Niels Kokot

CD8+ T Cell Tolerance to a Tumor-associated Antigen Is Maintained at the Level of Expansion Rather than Effector Function

CD8+ T cell tolerance to self-proteins prevents autoimmunity but represents an obstacle to generating T cell responses to tumor-associated antigens. We have made a T cell receptor (TCR) transgenic mouse specific for a tumor antigen and crossed TCR-TG mice to transgenic mice expressing the tumor antigen in hepatocytes (gag-TG). TCRxgag mice showed no signs of autoimmunity despite persistence of high avidity transgenic CD8+ T cells in the periphery. Peripheral CD8+ T cells expressed phenotypic markers consistent with antigen encounter in vivo and had upregulated the antiapoptotic molecule Bcl-2. TCRxgag cells failed to proliferate in response to antigen but demonstrated cytolytic activity and the ability to produce interferon γ. This split tolerance was accompanied by inhibition of Ca2+ flux, ERK1/2, and Jun kinasephosphorylation, and a block in both interleukin 2 production and response to exogenous interleukin 2. The data suggest that proliferation and expression of specific effector functions characteristic of reactive cells are not necessarily linked in CD8+ T cell tolerance.

The Supraclavicular Artery Island Flap in Head and Neck Reconstruction: Applications and Limitations

IMPORTANCE The supraclavicular artery island (SAI) rotational flap may have advantages compared with free-tissue transfer in head and neck reconstruction. Because this flap has not been extensively described for head and neck reconstruction of oncologic defects, guidelines for its indications would benefit the reconstructive surgeon. OBJECTIVE To describe the applications and limitations of the SAI flap as an alternative to free-tissue transfer in reconstruction of head and neck defects. DESIGN, SETTING, AND PARTICIPANTS Retrospective case series of 45 patients with defects related to malignant and nonmalignant disease undergoing reconstructive surgery from August 18, 2010, through September 28, 2012, at an academic, tertiary referral center. Each defect was deemed unsuitable for primary or local flap closure and would require regional tissue or free-tissue transfer. Mean follow-up was 10.3 (range, 1-31) months. INTERVENTION Use of the SAI flap for reconstruction of soft-tissue defects of the head and neck. MAIN OUTCOMES AND MEASURES Defect site, flap dimensions, time to raise the flap, and complications. RESULTS Defects of the oral cavity, oropharynx, laryngopharynx, esophagus, trachea, temporal bone, and cervicofacial skin underwent reconstruction. Mean flap dimensions were 6.1 cm wide and 21.4 cm long, with a mean skin paddle length of 7.9 cm. Harvest time was less than 1 hour. Donor-site complications included minor dehiscence in 6 patients and prolonged wound care in 2. Partial skin flap necrosis occurred in 8 patients, whereas 2 had complete loss of the skin paddle. Seven patients developed a salivary fistula, 4 of which healed spontaneously. Flap length greater than 22 cm correlated with flap necrosis (P = .02). A history positive for smoking correlated with an increased risk of flap dehiscence (P = .02). CONCLUSIONS AND RELEVANCE The SAI flap provides an alternative to free-tissue transfer for soft-tissue reconstruction after head and neck oncologic surgery. This flap is easy to harvest and versatile. However, the SAI flap has limitations in length and, because it is a rotational flap, is less capable of reconstructing some complex head and neck defects.

