Paul Friedlander

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.

Supraclavicular artery island flap for head and neck oncologic reconstruction: indications, complications, and outcomes.

Background: The supraclavicular island flap has been used successfully for difficult facial reconstruction cases, providing acceptable results without using microsurgical techniques. The authors use this regional flap in reconstructing various head and neck oncologic defects that normally require traditional regional or free flaps to repair surgical wounds. Methods: A pedicled supraclavicular artery flap was used to reconstruct head/neck oncologic defects. Complications and functional outcomes were assessed. Results: Head and neck oncologic patients underwent tumor resection followed by immediate reconstruction using a supraclavicular artery island flap. Ablative defects included neck, tracheal-stomal, mandible, parotid, and pharyngeal walls. All flaps (n = 18) were harvested in less than 1 hour. All ablative wounds and donor sites were closed primarily and did not require additional surgery. Major complications included a complete flap loss when the vascular pedicle was inadvertently divided and pharyngeal leaks. The leaks resolved without surgical intervention, and both patients regained the ability to swallow using their neo-esophagus. Minor complications included donor-site wound dehiscence and cellulitis. None of the patients reported functional donor-site morbidity. Conclusions: This thin flap is easy and quick to harvest, has a reliable pedicle, and has minimal donor-site morbidity. It is now the authors’ flap of choice for many common head and neck reconstructive problems. Early experience using the supraclavicular artery island flap suggests that it is an excellent flap option for head and neck oncologic disease patients.

Circumferential pharyngoesophageal reconstruction with a supraclavicular artery island flap.

Each year, 75,000 new cases of head and neck cancers are discovered in the United States. Laryngeal and pharyngeal cancers represent 20 percent of total new cases. Currently, these tumors are managed using a multidisciplinary approach (oncologist, radiation therapist, head and neck surgeon, and reconstructive surgeon). Advanced pharyngeal tumors are typically treated with chemoradiotherapy and/or total laryngopharyngectomy. Neopharynx reconstruction may require use of regional or free tissue transfer when the tumor (1) encompasses two-thirds of the hypopharynx circumference, (2) involves the posterior pharyngeal wall, (3) involves the postcricoid area, or (4) extends into the cervical esophagus. The resulting pharyngeal defect presents a difficult challenge for reconstructive surgeons. The goals of pharyngoesophageal reconstruction are to allow quick recovery, restore swallowing/speech, and withstand chemoradiation therapy. Patients undergoing laryngopharyngectomy often times have concomitant high-risk cardiac and pulmonary comorbidities. This subset of patients is also more prone to complications, such as impaired wound healing, orocutaneous fistulas, and strictures secondary to factors such as prior smoking, tissue radiation injury, diabetes, peripheral vascular disease, and poor nutritional status. Both regional (pectoralis, deltopectoral, and trapezius) and free flaps (forearm, jejunal, and anterolateral thigh) have been used successfully to reconstruct these complex defects.1–14 In this article, we report the utility of the supraclavicular artery island flap, a new regional fasciocutaneous flap option, in reconstructing both partial and circumferential pharyngeal defects.

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

Summary: 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 surgeons 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.

Motor and sensory branching of the recurrent laryngeal nerve in thyroid surgery

INTRODUCTION Recognition of extralaryngeal bifurcation of the recurrent laryngeal nerve (RLN) is crucial, because inadvertent intraoperative division may lead to significant morbidity. The purpose of this study was to examine the incidence of extralaryngeal bifurcation of the RLN and the distance that the initial bifurcation occurs from the cricothyroid insertion site of the RLN. We also sought to demonstrate the location of the RLN branches containing a predominance of motor fibers. METHODS This prospective study of 220 patients with data on 310 RLNs collected the type of operation, incidence of bifurcation, distance from the cricothyroid insertion point to the point of initial bifurcation, and location of the motor fibers by assessing a stimulus response on the Medtronic NIMS as they relate to the laryngeal muscles. RESULTS A total of 310 RLNs in 220 patients were studied. There were 133 RLNs (42.9%) that bifurcated before entering the larynx. These bifurcations occurred 51.1% on the right, 48.9% on the left, and 33.3% bilaterally. The median branching distance from the cricothyroid membrane on the right was 6.33 mm, and on the left was 6.37 mm. In all bifurcated RLNs, the motor fibers were located exclusively in the anterior branches. CONCLUSION Extralaryngeal bifurcation was found in 42.9% of the RLNs in this case series. The motor fibers are located in the anterior branches. Great caution is therefore required after the presumed identification of the RLN to ensure there is no unidentified anterior branch.

Aesthetic Restoration of Parotidectomy Contour Deformity Using the Supraclavicular Artery Island Flap

