Oropharyngeal tumor cells induce COX-2 expression in peripheral blood monocytes by secretion of IL-1α.

Oropharyngeal squamous cell cancer (OPC) accounts for 3% of all cancers and greater than 1.5% of all cancer deaths in the United States, with marked treatment-associated morbidity in survivors. More than 80% of OPC is caused by HPV16. Tumors induced by HPV have been linked to impaired immune functions, with most studies focused on the local tumor microenvironment. Fewer studies have characterized the effects of these tumors on systemic responses in OPC, especially innate responses that drive subsequent adaptive responses, potentially creating feed-back loops favorable to the tumor. Here we report that elevated plasma levels of PGE2 are expressed in half of patients with OPC secondary to overexpression of COX-2 by peripheral blood monocytes, and this expression is driven by IL-1α secreted by the tumors. Monocytes from patients are much more sensitive to the stimulation than monocytes from controls, suggesting the possibility of enhanced immune-modulating feed-back loops. Furthermore, control monocytes pre-exposed to PGE2 overexpress COX-2 in response to IL-1α, simulating responses made by monocytes from some OPC patients. Disrupting the PGE2/IL-1α feed-back loop can have potential impact on targeted medical therapies.

Phase I trial of dose-escalated stereotactic radiosurgery (SRS) boost for unfavorable locally advanced oropharyngeal cancer.

BACKGROUND AND PURPOSE: Patients with locally advanced oropharynx squamous cell carcinoma have suboptimal outcomes with standard chemoradiation. Here, we evaluated toxicity and oncologic outcomes of dose escalation using radiosurgical boost for patients with unfavorable oropharynx squamous cell carcinoma. MATERIALS AND METHODS: Between 2010-2017, Thirty four patients with intermediate- or high-risk oropharynx squamous cell carcinoma were enrolled onto this prospective phase I trial. Each patient received concurrent cisplatin and fractionated radiotherapy totaling 60 Gy or 66 Gy followed by radiosurgery boost to areas of residual gross tumor: single fraction of 8 Gy or 10 Gy, or two fractions of 5 Gy each. Primary endpoint was treatment toxicity. Secondary endpoints were local, regional, and distant disease control. RESULTS: Eleven, sixteen and seven patients received radiosurgery boost with 8 Gy in 1 fraction, 10 Gy in 1 fraction, and 10 Gy in 2 fractions respectively. Acute toxicities include 4 patients with tumor necrosis causing grade 3 dysphagia, of which 3 developed grade 4 pharyngeal hemorrhage requiring surgical intervention. At 24 months after treatment, 7%, 9%, and 15% had grade 2 dysgeusia, xerostomia, and dysphagia, respectively, and two patients remained feeding tube dependent. No grade 5 toxicities occurred secondary to treatment. Local, regional, and distant control at a median follow up of 4.2 years were 85.3%, 85.3% and 88.2%, respectively. Five patients died resulting in overall survival of 85.3%. CONCLUSIONS: This study is the first to report the use of radiosurgery boost dose escalation in patients with unfavorable oropharynx squamous cell carcinoma. Longer follow-up, larger cohorts, and further refinement of boost methodology are needed prior to implementation in routine clinical practice. TRIAL REGISTRATION: Northwell Health Protocol #09-309A (NCT02703493) ( https://clinicaltrials.gov/ct2/show/NCT02703493 ).

Schwannoma-Like Pleomorphic Adenoma: Two Cases and a Review of the Literature.

Schwannoma-like pleomorphic adenoma is a rare variant of the common benign salivary neoplasm, pleomorphic adenoma. This entity's cytomorphology closely mimics a schwannoma, potentially making a diagnosis of cytologic preparations or of surgical specimens a challenge. To the best of our knowledge, there are only six previous reports of schwannoma-like pleomorphic adenoma with eight total cases in the English language literature prior to the addition of the two cases detailed in this report. Our report includes what we believe to be the first documented case of this entity occurring in the submandibular gland. One of our cases occurred in the submandibular gland of a 90-year-old woman and the other occurred in the left parotid gland of a 40-year-old woman. We also examine the diagnostic considerations used to differentiate these two entities.

Predictive Factors for Preoperative Percutaneous Endoscopic Gastrostomy Placement: Novel Screening Tools for Head and Neck Reconstruction.

