Human Adipose Tissue-Derived Stromal/Stem Cells Promote Migration and Early Metastasis of Head and Neck Cancer Xenografts.

BACKGROUND: Fat grafting has become popular for repair of postsurgical/postradiation defects after head/neck cancers resection. Fat graft supplementation with adipose tissue-derived stromal/stem cells (ASCs) is proposed to improve graft viability/efficacy, although the impact of ASCs on head/neck cancer cells is unknown. OBJECTIVES: To determine whether ASCs affect growth, migration, and metastasis of human head/neck cancer. METHODS: Human Cal-27 and SCC-4 head/neck cancer cells were co-cultured human ASCs, or treated with ASC conditioned medium (CM), and cancer cell growth/migration was assessed by MTT, cell count, and scratch/wound healing assays in vitro. Co-injection of 3 × 10(6) Cal-27/green fluorescent protein (GFP) cells and ASCs into the flank of NUDE mice assessed ASC effect on tumor growth/morphology. Quantitation of human chromosome 17 DNA in mouse organs assessed ASC effects on micrometastasis. Primary tumors were evaluated for markers of epithelial-to-mesenchymal transition, matrix metalloproteinases, and angiogenesis by immunohistochemistry. RESULTS: Co-culture of Cal-27 or SCC-4 cells with ASCs from 2 different donors or ASC CM had no effect on cell growth in vitro. However, ASC CM stimulated Cal-27 and SCC-4 migration. Co-injection of ASCs from 2 different donors with Cal-27 cells did not affect tumor volume at 6 weeks, but increased Cal-27 micrometastasis to the brain. Evaluation of tumors sections from 1 ASC donor co-injection revealed that ASCs were viable and well integrated with Cal-27/GFP cells. These tumors exhibited increased MMP2, MMP9, IL-8, and microvessel density. CONCLUSIONS: Human ASCs did not alter growth of human head/neck cancer cells or tumor xenografts, but stimulated migration and early micrometastasis to mouse brain.

Tracheostoma reconstruction with the supraclavicular artery island flap.

Tracheostoma wounds are complex defects that commonly occur in patients with vessel-depleted necks after cervical lymphadenectomy, who have multiple medical comorbidities, and a history of radiation therapy. The authors report reconstruction of 5 tracheostoma wounds using a pedicled, supraclavicular artery island flap as a reconstructive alternative. There were no flap losses, fistulas or leaks, revisions, or other complications. The supraclavicular artery island flap is a versatile, reliable, and effective option for tracheostoma reconstruction.

Adipose stem cell therapy in cancer reconstruction: a critical review.

Found in most mesenchymally derived organs, mesenchymal stem cells are undifferentiated cells capable of developing into many cell types. Adipose stem cells are a type of mesenchymal stem cell easily extracted from lipoaspirate, often readily available, and are conformable to the tissue defect. Their ability for self-renewal, unlimited proliferation and proangiogenic, and immunomodulatory properties have made them attractive adjuncts in plastic surgery. Since the discovery of pluripotent cells in adipose tissue, plastic surgeons have applied the technology toward improving wound healing, soft tissue augmentation, and tissue engineering. More recently, some surgeons have used adipose stem cells in cancer reconstruction. By mixing lipoaspirate with concentrated fractions of adipose stem cells through a technique termed cell-assisted lipotransfer, plastic surgeons have claimed improved aesthetic results. Promising early results have been tempered by in vitro and animal studies demonstrating increased tumor proliferation and metastasis rates with the use of adipose and other mesenchymal stem cells. This review provides a succinct yet comprehensive overview of the current literature evaluating the oncologic risks associated with adipose stem cell use in cancer.

The use of multislice CT angiography preoperative study for supraclavicular artery island flap harvesting.

