Urjeet A. Patel

Impact of Pharyngeal Closure Technique on Fistula After Salvage Laryngectomy

IMPORTANCE No consensus exists as to the best technique, or techniques, to optimize wound healing, decrease pharyngocutaneous fistula formation, and shorten both hospital length of stay and time to initiation of oral intake after salvage laryngectomy. We sought to combine the recent experience of multiple high-volume institutions, with different reconstructive preferences, in the management of pharyngeal closure technique for post-radiation therapy salvage total laryngectomy in an effort to bring clarity to this clinical challenge. OBJECTIVE To determine if the use of vascularized flaps in either an onlay or interposed fashion reduces the incidence or duration of pharyngocutaneous fistula after salvage laryngectomy compared with simple primary closure of the pharynx. DESIGN Multi-institutional retrospective review of all patients undergoing total laryngectomy after having received definitive radiation therapy with or without chemotherapy between January 2005 and January 2012, conducted at 7 academic medical centers. SETTING Academic, tertiary referral centers. PATIENTS The study population comprised 359 patients from 8 institutions. All patients had a history of laryngeal irradiation and underwent laryngectomy between 2005 and 2012. They were grouped as primary closure, pectoralis myofascial onlay flap, or interposed free tissue. All patients had a minimum of 4 months follow-up. MAIN OUTCOMES AND MEASURES Fistula incidence, severity, and predictors of fistula. RESULTS Of the 359 patients, fistula occurred in 94 (27%). For patients with fistula, hospital stay increased from 8.9 to 12.1 days (P < .001) and oral diet initiation was delayed from 10.5 days to 29.9 days (P < .001). Patients were grouped according to closure technique: primary closure (n = 99), pectoralis onlay flap (n = 40), and interposed free tissue (n = 220). Incidence of fistula with primary closure was 34%. For the interposed free flap group, the fistula rate was lower at 25% (P = .07). Incidence of fistula was the lowest for the pectoralis onlay group at 15% (P = .02). Multivariate analysis confirmed a significantly lower fistula rate with either flap technique. For patients who developed fistula, mean duration of fistula was significantly prolonged with primary closure (14.0 weeks) compared with pectoralis flap (9.0 weeks) and free flap (6.5 weeks). CONCLUSIONS AND RELEVANCE Pharyngocutaneous fistula remains a significant problem following salvage laryngectomy. Use of nonirradiated, vascularized flaps reduced the incidence and duration of fistula and should be considered during salvage laryngectomy.

Pectoralis myofascial flap during salvage laryngectomy prevents pharyngocutaneous fistula

OBJECTIVE: To determine the rate of pharyngocutaneous fistula after salvage laryngectomy and assess if pectoralis myofascial flap reinforcement over primary pharyngeal closure prevents pharyngocutaneous fistula. STUDY DESIGN: Case series with chart review. SETTING: Tertiary-care public hospital. SUBJECTS AND METHODS: This study included 43 patients undergoing total laryngectomy between 2003 and 2008. Pectoralis myofascial flap reinforcement of the pharyngeal closure during salvage laryngectomy was performed on patients after June 2006. The main outcome measure was pharyngocutaneous fistula after primary laryngectomy, salvage laryngectomy, and salvage laryngectomy with pectoralis flap reinforcement. RESULTS: Of the 43 patients, 26 were treated with primary total laryngectomy while 17 received salvage laryngectomy. Seven of 26 patients (27%) undergoing primary total laryngectomy developed pharyngocutaneous fistula. All patients in this group were closed primarily with no flap reinforcement. For salvage laryngectomy, four of seven patients (57%) with primary pharyngeal closure developed pharyngocutaneous fistula; however, none of 10 patients (0%) undergoing salvage laryngectomy with pectoralis myofascial flap reinforcement developed fistula (P < 0.02; 0%-23%; 95% CI). CONCLUSIONS: With pectoralis myofascial flap reinforcement, pharyngocutaneous fistula rate after salvage laryngectomy dropped to 0 percent in this study (0%-23%; 95% CI). This is a simple, reliable technique that prevents postoperative pharyngocutaneous fistula and its associated morbidity after salvage laryngectomy.

