bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopic repair of an injured internal carotid artery utilizing femoral endovascular closure devices
Authors: Van Rompaey Jason , Bowers Greg , Radhakrishnan Jay , Panizza Benedict , Solares C. Arturo
Published: October 2013

Objectives/Hypothesis

Injury to the internal carotid artery is a feared complication of endoscopic endonasal surgery of the skull base. Such an event, although rare, is associated with high morbidity and mortality. Even if bleeding is controlled, permanent neurological defects frequently persist. Many techniques have been developed to manage internal carotid artery rupture with varying degrees of success. The purpose of this study was to explore endoscopic management of arterial damage with endovascular closure devices used for a femoral arteriotomy. The ability to remotely suture a damaged artery permits the possible adaptation of this technology in managing endoscopic arterial complications.

Study Design

Technical note.

Methods

After the creation of an endoscopic endonasal corridor in a cadaveric specimen, an arteriotomy was created at the cavernous portion of the internal carotid artery. The Angio‐Seal, StarClose, and MynxGrip vascular closure devices were utilized under endoscopic guidance to repair the arteriotomy. Angiography was then done on a cadaver sutured with the StarClose.

Results

Both the Angio‐Seal and StarClose were deployed quickly and appeared to provide sufficient closure of the arteriotomy. The Angio‐Seal required the use of a guidewire and was longer to deploy when compared with the StarClose. The StarClose deployment was quick and facile. The MynxGrip also deployed without difficulty.

Conclusions

The Angio‐Seal and StarClose systems were both successfully deployed utilizing an endoscopic endonasal approach. The MynxGrip was the easiest to deploy and has the greatest potential to be of benefit in this application. Further studies with hemodynamic models are required to properly assess the appropriateness in this setting.

Level of Evidence

NA Laryngoscope, 124:1318–1324, 2014
Adipose‐derived stem cell‐containing hyaluronic acid/alginate hydrogel improves vocal fold wound healing
Authors: Kim Young‐Mo , Oh Se H. , Choi Jeong‐Seok , Lee Songyi , Ra Jeong C. , Lee Jin H. , Lim Jae‐Yol
Published: October 2013

Objectives/Hypothesis

The purpose of this study was to investigate the regenerative efficacy of an injectable hyaluronic acid/mildly cross‐linked alginate hydrogel (HA/ALG hydrogel) containing human adipose‐derived mesenchymal stem cells (hAdMSCs) for vocal fold (VF) wound healing.

Study Design

Animal research.

Methods

HA/ALG hydrogel containing hAdMSCs was injected into the VFs of rabbits immediately after direct injury. Endoscopic evaluations were performed at 1 and 3 months after injury, and functional evaluations of mucosal vibration and viscoelastic properties were carried out posteuthanization at 3 months after injury. Histopathologic and immunohistochemical evaluations of extracellular matrix (ECM) components and of hepatocyte growth factor (HGF) activity were conducted in injured VFs. The engraftment of implanted hAdMSCs was investigated by detecting fluorescent‐labeled cells.

Results

The administration of hAdMSCs and hAdMSCs in HA/ALG hydrogel produced better macroscopic morphologies than the injection of phosphate‐buffered saline (PBS). Histologic evaluations revealed that treatment with hAdMSCs in HA/ALG produced more favorable ECM changes than hAdMSC. In particular, the treatment of hAdMSCs in HA/ALG hydrogel ameliorated excessive deposition of collagen type I and increased HGF activity in regenerating VFs. hAdMSCs in HA/ALG‐treated VFs also exhibited functional improvements in viscoelastic properties. hAdMSCs in HA/ALG remained viable in recipient VFs at 1 month after transplantation, and some were observed to be fostered to differentiate into fibroblasts.

Conclusions

The findings of the present study suggest that HA/ALG hydrogel is a promising biomaterial for prolonging the retention time of stem cells in VFs and for promotion of VF wound healing.

Level of Evidence

NA Laryngoscope, 124:E64–E72, 2014
Radiofrequency ablation for treatment of benign thyroid nodules: Systematic review
Authors: Fuller Colin W. , Nguyen Shaun A. , Lohia Shivangi , Gillespie M. Boyd
Published: October 2013

Objective

To summarize the literature published to date on the use of radiofrequency ablation (RFA) in the treatment of benign thyroid nodules, to evaluate the effectiveness of this treatment, and to attempt an evaluation of factors that may influence treatment outcome.

Study Design

Systematic review with meta‐analysis.

Methods

Systematic literature search was performed by two separate authors in four commonly used literature databases. Trials included in meta‐analysis included only those presenting prospective data. Meta‐analysis compared pretreatment values to post‐treatment outcomes.

Results

Of 46 full‐text articles identified, nine articles satisfied inclusion criteria. Two of these articles were randomized controlled trials comparing RFA to placebo or to some other treatment. One article was a randomized controlled trial comparing one RFA treatment to two treatments. The remaining six articles were noncontrolled, prospective observational studies. All analyzed outcomes showed statistically significant improvements from baseline to final follow‐up, including reduction in nodule size, improvement of symptom and cosmetic scores, and withdrawal from methimazole. Improvement in nodule size remained significant in both “hot” and “cold” nodule subgroups. Twelve adverse events were identified across all studies out of 306 total treatments. Two of these events qualified as significant adverse events. None of these events resulted in hospitalization or death.

Conclusions

Radiofrequency ablation is a safe and effective treatment for symptomatic thyroid nodules that are confirmed benign. However, the paucity of level 1 evidence comparing RFA to surgical or to other nonsurgical treatment modalities is concerning.

