Transoral lateral oropharyngectomy.

Based on a review of the indexed scientific medical literature, the authors document the key technical points, the errors to avoid, the limitations, indications and main oncologic and functional results when performing transoral lateral oropharyngectomy in cancer originating from the tonsillar region.

Injection augmentation of arytenoids after partial laryngectomy: case series.

BACKGROUND: We undertook collagen injection laryngoplasty to achieve arytenoid augmentation in patients with dysphagia and persistent aspiration following partial laryngectomy, and we evaluated the efficacy of arytenoid augmentation in aiding neoglottic closure and ensuring airway safety. METHODS: Two patients with persistent swallowing impairment after partial laryngectomy were studied. Swallowing was evaluated using fibre-optic endoscopy, and modified barium swallow study. Collagen was then injected into the arytenoid mucosa to achieve neoglottic competence. RESULTS: The patients were followed up for up to two years. Both patients showed a marked improvement in neoglottic competence, as evaluated by fibre-optic and flexible endoscopy at three-month and one-year follow-up appointments. CONCLUSION: Arytenoid augmentation by injection laryngoplasty can be considered a safe and effective surgical tool for the treatment of dysphagia with persistent aspiration following partial laryngectomy.

Evidence for mesenchymal-like sub-populations within squamous cell carcinomas possessing chemoresistance and phenotypic plasticity.

Variable drug responses among malignant cells within individual tumors may represent a barrier to their eradication using chemotherapy. Carcinoma cells expressing mesenchymal markers resist conventional and epidermal growth factor receptor (EGFR)-targeted chemotherapy. In this study, we evaluated whether mesenchymal-like sub-populations within human squamous cell carcinomas (SCCs) with predominantly epithelial features contribute to overall therapy resistance. We identified a mesenchymal-like subset expressing low E-cadherin (Ecad-lo) and high vimentin within the upper aerodigestive tract SCCs. This subset was both isolated from the cell lines and was identified in xenografts and primary clinical specimens. The Ecad-lo subset contained more low-turnover cells, correlating with resistance to the conventional chemotherapeutic paclitaxel in vitro. Epidermal growth factor induced less stimulation of the mitogen-activated protein kinase and phosphatidylinositol-3-kinase pathways in Ecad-lo cells, which was likely due to lower EGFR expression in this subset and correlated with in vivo resistance to the EGFR-targeted antibody, cetuximab. The Ecad-lo and high E-cadherin subsets were dynamic in phenotype, showing the capacity to repopulate each other from single-cell clones. Taken together, these results provide evidence for a low-turnover, mesenchymal-like sub-population in SCCs with diminished EGFR pathway function and intrinsic resistance to conventional and EGFR-targeted chemotherapies.

Feasibility and outcome of endoscopic staple-assisted esophagodiverticulostomy for Zenker's diverticulum.

OBJECTIVES/HYPOTHESIS: Endoscopic staple-assisted esophagodiverticulostomy (ESED) is a newly described method of surgically correcting Zenker's diverticulum. Initial reports on the ease and success of the surgery have been quite enthusiastic, making it seem the procedure of choice. We initiated the procedure in an algorithm of treatment of Zenker's diverticulum, to further explore the feasibility and outcome of this new technique. STUDY DESIGN: This is a case series of 23 patients with Zenker's diverticulum who have undergone surgical repair. For each patient, an attempt at ESED was made. If unsuccessful, an open approach was then taken. RESULTS: Seven of 23 patients (30%) were unable to be treated with ESED because of inability to expose the diverticulum or unfavorable anatomy of the diverticulum itself. Of the remaining 16 patients, ESED was successful in resolving the symptoms of diverticulum in 14 (87%). Two patients (13%) were somewhat improved but had persistent dysphagia. No significant complications occurred. All patients resumed oral diet within the first 24 hours after surgery. CONCLUSION: Esophagodiverticulostomy is an excellent method of surgically correcting Zenker's diverticulum in many patients, but anatomical considerations may prevent its use, making open approaches of continued importance in a surgeon's armamentarium.

Advanced oropharyngeal carcinoma treated with surgery and radiotherapy: oncologic outcome and functional assessment.

