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Treatment of recurrent pleomorphic adenomas of the parotid gland

Carew, J F; Spiro, R H; Singh, B; Shah, J P
Recurrent pleomorphic adenomas (RPAs) of the parotid gland are an uncommon but challenging problem. The records of 31 patients with RPAs were reviewed to assess the clinical presentation and treatment results. More than half of these patients underwent total parotidectomy. Local control was achieved in 94% of patients at 7 years (median follow-up 7.3 years). Patients who had surgery for recurrence after a formal parotidectomy were more likely to have another recurrence (63% local control at 7 years) than patients whose initial procedure was a limited excision (100% local control at 7 years; P < 0.01). Better local control was seen in 11 patients who received postoperative irradiation (100% at 10 years) than in 20 patients who did not (71% at 10 years; P < 0.28). Adequate surgical resection yields an acceptable local control rate in patients with RPAs. Postoperative radiation therapy may improve control in patients at high risk for another recurrence
PMID: 10547466
ISSN: 0194-5998
CID: 137189

Hemangiopericytoma of the head and neck

Carew, J F; Singh, B; Kraus, D H
OBJECTIVE/HYPOTHESIS: Hemangiopericytomas are uncommon neoplasms of vascular origin that may arise in the head and neck. Their rare occurrence and variable malignant potential have limited attempts to characterize their clinical behavior. This study reviews the experience in treating hemangiopericytomas of the head and neck at a single institution. STUDY DESIGN: Retrospective. METHODS: The records of 12 patients with hemangiopericytomas of the head and neck presenting between 1979 and 1995 were reviewed. Site of origin included the neck (4), oral cavity (3), parotid (2), orbit (1), maxillary sinus (1) and mandible (1). Five patients had lesions characterized as high or intermediate grade histologically, and six had lesions characterized as low grade. RESULTS: Nine patients were treated with curative intent; three presented either with pulmonary metastasis (2) or unresectable primaries (1) and were treated with radiation therapy and/or palliative Adriamycin-based chemotherapy. Patients treated with curative intent underwent a variety of surgical resections dictated by tumor location and size. Four patients received postoperative radiation therapy to a median dose of 60 Gy, for positive surgical margins (2), high-grade histology (1) or a recurrent lesion (1). Five-year overall survival in patients treated surgically was 87.5%. A single mortality occurred in a patient with a recurrent high-grade lesion who failed at local, regional, and distant sites. Median follow-up of survivors was 73 months. CONCLUSION: The clinical behavior of hemangiopericytomas appears to be related to their histological grade. Aggressive local therapy including surgery and radiation therapy appears to be effective in providing tumor control
PMID: 10499045
ISSN: 0023-852x
CID: 137188

Early complications. Recurrent nerve palsy

Carew, J F; Kraus, D H; Ginsberg, R J
Unilateral vocal cord paralysis following pneumonectomy has profound effects on deglutition, phonation, protection of the airway, and generation of an adequate cough. If untreated in patients with limited pulmonary reserve, these detrimental effects can have devastating consequences. Several techniques are currently available which allow adequate medialization and rehabilitation of the paralyzed vocal cord. Adequate diagnosis and treatment can minimize the negative consequences associated with vocal cord paralysis following pneumonectomy
PMID: 10459430
ISSN: 1052-3359
CID: 137187

Oncolytic viral therapy for human colorectal cancer and liver metastases using a multi-mutated herpes simplex virus type-1 (G207)

