bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Novel Cetuximab Resistance Pathway Leads to Improved Outcomes in Head and Neck Cancer
Authors: Lajud Shayanne A. , Nagda Danish , Kumar Sanjeev , Qiao Peter , Zheng Jun , O'Malley Bert W. , Li Daqing
Published: August 2013

Objectives:

1) Determine if cetuximab resistance in head and neck squamous cell carcinoma (HNSCC) is regulated by increased nuclear translocation of Epidermal Growth Factor Receptor (EGFR) through an MRN‐dependent Akt phosphorylation pathway. 2) Determine if targeted inhibition of the MRN complex, a key mediator of DNA damage response, can improve cetuximab sensitivity in HNSCC.

Methods:

Two well‐characterized human HNSCC tumor cell lines, with differential resistance to cetuximab, were chosen for this study. Mirin, a novel molecular MRN inhibitor was used for this study. MTT and clonogenic assays were used to evaluate in vitro cytotoxicity. Western blot analysis was performed to evaluate protein expression. In vivo tumor growth was evaluated using molecular imaging.

Results:

As compared with sensitive cells, cetuximab resistant cells demonstrated increased MRN expression, increased Akt phosphorylation, and increased nuclear EGFR. The inhibition of MRN led to a dose‐dependent decrease in Akt phosphorylation and nuclear EGFR translocation. Furthermore, MRN inhibition synergistically enhanced the cytotoxic effect of cetuximab in resistant cells (P < 0.01).

Conclusions:

The findings from this study suggest a novel cetuximab resistance pathway involving MRN‐mediated Akt phosphorylation, leading to increased nuclear translocation of EGFR. Furthermore, inhibition of MRN led to decreased Akt‐phosphorylation, subsequently decreasing nuclear EGFR translocation, a key molecular mechanism involved in cetuximab resistance. Based on this discovery, inhibition of this pathway may serve as an effective therapeutic approach for HNSCC patients resistant to cetuximab.
Inositol Polyphosphate‐5‐Phosphatase in the Development of Head and Neck Squamous Cell Carcinoma
Authors: Patel Alpen B. , Landry April M. , Sekulic Aleksandar , Hayden Richard E.
Published: August 2013

Objectives:

1) Evaluate the expression patterns of inositol polyphosphate‐5‐phosphatase (INPP5A), a negative regulator of inositol signaling, in the development and progression of head and neck mucosal squamous cell carcinoma (SCCA). 2) Compare and contrast previously reported reduction in INPP5A protein levels seen in the progression of cutaneous SCCA with that of mucosal head and neck SCCA.

Methods:

We analyzed a series of mucosal oropharyngeal lesions ranging from normal mucosa to invasive SCCA in order to identify genetic changes associated with SCCA development. Immunohistochemistry (IHC) was performed to evaluate INPP5A protein levels in primary SCCA tumors. Formalin fixed, paraffin embedded tissues were sectioned and incubated with anti‐INPP5A antibody and the INPP5A protein expression levels quantified.

Results:

Deletions of a region on chromosome 10q harboring the INPP5A gene in cutaneous SCCA have previously been reported. INPP5A protein levels have been found to be frequently reduced in primary cutaneous SCCA tissues and demonstrate an early event in the progression of SCCA with further reduction in metastatic disease. A direct comparison of INPP5A protein levels in oropharyngeal mucosal head and neck SCCA has been made with data previously seen with cutaneous SCCA.

Conclusions:

Previous studies have shown that INPP5A loss is seen with cutaneous SCCA proliferation. This study provides a comparison of INPP5A protein levels in progressive mucosal oropharyngeal SCCA with that seen in cutaneous SCCA.
An Institutional Experience with the Development of Pharyngocutaneous Fistulas following Total Laryngectomy with Free Flaps
Authors: Masroor Farzad , Newman Jason G.
Published: August 2013

Objectives:

Pharyngocutaneous fistulas (PCF) are common after salvage total laryngectomies (TL). Prior studies examining the role of fistula formation (FF) at the time of TL to reduce the incidence of PCF are conflicting. We studied our institutional experience, where in the last few years a more routine approach to using FFs with TLs has been adopted irrespective of the size of the mucosal defect resulting from the TL. It is hypothesized that this routine approach reduces the incidence of PCFs.

Methods:

This is a retrospective study reviewing the records of patients who had TLs with FF between 2007‐2012. The date of surgery, site of recurrent disease, and whether the TL was primary or salvage were recorded. The primary outcome was the presence of PCF.

Results:

50 patients had a FF at the time of TL. Nine of these developed a PCF. The overall PCF incidence was 18%. The incidence following salvage TL was 22% (8/36), and that after primary TL was 7% (1/14). Between 2007‐2009, the PCF incidence was 36% (7/19), while from 2010‐2012 it was 3% (1/31).

Conclusions:

Our institutional experience with the use of FFs for TLs shows an overall PCF incidence comparable to rates reported in the literature. Over the last two years a statistically significant lower PCF incidence is seen (3% vs 36%), which reflects our gradual change in approach from a less to more routine use of FF. The routine use of FFs at the time of TLs reduces the incidence of PCF.
Isolation of Mesenchymal Stem Cells (MSC) from Human Adenoid Tissue
Authors: Lee Yoon‐Se , Lee Jae‐Eun , Park Young‐Min , Park Chan‐Whi , Wang Soo‐Geun , Lee Byung‐Joo
Published: August 2013

Objectives:

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that originally derived from bone marrow. Clinical use of bone marrow‐derived MSC is difficult due to morbidity and low MSC abundance and isolation efficiency. Recently, MSCs have been isolated from various adult tissues. Here we report the isolation of adenoid tissue‐derived MSCs (A‐MSCs) and their characteristics.