BACKGROUND: The vascular anatomy of the supraclavicular artery island (SAI) flap has been investigated using both cadaveric anatomic dissections and angiographic studies. Accurate preoperative evaluation and localization of its vascular pedicle confirms its location, course, anatomic variation, and improves flap success. The objective of this report is to demonstrate the utility of multislice computed tomography (CT) angiography for confirming the presence of the vascular pedicle of the SAI flap when planning head and neck reconstruction. METHODS: Patients were studied using 64-multislice CT angiography (CTA) to localize the supraclavicular artery, including its origin and destination. Axial images, multiplanar reconstructions, and 3D volume-rendered images were analyzed on a Philips workstation. Radiologic image findings and clinical experience will be described. RESULTS: SAI CT angiography was successfully performed in 15 patients (30 shoulders) ranging from ages 22 to 81 years. Accurate identification of the main vascular pedicle was achieved in 14/15 patients. Location, course, pedicle length, and anatomic variations were reported for 23 of 30 arteries. Mean vessel diameter was found to be 1.49 mm (range, 0.8-2.0 mm) on the right and 1.51 mm (range, 1.0-2.1 mm) on the left. The mean length of the artery was 38.3 mm on the right (range, 26.6-59.6 mm) and 38.4 mm on the left (range, 24.3-67.0 mm). In all patients, the supraclavicular artery originated off the transverse cervical artery-a branch of the thyrocervical trunk. Positioning of the patient's upper extremities at the side was helpful in the identification of the supraclavicular artery and its distribution. Contrast injection site should be contralateral to the side needed for the flap if sidedness is of importance, secondary to contrast bolus artifact. CONCLUSIONS: Preoperative evaluation of the SAI flap with multislice computed tomography angiography is feasible in patients. A radiologic study protocol has been developed which improves the ability to detect this vessel. This technique provides a noninvasive approach to the identification of the vascular anatomy and is easily standardized/reproducible. The identification of the vascular pedicle and its anatomy can be a benefit to the surgical team during preoperative design of the SAI flap; however, clinical experience confirming these radiologic findings will be needed to optimize surgical outcome.

Posterolateral skull base reconstruction using the supraclavicular artery island flap.

The supraclavicular artery island (SAI) flap is a viable fasciocutaneous option for the reconstruction of head and neck defects. Although authors have reported success using SAI flaps for various reconstructive indications, concerns of a tenuous blood supply and distal ischemia have previously limited its use in the posterolateral skull base. This case series reports the outcomes of 5 consecutive patients receiving SAI flaps for posterolateral skull base reconstruction. All flaps were harvested in less than 1 hour with primary closure of all donor sites. A single patient developed superficial necrosis of the distal flap, which was repaired with a full-thickness skin graft. There were no other complications, and no donor site morbidity was observed. The SAI flap is an excellent option for the reconstruction of posterolateral skull base defects. The close color match, easy harvest within 1 hour, lack of microsurgical anastomosis, and absence of donor site morbidity support its continued utilization.

Knowledge Gaps among Patients and Providers in HPV-Related Oropharyngeal Cancer: A Systematic Review.

OBJECTIVE: To describe the level of knowledge of human papillomavirus (HPV) and HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) among the general population and health care providers. DATA SOURCES: Systematic search was performed on December 20, 2018, using MEDLINE (1966 to December 2018), EMBASE (1975 to December 2018), Web of Science (1900 to December 2018), and CENTRAL (1996 to December 2018) databases. English-language literature involving human subjects was used, and studies were limited to case series, case-control, cohort, and randomized controlled trial designs. REVIEW METHODS: Studies were included if they assessed knowledge of HPV and HPV-associated OPSCC. The primary outcome measure was the knowledge of HPV-associated OPSCC among the general population and with health care providers. Meta-analysis of proportions was attempted using random-effects model. The PRISMA guidelines were used for accuracy of reporting. RESULTS: Thirty-two studies were included with 17,288 participants. There was a high degree of heterogeneity preventing completion of a meta-analysis. Knowledge of HPV and HPV-associated OPSCC varied between the general population and health care providers. The proportion of the general population and health care providers with knowledge of HPV ranged from 16% to 75% and 21% to 84%, respectively. Knowledge of HPV-associated OPSCC was greater in health care providers and ranged from 22% to 100% compared with the general population, which ranged from 7% to 57%. CONCLUSION: There is a knowledge gap of HPV-associated OPSCC for both the general population and health care providers. Additional education may not only increase awareness but may also result in prevention and earlier detection.

A novel gene panel for prediction of lymph-node metastasis and recurrence in patients with thyroid cancer.

