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.

Oncolytic herpesvirus effectively treats murine squamous cell carcinoma and spreads by natural lymphatics to treat sites of lymphatic metastases.

Oncolytic herpesviruses have significant antitumoral effects in animal models when delivered directly to established tumors. Lymphatic metastases are a common occurrence for many tumor types. This study investigates the potential of an attenuated, replication-competent, oncolytic herpes simplex virus (NV1023) both to treat a primary tumor by direct injection and to travel through the lymphatic system to treat metastatic tumor within the lymph nodes draining lymph from the site of primary cancer. Isosulfan blue dye was injected into murine auricles to determine normal lymphatic drainage patterns and demonstrated consistent blue staining of a group of ipsilateral cervical lymph nodes. Auricular injections of NV1023 resulted in viral transit to these lymph nodes as measured by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside histochemistry and viral plaque assay. An oncolytic herpesvirus (NV1066) expressing green fluorescent protein also demonstrated viral transit from the auricle to the cervical lymph nodes on fluorescence microscopy. Using the SCC VII cell line, a novel murine model of auricular squamous cell carcinoma was developed with an approximately 20% incidence of cervical lymph node metastases. Delivery of NV1023 or NV1066 to the surgical beds after excision of auricular SCC VII tumors resulted in successful viral infection of metastatic SCC VII cells within the cervical lymph nodes. After a 7-week follow-up, significantly enhanced locoregional control (p < 0.05, Fisher exact test) and disease-free survival (p < 0.05, log rank test) were evident with NV1023 treatment. This study demonstrates that the delivery of an oncolytic herpesvirus to a primary tumor site after surgical excision may have a significant impact on reducing both primary site recurrence and regional nodal metastases.

Ionizing radiation potentiates the antitumor efficacy of oncolytic herpes simplex virus G207 by upregulating ribonucleotide reductase.

BACKGROUND: Replication-competent herpes simplex virus-1 (HSV-1) mutants have an oncolytic effect on human and animal cancers. The aim of this study was to determine whether G207, an HSV-1 mutant, can be combined with ionizing radiation (IR) to increase antitumor activity while decreasing treatment-associated toxicity. METHODS: This study was performed by using G207, a replication-competent HSV-1 mutant deficient in viral ribonucleotide reductase (RR) and the gamma(1)34.5 neurovirulence protein. The antitumor activity of G207 or IR was tested against HCT-8 human colorectal cancer cells in vitro and in an in vivo mouse subcutaneous tumor model. RESULTS: We demonstrated that G207 has significant oncolytic effect on HCT-8 cells in vitro in a cytotoxicity assay and in vivo in a mouse flank tumor model and that these effects are improved with low-dose IR. We further illustrated that the increased tumoricidal effect is dependent on the up-regulation of cellular RR by IR measured by a functional bioassay for RR activity. Chemical inhibition of RR by hydroxyurea abrogates the enhanced effect. In contrast to G207, R3616, the parent virus of G207 that expresses functional RR, does not exhibit enhanced oncolysis when combined with IR. CONCLUSIONS: These data encourage clinical investigation of combination radiation therapy and HSV oncolytic therapy.

Septectomy and septal dermoplasty for the treatment of severe transfusion-dependent epistaxis in patients with hereditary hemorrhagic telangiectasia and septal perforation.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by abnormal angiogenesis with resultant telangiectasia formation in mucocutaneous tissues, visceral organs, and the central nervous system. The most common manifestation of HHT is epistaxis resulting from trauma to thin-walled telangiectasias. Many patients with HHT experience worsened epistaxis due to the presence of a septal perforation. Septal perforation in HHT patients results from aggressive noncartilage sparing treatments such as monopolar cauterization. Although the mainstay of treatment for patients with severe transfusion-dependent HHT remains to be septal dermoplasty (SD), patients with a septal perforation are less likely to have a successful outcome. In this small subset of patients, septectomy (ST) combined with SD is proposed to eliminate this variable to improve skin graft uptake and therefore outcome. This study reviews the indications, procedure, and outcome of nine patients with severe transfusion-dependent HHT and septal perforation who underwent the combined procedure of SD/ST. METHODS: Nine HHT patients with severe transfusion-dependent epistaxis and septal perforation underwent SD/ST at our institution over a 5-year period. Quality of life, including number of daily events of epistaxis, and transfusion requirements were determined before and after surgery. Technical aspects of the procedure as well as complications were reviewed. RESULTS: The combined procedure of SD/ST resulted in a long-lasting subjective improvement in quality of life for all patients. Similarly, transfusion requirements were reduced from 22.61 to 9.57 (p < 0.05). There were no complications or increased morbidity from the procedure. CONCLUSION: Combined SD/ST is a safe and effective treatment for HHT patients with transfusion-dependent epistaxis and septal perforation.

Postoperative concurrent chemoradiotherapy with mitomycin in advanced squamous cell carcinoma of the head and neck: results from three prospective randomized trials.