Surgical treatment of head and neck malignancies is often associated with undesirable aesthetic and complex functional sequelae. In particular, parotidectomy may result in facial contour depression, Frey syndrome, and facial paralysis. A variety of autologous (regional and free flap transfer) and nonautologous techniques have been described to restore parotidectomy-associated parotid contour deformities. These techniques include nonvascularized fat grafting, dermal-fat grafts,1,2 and subcutaneous implants.3 Autologous vascularized techniques include superficial musculoaponeurotic system reconstruction,4 temporoparietal fascia flap transfer,5 rectus abdominis myocutaneous flaps,6 rotational sternocleidomastoid muscle flaps,7 the pectoralis major myocutaneous pedicle flaps,8 lateral arm free tissue transfer,9 gracilis/latissimus dorsi neurovascular free-muscle transfer,10 deep inferior epigastric perforator flaps,11 and anterolateral thigh flaps.12 Recent reports describing advances in microsurgical free-flap transfers, acellular human dermal matrix graft, or dermal-fat fillers have established their use as “most ideal”13 but with an increase in operation time and recurrence rate. Thus, within this patient demographic group, regional flaps are emerging as an alternative technique for treating head and neck oncologic defects including parotid contour deformities. In this study, we explore the viability and practicality of the pedicled supraclavicular artery island flap for aesthetic restoration of parotid contour deformities. The supraclavicular artery island flap, nourished by the supraclavicular artery and drained by the transverse cervical vein, was initially described for skin resurfacing of burn-related neck contracture.14 The supraclavicular vessel originates from the thyrocervical trunk and emerges within an anatomical triangle bordered by the sternocleidomastoideus laterally and the clavicle ventrally. In 2000, Pallua and Magnus Noah, using cadaveric models, described the use of a tunneled supraclavicular island flap, and later demonstrated this technique as a method of choice with optimal color match and tissue volume for reconstruction of head and neck defects, including postburn neck scar contracture, upper lip, chin, cheek, partial facial and full facial procedures, and following soft-tissue ablation during tumor resection.15 The supraclavicular artery island flap has been used to reconstruct a variety of chest and facial defects, including various forms of postburn contracture16 and in progressive hemifacial atrophy17 as well. It can be used for the reconstruction of head and neck oncologic defects.18

Association of Socioeconomic Status, Race, and Ethnicity With Outcomes of Patients Undergoing Thyroid Surgery

IMPORTANCE For the management of thyroid diseases, there have been few studies aimed at examining the association between disparities and outcomes. OBJECTIVE To measure the effects of race, ethnicity, and socioeconomic status on outcomes following thyroid surgery. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analysis of 62,722 thyroid procedures identified in the Nationwide Inpatient Sample (NIS) from 2003 through 2009. INTERVENTIONS Thyroidectomy. MAIN OUTCOMES AND MEASURES The first set of outcomes included postoperative complication, length of stay (LOS), and overall cost in relation to selected hospital and surgeon characteristics. The second set encompassed accessibility to different surgeon and hospital volumes, hospital locations, and hospital teaching status based on race/ethnicity, income, and health service payer. RESULTS The majority of cases were total thyroidectomies (57.9%) for benign conditions (60.8%). Low-volume surgeons performed most operations (90.8%). Low surgeon volume was associated with higher risk of postoperative complications compared with higher surgeon volume (17.2% vs 12.1%; P < .001). Low-volume compared with high-volume hospitals had higher rates of postoperative complications (17.7% vs 15.1%; P < .001). High surgeon volume was associated with a decreased LOS (mean [SD], 1.74 [0.02] vs 1.20 [0.07] days; P < .001). In addition, LOS was longer at low-volume hospitals (1.85 [0.02] vs 1.57 [0.03] days; P = .001). Hispanics were more likely to be operated on by low-volume surgeons (odds ratio [OR], 2.04; 95% CI, 1.19-3.48), and in certain regions throughout the United States, blacks were more likely to be operated on by low-volume surgeons. Patients with Medicare (OR, 1.30; 95% CI, 1.13-1.53) and lower income (OR, 1.73; 95% CI, 1.19-2.53) were more likely to be treated at low-volume centers. Minorities, including Hispanics, blacks, and other race/ethnicity, were more likely to have their operation in an urban setting (P < .005 for all). Blacks were less likely to have operations performed at nonteaching institutions (OR, 0.48; 95% CI, 0.38-0.60), as were people without private insurance (P < .05 for Medicare, Medicaid, and self-pay). CONCLUSIONS AND RELEVANCE There are significant socioeconomic and racial disparities in thyroid surgery outcomes. Low-volume centers and surgeons had a significantly longer LOS and higher risk of complications, and inequalities were prevalent concerning access to these high-volume hospitals and surgeons.

Supraclavicular artery island flap innervation: Anatomical studies and clinical implications

BACKGROUND Recently, the supraclavicular artery island flap has gained popularity as a regional flap for head and neck reconstruction. During clinical follow-up, some patients report referred sensation to the shoulder when there is contact with the flap skin island surface. The authors examine the anatomical origin/characteristics of the supraclavicular nerves (C3-4) to this flap and its relationship to the flap pedicle and anatomical boundaries. METHODS SAI flap harvest and nerve dissection was performed in seven fresh frozen cadavers (n = 10) using loupe magnification in order to further elucidate the sensory nerve branches in a typical SAI flap. RESULTS Branches of the supraclavicular nerve innervating the SAI flap were found to emerge from the deep fascia at a separate location from the vascular pedicle with the major nerve root exiting underneath the sternocleidomastoid muscle near the midpoint of the muscle belly. The nerve branches proximal to the pedicle with one branch exiting anterior to the flap and another running axially along the length of the flap. The majority (9/10) flaps had a major cutaneous nerves located 1-2 cm anterior to the pedicle. One (1/10) of the flaps had a major cutaneous nerve located 1-2 cm posterior to the pedicle toward the trapezius muscle. In 3 of the 10 flaps, smaller cutaneous nerves were also found posterior to the pedicle in a more distal location of the flap. CONCLUSIONS The supraclavicular nerves innervating the SAI flap are easily identifiable and can be preserved or ligated, depending on the desired flap function, when present close to the pedicle. Further clinical investigation is warranted to confirm the potential benefit of using the SAI flap as a neurotized regional flap for head/neck reconstruction.

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.

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.