Methods:

We compared the surface markers, morphologies, and differentiation and proliferation capacities of previously established tonsil‐derived MSCs (T‐MSCs) with cells isolated from adenoid tissue. The immunophenotype of A‐MSCs was investigated upon interferon (IFN)‐Î3 stimulation.

Results:

Both T‐MSCs and A‐MSCs showed negative CD45, CD31 HLA‐DR, and positive CD 90, CD44, and CD73 expression. A‐MSCs were fibroblast‐like, spindle‐shaped non‐adherent cells, similar to T‐MSCs. Adipogenesis was observed in A‐MSCs by the formation of lipid droplets after Oil Red O staining. Osteogenesis was observed by the formation of the matrix mineralization in Alizarin Red staining. Chondrogenesis was observed by the accumulation of sulfated glycosaminoglycan‐rich matrix in collagen type II staining. These data were similar to those of T‐MSCs. Expression of marker genes (ie, adipogenesis; lipoprotein lipase, proliferator‐activator receptor‐gamma, osteogenesis; osteocalcin, alkaline phasphatase, chondrogenesis; aggrecan, collagen type II Î±1) in A‐MSCs were not different from those in T‐MSCs.

Conclusions:

A‐MSCs possess the characteristics of MSCs in terms of morphology, multipotent differentiation capacity, cell surface markers, and immunogeneity. Therefore, A‐MSCs fulfill the definition of MSCs and represent an alternate source of MSCs.
Long‐term Change of Body Mass Index after Head and Neck Cancer Treatment
Authors: Zhang Zi , Brown Justin C. , O'Malley Bert W. , Weinstein Gregory S. , Schmitz Kathryn H.
Published: August 2013

Objectives:

Although head and neck cancer (HNC) is associated with weight loss, little is known about the long‐term body mass index (BMI) change in HNC survivors. Our goal was to determine the long‐term BMI change after HNC treatment.

Methods:

Retrospective cohort study on patients with oral cavity and pharyngeal squamous cell carcinoma who received initial treatment at the University of Pennsylvania Health System in 2009, and were then followed for 3 years. Patient demographics, height, tobacco and alcohol use, cancer type, AJCC stage, treatments, and weight at all visits were collected from medical records. Underweight was defined as BMI<18.5, normal was BMI 18.5‐24.9, overweight was BMI 25.0‐29.9, and obesity was BMI > 30. Logistic regression was performed to identify factors associated with long‐term BMI changes.

Results:

We identified 211 patients with complete data and follow‐up visits. At the time of diagnosis, 7% patients were underweight (n = 15), 34% had normal‐weight (n = 72), 36% were overweight (n = 75) and 23% were obese (n = 49). At the last follow‐up visit, 7% were underweight (n = 14), 42% were normal‐weight (n = 82), 33% were overweight (n = 65) and 18% were obese (n = 36). Thus, 17% patients (n = 21) who were overweight or obese at diagnosis improved to normal weight at the end of 3‐year follow‐up, and this change was not significantly affected by patients’ age, gender, race, tobacco and alcohol use, cancer site, AJCC stage, and treatment type.

Conclusions:

Our study suggests BMI improves in overweight or obese HNC survivors after 3‐year follow‐up, and this change is independent of cancer severity and treatment type.
Microvascular Reconstruction in the Setting of Difficult Vascular Anatomy: The Reverse Arterial Flow Technique
Authors: Deschler Daniel G. , Lin Alice
Published: August 2013

Objectives:

We present one case where challenging vascular anatomy was circumvented by changing the conventional vascular dissection and geometry successfully.

Methods:

Variations in the quality and suitability of donor vessel anatomy can significantly impact microvascular free tissue transfer reconstruction and may require innovative approaches to allow successful revascularization. Although greatest variability is noted in the venous system of transferred tissue segments, arterial anatomy and quality can also be severely limiting. However, unlike the recipient vessels where multiple options may be available, there is only one available donor artery. In the setting of unfavorable physical properties of the artery, the reconstructive surgeon is often forced to sacrifice the flap in favor for a second harvest.

Results:

In our case, the artery was affected by Monckeberg's arteriosclerosis, which is a process of arterial calcification classically described as calcification of the tunica media of the arterial wall. This creates a hardened wall through which microvascular suture cannot be passed and microvascular anastomosis is not successful.

Conclusions:

In our case, the fibula free flap was salvaged by using the distal end of the artery for anastamosis to create reverse flow perfusion of the flap. We present the details of the technique required for harvest and inset of a reverse arterial flow fibula free flap.
Negative Prognostic Implication of Fibrotic Pattern in Papillary Thyroid Cancer
Authors: Lee Rang , Park Young‐Min , Woo Chang‐Ki , Lee Il‐Woo , Wie Chan‐Eun , Wang Soo‐Geun , Lee Byung‐Joo
Published: August 2013

Objectives:

Lymph node metastasis in papillary thyroid cancer occurs 40‐60% of the time. Extrathyroidal extension and large tumor size are the most reliable predicting factors for central lymph node metastasis whose prognostic value is controversial. In this study, we evaluated the relationship between a specific finding of primary tumor in the thyroid, fibrosis, and negative prognostic factors.

Methods:

We reviewed patients who underwent total thyroidectomy and central lymph node dissection with or without lateral lymph node dissection for papillary thyroid cancer (PTC), from January to December, 2011. We defined (+) finding when the degree of fibrosis comprised 10% or more of the primary tumor. Correlation between degree of fibrosis and negative prognostic factors, including age, gender, tumor size, extrathyroidal extension (ETE), number of central lymph node (CLN) metastases, and lateral cervical lymph node metastasis (LCLNM), was analyzed.