OBJECTIVE: The treatment of head and neck cancer has varying impact on postoperative recovery and return of swallowing function. The authors aim to establish screening tools to assist in preoperatively determining the need for gastrostomy tube placement. METHODS: The authors prospectively assessed all patients undergoing complex head and neck reconstructive surgery during a 1-year study period. Only patients tolerating an oral diet, without preoperative gastrostomies, were enrolled for study. Eight parameters were assessed including: body mass index (BMI), prealbumin, albumin, smoking history, comorbidities [including coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), and diabetes mellitus (DM)], age, use of microvascular reconstruction, and type of defect. Two specific screening tools were assessed. In the first, a multivariate logistic regression model was employed to determine factor(s) that predict postoperative gastrostomy tube. In a second screening tool, the 8 parameters were scored between 0 to 1 points. The total score obtained for each patient was correlated with postoperative gastrostomy placement. RESULTS: Out of the 60 study patients enrolled in the study, 24 patients (40%) received a postoperative gastrostomy. In the logistic regression model, albumin level was the only factor that was significantly associated with need for postoperative gastrostomy (P < 0.0023). A score of 4 or greater was determined to have a sensitivity of 83% and specificity of 61% for postoperative gastrostomy. CONCLUSIONS: Patients with a score of 4 or more with this screening scoring system or those patients with an albumin level <3.5 g/dL were at high risk for postoperative feeding tube placement.

Giant Cell Tumor of the Larynx Treated by Surgery and Adjuvant Denosumab: Case Report and Review of the Literature.

Giant cell tumor of the larynx (GCTL) is a rare entity; only 34 cases have been reported in the literature. We report a case of GCTL in a 46 year-old male presenting clinical, radiographic, histological and therapeutic features. Previously reported cases are also reviewed.

Melanotic neuroectodermal tumor of infancy: a wolf in sheep's clothing.

INTRODUCTION: The melanotic neuroectodermal tumor of infancy (MNTI) is an exceptionally rare neoplasm. Despite their potential for local invasion, MNTI are considered benign neoplasms. Sporadic cases have been reported of MNTI acting in a malignant fashion; however, the majority of these tumors were of extragnathic origin. METHODS: A 2-month-old male presented with a rapidly expanding maxillary mass. The patient underwent excisional biopsy of the mass and a diagnosis of MNTI was returned. Tumor recurrence was appreciated postoperatively. Neoadjuvant chemotherapy was initiated to render it more amenable to surgical resection. Chemotherapy was suspended prematurely and the patient returned to the operating room for hemimaxillectomy. The postchemotherapy surgical pathology report demonstrated a unique mixed chemotherapy response. DISCUSSION: This report highlights the aggressive nature of gnathic MNTI, the importance of early diagnosis and definitive intervention, and the mixed clinical and histologic response of the lesion to neoadjuvant chemotherapy.

Backyard hazard: a case series of ingested grill brush bristles and a novel approach to extraction.

OBJECTIVES: To report a small case series of an unusual ingested foreign body and a new method for removal of tongue base foreign bodies. METHODS: Three patients were identified with wire bristle foreign bodies between 2009 and 2011 at our academic tertiary medical center. Their medical records were reviewed and are described in this report. RESULTS: Each patient presented to our medical center with progressive pain after ingestion of barbecued food. For 2 patients, the metallic bristle foreign body was imbedded within the lingual tonsil. In these 2 cases, radiofrequency plasma ablation (coblation) assisted partial lingual tonsillectomy was performed to identify the foreign body. In a third case, the foreign body presented as a complex deep space neck abscess and an open trans-cervical approach was required. CONCLUSION: While oropharyngeal and esophageal foreign bodies are common, there are only a few case reports describing this particular foreign body. The presentation of an imbedded wire grill brush bristle can be insidious. Persistent pain and foreign body sensation should be taken seriously in patients with a history of barbecue food ingestion. Intraoperatively, wire bristles can be difficult to localize and extract. Radiofrequency plasma assisted lingual tonsillectomy may be helpful for identifying and removing foreign bodies that are imbedded in the tongue base. Grill brushes should undergo stringent safety regulation, as ingested wire bristles are difficult to localize and remove and may cause significant morbidity.

Feasibility of flap reconstruction in conjunction with intraoperative radiation therapy for advanced and recurrent head and neck cancer.

BACKGROUND: Radiation is a known risk factor for poor wound healing. Patients undergoing intraoperative radiation therapy (IORT) typically receive higher cumulative doses to their wound beds than patients treated with conventional radiation therapy. We review our experience with IORT in patients undergoing resection of head and neck cancer and flap reconstruction. Logistics of delivery and outcomes are discussed. METHODS: A retrospective chart review was performed on all patients at Beth Israel Medical Center who underwent IORT for head and neck cancer between 2000 and 2007. Twenty-one patients receiving 22 treatments involving flap reconstruction were identified. The results of these reconstructions were evaluated for complications and functional outcome. RESULTS: All patients had complex surgical wounds of the face, upper aerodigestive tract, or neck who received IORT in conjunction with pedicled or free flap closure. Twenty-five flaps in 21 patients were performed in the setting of IORT. All patients received between 10 and 15 Gy of IORT administered directly to the wound bed. There were no perioperative mortalities. Wound breakdown occurred in three cases, all of which were treated successfully by operative revision. Functionally, most patients did well and performed similarly to historic controls for their type of reconstruction. CONCLUSIONS: Reconstruction using flaps in the context of IORT can be achieved with expectation of good wound healing in the majority of cases despite heavy cumulative doses of radiation to recipient wound beds.

