Malignant melanoma metastatic to the larynx: treatment and functional outcome.

The review considers management strategies for malignant melanoma metastatic to the larynx. This rare clinical entity lacks clear treatment recommendations because extirpative surgery can often result in severe functional debilitation in patients with limited life expectancy. Here, we report a case of melanoma metastatic to the larynx in a patient with a prior history of Hodgkin lymphoma. The patient was treated with partial laryngectomy and local radiation therapy. The rationale for treatment decisions and for surgical and radiotherapeutic techniques and the associated literature are discussed.

Lymph node central necrosis on computed tomography as predictor of extracapsular spread in metastatic head and neck squamous cell carcinoma: pilot study.

OBJECTIVE: This study aimed (1) to investigate the relationship between the presence of lymph node central necrosis, viewed on pre-operative computed tomography imaging, and the occurrence of histopathologically determined metastatic lymph node extracapsular spread and (2) to determine whether a larger scale study would be valuable. MATERIALS AND METHODS: Pre-operative computed tomography scans, surgical records and post-operative histopathological analysis results were reviewed for 19 consecutive neck dissections performed in 17 patients with head and neck squamous cell carcinoma. RESULTS: A total of 20/26 (77 per cent) lymph nodes with central necrosis had extracapsular spread on histopathological analysis. Twenty of 21 (95 per cent) lymph nodes with extracapsular spread had central necrosis on pre-operative computed tomography. Thirty-four of 40 (85 per cent) lymph nodes without extracapsular spread had no evidence of central necrosis on computed tomography. Only three of 12 (25 per cent) patients with lymph node central necrosis identified on pre-operative computed tomography were found to have actual necrosis on final histopathological analysis. CONCLUSIONS: Lymph node central necrosis viewed on pre-operative computed tomography scans is a useful indicator of metastatic lymph node extracapsular spread, with a sensitivity of 95 per cent, a specificity of 85 per cent, a positive predictive value of 69 per cent and a negative predictive value of 98 per cent. Lymph node diameter is not a sensitive indicator of extracapsular spread.

Selection and validation of differentially expressed genes in head and neck cancer.

We applied a robust combinatorial (multi-test) approach to microarray data to identify genes consistently up- or down-regulated in head and neck squamous cell carcinoma (HNSCC). RNA was extracted from 22 paired samples of HNSCC and normal tissue from the same donors and hybridized to the Affymetrix U95A chip. Forty-two differentially expressed probe sets (representing 38 genes and one expressed sequence tag) satisfied all statistical tests of significance and were selected for further validation. Selected probe sets were validated by hierarchical clustering, multiple probe set concordance, and target-subunit agreement. In addition, real-time PCR analysis of 8 representative (randomly selected from 38) genes performed on both microarray-tested and independently obtained samples correlated well with the microarray data. The genes identified and validated by this method were in comparatively good agreement with other rigorous HNSCC microarray studies. From this study, we conclude that combinatorial analysis of microarray data is a promising technique for identifying differentially expressed genes with few false positives.

The external approach for submucosal lesions of the larynx.

OBJECTIVE: The surgical excision of benign submucosal lesions of the larynx can be performed using a variety of techniques including direct laryngoscopy and external approaches. We propose that small submucosal lesions of the larynx can be removed via the external approach without a tracheotomy. STUDY DESIGN: Retrospective chart review. SETTING: Six patients at The Long Island Jewish Medical Center and at the New York University School of Medicine underwent an external approach for the removal of benign submucosal laryngeal lesions without tracheotomies. Lesions included a mixed laryngopyocele, an internal laryngopyocele, a mixed laryngocele, a paraganglioma, a neurilemmoma and a lymphoma. Follow-up ranged from 1 to 9 years. RESULTS: All patients were female with an average age of 72. No patient required a tracheotomy. One patient remained intubated for 24 hours postoperatively to ensure an adequate airway. Mild dysphagia was noted in all patients, but it was short-lived and did not require alternate methods of alimentation. There have been no recurrences of disease. CONCLUSION: The external approach without tracheotomy allows for good exposure with minimal functional disability for the removal of benign submucosal lesions of the larynx.

Motility-related proteins as markers for head and neck squamous cell cancer.