Level of Evidence

NA Laryngoscope, 124:346–353, 2014
CD34‐positive fibroblasts in Reinke's edema
Authors: Díaz‐Flores Lucio , Gutiérrez Ricardo , del Pino García María , Álvarez‐Argüelles Hugo , Díaz‐Flores Lucio , López‐Campos Daniel
Published: October 2013

Objectives/Hypothesis

To elucidate whether and to what extent CD34+ fibroblasts (so‐called CD34+ fibrocytes, CD34+ dendritic cells, and CD34+ stromal cells) occur in normal human vocal folds and in Reinke's edema.

Study Design

Histological study.

Methods

Conventional, immunohistochemical, and ultrastructural procedures were performed in histological blocks of 18 selected cases of Reinke's edema (with typical findings including acellular edematous spaces in the subepithelial connective tissue of vocal folds, and disarrangement of elastic, collagen, and reticular fibers). For control purposes, four normal vocal folds were analyzed.

Results

In normal vocal folds, most stromal cells were spindle‐shaped CD34+ fibroblasts. In Reinke's edema, increased density and changes in the morphology and size of this subpopulation of fibroblasts were demonstrated in the connective tissue surrounding the edematous spaces, particularly in their borders, where together with some macrophages they formed boundaries, mimicking the walls of distended lymphatic vessels when conventional stains were used. These activated CD34+ fibroblasts acquired a dendritic morphology (with long, moniliform, often bifurcated, overlapping multipolar processes), and their cytoplasmic organelles were increased in number. In addition to CD34, they expressed vimentin, CD10 and CD99, but no α‐smooth muscle actin (α‐SMA), CD31, CD117, CD68, h‐caldesmon, desmin, or S‐100 protein.

Conclusions

CD34+ fibroblasts are a major cell component in the stroma of vocal folds in Reinke's edema, and their activation, with increased density and morphologic changes around the edematous spaces, occurs without immunophenotypic transformation toward myofibroblasts (no expression of α‐SMA). The mechanisms by which these cells act in Reinke's edema require further study.

Level of Evidence

NA Laryngoscope, 124:E73–E80, 2014
Observation versus neck dissection for positron‐emission tomography–negative lymphadenopathy after chemoradiotherapy
Authors: Khodayari Behnood , Daly Megan E. , Bobinski Matthew , Farwell D. Gregory , Shelton David K. , Chen Allen M.
Published: October 2013

Objectives/Hypothesis

To analyze outcomes among patients with residual positron‐emission tomography (PET)‐negative lymphadenopathy after chemoradiotherapy for head and neck cancer based on whether or not they underwent neck dissection.

Study Design

Retrospective review.

Methods

Fifty‐five patients with stage III/IV squamous cell carcinoma of the head and neck were identified with residual PET‐negative lymphadenopathy based on standardized uptake value of <3. All patients had been treated with chemoradiotherapy to a median dose of 70 Gy (range, 60–4 Gy).

Results

With a median follow‐up of 30 months (range, 6–67 months), the 3‐year overall survival (85% vs. 81%, P = .57), progression‐free survival (88% vs. 88%, P = .42), and local‐regional control (96% vs. 100%, P = .68), did not differ between patients treated by neck dissection or observation.

Conclusions

Omission of neck dissection appears to be reasonable for patients with residual lymphadenopathy but negative PET after chemoradiotherapy for head and neck cancer.

Level of Evidence

4. Laryngoscope, 124:902–906, 2014
Restoration of scarred vocal folds using 5 amino acid‐deleted type hepatocyte growth factor
Authors: Mizuta Masanobu , Hirano Shigeru , Ohno Satoshi , Kanemaru Shin‐ichi , Nakamura Tatsuo , Ito Juichi
Published: October 2013

Objectives/Hypothesis

Our previous studies demonstrated a regenerative effect of recombinant human hepatocyte growth factor (HGF) on vocal fold scarring using full‐length HGF. However, clinical application has not yet been achieved because of the lack of a good manufacturing practice (GMP) for full‐length HGF. Another natural form of human HGF, 5 amino acid‐deleted type HGF (dHGF), has been newly produced under a GMP procedure. In the current study, we investigated the effect of dHGF in comparison with full‐length HGF for the treatment of vocal fold scars using a canine model.

Study Design

Prospective animal experiment.

Methods

The vocal folds of nine beagles were unilaterally injured. Four weeks after injury, the vocal folds were treated with an intracordal injection of full‐length HGF (full HGF group), dHGF (dHGF group), or phosphate‐buffered saline (sham group). Vibratory and histological examinations were performed for each group 6 months after injury.

Results

Vibratory examinations demonstrated significantly lower phonation threshold pressure and a higher ratio of normalized mucosal wave amplitude in both the full HGF and dHGF groups as compared to the sham group. Histological examination showed restoration of hyaluronic acid in both the full HGF and dHGF groups as compared to the sham group. No significant differences were observed for each parameter between the full HGF group and the dHGF group.

Conclusions

dHGF showed the same potential for regenerative effects on vocal fold scars as full‐length HGF. dHGF should be applicable for human clinical trials in patients with vocal fold scars.

Level of Evidence

NA Laryngoscope, 124:E81–E86, 2014
Organ preservation surgery for low‐ and intermediate‐grade laryngeal chondrosarcomas: Analysis of 16 cases
Authors: Piazza Cesare , Del Bon Francesca , Grazioli Paola , Mangili Stefano , Barbieri Diego , Nicolai Piero , Peretti Giorgio
Published: October 2013

Objectives/Hypothesis

To demonstrate that endoscopic resection (ER), open partial laryngectomies, and cricotracheal resection and anastomosis (CTRA) achieve a good balance between oncologic radicality and organ preservation for laryngeal low‐grade chondrosarcoma (LCS) and intermediate‐grade chondrosarcoma (ICS).

Study Design

Retrospective series in an academic institution.