Results:

Of the 481 patients, fibrosis (+) group included 387 patients (80.5%). On the chi‐square test, age, gender, tumor size, and LCLNM were not correlated with fibrosis. ETE (+) group comprised of higher rate of fibrosis (+) group (90.4%) compared to ETE (‐) group (64.9%, P < 0.001). CLN metastasis (+) comprised of higher rate of fibrosis (+) group (84.6%) compared to CLN metastasis (‐) group (76.5%, P = 0.017). On the multivariate analysis, ETE was a significant risk factor of fibrosis (odds ratio = 2.545, P < 0.001, confidence interval from 1.775 to 3.649).

Conclusions:

Fibrosis in PTC can be a risk factor of extrathyroidal extension, a negative prognostic factor. This suggests that the behavior of fibrotic tumor is, possibly, more aggressive than non‐fibrotic tumor.
Non‐localizing Parathyroid Adenomas: Radiologic Error or True Entity
Authors: Goldenberg David , Portela Rafael A. , Smucker Joanne , Bruno Michael , Winner Louis , Saunders Brian
Published: August 2013

Objectives:

Investigate radiographic assessment of non‐localizing parathyroid adenomas (NLPA). Our goal was to determine whether non‐localization is a result of radiologic interpretive error, or truly representative of non‐visible parathyroid adenoma.

Methods:

We performed a retrospective chart review of 364 patients who underwent parathyroidectomy over a 5‐year period. Thirty patients who were identified as having NLPA on pre‐operative imaging were included. All available patient images were re‐reviewed by two senior radiologists. Both readers were blinded to surgical outcomes and adenoma location on the first read of the imaging studies. Surgical outcomes were then revealed and the imaging was re‐reviewed. The two reader's results were subsequently compared for inter‐reader reliability using Cohen's kappa test.

Results:

All 30 patients with NLPA had pre‐operative 99mTc sestamibi imaging available and 18 also had an ultrasound performed. Adenomas were identified intra‐operatively and removed in all cases. Twenty‐nine of the thirty (97%) 99mTc sestamibi studies were scored by the two readers as either negative or equivocal. There was excellent inter‐observer agreement between the readers, with a kappa value of 0.706. For the ultrasound studies, however, the two readers’ inter‐observer agreement was only fair, with a kappa value of 0.351.

Conclusions:

The inter‐reader agreement in our series supports the conclusion that, for a sub‐population of patients with parathyroid adenoma, pre‐operative imaging will be truly negative/non‐localizing.
North American Survey on HPV and p16 Testing in Head and Neck Cancer
Authors: Maniakas Anastasios , Moubayed Sami Pierre , Ayad Tareck , Guertin Louis , Nguyen‐Tan Phuc‐Felix , Gologan Olga E. , Christopoulos Apostolos
Published: August 2013

Objectives:

1) Evaluate systematic testing of human papillomavirus (HPV) and p16 status on head and neck cancer in North America. 2) Assess if HPV or p16 status is used to influence treatment in this population.

Methods:

An online survey was sent to three professional associations: the American Head & Neck Society, the Canadian Society of Otolaryngology, and the Quebec Association of Otolaryngology. Inclusion criteria were physicians practicing in North America. Incomplete surveys were disregarded. Chi‐square analyses were conducted.

Results:

There was a response rate of 20% with a total of 216 complete responses. Most respondents were otolaryngologists (196; 90.7%), English‐speaking (178; 82.4%), and practicing in an academic setting (138; 63.9%). Routine HPV or p16 testing was performed by 146 respondents for the oropharynx, 69 for oral cavity, and 44 for other subsites. Most physicians (113; 77.4%) test for both HPV and p16, while 58.3% indicated that HPV/p16 status influences their treatment approach for oropharyngeal cancer. In Quebec, 15.4% of respondents test for HPV/p16, versus 61.0% in the rest of Canada and 88.1% of the American Head & Neck Society members (P < 0.001). Practicing in an academic center of having a primarily (≥50%) oncology practice was associated with a higher rate of HPV/p16 testing (P < 0.001).

Conclusions:

The majority of North American otolaryngologists test for HPV or p16 status in head and neck cancer. Furthermore, the majority indicate that this testing influences their treatment approach for oropharyngeal cancer. Concurrently, multiple treatment deintensification protocols for this type of cancer are currently underway.
A Novel Use of Data Mining to Inform Outcome of Oropharyngeal Squamous Cell Carcinoma
Authors: Martin James , Mehrotra Swati , Wirth Sarah , Strus Maria , Malliaris Mary , Bier‐Laning Carol M.
Published: August 2013

Objectives:

1) Recognize that data mining is useful to analyze multiple patient and tumor factors and make predictions about outcome in head and neck cancer patients.

Methods:

Retrospective study of 124 patients with oropharyngeal squamous cell carcinoma treated at a tertiary care institution from 2000‐2009 for whom 2 year outcome was known. Data was collected from the medical chart. PASW Modeler was used to analyze the data. The outcome measurement was overall 2 year survival. Receiver‐operating characteristic (ROC) values (false positive rate (FPR), true positive rate (TPR)) were calculated for each outcome predictor model.

Results:

For the entire group, overall two year survival was 82%. The models used to predict survival were p16 status, Stage IV status and PASW Modeler Decision Tree analysis. ROC values for each model were as follows: p16 training 0.56, 0.74; p16 validation 0.25, 0.83. Stage IV training 0.83, 0.73; Stage IV validation 0.75, 0.61. Decision Tree training 0.00, 0.88; Decision Tree validation 0.75, 0.78.