BACKGROUND: Although well-differentiated papillary thyroid cancer may remain indolent, lymph node metastases and the recurrence rates are approximately 50% and 20%, respectively. No current biomarkers are able to predict metastatic lymphadenopathy and recurrence in early stage papillary thyroid cancer. Hence, identifying prognostic biomarkers predicting cervical lymph-node metastases would prove very helpful in determining treatment. METHODS: The database of the Cancer Genome Atlas included 495 papillary thyroid cancer samples. Using this database, we developed a machine learning model to define a gene signature that could predict lymph-node metastasis (N0 or N1). Kruskal-Wallis tests, univariate and multivariate logistic and Cox regression models, and Kaplan-Meier analyses were performed to correlate the gene signature with clinical outcomes. RESULTS: We identified a panel of 25 genes and constructed a risk score that can differentiate N0 and N1 papillary thyroid cancer samples (P < .001) with a sensitivity of 86%, a specificity of 62%, a positive predictive value of 93%, and a negative predictive value of 42%. This panel represents an independent biomarker to predict metastatic lymphadenopathy (OR = 8.06, P < .001) specifically in patients with T1 lesions (OR = 7.65, P = .002) and disease-free survival (HR = 2.64, P = .043). CONCLUSION: This novel 25-gene panel may be used as a potential prognostic marker for accurately predicting lymph-node metastasis and disease-free survival in patients with early-stage papillary thyroid cancer.

Risk of SARS-CoV-2 Transmission During Flexible Laryngoscopy: A Systematic Review.

IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reportedly infected otolaryngologists disproportionately in the early parts of the coronavirus disease 2019 pandemic. Recommendations from national and international health organizations suggest minimizing the use of flexible laryngoscopy as a result. OBJECTIVE: To review evidence on the risks of aerosolization and transmission of SARS-CoV-2 from patients to health care personnel during endoscopy of the upper aerodigestive tract. EVIDENCE REVIEW: A comprehensive review of literature was performed on April 19, 2020, using the PubMed/MEDLINE (1966-April 2020), Embase (1975-April 2020), and Web of Science (1900-April 2020) databases. All English-language primary research studies were included if they assessed the transmission of SARS-CoV-2 or SARS-CoV-1 during procedures in the upper aerodigestive tract. The primary outcome measure was disease transmission among health care workers. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for accuracy of reporting. FINDINGS: The queries for SARS-CoV-2 and SARS-CoV-1 identified 6 articles for systematic review. No studies included in this review provided data for SARS-CoV-2 transmission during flexible laryngoscopy. A total of 204 of 1264 health care workers (16.1%) had procedure-specific infections of SARS-CoV-1 or SARS-CoV-2. Among those, 53 of 221 (24.0%) were exposed during intubation, 1 of 15 (6.7%) during bronchoscopy, and 1 of 1 (100%) during endoscopy-assisted intubation. CONCLUSIONS AND RELEVANCE: A substantial lack of research precludes formal conclusions about the safety of flexible laryngoscopy and transmission of SARS-CoV-2 from patients to health care workers. The use of appropriate precautionary measures and personal protective equipment appears to reduce the risk of transmission. Given the uncertainty in transmission and the known benefits of safety precautions, upper airway endoscopy may be reasonable to perform if precautionary steps are taken.

Association of Continued Preoperative Aspirin Use and Bleeding Complications in Patients Undergoing Thyroid Surgery.

IMPORTANCE: No evidence exists to direct the management of preoperative aspirin (acetylsalicylic acid) use in patients undergoing thyroid surgery. Nevertheless, a considerable number of patients interrupt receiving aspirin therapy during the preoperative period to minimize bleeding complications despite the increased risk of experiencing major adverse cardiac events. OBJECTIVE: To determine whether aspirin therapy continued preoperatively increases bleeding complications in patients undergoing thyroid surgery. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of a consecutive sample of 570 patients, aged 18 to 100 years, who underwent thyroid surgery for benign and malignant disease from January 1, 2010, to December 31, 2015, by a single surgeon at a tertiary referral hospital center in New Orleans, Louisiana. EXPOSURES: Patients receiving aspirin therapy and patients not receiving aspirin therapy (aspirin naive) preoperatively. MAIN OUTCOMES AND MEASURES: Comparison of estimated blood loss, substantial blood loss, operative hematoma, nonoperative hematoma, and recurrent laryngeal nerve injury. RESULTS: Of 570 patients who underwent thyroid surgery, 106 (18.6%) were performed in patients receiving aspirin; of these, 23 (21.7%) were men and 105 (99.1%) were older than 45 years. Those receiving aspirin therapy displayed a 14.4-year difference in age (95% CI, 11.6-17.1). The aspirin group displayed a 20.3% absolute increase (95% CI, 9.3-30.7) in African American patients. Aspirin therapy was not associated with a statistically significant or clinically meaningful increase in intraoperative blood loss (2.5 mL; 95% CI, -0.4 to 5.3). Aspirin therapy was associated with a statistically significant increase in total hematoma formation (3.3%; 95% CI, 0.4-9.0), but the results were inconclusive. Aspirin therapy was not associated with a statistically significant increase in recurrent laryngeal nerve injury (2.6%; 95% CI, -1.1 to 8.6), but the results were inconclusive. CONCLUSIONS AND RELEVANCE: These results suggest that aspirin therapy can be maintained prior to thyroid surgery without increased intraoperative bleeding. Further research with a larger sample size and more outcome events are required to make definitive conclusions regarding the association between aspirin use and complications, including hematoma and recurrent laryngeal nerve injury.