Methods

Between 2001 and 2013, we treated 13 cricoid, two thyroid, and one arytenoid LCS and ICS. Two cricoid and the only arytenoid LCS were managed by ER. Two thyroid ala LCS were submitted to laminectomy. Five ICS and six LCS of the cricoid received CTRA.

Results

Nine patients only required tracheotomy, removed after a maximum of 14 days. Three patients required a nasogastric feeding tube, removed after a maximum of 8 days. Immediate complications included one bleeding, one cervical emphysema, and one partial anastomotic dehiscence. The only late complication was anastomotic stenosis that was resolved by laser resection. All patients regained regular oral feeding and a voice ranging from normal to moderate dysphonia. At the last follow‐up, two patients died of unrelated causes, seven are alive with asymptomatic and radiologically stable residual disease, and seven are alive without evidence of persistent disease. One patient received total laryngectomy 11 years after CTRA for recurrent symptomatic disease.

Conclusions

Organ preservation surgery for laryngeal LCS and ICS represents a treatment option with low morbidity, good quality of life, and fair possibility to obtain oncologic radicality.

Level of Evidence

4. Laryngoscope, 124:907–912, 2014
Incidence and management of rhinosinusitis after complex orbitofacial reconstruction
Authors: Parkes William J. , Nyquist Gurston G. , Rizzi Christopher , Zhang Sarah , Evans James J. , Heffelfinger Ryan N. , Rosen Marc R. , Curry Joseph M.
Published: October 2013

Objectives/Hypothesis

To examine the sinus‐related sequelae of free flap reconstruction for complex orbitofacial defects.

Study Design

Retrospective chart review.

Methods

Demographic, clinical, and radiographic data on a series of 55 patients who had undergone free tissue transfer for orbitofacial reconstruction was retrospectively reviewed. Follow‐up of ≥ 3 months was available for 49 patients.

Outcome measures studied included clinical or radiographic evidence of sinusitis and the need for sinus surgery.

Results

The most commonly involved sinuses were the ethmoid (n = 40) and maxillary (n = 38) sinuses, and the anterolateral thigh was the most common flap used (n = 41). Clinical and/or radiographic sinusitis was evident in 21 patients (43%), and 10 patients (20%) required sinus surgery at some point during follow‐up. Involvement of multiple sinuses in the initial orbitofacial surgery was associated with a significantly increased need for subsequent sinus surgery (P = 0.009). Adjuvant radiotherapy and adjuvant chemoradiotherapy were associated with a significantly increased risk for the development of rhinosinusitis (P = 0.045 and 0.016, respectively).

Conclusion

Rhinosinusitis and the need for operative management of sinus obstruction are common in patients having undergone complex orbitofacial reconstruction. Careful management of the paranasal sinuses is an important component of the multidisciplinary treatment of such patients.

Level of Evidence

4. Laryngoscope, 124:1059–1065, 2014
Protective effect of dexmedetomidine on noise‐induced hearing loss
Authors: Wen Jian , Xiao Ying , Bai Yan‐Xia , Xu Min
Published: October 2013

Objectives/Hypothesis

Noise generated by instruments, such as mastoid or craniotomy drills, may cause hearing damage by reducing the cochlear blood flow (CoBF). This study investigated whether dexmedetomidine can lessen noise‐induced hearing loss (NIHL) in a guinea pig model.

Study Design

Animal study using noise stimulation and measurement of hearing and CoBF in guinea pigs.

Methods

Guinea pigs (n = 8 animals/group) were treated by saline vehicle (control group), dexmedetomidine (1, 3, and 10 μg/kg dex groups), saline and noise (noise group), or 3 μg/kg dexmedetomidine and noise (dex+noise group). For noise exposure, octave band noise at 124 dB sound pressure level was administered to animals for 2 hours. Blood pressure (BP) and CoBF were monitored continuously. Auditory function was measured by the auditory brain‐stem response (ABR) before and 1 hour, 3 hours, 8 hours, and 10 days after noise exposure. Plasma norepinephrine (NE) was measured at baseline and 30, 60, 90, and 120 minutes after noise exposure by high‐performance liquid chromatography (HPLC).

Results

Noise exposure caused temporary and permanent hearing damage. Dexmedetomidine concentrations of 1 μg/kg and 3 μg/kg dose dependently improved CoBF. Administration of 10 μg/kg dexmedetomidine drastically reduced BP and CoBF. Pretreatment with 3 μg/kg dexmedetomidine alleviated the noise‐induced reduction in CoBF and improved hearing function by decreasing the permanent and temporary threshold shifts.

Conclusion

Dexmedetomidine displayed protective effects against NIHL in this animal model, suppressing activation of the sympathetic nervous system and improving CoBF. These findings could have clinical relevance and deserve further investigation.

Level of Evidence

N/A. Laryngoscope, 124:E188–E193, 2014
External laryngotracheal trauma
Authors: Randall Derrick R. , Rudmik Luke R. , Ball Chad G. , Bosch J. Douglas
Published: October 2013

Objectives/Hypothesis

Laryngotracheal trauma encompasses a subset of relatively uncommon yet life‐threatening injuries requiring prompt intervention to prevent short‐ and long‐term aerodigestive tract sequelae. Minimal literature exists regarding laryngotracheal injuries on a population level, particularly among Canadian centers.

Study Design

Case series.

Methods

Regional health databases containing in‐patient admissions, emergency department visits, and trauma service activations using International Classification of Diseases (ICD) diagnostic codes were queried to identify all laryngotracheal injuries diagnosed from April 1, 1995, to December 31, 2011. Health records and diagnostic imaging were evaluated for mechanism, injuries, airway management, and long‐term aerodigestive function.