Conclusions:

Data mining shows promise in making outcome predictions in patients with head and neck cancer. This study shows that data mining performs better than outcome prediction using a stage‐based model. Although the ROC curve analysis for the Decision Tree training set was excellent, the validation set fell below the p16 validation set. We suspect that this may be due to the small size of our data set. To overcome this downfall, we will discuss the results from a K‐fold cross‐validation process which sequentially uses all the data in the validation set.
Outcomes of Primary Surgery with Radiotherapy for pN2 Head and Neck Squamous Cell Carcinoma
Authors: Kim Chung Soo , Nam In‐Chul , Park Jun‐Ook , Cho Kwang‐Jae , Kim Min‐Sik
Published: August 2013

Objectives:

Examine treatment outcomes and define factors that influence survival in patients underwent primary surgery with postoperative radiotherapy for pN2 head and neck carcinoma.

Methods:

Two hundred nine patients underwent primary surgery with postoperative radiotherapy between 1994 and 2011. Primary tumor sites were 70 oropharynx, 48 hypopharynx, 47 larynx, 41 oral cavity, and 3 sinonasal cavity. There were 21, 83, 60 and 45 patients with stage T1 to T4 cancers, respectively. The N stages were 20 N2a, 129 N2b, and 60 N2c.

Results:

The recurrence rate was 40% (83/209) over a mean observation period of 39 months. The 5‐year disease free survival (DFS), disease specific survival (DSS), and overall survival (OS) rate in our cohort was 44%, 60%, and 56%, respectively. Patients with advanced T stage or extracapsular spread had a significant adverse effect on 5‐year DFS, DSS, OS rate according to the Kaplan‐Meier survival curves. Multivariate Cox regression analysis confirmed the significant association between 5‐year DSS rate and advanced T stage (hazard ratio (HR), 2.20; 95% confidence interval (CI), 1.26‐3.82; P = 0.005) and extracapsular spread (HR, 2.29; 95% CI, 1.24‐4.21; P = 0.008).

Conclusions:

Factors that affected prognosis were T stage and extracapsular spread in patients who underwent primary surgery with postoperative radiotherapy for pN2 head and neck carcinoma. An aggressive therapeutic approach may be suitable for these patients.
Overexpression of EphB4, EphrinB2, and EGFR in Papillary Thyroid Carcinoma
Authors: Sharma Giriraj K. , Dhillon Vaninder , Maceri Dennis R.
Published: August 2013

Objectives:

1) Analyze the expression of EphB4, EphrinB2 and epidermal growth factor receptor (EGFR) in papillary thyroid carcinoma (PTC). 2) Analyze the association of each of these biomarkers with lymph node disease.

Methods:

Twenty one patients with newly diagnosed PTC (stages I‐III) were enrolled in this study between 2009‐2012. All 21 patients were treated with total thyroidectomy and central (level VI) neck dissection. EphB4, EphrinB2 and EGFR expression in tumor and surrounding normal thyroid tissue was evaluated by complimentary DNA (cDNA) microarray (n = 4), Western blot (n = 21) and immunohistochemistry (IHC) (n = 21). Clinicopathologic data (tumor size, histologic extension, lymph node disease, stage) was collected from patient records.

Results:

cDNA microarray analysis showed a statistically significant average fold change in gene expression for EphB4 (2.5, P =. 004), EphrinB2 (2.4, P =. 001) and EGFR (2.9, P =. 003) in tumor samples compared to normal tissue. Linear regression analysis of IHC integrated optical density (IOD) measurements confirmed overexpression of EphB4 (P <. 001), EphrinB2 (P <. 001) and EGFR (P <. 001) in tumor versus benign tissue. We noted an association between lymph node disease and EphB4 (P <. 001), EphrinB2 (P <. 001) and EGFR (P =. 069) expression in tumor samples.

Conclusions:

Overexpression of EphB4, EphrinB2 and EGFR is associated with PTC. Our results are the first to demonstrate the association between EphB4, EphrinB2 and EGFR overexpression with lymph node metastases in PTC. These three genes may be used as biomarkers for early identification of lymph node involvement in PTC and potential small‐molecule targets for future research in PTC pharmacotherapy.
Patients with Thyroid Carcinoma Distant Metastasis Are Identified at Initial Treatment
Authors: Tavares Marcos R.
Published: August 2013

Objectives:

Distant metastases (DM) worsen prognosis in patients with well differentiated thyroid carcinoma (WDTC), and. DM can be identified at initial evaluation or follow up. These patients must be followed aggressively and treated appropriately. Our goal was to identify when distant metastases are identified in patients with WDTC and patients’ initial clinical features.

Methods:

Retrospective chart review of patients with WDTC and distant metastasis treated with radioactive iodine at our department.

Results:

Between 1988 and 2009, 73 patients with WDTC and distant metastasis had radioactive iodine at our hospital. Sixty were female; patient ages ranged from 7 to 74 years old (mean 47), 40% under 45 y/o. The lung was the most affected organ (70%); bones (12%); lungs and bones (12%); liver and breast. Tumor diameter was ≤4cm in 74% of the patients (15% ≤1cm) and ≤4cm in 26%. In 48% of patients, the primary tumor histology was a classic papillary thyroid cancer, followed by follicular carcinoma or follicular variant of papillary carcinoma in 41% of the patients and Hurthle cell carcinoma in 3%. Only 8% had poorly differentiated carcinoma. Lymph node metastases were present in 64% of patients, 14% in both central and lateral neck compartments. Distant metastases were present in the first postoperative whole body scan in 90% of the patients.

Conclusions:

The majority of patients with distant metastasis (90%) were identified at initial treatment. Follow up intensity can be reduced in the remaining patients. Clinical features do not prevent complete evaluation of patients with WDTC. Patients with distant metastasis of thyroid cancer had small well differentiated carcinomas and were under 45 years old.
Mucoepidermoid Carcinoma of Parotid Gland
Authors: Alkhalifa Salman A. , Abdulkarim Noor Y. , Abulfateh Fatima N.
Published: August 2013

Objectives:

Present a case of mucoepidermoid carcinoma of the left parotid gland, which has been removed surgically.