Replication of an adenoviral vector controlled by the human telomerase reverse transcriptase promoter causes tumor-selective tumor lysis.

Telomerase reactivation is a critical step for tumorigenesis, allowing cancer cells to proliferate indefinitely. Taking advantage of this property, we generated an adenovirus vector in which E1 gene expression, and therefore viral replication, is under control of the human telomerase reverse transcriptase (hTERT) promoter. This vector, referred to as Ad5-hTERT-E1, replicated in cancer cells and demonstrated efficient cancer-selective cytolysis in a variety of tumor cell lines, including HT-1080 (fibrosarcoma cells); HeLa (cervical carcinoma cells); A549 (lung carcinoma cells); Hep G2 (hepatocellular carcinoma cells); SCC-4, SCC-25, and SCCLSU-1 (head and neck squamous cell carcinoma cells); T24 (bladder carcinoma); and DU 145 (prostate carcinoma). In contrast, the identical multiplicities of infection of Ad5-hTERT-E1 had no effect on primary cultures of normal human fibroblasts, airway epithelial cells, and bone marrow mesenchymal stem cells. Moreover, a single injection of Ad5-hTERT-E1 into preexisting HT-1080 solid tumors, established s.c. in nu/nu mice, efficiently suppressed tumor growth. Interestingly, this conditionally replicating vector transactivated the replication of an E1-deleted antitumor adenoviral vector, Ad5-RSV-hsvTK, in tumor cells, demonstrating a synergistic antitumor effect in vivo. Combinational injection of a single dose of Ad5-hTERT-E1 and Ad5-RSV-hsvTK vector resulted in significant tumor suppression and regression after ganciclovir treatment. These results suggest that the Ad5-hTERT-E1 vector has potential as a broad-spectrum antitumor agent.

Efficacy of a Human Papillomavirus Vaccination Educational Platform in a Diverse Urban Population.

IMPORTANCE: Human papillomavirus (HPV) is a preventable disease that plays a causative role in a significant proportion of malignant neoplasms of the head and neck. Inner-city populations are at risk for HPV-related oropharyngeal cancer, are least likely to receive HPV vaccination, and report a lack of information regarding HPV. OBJECTIVE: To determine whether an educational platform affects knowledge, attitudes, and practices regarding HPV vaccination in an inner-city community. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study, conducted from March 1 to December 31, 2014, surveyed 128 participants at multiple inner-city community centers regarding their knowledge of, attitudes toward, and practices regarding HPV vaccination before and after a brief educational presentation. No eligible individuals refused to participate in the educational session. Surveys were excluded from analysis if they were incomplete. INTERVENTIONS: Participants completed two 20-question surveys separated by a 15-minute educational session on HPV-related disease, including a short PowerPoint presentation. MAIN OUTCOMES AND MEASURES: Presence of statistically significant differences in survey scores before and after the educational session. RESULTS: Eighty-six participants met eligibility criteria (61 male [70.9%]; 68 with a high school education [79.1%]). Baseline knowledge of HPV, its causal association with cancer, and the existence of a vaccine against HPV were poor: of a total composite score of 20, the mean knowledge score before the educational session was 9.69. Participants' self-rated knowledge regarding HPV disease and vaccination improved significantly as a result of the educational session; the absolute increase in mean knowledge composite score from before the educational session to after the session was 3.52 (17.6%) (95% CI, -2.87 to 9.92; P < .01). Attitudes regarding government involvement in vaccination did not change as a result of the educational session (composite attitudes score before the educational session, 16.57 of 28; score after the session, 15.22; P = .98). Participants' intent to vaccinate their children increased significantly following the educational presentation: before the presentation, 34 respondents (40%) intended to have their children vaccinated; after the presentation, 60 (70%) intended to do so (P = .002). CONCLUSIONS AND RELEVANCE: Lack of knowledge regarding HPV vaccination and unwillingness to undergo vaccination contribute to low rates of HPV vaccination within urban populations. Community-based educational sessions successfully teach the link between HPV and various cancers, provide information regarding the risks and benefits of vaccination, and increase participants' willingness to vaccinate their children against HPV. Attitudes regarding government involvement in health programs are resistant to change.