True vocal fold immobility in the setting of well-differentiated thyroid carcinoma: unusual illustrative cases and recommendations for operative strategy.

OBJECTIVES: We present cases of transient true vocal fold (TVF) immobility caused by well-differentiated thyroid carcinoma (WDTC), and review the literature concerning management of WDTC invading the recurrent laryngeal nerve (RLN). METHODS: A description of the clinical course of 2 patients with WDTC and transient TVF immobility is presented in the context of a review of the literature concerning locally advanced WDTC with extrathyroidal extension and RLN involvement. RESULTS: Both patients had papillary thyroid carcinoma with ipsilateral TVF paralysis that resolved completely before operation. During the operation, the RLN was found to be grossly involved with disease and inseparable from the tumor, necessitating resection. Review of the literature revealed the following points that should be considered when confronting an RLN invaded by WDTC. (1) Benign disease can mimic invasive WDTC and must be ruled out. (2) RLN invasion does not carry the same prognostic implications as other categories of extrathyroidal extension of WDTC. (3) RLN sacrifice does not increase the overall survival rate. (4) There is no evidence that a paralyzed RLN will regain function when preserved. (5) The majority of RLNs that function before operation can be expected to function after the operation if preserved. CONCLUSIONS: Resolution of TVF paralysis should not reduce suspicion of RLN involvement by WDTC. When RLN involvement is discovered during operation, every attempt should be made to preserve a functioning RLN.

Connexin expression and gap junctional intercellular communication in human squamous cell carcinoma of the head and neck.

OBJECTIVE: Our laboratory is investigating the role that gap junction intercellular channels (composed of proteins called connexins) play in communicating apoptotic signals from therapeutically targeted squamous cell carcinoma of the head and neck (SCCHN) cells to adjacent, untreated, "bystander" cells (bystander effect). The nature of this research underscores the importance of delineating connexin expression patterns in SCCHN, and how this correlates with gap junctional intercellular communication (GJIC) and bystander effects. STUDY DESIGN: The GJIC activity of a diverse panel of SCCHN cell lines, as well as normal oral epithelial (NOE) cell controls was determined in vitro. These data were correlated with connexin expression patterns determined through connexin 43 and connexin 26 immunofluorescence. RESULTS: Cell lines with retained GJIC activity all expressed connexin 43 on the cell membrane. Cell lines that did not communicate microinjected lucifer yellow (lost GJIC activity) showed no connexin expression, either at the cell membrane or in the cytosol. Connexin 26 was not expressed in any of our SCCHN cell lines, whereas both connexin 43 and connexin 26 were expressed in the NOE cell controls. Furthermore, connexin 43 introduction into a GJIC (and connexin) deficient SCCHN cell line conferred no growth inhibitory effect. CONCLUSION: Connexin 43 expression correlates with retained GJIC in SCCHN in vitro. Connexin 26 may have a role as a tumor suppressor in SCCHN. SIGNIFICANCE: The data presented have relevance to our ongoing investigations of gap-junction mediated bystander effects in SCCHN and are being expanded to investigations on actual SCCHN tumor specimens.

Single-cell microinjection of cytochrome c can result in gap junction-mediated apoptotic cell death of bystander cells in head and neck cancer.

BACKGROUND: Gap junction intercellular channels are required for metabolic cooperation between cells and regulate normal tissue homeostasis by means of the transfer of small molecules between contacting cells. Not surprisingly, the gap junction phenotype is frequently lost during carcinogenesis in human tissues (including those of the upper aerodigestive tract), freeing individual cancer cells from the growth control signals of normal surrounding tissues and less aggressive adjacent cancer cells. We hypothesized that gap junctional intercellular communication (GJIC) could mediate a bystander effect (apoptotic cell death) in squamous cell carcinoma of the head and neck (SCCHN) cells adjacent to individually targeted SCCHN cells. METHODS: Single-cell microinjection of cytochrome c was used to induce apoptosis in target SCCHN cells with endogenous GJIC activity and in an SCCHN cell line with exogenously introduced GJIC activity. Apoptosis was followed in target and surrounding bystander cells through light and time course microscopic characterization. All of the preceding experiments were carried out in the absence and presence of 18-beta-glycerretinic acid, a pharmacologic inhibitor of GJIC. RESULTS: When cytochrome c was introduced into SCCHN cells with endogenous GJIC activity through single-cell microinjection, bystander effects (apoptosis of nontarget cells) were observed. When GJIC activity was blocked with the specific pharmacologic inhibitor of gap junctions, 18-beta-glycerretinic acid, a bystander effect was never seen in GJIC active SCCHN cell lines. CONCLUSIONS: Gap junction intercellular channels can mediate a bystander effect in SCCHN. Inconsistencies in our data will be discussed in the context of recent advances in this field, as well as our future research directions.