Use of the Supraclavicular Artery Island Flap for Reconstruction of Cervicofacial Defects

Objective To describe the supraclavicular artery island (SAI) flap as an alternative flap for reconstruction of cervicofacial defects. Study Design Case series with chart review. Setting Academic, tertiary referral center. Subjects and Methods Twenty-two patients with defects of the face, temporal bone, and neck were reconstructed with an SAI flap. Each defect was deemed unsuitable for primary or local flap closure and would require regional or free tissue transfer. Outcome measures included size and location of the defect, time to raise the flap, flap size and viability, and complications. Mean follow-up was 7.4 months (range, 1-31 months). Statistical analysis was performed using SAS 9.1 (SAS Institute, Cary, North Carolina). Results Defects of the cervical skin (n = 10), face (n = 8), and temporal bone (n = 4) were reconstructed. Mean flap dimensions were 6.1 cm (range, 5-7 cm) wide and 21.8 cm (range, 16-28 cm) long. The proximal portion of the flap was deepithelialized to match the defect, resulting in a mean skin paddle length of 9.6 cm (range, 5-18 cm). Minor donor site dehiscence occurred in 3 patients. Partial skin flap necrosis occurred in 2 patients, while 1 patient had complete loss of the skin paddle. There was no statistical correlation between flap necrosis and flap length (P = .3, χ2) or defect location (P = .13, χ2). Conclusion The SAI flap is a viable alternative to cervicofacial advancement or microvascular reconstruction of cervicofacial defects in select cases. This flap is reliable, easy to harvest, and versatile, and it provides a good color match for cervicofacial defects.

Pigmented villonodular synovitis of the temporomandibular joint: Case report and review of the literature.

We present a case of a 51‐year‐old male patient with pigmented villonodular synovitis (PVNS) of the left temporomandibular joint (TMJ) that initially presented as a slow‐growing left facial mass. Upon further workup, a contrast‐enhanced CT scan demonstrated an expansile soft tissue mass in the left TMJ.

Bacterial biofilms and increased bacterial counts are associated with airway stenosis.

Objectives Most airway stenoses are acquired secondary to the use of prolonged endotracheal intubation. Antibiotics have been shown to decrease local inflammation and granulation tissue formation in the trachea. However, antibiotic therapy is not 100% effective in preventing or treating granulation tissue formation. Development of bacterial biofilms may explain this finding. This study evaluates the difference between tracheal stenotic segments and normal trachea in terms of (1) presence of bacterial biofilms, (2) quantitative bacterial counts, and (3) inflammatory markers. Study Design Cross-sectional study. Setting Tertiary care academic medical center. Subjects A total of 12 patients were included in the study. Tissue from stenotic segments from 6 patients with airway stenosis undergoing open airway procedures were compared with tracheal tissue from 6 patients without airway stenosis undergoing tracheostomy. Methods Scanning electron microscopy for biofilm detection, quantitative polymerase chain reaction for quantitative analysis of bacterial count, and immunohistochemistry were performed for inflammatory markers transforming growth factor β1 (TGF-β1) and SMAD3. Results Compared with the patients without airway stenosis, patients in the airway stenosis group showed presence of bacterial biofilms, a significantly higher expression of 16S rRNA gene copies per microgram of tissue (187.5 vs 7.33, P = .01), and higher expression of TGF-β1 (91% vs 8%, P < .001) and SMAD3 (83.5% vs 17.8%, P < .001). Conclusion Bacterial biofilms, increased bacterial counts, and higher expression of TGF-β1 and SMAD3 are associated with airway stenosis.

The Role of HPV in Head and Neck Cancer Stem Cell Formation and Tumorigenesis

The cancer stem cell (CSC) theory proposes that a minority of tumor cells are capable of self-replication and tumorigenesis. It is these minority of cells that are responsible for cancer metastasis and recurrence in head and neck squamous cell cancers (HNSCC). Human papilloma virus (HPV)-related cancer of the oropharynx is becoming more prevalent, which makes understanding of the relationship between HPV and CSCs more important than ever. This relationship is critical because CSC behavior can be predicted based on cell surface markers, which makes them a suitable candidate for targeted therapy. New therapies are an exciting opportunity to advance past the stalled outcomes in HNSCC that have plagued patients and clinicians for several decades.