Interferon gamma-induced apoptosis of head and neck squamous cell carcinoma is connected to indoleamine-2,3-dioxygenase via mitochondrial and ER stress-associated pathways.

BACKGROUND: Tumor response to immunotherapy is the consequence of a concerted crosstalk between cytokines and effector cells. Interferon gamma (IFNγ) is one of the common cytokines coordinating tumor immune response and the associated biological consequences. Although the role of IFNγ in the modulation of tumor immunity has been widely documented, the mechanisms regulating IFNγ-induced cell death, during the course of immune therapy, is not described in detail. RESULTS: IFNγ triggered apoptosis of CLS-354 and RPMI 2650 cells, enhanced the protein expression and activation of indoleamine 2,3-dioxygenase (IDO), and suppressed the basal expression of heme oxygenase-1(HO-1). Interestingly, IFNγ induced the loss of mitochondrial membrane potential (Δψm) and increased accumulation of reactive oxygen species (ROS). The cytokine also induced the activation of Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT)1, apoptosis signal-regulating kinase 1 (ASK1), p38, c-jun-N-terminal kinase (JNK) and NF-κB pathways and the transcription factors STAT1, interferon regulatory factor 1 (IRF1), AP-1, ATF-2, NF-κB and p53, and expression of Noxa protein. Furthermore, IFNγ was found to trigger endoplasmic reticulum (ER) stress as evidenced by the cleavage of caspase-4 and activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and inositol-requiring-1α (IRE1α) pathways. Using specific inhibitors, we identified a potential role for IDO as apoptotic mediator in the regulation of IFNγ-induced apoptosis of head and neck squamous cell carcinoma (HNSCC) cells via Noxa-mediated mitochondrial dysregulation and ER stress. CONCLUSION: In addition to the elucidation of the role of IDO in the modulation of apoptosis, our study provides new insights into the molecular mechanisms of IFNγ-induced apoptosis of HNSCC cells during the course of immune therapy.

Outcome analysis of patients with squamous cell carcinoma of the head and neck and hepatitis C virus.

OBJECTIVE/HYPOTHESIS: Infection with the hepatitis C virus (HCV) is a global problem with over 170 million people infected. Recently, we have noticed that a large number of patients diagnosed with squamous cell carcinoma of the head and neck (SCCHN) have also been diagnosed with HCV. A review of the literature reveals little information concerning this patient population. The objective of this study was to compare the outcome of SCCHN patients who have been exposed to HCV with naïve SCCHN patients. STUDY DESIGN: Retrospective chart review. METHODS: A retrospective chart review from June 1991 through December 2002 was performed to identify patients diagnosed with SCCHN who were screened for HCV. Patients were stratified into two groups (HCV positive and HCV negative). Data were recorded on patients for status of disease at last clinic visit, pretreatment serum albumin and hematocrit levels, and RNA quantities of HCV. Statistical analysis was performed using paired t test to compare serum albumin and hematocrit levels. Kaplan-Meier survival curves were used to compare outcomes. The log-rank test was used to determine significance. Cox regression was used to examine the association of prognostic predictor variables with overall survival and disease-free survival. RESULTS: There was no difference noted in 5 year survival between hepatitis C positive and hepatitis C negative groups in overall outcomes (66.7% vs. 67.9%, P = 1.000) or 5 year disease-free survival (90.5% vs. 80.8%, P = .514). The two groups, HCV positive versus HCV negative, also had similar serum albumin levels (3.62 g/dL vs. 3.72 g/dL, P = .37) as well as serum hematocrit levels (42.9% vs. 41.0%, P = .12). Serum levels of hepatitis C RNA were obtained in seven patients, with only one being undetectable. The only prognostic predictor variable that was significantly associated with overall survival was age. None of the predictor variables were significantly associated with disease-free survival. CONCLUSION: Co-infection with HCV, although prevalent in the Veterans Administration Hospital population, did not affect patient outcome as defined by disease-free survival. Patients who were seropositive for HCV had comparable serum albumin levels as well as serum hematocrit when compared with HCV negative patients.