Results

Eighty‐nine patients met inclusion criteria, equating to 1/1042 admissions and 1/2478 emergency presentations. Nineteen percent of injuries were severe (Schaefer‐Fuhrman score ≥ 4). Airway intervention was performed at presentation in 65% of patients, with 13.5% necessitating emergent surgical airway; 52% underwent investigative or interventional airway surgery. Nine patients (16%) had long‐term moderate or severe dysphonia; 14.5% had dysphagia. Odds ratio for death and long‐term dysphonia among severe compared to minor laryngotracheal injuries were 7.1 (95% CI = 1.4–35.4) and 17.2 (95% CI = 3.3–91.1), respectively. Several factors were identified that predicted airway management and outcomes.

Conclusion

Traumatic laryngotracheal injuries are more common than previously reported, due to increased recognition. Many can be managed nonoperatively; however, cases require individual evaluation with judicious airway management and intervention to minimize aerodigestive sequelae. Severe injuries are associated with death and dysphonia but not with dysphagia.

Level of Evidence

4. Laryngoscope, 124:E123–E133, 2014
Central skull base osteomyelitis
Authors: Johnson Andrew K. , Batra Pete S.
Published: October 2013

Objectives/Hypothesis

Skull base osteomyelitis (SBO) most commonly results as a complication of otitis externa in diabetic patients. Central or atypical presentations, unrelated to aural pathology, have been documented, though restricted to small patient series or case reports. The current study systematically analyzed the literature to construct the clinical profile of this rare entity.

Study Design

Systematic review of case series.

Methods

The MEDLINE database was searched for all published cases of central SBO. Four additional cases were included from the University of Texas Southwestern Medical Center. Statistical analysis was performed to identify trends affecting overall outcomes or differences in treatment.

Results

A total of 42 cases were included with mean age of 52 years and male:female ratio of 2.2:1. The most common presenting symptoms were headaches and cranial nerve palsies, including VI (31%), IX (29%), and X (29%). Staphylococcus aureus (21%) and Pseudomonas aeruginosa (19%) were the two most common causative pathogens. The mean duration of antimicrobial therapy was 21 weeks, with 55% requiring intravenous antibiotics for a mean duration of 6.9 weeks. Twenty of 42 patients (48%) received surgical biopsy for diagnosis, whereas 18 patients (43%) required adjunct surgical debridement. Women were more likely than men to require multiple courses of therapy (46% vs. 7%, P = .01). The overall mortality was 9.5%, with an additional 31% experiencing residual neurological dysfunction.

Conclusions

Osteomyelitis of the central skull base poses significant challenges for timely and accurate diagnosis. Aggressive management with antimicrobials, coupled with surgical debridement in select cases, may avoid serious neurologic morbidity and mortality.

Level of Evidence

NA Laryngoscope, 124:1083–1087, 2014
Adjuvant stereotactic body radiotherapy ± cetuximab following salvage surgery in previously irradiated head and neck cancer
Authors: Vargo John A. , Kubicek Gregory J. , Ferris Robert L. , Duvvuri Umamaheswar , Johnson Jonas T. , Ohr James , Clump David A. , Burton Steven , Heron Dwight E.
Published: October 2013

Objectives/Hypothesis

Locoregional recurrence remains the primary failure pattern following salvage surgery for previously irradiated head and neck cancer; randomized trials have suggested a complimentary role for adjuvant chemotherapy and conventional reirradiation at the expense of significant increases in toxicity. We aimed to identify if stereotactic body radiotherapy (SBRT) ± cetuximab improves tumor control while reducing treatment‐related toxicity following salvage surgery.

Study Design

Retrospective review (2005–2011) of 28 patients with high‐risk features (positive surgical margins or extranodal extension) following macroscopic complete (R0/R1) salvage surgery treated with adjuvant SBRT ± cetuximab.

Methods

SBRT consisted of 40 to 44 Gy in five fractions over 1 to 2 weeks with concurrent cetuximab (n = 7) administered at 400 mg/m2 day −7 + 250 mg/m2 days 0 and +8. Toxicity was physician recorded, and University of Washington Quality of Life Revised surveys were prospectively collected.

Results

All patients received prior radiotherapy (median, 70 Gy; range, 54–99 Gy) with a median reirradiation interval of 25 months (range, 6–156 months). At a median follow‐up of 14 months (range, 2–69 months), the 1‐year locoregional control, distant control, disease‐free survival, and overall survival were 51%, 90%, 49%, and 64%, respectively. Rates of acute and late severe (≥grade 3) toxicity were low at 0% and 8%, respectively. At a median follow‐up survey time of 6 months, 56% of patients reported improved/stable overall quality‐of‐life scores.

Conclusions

Adjuvant SBRT ± cetuximab following salvage surgery is well tolerated with acceptable oncologic outcomes and little toxicity. Future prospective trials should evaluate adjuvant SBRT ± cetuximab versus a wait‐and‐see approach for recurrent head and neck cancers with high‐risk features following salvage surgery.

Level of Evidence

4 Laryngoscope, 124:1579–1584, 2014
Robotic microlaryngeal surgery
Authors: Lalich Ian J. , Olsen Steven M. , Ekbom Dale C.
Published: October 2013

Objectives/Hypothesis

Robotic surgery is increasingly used for a variety of head and neck surgical procedures but has yet to be adapted for routine robotic microlaryngeal surgery (RMLS). Current retractor technology is limited by the following: poor tongue retraction, poor oral commissure retraction, poor larynx visualization, and laryngeal blades that do not take advantage of the robot's ability to operate without line‐of‐site exposure. Additionally, adequate instrumentation for RMLS is lacking.

Study Design

Feasibility study.

Methods

We performed a feasibility study of RMLS using a newly designed robotic retractor in a cadaver model with the goal of routinely exposing the glottis. Microlaryngeal instrumentation was also adapted for the da Vinci Surgical Robot effector arms.