Planned neck dissection after concomitant radiochemotherapy for advanced head and neck cancer.

OBJECTIVES/HYPOTHESIS: Since 1998, at our academic, multidisciplinary head and neck cancer treatment center, it has been our policy to treat appropriate patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) with concomitant radiochemotherapy followed within 6 weeks by planned neck dissection(s). Our objective was to investigate the oncologic efficacy of planned neck dissection, to date, in this patient population with a focus on outcomes in the neck. STUDY DESIGN: Retrospective analysis of a cumulative patient database. METHODS: The medical records of all patients who underwent planned neck dissection(s) after concomitant radiochemotherapy for locoregionally advanced SCCHN at Beth Israel Medical Center and The Institute for Head and Neck Cancer in New York City were reviewed. For each patient, preradiochemotherapy primary and neck stage, postradiochemotherapy/preneck dissection clinical and radiographic neck status, type of neck dissection(s) performed, pathologic status of the neck dissection specimen(s), length of follow-up (after planned neck dissection), disease status at last follow-up, and site(s) of recurrence were recorded. Local, regional, and distant disease control rates were calculated by the Kaplan-Meier method. RESULTS: Fifty-one planned neck dissections were performed on 39 radiochemotherapy patients (12 patients had bilateral operations) between early 1998 and October, 2003. Thirty-two (82%) patients had N2 or greater neck disease, with 29 (74%) having T3/T4 disease at various upper aerodigestive tract primary sites. Patients received an average of 6,700 cGy and 6,000 cGy external beam radiation therapy to primary disease sites and involved cervical lymphatics respectively, concomitant with one of three platinum-based chemotherapy schedules. At a mean follow-up time of 24 (range 8-57) months for the entire study population, there has been only one neck recurrence (N2A neck). No patient with N2B (n = 11), N2C (n = 13, with majority of heminecks staged N2B), or N3 (n = 5) disease has recurred in the neck. No recurrences have occurred in the 41 heminecks (in 33 patients) where modified neck dissection (including 24 selective procedures) was performed despite the presence of residual carcinoma in 13 (32%) of these heminecks on pathologic review. Among all heminecks with residual carcinoma present (n = 18) in the neck dissection specimen, there has been only one neck recurrence. There have been no recurrences in the 26 heminecks (in 19 patients) with incomplete clinical response after radiochemotherapy despite the presence of residual carcinoma in 14 (54%) of these necks on pathologic review. The clinical and radiographic absence of residual disease after radiochemotherapy did not always predict a complete pathologic response. Surgical complications have been limited (1 chyle leak, 1 wound breakdown). CONCLUSIONS: The integration of planned neck dissection into the multidisciplinary management of patients with locoregionally advanced SCCHN is highly effective in controlling cervical metastatic disease. Modified and selective neck dissection procedures can be performed in the majority of patients, regardless of the response in the neck subsequent to concomitant radiochemotherapy. We recommend a planned neck dissection(s) in all patients staged (pretreatment) with N2 or greater neck disease and in select N1 cases.

Management of cancer of the base of tongue.

The management of base of tongue cancer has evolved steadily over time. Organ preservation with primary radiation therapy has produced excellent oncologic and functional outcomes. Concomitant chemotherapy has become important in patients with locoregionally advanced disease. Planned neck dissection after organ preservation therapy continues to be an integral step for regional control. This article reports the results of a literature review of base of tongue cancer emphasizing a multidisciplinary approach to obtain optimal results in terms of cure and quality of life.

Gene therapy for head and neck cancer.

Head and neck cancer, because of its anatomic accessibility and poor overall survival rate, has become a frequent target of novel gene therapy intervention strategies. Viral and nonviral vectors have been used to transfer a variety of tumor suppressor genes, suicide genes, and immunologic genes into head and neck cancer cells in both the laboratory and clinical setting. Gene therapy as an isolated treatment modality will probably not replace standard treatment modalities in the management of head and neck cancer. It seems likely, however, that gene transfer will find its way into the multidisciplinary care of the head and neck cancer patient, where novel treatments are combined with standard therapies in order to maximize tumor response.