Kooby, D A; Carew, J F; Halterman, M W; Mack, J E; Bertino, J R; Blumgart, L H; Federoff, H J; Fong, Y
G207 is a multi-mutated, replication-competent type-1 herpes simplex virus designed to target, infect, and lyse neurological tumors. This study examines the feasibility of using G207 in the treatment of human colorectal cancer and defines the biological determinants of its antitumor efficacy. This virus was tested on five human colorectal cancer cell lines in vitro to determine efficacy of infection and tumor cell kill. These results were correlated to measures of tumor cell proliferation. In vivo testing was performed through direct injections of G207 into xenografts of human colorectal cancer tumors grown in flanks of athymic rats. To evaluate an alternate method of administration, hepatic portal vein infusion of G207 was performed in a syngeneic model of liver metastases in Buffalo rats. Among the five cell lines tested, infection rates ranged between 10% and 90%, which correlated directly with S-phase fraction (8.6%-36.6%) and was proportional to response to G207 therapy in vitro (1%-93%). Direct injection of G207 into nude rat flank tumors suppressed tumor growth significantly vs. control (0.58 +/- 0.60 cm(3) vs. 9.16 +/- 3.70 cm(3), P<0. 0001). In vivo tumor suppression correlated with in vitro effect. In the syngeneic liver tumor model, portal infusion resulted in significant reduction in number of liver nodules (13 +/- 10 nodules in G207-treated livers vs. 80 +/- 30 nodules in control livers, P<0.05). G207 infects and kills human colorectal cancer cells efficiently. In vitro cytotoxicity assay and tumor S-phase fraction can be used to predict response to treatment in vivo. This antineoplastic agent can be delivered effectively by both direct tumor injection and regional vascular infusion. G207 should be investigated further as therapy for colorectal cancer and liver metastases
PMID: 10428757
ISSN: 0892-6638
CID: 137186

Parathyroid biopsy to facilitate the preservation of functional parathyroid tissue during thyroidectomy

Kuhel, W I; Carew, J F
BACKGROUND: The preservation of viable parathyroid tissue, either by preserving parathyroid glands in situ with an intact blood supply or by autotransplantation, is an integral element of thyroid surgery. There is a general impression that nonviable parathyroid glands can be recognized on the basis of black or purple-black discoloration of the gland. We came to believe that this is not a reliable way to assess the viability of parathyroid glands because we observed that when we excised parathyroid glands (with the intention of reimplanting them) in situations where it was not feasible to preserve their blood supply, they did not become discolored. METHODS: To assess the status of the parathyroid blood supply, we performed incisional biopsies of suspected parathyroid glands during 14 consecutive thyroid operations (9 hemithyroidectomies, 1 completion thyroidectomy, 4 total thyroidectomies), and observed the biopsy site for evidence of active bleeding. RESULTS: Thirty-four of 36 possible parathyroid glands were histologically confirmed. Seventeen bled actively from the biopsy site and were preserved in situ. The other 17 were felt to be nonviable: 5 were severely discolored (black) and either no bleeding or minor venous oozing was seen when they were biopsied; 12 with normal coloration (3 were harvested prior to biopsy), did not bleed actively following an incisional biopsy. Parathyroid glands that were judged to be devascularized were autotransplanted into the sternocleidomastoid muscle. CONCLUSIONS: The absence of discoloration is not a reliable way to determine whether the parathyroid blood supply is intact. Biopsy of the parathyroid glands during thyroid surgery facilitates the identification of devascularized parathyroid glands that can be salvaged with autotransplantation
PMID: 10402525
ISSN: 1043-3074
CID: 137184

Selective infection and cytolysis of human head and neck squamous cell carcinoma with sparing of normal mucosa by a cytotoxic herpes simplex virus type 1 (G207)

Carew, J F; Kooby, D A; Halterman, M W; Federoff, H J; Fong, Y
This study evaluates inhibition of human squamous cell carcinomas (SCCs) by a replication-competent multimutated herpes simplex virus type 1 (G207). Infectivity and cytotoxicity of the G207 virus were evaluated in vitro in seven human SCC cell lines. In vivo effects of the G207 virus on human tumor xenografts in an athymic rat model were then investigated by injecting established tumors with 1 x 10(7) virus particles and monitoring tumor growth. In addition, oral cavity tumors in immunocompetent hamster were infected with the G207 virus by selective intraarterial perfusion and the tumor response was monitored. In vitro studies demonstrated infection rates, measured 24 hr after exposure, exceeding 40% at an MOI of 2 in five of seven human SCC cell lines. Cytotoxic effects, as measured by percent cell death on day 5, exceeded 90% in five of seven SCC cell lines. In vivo inhibition of tumor growth in an athymic rat model was seen (p < 0.005) and in two of the cell lines a complete clinical response was seen in 12 of 14 tumors. In the hamster model, selective intraarterial perfusion with G207 virus showed selective infection of the tumor cells, with sparing of the adjacent normal mucosa, which leading to significant suppression of tumor growth (p < 0.005). The G207 virus displayed efficient and selective cytotoxicity and tumor growth inhibition against human SCC and may prove useful as a therapeutic agent for head and neck SCC
PMID: 10428205
ISSN: 1043-0342
CID: 137185