Results

RMLS surgery was successfully performed including microflap elevation, anterior commissure surgery, false cordectomy, true cordotomy/cordectomy, and arytenoidectomy. Photographic and video documentation was obtained demonstrating feasibility.

Conclusions

We present a newly designed laryngeal robotic retractor and novel microlaryngeal instrumentation in a cadaveric model. This allows for glottic and anterior commissure exposure, effector arm access to the glottis, and performance of delicate endolaryngeal procedures with the robot. The overall efficacy of our retractor will need to be examined in an in vivo human model.

Level of Evidence

NA Laryngoscope, 124:1624–1630, 2014
Truncus bicaroticus: An underestimated anatomic variation
Authors: Becker Christoph , Csatari Zoltan , Pfeiffer Jens
Published: October 2013

Objectives/Hypothesis

To illustrate that a truncus bicaroticus and an elongated truncus brachiocephalicus are underestimated anatomic variations; and to highlight the risk of injury of these vessel anomalies during routine surgical interventions.

Data Source

Report of a woman with long‐term ventilation who was planned for conventional surgical tracheostomy. Due to a strong pulsatile vessel crossing the cricoid cartilage, the procedure was stopped. Further diagnostics revealed anomalies of the supraaortic vessels, including a truncus bicaroticus.

Conclusion

Anomalies of supraaortic vessels are not rare and injuries may cause severe bleeding; therefore, we recommend performing a preoperative ultrasound, particularly before starting dilatative tracheostomy. Laryngoscope, 124:1141–1142, 2014
Preventing pharyngo‐cutaneous fistula in total laryngectomy: A systematic review and meta‐analysis
Authors: Sayles Mark , Grant David G.
Published: October 2013

Objectives/Hypothesis

Concurrent chemoradiotherapy is the gold‐standard nonsurgical organ‐preservation treatment for advanced laryngeal carcinoma. Total laryngectomy (TL) is increasingly reserved for surgical salvage. Salvage surgery is associated with more complications than primary surgery. A systematic review and meta‐analysis was undertaken to establish the impact of organ preservation protocols on pharyngo‐cutaneous fistula incidence following TL, and to synthesize evidence on the role of “onlay” prophylactic tissue flaps in reducing this complication in salvage TL.

Data Sources

The English language literature (January 1, 2000, to September 1, 2013) was searched, using PUBMED and EMBASE databases, for the terms “laryngectomy” and “fistula.” Of 522 studies identified from database searches, 33 were included in the quantitative synthesis.

Review Methods

Studies reporting fistula incidence following primary TL (PTL), salvage TL (STL), and STL with “onlay” flap‐reinforced pharyngeal closure were included. Data were extracted by the first author (M.S.). Meta‐analysis of fistula incidence was performed.

Results

PTL fistula incidence is 14.3% (95% CI 11.7–17.0), STL 27.6% (23.4–31.8), and STL with flap‐reinforced closure 10.3% (4.6–15.9). Chemoradiotherapy is associated with a pooled fistula incidence of 34.1% (22.6–45.6), compared to 22.8% (18.3–27.4) for radiotherapy alone. Relative risk of fistula is 0.566 (0.374–0.856, P = 0.001) for STL with flap‐reinforced closure compared to STL alone. The number needed to treat (NNT) to prevent one fistula is 6.05.

Conclusion

Prophylactic flaps used in an “onlay” technique reduce fistula incidence in STL. Chemoradiotherapy increases fistula incidence more than radiotherapy alone. Prophylactic flaps should be offered in salvage cases after failed chemoradiation protocols.

Level of Evidence

3A.Laryngoscope, 124:1150–1163, 2014
Clival keloid after nasopharyngeal radium irradiation masquerading as skull base malignancy
Authors: Kanumuri Vivek V. , Raikundalia Milap D. , Khan Mohemmed N. , Husain Qasim , Vasquez Alejandro , Eloy Jean Anderson
Published: October 2013

Objectives/Hypothesis

Nonchordomatous lesions of the clivus are rare entities. Nasopharyngeal radium irradiation (NRI) treatment consists of application of radium to the posterior nasopharynx near the orifice of the Eustachian tubes, an area adjacent to the clivus. Here we present a unique case of a patient with a history of NRI 70 years prior to presentation with a space‐occupying clival lesion suspicion for a skull‐based malignancy. This lesion was resected using an endoscopic endonasal approach. Histopathological analysis revealed a clival keloid, an entity not previously reported in the literature. Laryngoscope, 124:1767–1770, 2014
Codeine‐related adverse drug reactions in children following tonsillectomy: A prospective study
Authors: Prows Cynthia A. , Zhang Xue , Huth Myra M. , Zhang Kejian , Saldaña Shannon N. , Daraiseh Nancy M. , Esslinger Hope R. , Freeman Edita , Greinwald John H. , Martin Lisa J. , Sadhasivam Senthilkumar
Published: October 2013

Objectives/Hypothesis

To prospectively determine factors associated with codeine's adverse drug reactions (ADRs) at home in a large homogenous population of children undergoing outpatient tonsillectomy.

Study Design

Prospective, genotype blinded, observational study with a single group and repeated ADR measures documented by parents at home.

Methods

A total of 249 children 6 to 15 years of age scheduled for tonsillectomy were enrolled. The primary outcome was number of daily codeine‐related ADRs. We examined the number and type of ADR by race and by days and further modeled factors potentially associated with ADR risk in a subcohort of white children. Sedation following a dose of codeine was a secondary outcome measure. Parents recorded their children's daily ADRs and sedation scores during postoperative days (POD) 0 to 3 at home.

