < .001). Surgeon productivity remained stable (109% ± 11% vs 113% ± 6%, P = .56). Patient satisfaction in seeing APs versus surgeons was comparable (94 ± 2 vs 94 ± 3, P = .79). DISCUSSION: Incorporation of APs into the HNTC increases the number of new patients seen by the surgeon, decreases wait times for all appointments, and decreases overbooking while maintaining patient satisfaction and surgeon productivity. IMPLICATIONS FOR PRACTICE: AP incorporation significantly improves access to head and neck surgical services. With improved access, new cancer patients could start treatment sooner, potentially affecting outcome.

The anterolateral thigh fold-over flap for total and subtotal glossectomy reconstruction.

BACKGROUND: We present a fold-over technique for total and subtotal glossectomy reconstruction utilizing the ALT flap with the goal of increasing soft tissue bulk. METHODS: Retrospective review of total and subtotal glossectomy patients undergoing ALT fold-over flap reconstruction from January 2007 to December 2012. RESULTS: Eight patients fit inclusion criteria. Average length of follow-up was 35 months. There were no flap failures. At last follow-up, no patients were tracheostomy dependent. Six out of 8 patients (75%) did not require a g-tube and were able to maintain their weight. Speech intelligibility was good in 6/8 patients (75%). CONCLUSIONS: The ALT fold-over flap technique provides sufficient bulk to allow decannulation and airway protection as well as PO intake in most patients. Given the minimal donor site morbidity, it is our technique of choice for total and subtotal glossectomy defects. © 2016 Wiley Periodicals, Inc. Microsurgery 36:297-302, 2016.

Management of a Parturient with Diastrophic Dysplasia.

A 27-year-old primigravida patient with diastrophic dysplasia (DTD) presented to our obstetrics clinic at 8 weeks' gestational age. Diastrophic dysplasia is a rare, autosomal-recessive abnormality that presents multiple challenges to perinatal anesthetic management, including difficult airway management and relative contraindications to neuraxial anesthesia. The patient underwent elective cesarean delivery at 35 weeks' gestational age under general anesthesia. In this report, we describe our preoperative evaluation and management strategy that involved a multidisciplinary care team.

In vivo Cigarette Smoke Exposure Decreases CCL20, SLPI, and BD-1 Secretion by Human Primary Nasal Epithelial Cells.

Smokers and individuals exposed to second-hand cigarette smoke have a higher risk of developing chronic sinus and bronchial infections. This suggests that cigarette smoke (CS) has adverse effects on immune defenses against pathogens. Epithelial cells are important in airway innate immunity and are the first line of defense against infection. Airway epithelial cells not only form a physical barrier but also respond to the presence of microbes by secreting antimicrobials, cytokines, and chemokines. These molecules can lyse infectious microorganisms and/or provide signals critical to the initiation of adaptive immune responses. We examined the effects of CS on antimicrobial secretions of primary human nasal epithelial cells (PHNECs). Compared to non-CS-exposed individuals, PHNEC from in vivo CS-exposed individuals secreted less chemokine ligand (C-C motif) 20 (CCL20), Beta-defensin 1 (BD-1), and SLPI apically, less BD-1 and SLPI basolaterally, and more CCL20 basolaterally. Cigarette smoke extract (CSE) exposure in vitro decreased the apical secretion of CCL20 and beta-defensin 1 by PHNEC from non-CS-exposed individuals. Exposing PHNEC from non-CS exposed to CSE also significantly decreased the levels of many mRNA transcripts that are involved in immune signaling. Our results show that in vivo or in vitro exposure to CS alters the secretion of key antimicrobial peptides from PHNEC, but that in vivo CS exposure is a much more important modifier of antimicrobial peptide secretion. Based on the gene expression data, it appears that CSE disrupts multiple immune signaling pathways in PHNEC. Our results provide mechanistic insight into how CS exposure alters the innate immune response and increases an individual's susceptibility to pathogen infection.

MCM2/TOP2A (ProExC) immunohistochemistry as a predictive marker in head and neck mucosal biopsies.

Mucosal biopsies from the head and neck are often small and poorly oriented, which impedes diagnostic interpretation, especially in patients with a history of cancer, being monitored for recurrence. A cocktail of antibodies targeted against DNA topoisomerase IIA and mini-chromosome maintenance protein 2 (MCM2/TOP2A, ProExC), markers of aberrant S-phase induction, have been used with success as a diagnostic adjunct in the evaluation of squamous dysplasia of the uterine cervix. We tested the utility in head and neck biopsies to see if ProExC could be used to discriminate reactive/inflammatory from true pre-neoplasia. Sixty-four archival biopsies were selected from patients who presented to the surgeon with an indication for biopsy to "rule out" dysplasia. Histologically, all biopsies showed nonspecific atypia that was difficult to discriminate from dysplasia. Twenty-three of the patients progressed to squamous carcinoma and the rest remained benign over five years follow-up. Cases stained with ProExC by IHC methods showed a significant pattern of expression (p=0.026). The staining was greatest in patients without a history of prior head and neck cancer but was not significant. Our results show that ProExC, used in conjunction with the H&E slide, can enhance the predictive power of a mucosal biopsy in a cohort of patients.

Haemophilus influenzae lymphadenopathy in a patient with agammaglobulinemia: clinical-histologic-microbiologic correlation and review of the literature.

Agammaglobulinemia is the most common primary immunodeficiency, with an incidence of approximately 1 in 250,000 males in the United States. These patients are at risk for frequent recurrent infections, which may become fatal if untreated. Patients have increased susceptibility to encapsulated pyogenic bacteria. Haemophilus influenzae is second only to Streptococcus pneumoniae as the bacteria most frequently implicated in infections in these patients. We present a case involving an adolescent boy with X-linked agammaglobulinemia and H influenzae cervical adenopathy, confirmed twice by culture. We correlate the clinical, microbiologic, and histologic findings. Owing to the severity of infections in this population, surgical intervention is more common than in the immunocompetent population. This description may help the pathologist in considering a differential diagnosis when examining a diagnostic lymph node biopsy in these patients.

Localized amyloidosis of the tongue: a review.

Amyloidosis is a disease entity defined by the presence of extracellular deposits of proteinacious material. These deposits have a characteristic apple-green birefringence with polarized light after staining with Congo red. Amyloid involvement of the tongue is almost universally secondary to systemic disease. The mean survival of patients with a systemic form of amyloidosis is between 5 to 15 months, whereas those with the localized form have an excellent prognosis. This article presents a case of the more unusual localized form. A thorough evaluation, including abdominal fat or rectal biopsy, is essential in every patient to identify any systemic involvement. The absence of systemic amyloidosis offers a much more favorable prognosis and may be treated with simple surgical excision.