Laryngeal cancer in patients with acquired immunodeficiency syndrome [Letter]

Singh, B; Carew, J F; Shaha, A R
PMID: 9856669
ISSN: 0277-3732
CID: 137264

Efficient gene transfer to human squamous cell carcinomas by the herpes simplex virus type 1 amplicon vector

Carew, J F; Federoff, H; Halterman, M; Kraus, D H; Savage, H; Sacks, P G; Schantz, S P; Shah, J P; Fong, Y
BACKGROUND: This study evaluates the efficiency of herpes simplex virus (HSV) mediated gene transfer in human squamous cell carcinoma (SCC) cell lines in vitro and in vivo when delivered by selective intra-arterial perfusion. METHODS: Human head and neck SCC were exposed to HSV-LacZ and HSV-interleukin-2 (IL-2) and gene transfer and expression assessed by X-gal staining and enzyme-linked immunosorbent assay, respectively. Hamster cheek pouch tumors were perfused with HSV-LacZ or HSV-IL-2, by microcannulating the external carotid artery, and gene transfer determined. RESULTS: A ratio of 5 viral particles per tumor cell achieved gene transfer rates exceeding 50%. Interleukin-2 levels of 287 +/- 17 to 424 +/- 8.4 ng per million cells were achieved at a ratio of 2 viral particles per tumor cell. Selective intra-arterial perfusion of the HSV-IL-2 vector yielded IL-2 levels of 45.8 +/- 17.0 pg per g tumor. CONCLUSIONS: HSV amplicon vectors are efficient vehicles for gene transfer in vitro in human head and neck SCC cell lines and in vivo when introduced by selective intra-arterial perfusion
PMID: 9874422
ISSN: 0002-9610
CID: 137265

Advances in multimodality therapy for laryngeal cancer

Carew, J F; Shah, J P
Combined induction chemotherapy and external beam radiation therapy is an effective treatment for selected patients with advanced-stage laryngeal cancer. The larynx can be preserved in two-thirds of patients receiving this treatment. Investigations continue to evaluate the ideal treatment regimen, the delivery of chemotherapy, patient selection, biologic markers predicting response, functional outcome, and the effectiveness of this treatment at other sites
PMID: 9676535
ISSN: 0007-9235
CID: 137263

Regional lymph node metastasis from cutaneous squamous cell carcinoma

Kraus, D H; Carew, J F; Harrison, L B
OBJECTIVE: To characterize clinical presentation and prognostic factors in patients with histologically proven regional lymph node metastasis from cutaneous squamous cell carcinoma of head and neck origin. DESIGN: Retrospective, nonrandomized case series. SETTING: Tertiary referral center. PATIENTS: Forty-five patients treated between 1984 and 1995 with regional metastatic squamous cell carcinoma of cutaneous head and neck origin. INTERVENTION: Forty-one patients underwent neck dissection (20 with parotidectomy) and 4 patients underwent parotidectomy alone. Thirty-six patients (80%) received postoperative radiation therapy with a mean dose of 60 Gy (range, 34-71 Gy). MAIN OUTCOME MEASURES: Recurrences and survival by univariate analysis using the Kaplan-Meier product-limit method. The log-rank test was used to evaluate prognostic significance of clinical variables. RESULTS: Follow-up ranged from 2 months to 10 years (mean, 21 months). Compared with historical controls, a greater percentage of patients in our population with regional lymph node metastasis had primary lesions greater than 2 cm in diameter and 4 mm deep. Overall 2- and 5-year survival rates were 33% and 22%, respectively, while 5-year disease-free survival rate was 34%. Clinical staging of the neck proved to be the only factor of prognostic value (P<.01). Treatment failures occurred in 22 patients. CONCLUSIONS: For the small subset of patients with regional metastasis from cutaneous squamous cell carcinoma, survival remains poor despite multimodality treatment. Clinical stage of the neck was the only factor that predicted outcome
PMID: 9604987
ISSN: 0886-4470
CID: 137262