Faculty Bibliography

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

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 &mgr;g x 10 doses) or with a single dose of IL-12-loaded microspheres ( approximately 1.65 &mgr;g 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.

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

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

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

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

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