Methods:

A thirty‐five year‐old gentleman presented with swelling of the left cheek for 6 months. The swelling was gradually increasing and painless; the patient had facial weakness since childhood. A swelling 3x2 cm was seen in the parotid area, which was normothermic, non‐tender, firm in consistency, not fluctuant, and fixed to the skin. The facial nerve was intact, and the regional lymph nodes were not palpable.

Results:

Excisional biopsy was done. The histopathology revealed mucoepidermoid carcinoma of low grade. Repeated ultrasound showed normal echogenicity of the left parotid gland and no discrete nodule seen. One cm hypoechoic mass was seen in the subcutaneous tissue of the left cheek, which indicates a residual mass or postoperative fibrosis. Magnetic resonance imaging of the parotid glands showed one cm mass of the left cheek. The patient had excisional biopsy and transposition flap of the left cheek. The lesion excised with 5 mm clear radial margins and 5 mm clear deep layer. The zygomatic branch of the VII cranial nerve was sacrificed because it was intralesional. Transposition of S‐shaped flap was created and fixed through layers.

Conclusions:

A case of excised parotid mucoepidermoid carcinoma was presented; the patient was disease free at 79 months. Clinical stage and histological grade of mucoepidermoid carcinoma are the main prognostic factors.
A Preliminary Report on Platelet‐Rich Plasma (PRP) Gel Application in Exofacial Parotidectomy
Authors: Raimondo Luca , Garzaro Massimiliano , D'Antico Sergio , Sensini Matteo , Naqe Nertila , Mastrapasqua Rodolfo , Pecorari Giancarlo
Published: August 2013

Objectives:

Platelet‐rich plasma (PRP) is widely used in different kind of surgeries to improve hemostasis and wound healing. We set out to evaluate PRP gel efficacy, in drainage, drainage tube stay duration, and pain and length of hospital stay reduction after exofacial parotidectomy for pleomorphic adenoma.

Methods:

Between November and December 2012, exofacial parotidectomy was performed on 12 consecutive patients enrolled in this prospective randomized controlled clinical trial. Autologous PRP gel was applied on the remaining gland before wound closure in the treatment group (6 pts), while direct closure was applied in the controls (6 pts).

Results:

The mean 24‐hour cumulative drainage was 128.64 ml vs. 50.33 ml (P = 0.049), mean pain score at 4 hours was 5.3 vs 1.5 (P = 0.046) and 5.2 vs 1.5 (P = 0.037) at 8 hours in treatment and control group respectively; the drainage tube was removed after a mean of 5.6 days in control group and after 3.3 days in the treatment one (P = 0.037); PRP gel pts were discharged after a mean of 3.33 days whereas no‐PRP gel pts after a mean of 6.33 days (P = 0.046).

Conclusions:

These preliminary data suggest that PRP gel application in parotid surgery could be a feasible, low cost, and efficient tool in improving surgical outcomes and in reducing patients effort in terms of pain, drainage tube endurance and hospital staying.
Preoperative Vitamin D Deficiency as a Predictor of Post‐total‐thyroidectomy Hypocalcemia
Authors: Falcone Todd E. , Noordzij J. Pieter , Jalisi Scharukh , McAneny David , Pearce Elizabeth N. , Holick Michael F. , Stein Daniel J.
Published: August 2013

Objectives:

Understand the relationship between preoperative vitamin D deficiency and post‐total‐thyroidectomy hypocalcemia.

Methods:

Retrospective study examining 264 total and completion thyroidectomies between 2007‐2011. Included patients had a recorded 25OH‐D level within 21 days prior to or 1 day following surgery, were not taking ergocalciferol (D2) at the time of their lab draw, did not have a primary parathyroid gland disorder, and were not taking calcitriol (1,25 dihydroxy‐D3) prior to surgery. Some patients were repleted preoperatively if a low 25OH‐D level was identified. Preoperative 25OH‐D, concurrent neck dissection, integrity of parathyroid glands, final pathology, postoperative parathyroid hormone (PTH), calcium nadir and repletion, and length of stay were examined.

Results:

In this cohort, a mean of 3 parathyroid glands were identified during surgery. Multinodular goiter and papillary thyroid carcinoma were the most common pathologies. Hypocalcemia, defined as a corrected calcium <8.4 mg/dL, and drain placement were the most common reasons for length of stay >1 night. The average preoperative 25OH‐D for all patients was 24.98 ng/mL and the overall rate of hypocalcemia was 37.5%. Low preoperative 25OH‐D did not predict postoperative hypocalcemia (P = 0.96), however, it did predict the need for postoperative calcitriol administration (p=0.01). Lower postoperative PTH levels (P = 0.001) predicted postoperative hypocalcemia.

Conclusions.

Lower postoperative PTH predicts post total thyroidectomy hypocalcemia. Preoperative 25OH‐D did not predict hypocalcemia as has been previously described although it did predict the use of calcitriol postoperatively. We recommend that 25OH‐D be assessed and, if indicated, repleted preoperatively in patients undergoing total thyroidectomy.
Primary Parotid Gland Lymphomas
Authors: Felekis Dimitrios , Giopanou Maria , Grigoropoulos Ilias , Aggelidaki Eirini , Gotsis Antonis , Zacharioudaki Evaggelia , Papouliakos Sotirios
Published: August 2013

Objectives:

1) Describe our experience in the diagnosis and management of the parotid gland lymphomas. 2) Present a rare case of synchronous MALT lymphoma of the parotid and high‐ grade non‐Hodgkin lymphoma of the breast (DLBCL). Primary lymphomas of the salivary glands are rare, consisting less than 5% of all cases of extranodal lymphomas and about 2%‐5% of salivary gland neoplasms. The most common subtype in the parotid is marginal zone B‐cell mucosa‐associated lymphoid tissue type lymphoma (MALT).