Prevalence and epidemiology of hepatitis C virus in patients with squamous cell carcinoma of the head and neck.

OBJECTIVE: Recently, we have noticed that a large number of patients with squamous cell carcinoma of the head and neck (SCCHN) are also infected with the hepatitis C virus (HCV). A review of the literature has revealed no published studies examining this association. The objective of this study was to determine the incidence and epidemiology of HCV infection in patients with SCCHN. STUDY DESIGN: A retrospective chart review. METHODS: Patients diagnosed with SCCHN were analyzed to determine whether they were screened for HCV. Patients were then stratified into two groups (HCV positive and HCV negative). The patient's age at onset, site and stage of the tumor at presentation were determined, and statistical analysis was performed. RESULTS: Ninety-nine (26%) patients were screened, and 21 (21.2%) were HCV positive. This incidence was increased when compared with previously published data (9.9%) (P < .0038). HCV-positive patients presented at an earlier age (51 years) versus the HCV-negative group (60 years) (P < .0002). There were no significant differences in the site or stage at presentation. CONCLUSIONS: In this study, 21% of patients diagnosed with SCCHN were found to be infected with HCV. These patients presented at an earlier age but had similar presentation with respect to site and stage. More research is needed to determine the significance of HCV infection in this patient population.

Gender, race, and electrophysiologic characteristics of the branched recurrent laryngeal nerve.

OBJECTIVES/HYPOTHESIS: The extralaryngeal branching of recurrent laryngeal nerves (RLN) conveys an increased risk of nerve injury during thyroid surgery. We hypothesized that racial and gender variations in prevalence of branched RLN exist. STUDY DESIGN: A retrospective review of all patients who underwent thyroid surgery in a 4-year period in a single surgeon practice. METHODS: The RLN was routinely identified during thyroid surgery. Presence of RLN branching, its distance from the laryngeal nerve entry point (NEP), and functionality of the branches were ascertained. Patient demographics, rates of neural branching, and distance of bifurcation from the NEP were evaluated using statistical analysis. RESULTS: We identified 719 RLNs at risk in 491 patients who underwent central neck surgery. Four hundred and five (82.5%) patients were female and 86 (17.5%) patients were male. There were 218 (44.4%) African American patients and 251 (51.1 %) Caucasian patients. In African American patients, 42.1% RLNs bifurcated compared to 33.2% RLNs in Caucasian (P = 0.017) patients. The RLNs of African American and Caucasian patients bifurcated at comparable distances (P = 0.30). In male patients, 39.1% RLNs bifurcated; whereas in female patients 36.2% RLNs bifurcated (P = 0.53). On average, RLN bifurcation in female patients was at a longer distance from NEP compared to that of male patients (P = 0.012). Electrophysiologic testing found motor fibers in all anterior branches and three posterior extralaryngeal RLN branches. CONCLUSION: African American patients have a higher rate of RLN bifurcation compared to Caucasian patients but no statistically significant difference in distance from NEP. Female patients tend to have longer branching variants of bifid RLNs. RLN motor fibers reside primarily in the anterior branch but may occur in the posterior branch.

Human adipose tissue-derived stromal/stem cells promote migration and early metastasis of triple negative breast cancer xenografts.