HYPOTHESIS: Increased cell motility is a hallmark of cancer cells. Proteins involved in cell motility may be used as molecular markers to characterize the malignant potential of tumors. METHODS: Molecular biology and immunohistochemistry techniques were used to investigate the expression of a selected panel of motility-related proteins (Rho A, Rac 2, Cdc42, PI3K, 2E4, and Arp2) in normal, premalignant, and squamous cell cancer cell lines of human head and neck origin. To assess the clinical potential of these proteins as molecular markers for cancer, immunohistochemistry was performed on paraffin-fixed head and neck cancer specimens (n = 15). RESULTS: All six motility-associated proteins were overexpressed in the premalignant and squamous cell cancer cell lines relative to normal keratinocytes. Immunohistochemistry with Rho A and Rac 2 showed increased staining in areas of cancer but not in normal tissue. CONCLUSION: Proteins involved in cell motility can be used as markers for head and neck squamous cell carcinoma. The head and neck cell lines used in this study may be used as a model to further investigate cell motility. Molecular markers of motility could have a significant impact on the diagnosis and staging of cancers originating from differentiated non-motile cells.

Adhesion molecules as prognostic factors in nasopharyngeal carcinoma.

OBJECTIVE/HYPOTHESIS: To identify the significance of molecular markers in determining the risk of recurrence and distant metastases in nasopharyngeal carcinoma. STUDY DESIGN: In this retrospective case study, we evaluated archival nasopharyngeal carcinoma specimens for patterns of expression of E-cadherin, beta-catenin, c-erb-B2, and Ki-67, which have been demonstrated to be important in other tumors. METHODS: Fifty-four cases of nasopharyngeal carcinoma were identified, with a maximum follow-up of 13 years. The histopathological sections were stained using an automated immunohistochemical stainer (NexES, Ventana Medical Systems, Tucson, AZ) for E-cadherin (Zymed Laboratories [San Francisco, CA] and Transduction Laboratories [Lexington, KY] clones), beta-catenin (Zymed), c-erb-B2 (Ventana Medical Systems), and Ki-67 (Novocastra, Burlingame, CA). The numbers of positively staining cells were scored as follows: 0%, 1% to 33%, 34% to 66%, or greater than 67%. RESULTS: E-cadherin (Zymed) stained positively in only one case. The Transduction Laboratories clone demonstrated a spectrum of staining in all cases, from complete to disrupted to no identifiable membranous staining. The staining was consistently absent at the advancing tumor border, regardless of stage. The loss of beta-catenin expression did not correlate with that of E-cadherin or with clinical outcomes. No staining was identified for c-erb-B2. Ki-67 staining was variable and did not correlate with clinical outcomes. CONCLUSIONS: Altered expression or loss of E-cadherin, or both, may result in loss of function, particularly at the infiltrating edge, with resultant loss of cell polarity, cell migration, and eventual metastasis. The interpretation of E-cadherin staining depends on antibody source. In contrast to recent studies, beta-catenin expression is not altered and c-erb-B2 expression not identified, suggesting that these markers are not important in the prognosis of nasopharyngeal carcinoma.

Tumour volume estimated by computed tomography as a predictive factor in carcinoma of the tongue.

This retrospective study evaluated tumour volume, estimated by computed tomography (CT), as a predictive factor in carcinoma of the tongue. Tumour volume was measured from pretreatment CT scans of 20 consecutive patients, followed up for at least 3 years, and this measurement was compared with tumour volume estimated from pathological specimens. T-stage and CT-derived tumour volume were compared with the clinical and pathological status of the nodes, and with the outcome of treatment. The measurement of tumour volume derived from CT correlated well with measurements derived from pathological examination, and tumour volume also predicted overall treatment failure. The disease-specific survival rate was 100% for patients with low-volume tumours (<13 cc) compared with 79% for those with stage T1 and T2 tumours.CT is a reliable way of measuring the volume of tumours in carcinoma of the tongue, and tumour volume is useful adjunct to the clinical tumour-node-metastases staging system.

A novel approach to laryngeal suspension after partial laryngectomy.