Results

Diaries were returned for 134 children, who were given codeine. A total of 106 (79%) reported at least one ADR. The most common ADRs were nausea, lightheadedness/dizziness for white children and nausea, and vomiting for African American children. In a subcohort of white children ≤ 45 kg, increased ADR risk was associated with the presence of one or more full function CYP2D6 alleles (P < 0.001), POD (P < 0.001), and sex (P = 0.027). Increased pain intensity (P = 0.009) and PODs 0 and 1 (P = 0.001) contributed to a higher sedation risk. Neither obstructive apnea nor predicted CYP2D6 phenotype were associated with sedation risk.

Conclusions

Our results provide evidence that multiple factors are associated with codeine‐related ADRs and support the FDA recommendation to avoid codeine's routine use following tonsillectomy in children.

Level of Evidence

4. Laryngoscope, 124:1242–1250, 2014
Effects of botulinum toxin A on patient‐specific keloid fibroblasts in vitro
Authors: Haubner Frank , Leyh Michaela , Ohmann Elisabeth , Sadick Haneen , Gassner Holger G.
Published: October 2013

Objectives/Hypothesis

To test whether therapeutic effects of botulinum toxin A on patient‐ specific keloid tissue can be reproduced on the cellular level. Specifically, effects on cell proliferation and expression of growth factors and cytokines relevant for wound healing were to be tested.

Study Design

Experimental study including patient specific cell cultures of keloids.

Methods

Patient‐specific keloid tissue was tested in a cell culture model for effects of botulinum toxin incubation on cell proliferation and expression of the following cytokines and growth factors: IL‐6 (interleukin‐6), VEGF (vascular endothelial growth factor), TGF‐β (transforming growth factor‐β).

Results

None of the tested parameters of human keloid tissue were affected by botulinum toxin A incubation.

Conclusion

The present study does not add evidence to suggest a significant therapeutic role of botulinum toxin injections for the treatment of keloids.

Level of Evidence

N/A. Laryngoscope, 124:1344–1351, 2014
Expression of IL‐33 and its receptor ST2 in chronic rhinosinusitis with nasal polyps
Authors: Baba Shintaro , Kondo Kenji , Kanaya Kaori , Suzukawa Keigo , Ushio Munetaka , Urata Shinji , Asakage Takahiro , Kakigi Akinobu , Suzukawa Maho , Ohta Ken , Yamasoba Tatsuya
Published: October 2013

Objectives/Hypothesis

Interleukin (IL)−33 is a novel member of the IL‐1 cytokine family and a ligand for the orphan IL‐1 family receptor ST2. IL‐33 induces T helper 2‐type inflammatory responses and is considered to play a crucial role in allergic inflammatory reactions such as asthma and atopic dermatitis. However, the role of IL‐33 and its receptor ST2 in chronic rhinosinusitis remains unclear.

Study Design

In vitro study.

Methods

The expression patterns of IL‐33 and ST2 at both mRNA and protein levels in nasal polyps from eosinophilic chronic rhinosinusitis (ECRS) patients (n = 10) and non‐ECRS patients (n = 13), as well as in seemingly normal mucosa of the uncinate processes in patients without sinusitis (control; n = 5), were compared using immunohistochemical staining, enzyme‐linked immunosorbent assay, and real‐time polymerase chain reactions.

Results

ST2‐positive cells in the inflammatory cells in the subepithelial layer were significantly higher in the ECRS group than other groups. The expression of ST2 mRNA in polyps of the ECRS group was significantly increased compared with controls. Many ST2‐positive eosinophils were observed in the mucosa of ECRS but not in the mucosa of non‐ECRS patients. The expression level of IL‐33 mRNA was not significantly different among the three groups.

Conclusions

The current study suggests that IL‐33 and its receptor ST2 may play important roles in the pathogenesis of chronic rhinosinusitis, especially in ECRS, through the increased expression of ST2 in eosinophils.

Level of Evidence

N/A. Laryngoscope, 124:E115–E122, 2014
Fistula rates after salvage laryngectomy: Comparing pectoralis myofascial and myocutaneous flaps
Authors: Khan Nabeel A. , Medina Jesus E. , Sanclement Jose A. , Krempl Greg A.
Published: October 2013

Objectives/Hypothesis

Salvage laryngectomy after failed organ preservation often has a high complication rate, pharyngocutaneous fistulas being the most common. These fistulas increase morbidity, prolong hospitalization, and potentially delay adjuvant treatment. Fistula rates in the literature range from 3% to 65%. Use of the pectoralis flap to prevent fistula formation has been adopted as a common practice at our institution. A review of our experience using the overlay myofascial showed a higher than desired complication rate. The aim of this study is to assess whether the use of integrated myocutaneous flap results in a lower fistula rate.

Study Design

A retrospective review of 30 patients followed by a pilot study of 10 patients. All underwent salvage laryngectomy after failed organ preservation.

Methods

The operation notes of 40 laryngectomy patients were analyzed. The patient/tumor characteristics, pretreatment, neck dissection, flap type, and fistula rate were documented.

Results

The patient sample was 25% female. All patients received prior radiotherapy, but only 37.5% received prior chemoradiation. Neck dissections were performed in 80% of these patients, 76% of the myocutaneous group, and 84% of the myofascial group. Advanced tumor stage was found in 42% of the myofascial group and 52% of the myocutaneous group. Five of the 19 myofascial patients developed a fistula, whereas seven of the 21 myocutaneous patients developed a fistula.

Conclusions

The use of the pectoralis myocutaneous flap (PMCF) in this pilot series did not show a lower rate of fistula; other alternatives should be pursued to decrease this complication.

