Intratumoral multinucleated giant cells are not a prognostic pathologic feature in cutaneous melanoma.

BACKGROUND: Histopathologic diagnostic features such as tumor thickness, ulceration, mitoses, microsatellitosis and nodal metastases are principal pathologic staging components of cutaneous melanomas. We chose to focus on evaluating the presence of multinucleated giant cells in microscopic sections as a putative novel prognosticating diagnostic feature of melanoma. METHODS: We assembled a retrospective cohort comprised of 562 cases of melanoma. We annotated each case for a multitude of known clinicopathologic variables to allow robust statistical evaluation of our cohort. RESULTS: Only 37 cases (6.6%) exhibited the multinucleated giant cells phenotype. Virtually all multinucleated giant cells were localized in the reticular dermis. Of interest, melanomas with multinucleated giant cells were roughly twice more likely to occur on head and neck sites (p = 0.04). Melanomas with multinucleated giant cells phenotype had both comparable melanoma recurrence (p = 0.12) and similar melanoma-specific mortality when compared with melanomas without multinucleated giant cells phenotype (p = 0.26). CONCLUSION: Despite prior anecdotal reports possibly linking multinucleated giant cells phenotype to more aggressive clinical course, we find that melanomas with multinucleated giant cells phenotype is not associated with shorter survival.

Use of the external pectoralis myocutaneous major flap in anterior skull base reconstruction.

Despite the emergence of free tissue transfer, the pectoralis major myocutaneous flap (PMMF) still has a role in anterior base skull reconstruction (when free tissue transfer is not feasible). The aim of this study is to evaluate the results of external PMMF in anterior skull base reconstruction. A retrospective study from 1977 to 2006 was conducted at Yale New Haven Hospital. 16 patients (mean age 64 years), presenting with a malignant tumour of the anterior base skull, were included. The primary pathology was recurrent squamous carcinoma. Tumour resection resulted in orbital exenteration in 60%, and bone resection of the anterior skull base in 81% of patients. The initial skin defect was 49 cm(2) (range 16-100 cm(2)). The PMMF was the primary reconstructive choice in 87%, and utilized after free flap failure in two cases. Three minor complications were noted. Orbital exenteration and anterior base skull resection is a surgical procedure that leads to significant reconstructive challenges. The PMMF remains a safe and versatile reconstructive tool in anterior skull base tumour resection. The externalized pedicle allows this flap to reach periorbital and anterior skull base.

End-to-side venous anastomosis with an anastomotic coupling device for microvascular free-tissue transfer in head and neck reconstruction.

OBJECTIVE: The purpose of this study is to demonstrate the success rate of using a coupling device for end-to-side venous anastomosis in patients undergoing free-tissue transfer (FTT) in head and neck reconstruction. METHODS AND MEASURES: Retrospective data were collected in consecutive series of 134 patients undergoing surgical resection of head and neck tumors followed by FTT. All microvascular FTTs were performed at Yale-New Haven Hospital between November 2001 and August 2007. The Unilink coupling device was used to perform arterial and venous anastomosis in this case series. Flap survival and thrombosis of the venous anastomoses were determined. RESULTS: One hundred thirty-four consecutive patients underwent a total of 137 microvascular FTTs using a coupling device. In our series, a total of 173 end-to-side anastomoses were completed in 96 patients. Of these, 77 patients had both venous anastomoses, 17 underwent one end-to-side and one end-to-end anastomoses, and two patients had one venous anastomosis per patient performed in end-to-side fashion. Reconstruction included 76 radial forearm, 17 fibula, and three rectus abdominis free flaps. There were three vascular insufficiency related complications of which two were salvageable. There was one case of flap failure (1%), resulting in a free flap survival rate of 99%. CONCLUSION: This largest reported series of end-to-side venous anastomoses with an anastomotic coupling device demonstrates feasibility and efficacy of this technique in head and neck reconstruction.

Arterial coupling for microvascular free tissue transfer.