Methods:

We retrospectively reviewed the histopathologic reports of 251 parotidectomies that were performed in our department during the last decade. All patients presented with parotid gland swelling and had no previous diagnosis or symptoms of lymphoma. Management included computed tomography and/or magnetic resonance imaging scan and fine‐needle aspiration (FNA).

Results:

Of the 251 patients, 10 were diagnosed with non‐ Hodgkin lymphoma (3.98%). Among them, 3 were identified as MALT subtype (30% of parotid lymphomas, 1.2% of all parotid neoplasms). FNA accuracy was 100% for the7 non‐Hodgkin lymphomas, but only 33.3% (1 in 3 cases) regarding the MALT subtype. Interestingly, in these two patients, Warthin's tumor was diagnosed by FNA. In one of the 3 cases of MALT lymphoma we came across a synchronous MALT lymphoma of the left parotid and high‐grade non‐Hodgkin lymphoma of the right breast (DLBCL).

Conclusion:

Our data suggest that MALT lymphoma of the parotid gland is rare and could be difficult to diagnose with FNA, probably due to similar underlying cytologic features to benign tumors.
Prognostic Factors in Head and Neck Sarcomas: Analysis of the SEER Database
Authors: Peng Kevin A. , Wang Marilene B.
Published: August 2013

Objectives:

1) Summarize the epidemiology of sarcomas occurring in the head and neck. 2) Identify prognostic factors for patient survival.

Methods:

Cross‐sectional analysis of the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program.

Results:

The SEER 18 database, spanning the years 1973 to 2009, was analyzed. A total of 2134 cases of sarcoma arising in the head and neck were identified, accounting for 3.9% of all sarcomas. Of head and neck sites, the bones of the skull and face were most commonly affected (n = 856), followed by the oral cavity and pharynx (n = 532), nasal cavity and paranasal sinuses (n = 365), and major salivary glands (n = 192). Overall disease‐specific 2‐, 5‐, and 10‐year survival rates for head and neck sarcoma were 69.5%, 55.9%, and 49.9%, respectively. On Cox regression analysis, histologic subtype, tumor location, gender, and patient age were found to influence mortality rate significantly (P < 0.05), with male gender and older age portending worse outcomes.

Conclusions:

Sarcomas, a heterogeneous group of malignant mesenchymal tumors, are uncommonly found in the head and neck. This study represents the largest analysis of patients with head and neck sarcoma in the literature and demonstrates the impact of histology, tumor location, age, and gender on overall prognosis.
Osteomyelitis following Palatoplasty: A Rare Complication
Authors: Lee Arnold , Insalaco Louis , Scott Andrew R.
Published: August 2013

Objectives:

Raise awareness of potential serious complications of oropharyngeal surgery such as osteomyelitis and discuss the role of perioperative antibiotics in such operations. Explore the events leading up to the development of osteomyelitis in a 13‐month‐old boy following palatoplasty. Discuss the role of perioperative antibiotics in oropharyngeal surgery. Study Design: Single case report with chart and literature review.

Methods:

We present the case of a 13‐month‐old boy who underwent palatoplasty, received perioperative antibiotics, and subsequently developed group A streptococcal bacteremia along with osteomyelitis of the right calcaneus. A literature review was done to explore the role of antibiotics in oropharyngeal surgery.

Results:

The patient underwent treatment with antibiotics, and the osteomyelitis resolved.

Conclusions:

Surgeons and clinicians should maintain a high level of suspicion for bone and joint infections in any child presenting postoperatively with fevers, bacteremia, and musculoskeletal symptoms. The role of perioperative antibiotics in the prevention of severe postoperative infections such as osteomyelitis is unclear. In the era of evidence‐based medicine there is a movement to temper, if not eliminate, the once standard practice of discharging children on a short course of prophylactic antibiotics following palate repair. It should therefore be noted that even when these antibiotics are given, rare infectious complications may still occur.
Radon Levels in Pennsylvania and the Rise in Incidence of Thyroid Cancer
Authors: Goyal Neerav , Camacho Fabian , Mangano Joseph , Goldenberg David
Published: August 2013

Objective:

Determine if there is a temporal association between radon levels and the rise in incidence of thyroid cancer in Pennsylvania.

Methods:

Ecological study: The Pennsylvania Cancer Registry and the Department of Environmental Protection were used as data sources for this study for the years 1990‐2009. From the registry, geographic information regarding thyroid incidence was recorded. Using SAS, Poisson regression models were fit predicting county level thyroid incidence and change as a function of radon/ lagged radon levels. To account for measurement error in radon levels, a Bayesian Model extending the Poisson models was fit using the winBUGS program.

Results:

Contour plots showing correlations between radon levels by year and yearly thyroid incidence rates failed to detect any association consistent with a causal connection. In the Poisson modeling, no significant association was noted between county radon level and thyroid cancer incidence (P = 0.23). Looking for a lag between the radon level and its effect, no significant effect was seen for a lag of 0 to 6 years between exposure and expected effect (P = 0.063 to P = 0.59). The Bayesian models fit also failed to show a statistically significant association.

Conclusions:

While there is evidence of rising levels of radon as well as thyroid cancer in Pennsylvania, the two do not correlate according to our analysis. Through a variety of models, no association could be elicited between radon levels in Pennsylvania and the rising incidence of thyroid cancer. Further studies, such as using an animal model, may be helpful in determining an association.
Reconstruction of the Maxilla with Pedicled Temporalis Muscle
Authors: Bundgaard Troels
Published: August 2013

Objectives:

Resection of the maxilla requires adequate restoration of the maxilla structure to replace form and functions, especially vocal and eating functions. A host of reconstructive options are available to restore the maxilla, most of which include free flap reconstruction. The aim of this study was to clinically evaluate the use of pedicled temporalis flap for reconstruction of the maxilla and to assess patient quality of life.