Evidence Level

4. Laryngoscope, 124:1615–1617, 2014
Association between sarcopenia and the risk of serious infection among adults undergoing liver transplantation
Authors: Krell Robert W. , Kaul Daniel R. , Martin Andrew R. , Englesbe Michael J. , Sonnenday Christopher J. , Cai Shijie , Malani Preeti N.
Published: October 2013

Although sarcopenia (muscle loss) is associated with increased mortality after liver transplantation, its influence on other complications is less well understood. We examined the association between sarcopenia and the risk of severe posttransplant infections among adult liver transplant recipients. By calculating the total psoas area (TPA) on preoperative computed tomography scans, we assessed sarcopenia among 207 liver transplant recipients. The presence or absence of a severe posttransplant infection was determined by a review of the medical chart. The influence of posttransplant infections on overall survival was also assessed. We identified 196 episodes of severe infections among 111 patients. Fifty-six patients had more than 1 infection. The median time to the development of an infection was 27 days (interquartile range = 13-62 days). When the patients were grouped by TPA tertiles, patients in the lowest tertile had a greater than 4-fold higher chance of developing a severe infection in comparison with patients in the highest tertile (odds ratio = 4.6, 95% confidence interval = 2.25-9.53). In a multivariate analysis, recipient age (hazard ratio = 1.04, P = 0.02), pretransplant TPA (hazard ratio = 0.38, P < 0.01), and pretransplant total bilirubin level (hazard ratio = 1.05, P = 0.02) were independently associated with the risk of developing severe infections. Patients with severe posttransplant infections had worse 1-year survival than patients without infections (76% versus 92%, P = 0.003). In conclusion, among patients undergoing liver transplantation, a lower TPA was associated with a heightened risk for posttransplant infectious complications and mortality. Future efforts should focus on approaches for assessing and mitigating vulnerability in patients undergoing transplantation. Liver Transpl 19:1396–1402, 2013. © 2013 AASLD.
Neoadjuvant stereotactic body radiation therapy, capecitabine, and liver transplantation for unresectable hilar cholangiocarcinoma
Authors: Welling Theodore H. , Feng Mary , Wan Shanshan , Hwang Sin Ye , Volk Michael L. , Lawrence Theodore S. , Zalupski Mark M. , Sonnenday Christopher J.
Published: October 2013

Hilar cholangiocarcinoma (CCA) is a difficult malignancy to treat surgically because of its anatomical location and its frequent association with primary sclerosing cholangitis. Neoadjuvant chemoradiotherapy followed by liver transplantation in lymph node–negative patients has been advanced by select liver transplant centers for the treatment of patients with unresectable disease. This approach has most commonly used external-beam radiotherapy in combination with biliary brachytherapy and 5-fluorouracil–based chemotherapy. Our center recently embarked on a protocol using stereotactic body radiation therapy (SBRT) followed by capecitabine in lymph node–negative patients until liver transplantation. We, therefore, retrospectively determined the tolerability and pathological response in this pilot study. During a 3-year period, 17 patients with unresectable hilar CCA were evaluated for treatment under this protocol. In all, 12 patients qualified for neoadjuvant therapy and were treated with SBRT (50-60 Gy in 3-5 fractions over the course of 2 weeks). After 1 week of rest, capecitabine was initiated at 1330 mg/m2/day, and it was continued until liver transplantation. During neoadjuvant therapy, there were 35 adverse events in all, with cholangitis and palmar-plantar erythrodysesthesia being the most common. Capecitabine dose reductions were required on 5 occasions. Ultimately, 9 patients were listed for transplantation, and 6 patients received a liver transplant. The explant pathology of hilar tumors showed at least a partial treatment response in 5 patients, with extensive tumor necrosis and fibrosis noted. Additionally, high apoptotic indices and low proliferative indices were measured during histological examinations. Eleven transplant-related complications occurred, and the 1-year survival rate after transplantation was 83%. In this pilot study, neoadjuvant therapy with SBRT, capecitabine, and liver transplantation for unresectable CCA demonstrated acceptable tolerability. Further studies will determine the overall future efficacy of this therapy. Liver Transpl 20:81–88, 2014. © 2013 AASLD.
Abusive drinking after liver transplantation is associated with allograft loss and advanced allograft fibrosis
Authors: Rice John P. , Eickhoff Jens , Agni Rashmi , Ghufran Aiman , Brahmbhatt Rinjal , Lucey Michael R.
Published: October 2013

In patients who undergo liver transplantation for alcoholic liver disease (ALD), alcohol relapse is common. A return to abusive or excessive drinking likely decreases overall survival; however, the effects of alcohol use on allograft outcomes and histopathology are less well defined. We reviewed all cases of liver transplantation with ALD as an indication between January 1, 1995 and December 31, 2007. Allograft outcomes and histopathological results were compared for patients who relapsed into alcohol use and patients who maintained abstinence. Three hundred patients who underwent transplantation for ALD during this period survived at least 1 year, and 48 (16.0%) relapsed into alcohol use that came to clinical attention. The pattern of relapse was a single event for 10 patients (20.8%), intermittent relapses for 22 patients (45.8%), and continuous heavy drinking for 16 patients (33.3%). Continuous heavy drinking was associated with allograft loss in a univariate Cox proportional hazards analysis [hazard ratio (HR) = 2.43, 95% confidence interval (CI) = 1.26-4.68, P = 0.008] and in a multivariate Cox proportional hazards regression (HR = 2.57, 95% CI = 1.32-5.00, P = 0.006). A matched-pair analysis that controlled for the hepatitis C virus status and the time to biopsy compared the results of allograft histopathology for patients who relapsed into alcohol use and patients who maintained abstinence. Significant steatosis [odds ratio (OR) = 3.46, 95% CI = 1.29-9.31, P = 0.01], steatohepatitis (OR = 6.2, 95% CI = 1.70-22.71, P = 0.006), and advanced (stage 3 or higher) fibrosis (OR = 23.18, 95% CI = 3.01-177.30, P = 0.003) were associated with alcohol relapse. In conclusion, alcohol relapse after liver transplantation (particularly heavy drinking) is associated with decreased graft survival and advanced allograft fibrosis. Liver Transpl 19:1377-1386, 2013. © 2013 AASLD.
Thiol‐Click Chemistries for Responsive Neural Interfaces
Authors: Ware Taylor , Simon Dustin , Hearon Keith , Kang Tong H. , Maitland Duncan J. , Voit Walter
Published: October 2013