OBJECTIVES: Supraglottic laryngectomy is a well-established surgical therapy for selected carcinomas of the larynx and hypopharynx. Most compromised by this procedure and its variations is the laryngeal mechanism that protects the lower respiratory tract from aspiration. Laryngeal suspension serves to compensate for the loss of the resected laryngeal elevator muscles by pulling the larynx upward and forward beneath the tongue base. In this study we describe a method of laryngeal suspension in supraglottic laryngectomy using a cartilage-anchored suture carrier device. STUDY DESIGN: Report of this novel approach to laryngeal suspension using seven suture anchors in two patients undergoing supraglottic laryngectomy. METHODS: Seven Mitek Micro anchors (Mitek, Westwood, MA) were used to perform laryngeal suspension in two patients undergoing supraglottic laryngectomy. Our technique is compared with traditional methods. Operative data as well as postoperative functional results are reviewed. RESULTS: Laryngeal suspension using suture anchors was successful, with failure of only one anchor. Oral alimentation was quickly reestablished in both patients. There were no perioperative or postoperative complications. CONCLUSIONS: We describe a novel approach to laryngeal suspension that overcomes some of the technical challenges inherent in traditional suturing techniques. This novel approach is technically easier and more efficient than traditional methods and accomplishes distribution of stress forces on the thyroid cartilage remnant.

Lymphoscintigraphy, sentinel lymph node biopsy, and Mohs micrographic surgery in the treatment of Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy with a high incidence of occult nodal metastases. MCC is believed to be similar in natural history to thick or ulcerated melanomas in its propensity for locoregional recurrence and early lymph node metastasis. Studies have shown that nodal status is statistically correlated to survival in MCC. Radiolocalization and superselective lymph node biopsy is a recent technique that has been proven to be of great value in evaluating the status of occult lymph node disease in malignant melanoma and breast cancer patients. OBJECTIVE: In previously untreated patients, an orderly progression of metastases is observed for both cutaneous carcinomas and malignant melanomas and is anticipated for MCC. METHODS/RESULTS. We present two patients with MCC of the head and neck who underwent simultaneous Mohs micrographic surgery and sentinel lymph node biopsy with intraoperative radiolocalization. CONCLUSION: Sentinel lymph node biopsy and intraoperative lymphoscintigraphy may prove to be a useful technique in evaluating occult nodal involvement and in limiting the potentially unnecessary morbidity of more comprehensive lymph node dissections in MCC patients who do not yet have metastatic involvement.

Interleukin-12 delivered by biodegradable microspheres promotes the antitumor activity of human peripheral blood lymphocytes in a human head and neck tumor xenograft/SCID mouse model.

BACKGROUND: The role of cytokines in tumor regression is now well established. The major limitation for the clinical use of cytokines is the lack of a simple and effective protocol for the local and sustained delivery of cytokines to the tumor milieu. This study reports suppression of human head and neck squamous cell carcinoma (HNSCC) by human peripheral blood lymphocytes (HuPBL) following local, sustained delivery of interleukin-12 (IL-12) to tumors with biodegradable microspheres in a human/SCID mouse chimeric model. Materials and Methods Nondisrupted biopsy pieces (120 mg) of primary HNSCC were implanted s.c. into severe combined immunodeficient (SCID) mice and were expanded by serial passage in mice. Tumors were then titrated with different doses of allogeneic HuPBL by coengraftment of tumor pieces and HuPBL into the subcutis of SCID mice to determine whether the HuPBL possessed antitumor activity (the SCID/Winn model). The lymphocyte subsets that were responsible for the suppression of tumor engraftment were identified by selective depletion of the CD4+, CD8+, and CD56+ cells from the HuPBL prior to engraftment into mice. Attempts were then made to augment the antitumor activity of the HuPBL either by repeated intralesional bolus injections of recombinant human IL-12 (0.5 microg x 10 doses) or with a single dose of IL-12-loaded microspheres ( approximately 1.65 microg IL-12/mg microspheres, 2 mg microspheres/mouse). RESULTS: Successful engraftment of HNSCC was observed in 12 of 19 different patient samples. Normal histological architecture of tumor was maintained up to four serial passages in the SCID mice. After the first tumor engraftment, but not in subsequent passages, human immunoglobulin produced by plasma cells present in the tumor infiltrating lymphocyte population was detected in the mouse sera. Allogeneic human PBL displayed antitumor cytotoxic activity in a cell dose-dependent fashion when coengrafted with the tumors passaged in SCID mice. Lymphocyte subset depletion studies established that tumor suppression was dependent on both the CD8+ T lymphocytes and the CD56+ natural killer cells. Treatment of tumors with a single intralesional injection of IL-12-loaded microspheres was highly effective, resulting in the complete suppression of tumor engraftment in 50% of the mice. In contrast, treatment of tumors with repeated bolus IL-12 injections suppressed tumor engraftment only transiently and did not result in complete tumor rejection in any of the mice. CONCLUSION: The coengraftment of HNSCC and allogeneic lymphocytes into SCID mice provides a viable model with which to evaluate immunotherapeutic strategies for human cancer. The use of biodegradable microspheres for local sustained delivery of cytokines to augment lymphocyte mediated antitumor immunity within the tumor microenvironment provides a safer and simpler alternative to current cytokine immunotherapy protocols.