The submental flap: A modified technique for resident training

INTRODUCTION The submental artery flap has become increasingly popular since its introduction in 1993.1 In head and neck reconstruction, it possesses many advantages of the radial forearm flap in that it is thin, pliable, and a large surface area may be harvested. It may be used for extensive intraoral reconstruction, and when used for external facial defects, it provides a better color match than tissue harvested remotely. Although the submental flap can be harvested for free tissue transfer, it is most frequently used as a pedicled flap and does not require advanced microvascular skills. Several authors cite its final advantage as the ease of harvest and find the dissection safe and reliable.2,3 Although this holds true for the experienced reconstructive surgeon who is accustomed to small-vessel dissection, the submental flap harvest is more hazardous in the hands of a resident in training. Training residents in the art of head and neck reconstruction is a difficult task. Bhaya et al. examined otolaryngology resident training in head and neck reconstruction and found that residents would likely benefit from more complete training in a wider variety of pedicled flaps.4 Such training requires not only exposure to these surgeries, but also the technical skills to perform the necessary vessel dissections. The difficulty arises from trying to teach these skills without jeopardizing the reconstruction. In the classic technique, the submental flap is dissected off the mylohyoid muscle. In this area, the arteries supplying the flap are small and have numerous branches to surrounding structures outside of the flap territory that must be addressed with cautery or ligation. There may be only one reliable perforator off the submental artery that will ultimately supply the flap.5,6 If dissected imprecisely, these maneuvers can jeopardize the arterial supply to the flap that is otherwise robust. Accordingly, we have adopted a modified technique when training a resident surgeon to raise this flap. This involves an early proximal dissection of the submental vessels up to the mylohyoid muscle followed by inclusion of the mylohyoid muscle in the submental flap.

Molecular complexes that contain both c-Cbl and c-Src associate with Golgi membranes

Cbl is an adaptor protein that is phosphorylated and recruited to several receptor and non-receptor tyrosine kinases upon their activation. After binding to the activated receptor, Cbl plays a key role as a kinase inhibitor and as an E3 ubiquitin ligase, thereby contributing to receptor down-regulation and internalization. In addition, Cbl translocates to intracellular vesicular compartments following receptor activation. We report here that Cbl also associates with Golgi membranes. Confocal immunofluorescence staining of Cbl in a variety of unstimulated cells, including CHO cells, revealed a prominent perinuclear colocalization of Cbl and a Golgi marker. Both the prominent Cbl staining and the Golgi marker were dispersed by brefeldin A. Subcellular fractionation of CHO cells demonstrated that about 10% of Cbl is stably associated with membranes, and that Golgi-enriched membrane fractions produced by isopycnic density centrifugation and free-flow electrophoresis are also enriched in Cbl, relative to other membrane fractions. The membrane-bound Cbl was hyperphosphorylated and it co-immunoprecipitated with endogenous Src. By immunofluorescence, some Src colocalized with Cbl and Golgi markers, and Src, like Cbl, was present in the Golgi-enriched fraction prepared by sequential density centrifugation and free-flow electrophoresis. Transfection of an activated form of Src, but not wild-type Src, increased the amount of Src that co-immunoprecipitated with Cbl, and increased the intensity of Cbl staining on the Golgi. This result, together with the increased tyrosine phosphorylation of the membrane-associated Cbl, suggests that Golgi-associated Cbl could be part of a molecular complex that contains activated Src. The localization and interaction of Src and Cbl at the Golgi and the regulation of the interaction of Cbl with Golgi membrane suggest that this complex may contribute to the regulation of Golgi function.

Submental Island Pedicled Flap vs Radial Forearm Free Flap for Oral Reconstruction Comparison of Outcomes

OBJECTIVE To compare intraoperative, postoperative, and functional results of submental island pedicled flap (SIPF) against radial forearm free flap (RFFF) reconstruction for tongue and floor-of-mouth reconstruction. DESIGN Multi-institutional retrospective review. SETTING Academic tertiary referral center. PATIENTS Consecutive patients from February 2003 to December 2009 undergoing resection of oral tongue or floor of mouth followed by reconstruction with SIPF or RFFF. INTERVENTION Two groups: SIPF vs RFFF. MAIN OUTCOME MEASURES Duration of operation, hospital stay, surgical complications, and speech and swallowing function. RESULTS The study included 60 patients, 27 with SIPF reconstruction and 33 with RFFF reconstruction. Sex, age, and TNM stage were similar for both groups. Mean flap size was smaller for SIPF (36 cm²) than for RFFF (50 cm²) (P < .001). Patients undergoing SIPF reconstruction had shorter operations (mean, 8 hours 44 minutes vs 13 hours 00 minutes; P < .001) and shorter hospitalization (mean, 10.6 days vs 14.0 days; P < .008) compared with patients who underwent RFFF. Donor site, flap-related, and other surgical complications were comparable between groups, as was speech and swallowing function. CONCLUSIONS Reconstruction of oral cavity defects with the SIPF results in shorter operative time and hospitalization without compromising functional outcomes. The SIPF may be a preferable option in reconstruction of oral cavity defects less than 40 cm².