Methods:

In the period 2000‐2007, a total of 32 patients with malignant tumors of the maxilla were operated with immediate reconstruction of the maxilla using pedicled temporalis flap at the ear, nose, and throat (ENT) department, Aarhus University Hospital. Follow up was implemented in 2007. Twenty‐seven of 28 patients alive at the time of follow up participated in the study. The patients were evaluated objectively as well as subjectively by answering the European Organisation for Research and Treatment of Cancer's (EORTC's) standard questionnaire concerning quality of life and functional results.

Results:

Few patients had complaints and these were mostly minor functional deficits. The most common complaints were slightly impaired mouth opening. One temporalis muscle flap necrotized and was removed. Three patients developed oro‐nasal/antral fistula, which were later closed using local flaps.

Conclusions:

The follow up study of 27 patients showed a most satisfactory result evaluated objectively as well as subjectively using the EORTC questionnaire.
Recurrent Genomic Alterations of FHIT Gene with Impact on Lymphatic Metastasis in Early Oral Carcinoma
Authors: Nam In‐Chul , Kim Chung‐Soo , Cho Kwang‐Jae , Kim Min Sik
Published: August 2013

Objectives:

Determine the role of genetic factors related to the lymph node metastasis (LNM) in early oral squamous cell carcinoma (OSCC).

Methods:

Array‐based comparative genomic hybridization with individual gene‐level resolution using primary tumor materials from 14 early OSCC patients with (n = 7) or without (n = 7) cervical LNM. To confirm the genomic copy number alterations, immunohistochenical stain was conducted in 30 early OSCC specimens.

Results:

The number of recurrent (>25%) copy number alterations with LNM group is 34, whereas that without LNM group is 23 by array‐based comparative genomic hybridization in the first cohort. We detected 10 recurrently altered regions (10 losses) associated with cervical LNM (P < 0.05). Among them, loss of 3p14.2 for the FHIT gene was the most frequent one (5 out of 7 patients with LNM, 71.4%) and significantly associated with a worse disease specific survival (P = 0.005). In the independent validation cohort of 30 early OSCC cases, loss of FHIT determined by an immunohistochemical analysis was associated with cervical LNM (P = 0.032) and disease specific survival (P = 0.045).

Conclusions:

Copy number alterations of FHIT are associated with LNM and poor prognosis, and risk stratification based on the copy‐number status of this gene is useful to select the optimal treatment strategy in early OSCC patients.
Relationship between the Number of Preserved Parathyroid Glands and Clinical Aspects after Thyroidectomy in PTC
Authors: Wie Chan‐Eun , Lim Yun‐Sung , Park Young‐Min , Lee Won‐Yong , Wang Soo‐Geun , Lee Jin‐Choon , Lee Byung‐Joo
Published: August 2013

Objectives:

Identify the relationship between the preservation status of the parathyroid gland and risk of hypoparathyroidism after total thyroidectomy in papillary thyroid carcinoma.

Methods:

Medical records of 63 patients with papillary thyroid carcinoma who satisfied our inclusion criteria were reviewed retrospectively. Patients with PTC who underwent total thyroidectomy with central lymph node dissection (CLND) were included. Patients were grouped according to the number of intact preserved parathyroid glands into Group 1 (more than four), Group 2 (three), Group 3 (under two). The total and ionized serum calcium, intact parathyroid hormone (PTH) levels of each group were monitored after the surgery. Patients with postoperative symptomatic hypocalcemia were considered to have postoperative hypoparathyroidism and received calcium/vitamin D therapy. The hypoparathyroidism was considered to be permanent when calcium/vitamin D therapy was still required six months after surgery.

Results:

31 cases (49.2%) showed postoperative hypoparathyroidism as demonstrated by laboratory findings. Permanent hypoparathyroidism did not occur in this case. The development of hypoparathyroidism was not significantly related with the number of preserved parathyroid glands.

Conclusions:

To prevent postoperative and permanent hypoparathyroidism following total thyroidectomy, at least two parathyroid glands should be preserved in situ with an intact blood supply. Patients with more extensive CLND procedure did not necessarily show an increased rate of transient hypoparathyroidism. With PTC, the rates of metastasis and recurrence in central lymph nodes are high. Therefore, this study suggests that CLND should be more routinely done for PTC. Hypoparathyroidism can be kept to a minimum by a thorough knowledge of the anatomy and by meticulous hemostasis and delicate surgical technique.
Reliability of Sentinel Node Biopsy in Head and Neck Cutaneous Squamous Cell Carcinoma
Authors: Ahmed Mostafa , Moore Brian A. , Schmalbach Cecelia E.
Published: August 2013

Objectives:

Sentinel lymph node biopsy (SLNB) is the standard of care for melanoma staging, but its role in cutaneous squamous cell carcinoma (cSCC) has not been established. This study seeks to: 1) analyze the feasibility and reliability SLNB for head and neck (H&N) cSCC and 2) identify risk factors associated with a positive SLN.

Methods:

A comprehensive systematic review of MEDLINE, PubMed, Cochrane, and ASCO databases was conducted to identify H&N cSCC SLNB studies with associated recurrence rates. Dual‐blinded data extraction was conducted. Primary outcomes were successful SLN harvest and false omission rate, with secondary outcomes of risk factors for a positive SLN.