Clinical experience in end-to-side venous anastomoses with a microvascular anastomotic coupling device in head and neck reconstruction.

BACKGROUND: Microvascular anastomosis remains one of the most technically sensitive aspects of free-tissue transfer reconstructions. Despite the availability of various mechanical anastomotic coupling systems for human clinical use during the last 8 years, reported clinical series remain rare. OBJECTIVE: To describe a clinical experience in applying a mechanical microvascular anastomotic coupling device (MACD) to end-to-side anastomotic configurations in head and neck free-flap reconstruction. METHODS: The MACD is a readily available high-density polyethylene ring-stainless steel pin system that has been found to be highly effective in clinical studies of end-to-end arterial and venous anastomosis and in laboratory studies of end-to-side anastomosis of rabbit arteries. RESULTS: Thirty-seven end-to-side venous anastomoses were attempted, of which 33 (89%) were completed. Of these, 9 patients had critical anastomoses (only 1 venous anastomosis per patient). In patients undergoing parallel venous anastomoses, 6 had both anastomoses performed using the MACD; in the remaining 12 patients, 1 of the anastomoses was performed using the MACD. A variety of donor flaps and clinical contexts were encountered. Flap survival in the MACD series was 100%. Four anastomoses were converted to conventional suture technique intraoperatively. CONCLUSIONS: The MACD is well suited to end-to-side venous anastomosis when carefully and selectively used by experienced microvascular surgeons. The most common clinical situation requiring this configuration and technique was the lack of ipsilateral recipient veins for end-to-end anastomosis or a ligated internal jugular vein stump that required this approach for device application. Previous radiation therapy does not appear to be a contraindication to its use.

Primary leiomyosarcoma of the mandible in a 7-year-old girl: report of a case and review of the literature.

Leiomyosarcoma is a malignant neoplasm of smooth muscle origin that manifests itself uncommonly in the oral cavity because of the paucity of smooth muscle in that location. To the best of our knowledge, only 10 cases of leiomyosarcoma primary to the jawbones have been reported in the English language literature. We report the first pediatric case of leiomyosarcoma arising from the mandible. Facial asymmetry and swelling were accompanied by a rapidly growing exophytic soft tissue mass that caused buccal displacement of the mandibular left permanent first molar. The lesion, observed radiographically as an extensive ill-defined area of osteolytic alveolar destruction, perforated the lingual cortex, displaced the inferior alveolar nerve canal inferiorly, and produced a "floating-in-air" appearance of the first molar. Diagnosis of leiomyosarcoma was made after initial incisional biopsy of the lesion. A 5-cm segmental mandibulectomy and supraomohyoid neck dissection were followed by reconstruction with a dynamic mandibular reconstruction plate and placement of a multidimensional mandibular distraction device in a transport rectangle of bone to promote bifocal distraction osteogenesis. Forty millimeters of distraction (the technical limit of the device) were performed; this was followed by terminal iliac crest bone grafting. Seventeen months after the definitive surgical procedure, the patient remains free of disease.

Differentiated thyroid carcinoma: risk group assignment and management controversies.