BACKGROUND: Fat grafting is used to restore breast defects after surgical resection of breast tumors. Supplementing fat grafts with adipose tissue-derived stromal/stem cells (ASCs) is proposed to improve the regenerative/restorative ability of the graft and retention. However, long term safety for ASC grafting in proximity of residual breast cancer cells is unknown. The objective of this study was to determine the impact of human ASCs derived from abdominal lipoaspirates of three donors, on a human breast cancer model that exhibits early metastasis. METHODOLOGY/PRINCIPAL FINDINGS: Human MDA-MB-231 breast cancer cells represents "triple negative" breast cancer that exhibits early micrometastasis to multiple mouse organs [1]. Human ASCs were derived from abdominal adipose tissue from three healthy female donors. Indirect co-culture of MDA-MB-231 cells with ASCs, as well as direct co-culture demonstrated that ASCs had no effect on MDA-MB-231 growth. Indirect co-culture, and ASC conditioned medium (CM) stimulated migration of MDA-MB-231 cells. ASC/RFP cells from two donors co-injected with MDA-MB-231/GFP cells exhibited a donor effect for stimulation of primary tumor xenografts. Both ASC donors stimulated metastasis. ASC/RFP cells were viable, and integrated with MDA-MB-231/GFP cells in the tumor. Tumors from the co-injection group of one ASC donor exhibited elevated vimentin, matrix metalloproteinase-9 (MMP-9), IL-8, VEGF and microvessel density. The co-injection group exhibited visible metastases to the lung/liver and enlarged spleen not evident in mice injected with MDA-MB-231/GFP alone. Quantitation of the total area of GFP fluorescence and human chromosome 17 DNA in mouse organs, H&E stained paraffin sections and fluorescent microscopy confirmed multi-focal metastases to lung/liver/spleen in the co-injection group without evidence of ASC/RFP cells. CONCLUSIONS: Human ASCs derived from abdominal lipoaspirates of two donors stimulated metastasis of MDA-MB-231 breast tumor xenografts to multiple mouse organs. MDA-MB-231 tumors co-injected with ASCs from one donor exhibited partial EMT, expression of MMP-9, and increased angiogenesis.

Brachial plexus compression: a rare sequelae of malignant papillary thyroid carcinoma.

Invasive papillary thyroid carcinoma (PTC) can rarely invade adjacent vital structures. There has been one report on secondary brachial plexopathy associated with locally invasive PTC. Here we report a patient with a large locally invasive PTC associated with secondary neoplastic brachial plexopathy. The case exhibits an extremely rare occurrence that has substantial impact on surgical planning and management.

A faith- and community-based approach to identifying the individual at risk for head and neck cancer in an inner city.

OBJECTIVES/HYPOTHESIS: To perform a subset analysis of faith- and community-based screening events to further identify at-risk populations for head and neck cancer in hopes of further focusing screening efforts. STUDY DESIGN: Prospective cohort study. METHODS: Three hundred fifty-three individuals (n=353) presented to community events and self-selected for head and neck cancer screenings. A subgroup analysis focusing on risk factors for the development of head and neck cancer and for poor overall prognosis was performed. Subgroups analyzed were individuals screened at church-affiliated events, social events, or community outreach events at homeless shelters. Statistical analysis was performed using one-tailed analysis of variance test. RESULTS: The outreach group had more risk factors for development of cancer, and a significantly higher proportion who used tobacco (P<.05) and consumed >1 drink/day (P<.05). Those in the outreach and church groups had a greater number of risk factors for a poor prognosis with and neck cancer in comparison with the social group: number of uninsured subjects (P<.05), fewer subjects with private insurance (P<.05), fewer subjects with a primary care provider (P<.05), and more subjects with a reported barrier to care (P<.05). CONCLUSIONS: Inhabitants of homeless shelters represent a particularly vulnerable population for both the development and poor prognosis of head and neck cancer. Members of urban church groups are also an at-risk subpopulation due to the prevalence of poor prognostic risk factors. These groups may benefit from future targeted screenings for head and neck cancer.

Oropharyngeal reconstruction using the supraclavicular artery island flap: a new flap alternative.

UNLABELLED: Oropharyngeal reconstruction following head and neck oncologic resection has utilized local, regional, and free tissue transfer flap options. The modality utilized is often guided by the type of defect created as well as the surgeon's preference. In this article, the authors introduce the application of the supraclavicular artery island flap as a reconstructive modality following oropharyngeal oncologic ablation. Five patients underwent head and neck oncologic resection for oropharyngeal squamous cell carcinoma followed by single-stage reconstruction with an ipsilateral supraclavicular artery island flap. There were no flap failures and only one postoperative complication consisting of a postoperative oral-cutaneous fistula that resolved without surgical intervention. There were no donor-site complications. The supraclavicular artery island flap is a viable alternative for oropharyngeal reconstruction following head and neck oncologic resection. It is a regional flap that can be harvested without microsurgical expertise and yields reliable postoperative results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.