OBJECTIVE: The purpose of this study was to demonstrate the efficacy of arterial coupling. STUDY DESIGN: Retrospective data were collected in a consecutive series of 124 patients undergoing surgical resection of head and neck tumors followed by free tissue transfer (FTT). METHODS AND MEASURES: The Unilink coupling device was used to perform arterial and venous anastomosis. Flap survival and thrombosis of the arterial anastomoses were determined. RESULTS: A total of 124 consecutive patients underwent a total of 127 microvascular FTTs. Reconstruction included 90 radial forearm, 26 fibula, 9 rectus abdominis, and 2 iliac crest myocutaneous free flaps. There were four (3.2%) complications related to arterial insufficiency in our series, three of which were salvageable. There were three (2.4%) flap failures, resulting in an overall free flap survival rate of 97.6 percent. CONCLUSION: The flap survival with the Unilink Microvascular Anastomotic System is similar to that of standard suture techniques. Use of a coupler device is the preferred method in performing microvascular FTT at our institution.

Arterial coupling for microvascular free tissue transfer in head and neck reconstruction.

OBJECTIVE: To demonstrate the efficacy of arterial coupling. DESIGN: We report our experience in head and neck reconstruction with the Unilink Microvascular Anastomotic System (Synovis MCA, Birmingham, Ala). Data were collected in a consecutive series of 49 patients undergoing composite resection of head and neck tumors followed by free tissue transfer. SETTING: All patient care took place at Yale-New Haven Hospital, New Haven, Conn, a university-based tertiary care facility. PATIENTS: Forty-nine consecutive patients aged 43 to 85 years underwent a total of 50 microvascular free tissue transfers using the Unilink coupling device. There were 18 women and 31 men, and the following 3 types of flaps were performed: radial forearm (n = 36), fibula (n = 12), and rectus abdominus (n = 2). INTERVENTIONS: The Unilink coupling device was used in this case series. Each arterial and venous anastomosis was performed with the coupling device. Free tissue transfers were monitored clinically and outcomes were recorded. MAIN OUTCOME MEASURES: Flap survival and thrombosis of the arterial anastomoses were determined, as was median length of stay. RESULTS: There were no flap failures in the series. Of the 50 coupled arterial anastomoses, the predominant coupler size used was 2.5 mm in diameter. Reconstructions included 36 radial forearm, 12 fibular osteocutaneous, and 2 rectus abdominus myocutaneous free flaps. One intraoperative arterial thrombosis occurred, requiring hand-sewn anastomosis, and another pulled away from the intact coupler in a steroid-dependent patient. There were no complications related to technical performance of the coupling device. The median length of stay was 14 days. CONCLUSION: While hand-sewn anastomoses in free tissue transfer remain the preferred technique for many microsurgeons, use of the coupler is a viable alternative to sutured anastomoses.

Abnormal acidification of melanoma cells induces tyrosinase retention in the early secretory pathway.

In tyrosinase-positive amelanotic melanoma cells, inactive tyrosinase accumulates in the endoplasmic reticulum. Based on studies described here, we propose that aberrant vacuolar proton ATPase (V-ATPase)-mediated proton transport in melanoma cells disrupts tyrosinase trafficking through the secretory pathway. Amelanotic but not melanotic melanoma cells or normal melanocytes display elevated proton export as observed by the acidification of the extracellular medium and their ability to maintain neutral intracellular pH. Tyrosinase activity and transit through the Golgi were restored by either maintaining the melanoma cells in alkaline medium (pH 7.4-7.7) or by restricting glucose uptake. The translocation of tyrosinase out of the endoplasmic reticulum and the induction of cell pigmentation in the presence of the ionophore monensin or the specific V-ATPase inhibitors concanamycin A and bafilomycin A1 supported a role for V-ATPases in this process. Because it was previously shown that V-ATPase activity is increased in solid tumors in response to an acidified environment, the appearance of hypopigmented cells in tyrosinase-positive melanoma tumors may indicate the onset of enhanced glycolysis and extracellular acidification, conditions known to favor metastatic spread and resistance to weak base chemotherapeutic drugs.