Use of Octreotide for the Management of Chyle Fistula Following Neck Dissection

IMPORTANCE Chyle fistula is an uncommon complication of neck surgery. A variety of management strategies have been described, including diet restriction, parenteral nutrition, use of pressure dressings, and revision surgery. Octreotide has been used with success in patients with neck and thoracic chyle fistulas, but data regarding efficacy in neck chyle fistulas are lacking. OBJECTIVE To evaluate the efficacy of octreotide for use in patients with postoperative chyle fistulas. DESIGN, SETTING, AND PARTICIPANTS Retrospective review of 12 patients who received octreotide for neck chylous fistula after neck dissection was performed during the period 2004 through 2014 at 2 tertiary care academic hospitals. EXPOSURES Patients with postoperative neck chyle fistulas were given a restricted diet and subcutaneous octreotide. MAIN OUTCOMES AND MEASURES The main outcome was fistula closure rate, defined as fistula resolution without surgical intervention. Secondary outcomes of fistula duration (days from detection until resolution), length of hospital stay (surgery to discharge), and treatment complications were also examined. RESULTS All 12 patients had resolution of their neck chyle fistula with octreotide therapy without need for revision surgery. Mean (SD) hospital stay was 8.7 (4.76) days, with a range of 3 to 18 days. The chyle fistula resolved after a mean (range) 5.5 (2-11) days. Self-resolving nausea was encountered in 1 patient from octreotide use, and 1 patient developed a salivary fistula as a result of the chylous fistula. CONCLUSIONS AND RELEVANCE In these patients, octreotide was safe and effective in resolving neck chylous fistulas. Octreotide therapy appears superior to traditional conservative measures of diet restriction and pressure dressings when compared with literature rates. A prospective study is needed to confirm results, but octreotide therapy should be considered as first-line conservative management for neck chyle fistulas that occur after neck surgery.

Split central venous sampling of parathyroid hormone: an adjunct to surgical exploration.

Minimally invasive parathyroid surgery mandates preoperative localization of the adenoma for a targeted operative approach. This technique uses split internal jugular vein parathyroid hormone (PTH) samples to determine a gradient that then directs the surgical exploration.

Device Life of Two Generations of Provox Voice Prostheses

Background: Tracheoesophageal voice prostheses are invaluable for speech rehabilitation in patients who have received total laryngectomy, but device failure impedes communication and creates psychosocial and financial burdens. This study compares the Provox 2 and Provox Vega voice prostheses on the parameter of device life. Methods: This was a retrospective observational study of 21 patients with 181 device replacements at an academic tertiary care medical center. Disparity in device life and factors that may influence device life were analyzed. Results: The mean device life for Provox 2, at 115.6 days (SE = 5.8), was longer than for Provox Vega, at 65.1 days (SE = 7.5) (P < .001). Conclusions: Device longevity was greater for Provox 2 over Provox Vega. These results will facilitate the design of prospective studies to assess reasons for variations in device life between patients and device types.

Transoral surgery vs intensity-modulated radiotherapy for early supraglottic cancer: a systematic review.

Purpose of review To provide clinicians with a critical review of outcomes for endolaryngeal surgery and intensity-modulated radiation therapy (IMRT) for early-stage supraglottic cancer. Recent findings A total of 971 potential articles were reviewed, with inclusion of 14 studies comparing IMRT with transoral surgery. One study analyzed IMRT, one transoral robotic surgery, and the remaining were transoral laser microsurgery studies. A weighted average and 95% confidence interval of all surgery patients showed a local control of 90.36 ± 1.14% (n = 118) for T1 lesions, 83.09 ± 1.36% (n = 232) for T2 lesions, and 86.38 ± 0.82% (n = 429) overall. The one study examining IMRT outcomes reported a local control of 70 ± 10.07% and overall survival of 63% over 5 years for T2 lesions (n = 78), with no reported T1 data or secondary outcomes. Summary Endolaryngeal surgery as definitive therapy for T1 and T2 supraglottic cancer has excellent local control. Although endolaryngeal surgery performed better than IMRT, the data are limited, and a definitive comparison with surgery cannot be made. Additional studies are required.