UNLABELLED: Recent prospective randomized trials have shown concurrent chemoradiotherapy improves locoregional control in postoperative patients with squamous cell carcinoma of the head and neck using cisplatin-based regimes. This report presents data pooled from three randomized trials employing mitomycin, selecting those patients treated postoperatively, to evaluate the long-term benefit of mitomycin in the postoperative setting and to compare these results with those of two other recently published randomized trials. METHODS AND MATERIALS: Between 1980 and 1999, a total of 331 patients with squamous cell carcinoma of the head and neck from the three prospective trials were enrolled. Of the 205 postoperative patients in these trials, 103 were randomized to receive mitomycin and radiation, while 102 received radiation alone or radiation with porfiromycin in the third trial. Patients were treated with standard daily radiotherapy to a total median dose of 60 Gy over 47 days. Patients who were randomized to mitomycin C received 15 mg/m2 of the drug on days 5 and 47 (or last day). RESULTS: The 5-year rate of locoregional control was higher in the mitomycin arms. There was no statistically significant difference in the rates of overall survival or distant metastasis. Patients had a lower percentage of high-risk factors in both arms of the study, compared with patients in the large prospective trials, including positive margins, two or more positive lymph nodes, or oropharynx primary tumors. The gains in locoregional control realized with mitomycin were similar to the improvements in the recently published randomized trials using platinum. CONCLUSIONS: These results confirm significant gains in locoregional control using concurrent chemoradiotherapy in the postoperative setting for patients with squamous cell carcinoma of the head and neck. The lack of consensus over a benefit in the rates of overall survival and distant metastasis emphasizes the need for further prospective trials in the postoperative management of squamous cell carcinoma of the head and neck.

Presence of a tracheotomy tube and aspiration status in early, postsurgical head and neck cancer patients.

BACKGROUND: We sought to investigate the effects, if any, that the presence of a tracheotomy tube has on aspiration status in early, postsurgical head and neck cancer patients. METHODS: Twenty-two consecutive adult, postoperative head and neck cancer patients were prospectively evaluated with fiberoptic endoscopic evaluation of swallowing (FEES) under three conditions: (1) tracheotomy tube present, (2) tracheotomy tube removed and tracheostoma covered with gauze sponge; and (3) tracheotomy tube removed and tracheostoma left open and uncovered. For each condition, the endoscope was first inserted transnasally to determine aspiration status during FEES and then inserted through the tracheostoma to corroborate aspiration status by examining the distal trachea inferiorly to the carina. Three experienced examiners determined aspiration status under each condition and endoscope placement. RESULTS: There was 100% agreement on aspiration status between FEES results and endoscopic examination through the tracheostoma. Specifically, 13 of 22 patients (59%) swallowed successfully and nine of 22 (41%) aspirated. There was also 100% agreement on aspiration status for tracheotomy tube present, decannulation and tracheostoma covered by gauze sponge, and decannulation and tracheostoma left open and uncovered. CONCLUSIONS: Neither presence of a tracheotomy tube nor decannulation affected aspiration status in early, postsurgical head and neck cancer patients. The clinical impressions that a tracheotomy or tracheotomy tube increases aspiration risk or that decannulation results in improved swallowing function are not supported. Rather, need for a tracheotomy indicates comorbidities (eg, respiratory failure, trauma, stroke, advanced age, reduced functional reserve, and medications used to treat the critically ill) that by themselves predispose patients for dysphagia and aspiration.

Salivary gland neoplasms.

Treatment and cure of salivary gland neoplasms requires surgical intervention in most cases. For parotid neoplasms, the most common surgical procedure performed is the superficial parotidectomy with facial nerve preservation. Postoperative radiation therapy is indicated in high-grade salivary gland malignancies and malignancies with increased risk of locoregional recurrence. Primary radiation, including neutron beam techniques, may play a role in certain histologic types or nonoperative candidates. Chemotherapy has yet to result in improvements in survival or quality of life in the treatment of salivary gland malignancy. Advances in radiation therapy techniques, including intensity-modulated radiation therapy, provide opportunities for reduced morbidity.

Oral cancer treatment.

Oral cancer is the sixth most common cancer in the world, and it continues to represent a serious public health problem. Oral cancer is a preventable disease, related to behavioral and lifestyle factors, including tobacco and alcohol. Prevention and early detection of oral cancer remain the goals of national efforts to reduce the impact of this disease on the public. Surgical treatment is the mainstay of therapy for patients with oral cancer, particularly in advanced stages of cancer. External beam radiation therapy and brachytherapy have been used successfully as the primary modality for treating patients with early stage oral cancer, and they are the standard of care for use as adjuvant therapy in postoperative cases of patients with advanced stage oral cancer. There is an emerging trend for the use of chemotherapy in combination with radiation therapy and surgery for patients with advanced, recurrent, and metastatic head and neck cancer, although evidence is limited regarding survival benefit when used for treating patients with oral cavity carcinoma. Any report on the treatment of oral cancer is incomplete without consideration of functional and aesthetic outcomes, particularly addressing speech, swallowing, masticatory efficiency, and dental rehabilitation. Future generations will continue to fight these dreadful diseases until scientists and clinicians are provided the opportunities to expand efforts to prevent, detect (early), and eradicate oral and other head and neck cancers.