Neural interfaces provide an electrical connection between computers and the nervous system: current penetrating devices are orders‐of‐magnitude stiffer than surrounding tissue. In this work, recent efforts in softening electronics and utilize thiol‐ene and thiol‐epoxy “click” reactions are built upon to incorporate fluid‐sensitive hydrogen bonding into smart substrates for high electrode density neural interfaces. The modulus of these substrates drops more than two orders of magnitude in response to physiological conditions, despite fluid uptake of less than 6%, and can be tuned by the covalent crosslink density and degree of hydrogen bonding in the polymer network. Intracortical and intrafascicular electrode arrays are fabricated and characterized with impedance spectroscopy and cyclic voltammetry.
Polyacrylonitrile Block Copolymers for the Preparation of a Thin Carbon Coating Around TiO2 Nanorods for Advanced Lithium‐Ion Batteries
Authors: Oschmann Bernd , Bresser Dominic , Tahir Muhammad Nawaz , Fischer Karl , Tremel Wolfgang , Passerini Stefano , Zentel Rudolf
Published: October 2013

Herein, a new method for the realization of a thin and homogenous carbonaceous particle coating, made by carbonizing RAFT polymerization derived block copolymers anchored on anatase TiO2 nanorods, is presented. These block copolymers consist of a short anchor block (based on dopamine) and a long, easily graphitizable block of polyacrylonitrile. The grafting of such block copolymers to TiO2 nanorods creates a polymer shell, which can be visualized by atomic force microscopy (AFM). Thermal treatment at 700 °C converts the polyacrylonitrile block to partially graphitic structures (as determined by Raman spectroscopy), establishing a thin carbon coating (as determined by transmission electron microscopy, TEM, analysis). The carbon‐coated TiO2 nanorods show improved electrochemical performance in terms of achievable specific capacity and, particularly, long‐term cycling stability by reducing the average capacity fading per cycle from 0.252 mAh g–1 to only 0.075 mAh g–1.

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Galactose‐Functionalized Cationic Polycarbonate Diblock Copolymer for Targeted Gene Delivery to Hepatocytes
Authors: Ong Zhan Yuin , Yang Chuan , Gao Shu Jun , Ke Xi‐Yu , Hedrick James L. , Yan Yang Yi
Published: October 2013

To mediate selective gene delivery to hepatocytes via the asialoglycoprotein receptors (ASGP‐Rs), we designed and synthesized well‐defined and narrowly dispersed galactose‐ and glucose‐functionalized cationic polycarbonate diblock copolymers (designated as Gal‐APC and Glu‐APC, respectively) using organocatalytic ring‐opening polymerization of functionalized carbonate monomers, with a subsequent quaternization step using bis‐tertiary amines to confer quaternary and tertiary amines for DNA binding and endosomal buffering, respectively. The sugar‐functionalized diblock copolymers effectively bound and condensed DNA to form positively charged nanoparticles (<100 nm in diameter and ≈30 mV zeta‐potential) that were stable under high physiological salt conditions. In comparison to the control Glu‐APC/DNA complexes, Gal‐APC/DNA complexes mediated significantly higher gene expression in ASGP‐R positive HepG2 cells with no significant difference observed in ASGP‐R negative HeLa cells. The co‐incubation of Gal‐APC/DNA complexes with a natural ASGP‐R ligand effectively led to a decrease in gene expression, hence providing evidence for the ASGP‐R mediated endocytosis of the polyplexes. Importantly, the Gal‐APC/DNA complexes induced minimal cytotoxicities in HepG2 cells at the N/P ratios tested. Taken together, the galactose‐functionalized cationic polycarbonate diblock copolymer has potential for use as a non‐viral gene vector for the targeted delivery of therapeutic genes to hepatocytes in the treatment of liver diseases.

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Porous Polymers by Controlling Phase Separation during Vapor Deposition Polymerization
Authors: Tao Ran , Anthamatten Mitchell
Published: October 2013

A template‐free method is described to fabricate continuous‐phase, porous polymer films by simultaneous phase separation during vapor deposition polymerization. The technique involves concurrent polymerization, crosslinking, and phase separation of condensed species and reaction products. Deposited films form open‐cell, macroporous structures consisting of crosslinked and glassy poly(glycidyl methacrylate). By limiting phase separation during vapor phase deposition, spatially dependent morphologies, such as layered morphologies, can be grown. Results show that combining vapor deposition polymerization with phase separation establishes morphological control, which may be applied to applications including cellular scaffolds, thin cushions and vibration dampers, and membranes for separations.

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Protein carbonylation: Proteomics, specificity and relevance to aging
Authors: Cabiscol Elisa , Tamarit Jordi , Ros Joaquim
Published: October 2013

Detection and quantification of protein carbonyls present in biological samples has become a popular, albeit indirect, method to determine the existence of oxidative stress. Moreover, the rise of proteomics has allowed the identification of the specific proteins targeted by protein carbonylation. This review discusses these methodologies and proteomic strategies and then focuses on the relationship between protein carbonylation and aging and the parameters that may explain the increased sensitivity of certain proteins to protein carbonylation. © 2013 Wiley Periodicals, Inc. Mass Spec Rev 33: 21–48, 2014.