In this review, we provide a framework for clinical decision-making in the treatment of differentiated thyroid cancer. The clinical discussion and treatment recommendations are relevant to an adult population (> 16 years of age). The natural history, pathogenesis, diagnostic tools, and treatment controversies in the management of this disease are explored. The roles of radioiodine therapy and thyroid-stimulating hormone (TSH) suppression and the treatment of locoregional disease are reviewed. This discussion provides a comprehensive assessment of management and treatment issues in differentiated thyroid cancer.

Magnetic resonance imaging assessment of a microvascular anastomotic device for ferromagnetism.

Microvascular free-tissue transfers have assumed particular importance as reconstructive techniques of choice in centers where ablative surgery for primary and recurrent malignant disease is a focus. In the context of malignant disease, issues of surveillance for recurrence are paramount. As clinical experience with the diagnostic imaging characteristics of flap reconstructions has been acquired, magnetic resonance imaging (MRI) has assumed a prominent role in the evaluation for recurrent malignant disease. This has provided an important supportive role for contemporary concepts of immediate reconstruction. The Precise-TM Microvascular Anastomotic Device (MACD) is based on the friction-fit union of implant rings composed of high-density polyethylene and surgical stainless steel. Many characteristics of the device have been described in histologic and laboratory studies. As yet uncharacterized is the effect of clinical MRI electromagnetic fields on the device, which is composed, in part, of type 316 stainless steel. The MACD is in wide use in centers where microsurgeons are experienced with the system and it is designed to facilitate the performance and reliability of microvascular anastomoses. The implications for MRI as a safe imaging modality for the acute perioperative evaluation of patients reconstructed with microvascular free flaps anastomosed with the MACD are obvious. MACD implants of varying sizes were evaluated for displacement in each of three orthogonal planes within a 1.5 Tesla magnetic field. No change in displacement was observed for any of the devices. Magnetic resonance imaging may thus be considered a safe imaging modality for the acute perioperative diagnostic imaging of free-tissue transfers that have been anastomosed with the MACD.

Ischemic conditioning (delay phenomenon) improves esophagogastric anastomotic wound healing in the rat.

BACKGROUND AND OBJECTIVES: Esophagogastric anastomotic leaks are a major source of morbidity after esophagectomy. Occult ischemia of the mobilized gastric fundus is an important etiological factor for this failure of healing. To test the hypothesis that ischemic conditioning (delay phenomenon) could improve esophagogastric anastomotic healing, anastomotic healing was studied in a rodent model of partial gastric devascularization. METHODS: Thirty-four Sprague-Dawley rats (two groups of 17 rats) underwent partial gastric devascularization and creation of esophagogastric anastomoses. In the acute ischemia group, devascularization and anastomosis were done at the same laparotomy. In the ischemic conditioned group, devascularization was done 3 weeks before anastomosis. Gastric tissue perfusion was assessed by laser-Doppler flowmetry before and after devascularization in both groups, and 3 weeks after devascularization in the ischemic conditioned group. All rats were killed 4 days after anastomosis, and the wounds assessed for dehiscence, breaking strength, and hydroxyproline concentration. RESULTS: Gastric tissue perfusion, measured in tissue perfusion units (TPU) decreased immediately after devascularization (before: 73.6 +/- 12.1 TPU; after: 25.0 +/- 6.5 TPU; P < 0.001). After 3 weeks, gastric tissue perfusion returned to baseline values in the ischemic conditioned rats (before: 72.3 +/- 11.0 TPU; 3 weeks, 71.1 +/- 15.1 TPU; P < 0.80). Ischemic conditioned rats had fewer anastomotic leaks (2 vs. 9, P < 0.023) and higher anastomotic wound breaking strengths (2.35 +/- 1.05 N vs. 1.56 +/- .76 N, P < 0.02) than the acute ischemic rats. Anastomotic would hydroxy-proline concentration was not significantly different in the two groups (acute ischemic--0.111 +/- .033 mumol/mg, ischemic conditions--0.097 +/- .026 mumol/mg, P < 0.20). CONCLUSIONS: In this rodent model of partial gastric devascularization, ischemic conditioning (delay phenomenon) ameliorated the harmful effect of ischemic on esophagogastric anastomotic wound healing.