Disparities in head and neck cancer: Assessing delay in treatment initiation

Disparities in outcome for head and neck cancer (HNC) treatment are related to diverse factors including tumor stage, socioeconomic status, and treatment compliance. Latency to initiation of therapy may contribute to worse outcomes for underserved populations. The objectives of this study were to measure the interval from diagnosis of HNC to initiation of cancer treatment (DTI) and to identify factors that prolong DTI.

Phase II Study of Cetuximab in Combination with Cisplatin and Radiation in Unresectable, Locally Advanced Head and Neck Squamous Cell Carcinoma: Eastern Cooperative Oncology Group Trial E3303

Purpose: Treatment with cisplatin or cetuximab combined with radiotherapy each yield superior survival in locally advanced squamous cell head and neck cancer (LA-SCCHN) compared with radiotherapy alone. Eastern Cooperative Oncology Group Trial E3303 evaluated the triple combination. Experimental Design: Patients with stage IV unresectable LA-SCCHN received a loading dose of cetuximab (400 mg/m2) followed by 250 mg/m2/week and cisplatin 75 mg/m2 q 3 weeks ×3 cycles concurrent with standard fractionated radiotherapy. In the absence of disease progression or unacceptable toxicity, patients continued maintenance cetuximab for 6 to 12 months. Primary endpoint was 2-year progression-free survival (PFS). Patient tumor and blood correlates, including tumor human papillomavirus (HPV) status, were evaluated for association with survival. Results: A total of 69 patients were enrolled; 60 proved eligible and received protocol treatment. Oropharyngeal primaries constituted the majority (66.7%), stage T4 48.3% and N2-3 91.7%. Median radiotherapy dose delivered was 70 Gy, 71.6% received all three cycles of cisplatin, and 74.6% received maintenance cetuximab. Median PFS was 19.4 months, 2-year PFS 47% [95% confidence interval (CI), 33%–61%]. Two-year overall survival (OS) was 66% (95% CI, 53%–77%); median OS was not reached. Response rate was 66.7%. Most common grade ≥3 toxicities included mucositis (55%), dysphagia (46%), and neutropenia (26%); one attributable grade 5 toxicity occurred. Only tumor HPV status was significantly associated with survival. HPV was evaluable in 29 tumors; 10 (all oropharyngeal) were HPV positive. HPV+ patients had significantly longer OS and PFS (P = 0.004 and P = 0.036, respectively). Conclusions: Concurrent cetuximab, cisplatin, and radiotherapy were well tolerated and yielded promising 2-year PFS and OS in LA-SCCHN with improved survival for patients with HPV+ tumors. Clin Cancer Res; 20(19); 5041–51. ©2014 AACR.

Patient Compliance to Radiation for Advanced Head and Neck Cancer at a Tertiary Care County Hospital

Background: Combined chemotherapy and radiotherapy are routinely used to treat advanced‐stage head and neck squamous cell carcinoma (HNSCC). Patient compliance is often difficult given increased toxicities. Medically underserved or uninsured patients may lack the necessary support to complete such treatment.

Advanced Stage of Head and Neck Cancer at a Tertiary‐Care County Hospital

Background: Public hospitals provide health care for uninsured and medically underserved patients in large metropolitan areas. Outcomes for head and neck cancer patients within this population are perceived as being worse than outcomes for the general population, perhaps because of advanced stage at presentation.

Flap outcomes when training residents in microvascular anastomosis in the head and neck.

OBJECTIVE Microvascular anastomosis is generally performed by attending surgeons or fellows, with published success rates >95%. Since otolaryngology residents do not typically perform microvascular anastomosis, it is unknown if they achieve similar results. The objective of this study is to determine the success rate and complication rate during free flap reconstruction when microvascular anastomosis is performed in part by otolaryngology chief residents. STUDY DESIGN Multi-institutional retrospective review. SETTING Academic, tertiary-care referral centers. SUBJECTS AND METHODS Consecutive patients who underwent microvascular reconstruction by the Department of Otolaryngology from 2004 through 2011. All patients had >50% of the arterial and venous anastomoses performed by the chief resident. RESULTS The study included 93 consecutive free flaps in 88 patients: 43 radial forearm, 14 anterolateral thigh, and 36 fibula. There were 71 males and 22 females with mean age of 53. The pre-operative diagnosis was squamous cell carcinoma in 78%, with 27% of patients having previously received radiotherapy and 13% of patients having had previous neck surgery. There were no instances when resident-placed sutures required revision, nor was there a perceived need to revise such an anastomosis intraoperatively. Overall flap success rate was 97%. The anastomotic complication rate was 4.3%, with venous thrombosis in three cases and arterial hemorrhage in one case. CONCLUSION Overall free flap success rate and anastomosis-related complications with residents performing portions of the microvascular anastomosis are comparable to published studies. Otolaryngology chief residents can safely participate in microsuturing, which is a single facet in the broader skill set of a microvascular surgeon.