Results:

221 articles were screened; 74 patients from 11 publications met inclusion criteria (3 case series; 8 prospective cohorts). Studies ranged from 1 to 15 patients (median 5), with a median follow‐up of 21 months. Median age was 73.5 years. Average tumor size was 3.08 cm. At least 1 SLN was identified in 100% of patients (median 2.5). 10 (13.5%) had a positive SLN; no additional metastatic nodes were identified in 9 patients receiving completion lymphadenectomy. Tumor size was not associated with SLN status (P = 0.09; 95% CI: ‐.27, 3.02). Additional high risk features (thickness, perineural invasion, location, and differentiation) were inconsistently recorded. 3 of 64 (4.7%) failed regionally in the setting of a negative SLNB.

Conclusions:

H&N cSCC SLNB is feasible and reliable for staging, with a false omission rate of 4.7%, mirroring that of melanoma. Prospective studies documenting high risk features are required.
The Role of Interventional Radiology in Head and Neck Cancer
Authors: Tulunay‐Ugur Ozlem E. , Kocdor Pelin , Rutledge Jonathan W. , Akdol Mehmet S. , Erdem Eren , Vural Emre
Published: August 2013

Objectives:

Evaluate the indications for endovascular techniques in the management of patients with head and neck squamous cell carcinoma.

Methods:

Retrospective chart review of patients with head and neck cancer who underwent endovascular embolization. Patients’ demographics, type of cancer, type of cancer treatment, TNM staging, bleeding site, and medical outcomes were recorded from 2004‐2012, at a university medical center.

Results:

A total of 14 patients out of 1000 undergoing endovascular procedures had an endovascular procedure due to a head and neck cancer. Their ages ranged from 33‐67 years old (mean = 54 years old). 7 patients had oropharyngeal, 3 laryngeal, 1 hypopharyngeal, 2 oral cavity and 1 skin squamous cell cancer. 8 patients had hypertension. 7 patients underwent chemoradiation therapy as a primary treatment. 9 patients with oral hemorrhage underwent emergency embolization due to bleeding and 5 patients underwent elective embolization. Bleeding arose from the common carotid artery in 2 patients, and external carotid artery and its branches in 6 patients, internal carotid artery in 3 patients, internal maxillary artery in 3 patients. Hemorrhage was successfully controlled in all patients. 2 patients had carotid rupture one month post‐embolization and one patient died. At last follow‐up 6 patients were alive with disease, 4 patients had no evidence of disease and 4 patients were dead due to disease.

Conclusions:

Interventional radiologic techniques are safe and effective treatment techniques not only for treating life‐threatening hemorrhage but also for pre‐emptive management in the treatment of head and neck cancer.
The Role of Macrophage‐Induced Inflammation in Thyroid Cancer Progression
Authors: Saman Masoud , Rajoria Shilpi , Tuli Neha , Hanley Elyse , Shin Edward J. , Tiwari Raj
Published: August 2013

Objectives:

Tumor microenvironment, specifically inflammation‐mediated molecular changes, define tumor phenotype. Papillary thyroid cancer (PTC) is the commonest thyroid cancer and those with tumor associated macrophages (TAMs) portend a poorer prognosis and higher metastatic propensity. Since epithelial‐mesenchymal transition (EMT) is closely linked to metastasis, in this study we examine the cross‐talk between macrophages and epithelial cells in modulating metastatic propensity. The aims of this study are to: 1) investigate ability of the macrophages to induce EMT in PTC, and 2) assess functional changes in PTC in their invasive properties.

Methods:

In this in vitro study performed in January 2013, normal thyrocytes (NThy‐ori 3‐1) and two papillary cancer cell lines (BCPAP and 8505C,) were treated with either physiologic media (PM) or macrophage conditioned media (MCM) and nuclear and cytoplasmic extracts were obtained. Western blot analysis was performed for expression of EMT markers including slug, twist and snail. Cell morphology, migration and invasion assays were also performed to examine in vitro phenotypic characteristics of tumor cells.

Results:

EMT markers were modulated in thyroid cells in response to MCM which potentially lead to changes in in vitro phenotypic characteristics of cells including statistically significant (p<.05) upregulation of migration and invasion.

Conclusions:

Secreted molecules from macrophages lead to EMT as well as increased migratory and invasive properties in PTC. Validation of these findings in human PTC samples is underway to define the clinical relevance the phenotypic changes.
Roux‐En‐Y Gastric Bypass and Thyroidectomy: Risks and Management of Critical and Refractory Hypocalcemia
Authors: Hong Steven S. , Rieth Katherine , Yheulon Christopher , Klem Christopher
Published: August 2013

Objectives:

Discuss the increasing prevalence of gastric bypass surgery and the subsequent metabolic and physiologic changes. Discuss the risks, pathophysiology, and management of critical and refractory hypocalcemia following total thyroidectomies in this population in order to optimize perioperative management.

Methods:

Retrospective review of three cases of patients with a history of Roux‐En‐Y gastric bypass surgery following total thyroidectomies with or without neck dissections at an academic medical center.

Results:

All three patients had Roux‐En‐Y gastric bypass surgeries prior to their thyroidectomies. One patient underwent a total thyroidectomy for Graves disease and became symptomatically hypocalcemic with a nadir serum calcium of 6.3 postoperative day three. Patient two underwent a total thyroidectomy with central and lateral neck dissection for papillary thyroid carcinoma (PTC). This patient became symptomatically hypocalcemic with a nadir serum calcium of 6.4 postoperative day two. Both patients required extensive oral and intravenous calcium supplementation with extended hospitalizations. Patient three underwent a total thyroidectomy and central neck dissection for PTC and discharged postoperative day two with stable calcium levels.

Conclusions:

With increasing popularity of gastric bypass surgeries, thorough evaluation of prior surgeries is crucial for optimal perioperative management in thyroidectomies. Postoperatively if hypocalcemic, these patients appear to be refractory to oral calcium and calcitriol supplementation. They may require extensive intravenous calcium supplementation and prolonged hospitalization to stabilize serum calcium levels.