INTRODUCTION/PURPOSE: Surgery and postoperative radiotherapy (XRT) is a standard therapy for locally advanced resectable oropharyngeal carcinoma. This maximizes local-regional control, but does not address the potential for occult distant metastases. Additionally, some patients may suffer poor functional outcome after this intensive local therapy. This report reviews our institutional experience with modern radical surgery and XRT for this disease. METHODS: A retrospective chart review was performed on 51 consecutive patients treated from 1991 to 1997 at the University of Pennsylvania with radical surgery and postoperative XRT. This study included patients with locally advanced, stage III/IV (exclusive of T1-2N1) squamous carcinoma of the oropharynx. All patients had a good performance status (ECOG 0-1). Patients who received adjuvant chemotherapy were excluded. No patient had gross residual disease after surgery; the median XRT dose was 63.7 Gy. Survival, local-regional control (LRC), and freedom from distant metastases (DM) were calculated actuarially. In patients who remained free of disease, functional status was determined using the List Performance Status Scale (PSS). RESULTS: With a median follow-up in surviving patients of 34 months, the 3-year actuarial overall survival was 51%. The 3-year LRC was 73%, and the freedom from DM was 69%. The most significant factor predicting for failure was the number of pathologically positive nodes (P <.001 for survival and DM; P =.003 for LRC). In 29 patients who were evaluable for the List PSS, the mean normalcy-of-diet score was 48; the mean eating-in-public score was 53; and the mean understandability-of-speech score was 75. There was a trend toward better PSS scores in patients with T1-2 tumors versus T3-4 tumors, although this did not reach statistical significance. CONCLUSIONS: Surgery and postoperative XRT offer relatively good LRC and moderate overall survival rates. Results, however, remain suboptimal, particularly with respect to the risk of DM and the functional outcome. These data provide a baseline for comparison with maturing results from multimodality trials in which radical surgery is not used in all patients with locally advanced oropharyngeal carcinoma.

Surgical approach to organ preservation in the treatment of cancer of the larynx.

Nonsurgical approaches to preservation of the larynx in the treatment of laryngeal carcinoma include either radiation alone or chemotherapy and radiation in combination. In light of the common use of total laryngectomy, these nonsurgical approaches have often been referred to as "organ-preservation" strategies. Within the context of this old paradigm, clinicians viewed surgery as offering the patient local control, with the caveat that the price would either be the loss of the larynx or the creation of a disability in swallowing or speech. Over the last 10 years, there has been a renaissance in the surgical approaches to laryngeal preservation, as evident in the surgical literature. A new paradigm has emerged in which both the surgical and nonsurgical approaches have equal value in laryngeal organ preservation. Today, a broad spectrum of surgical organ-preservation techniques are available that result in excellent oncologic outcomes as well as excellent and consistent functional outcomes in terms of speech and swallowing. The aim of this article is to present the options for organ-preservation surgery for laryngeal cancer.

Internal jugular vein versus external jugular vein anastamosis: implications for successful free tissue transfer.

BACKGROUND: Microvascular free flaps are becoming the reconstructive option of choice for many head and neck defects. Many previous studies have examined factors predicting free flap survival. No study has compared differences in free flap survival when anastomosed to the internal or external jugular systems. METHODS: Retrospective review of all free flaps performed at an academic medical center by a single head and neck microvascular surgeon during the period July 1995 to December 1999. Flaps were closely monitored postoperatively and taken back to the operating room urgently for arterial insufficiency or venous congestion. RESULTS: On hundred fifty-six free flaps were performed during this time period. Sixty-five free flaps were anastomosed to the external jugular (EJ) vein and 86 to the IJ system (62 to the proximal common facial vein, 17 end-side on the IJ, and 7 to other branches). Five had either two venous anastomoses or were anastomosed to other veins and were excluded from statistical analysis. Six (4%) vascular thromboses occurred; 5 were venous and 1 arterial. Success by group was 99% for IJ anastomosis (1 arterial thrombosis) and 92% for EJ anastomosis (5 venous thromboses, p =.03). Urgent anastomotic revision and reperfusion salvaged 5 of the 6 flaps (overall success 99%). CONCLUSIONS: Although the overall success rate (96% success with 99% success with salvage) is comparable to other large series, microvascular free flaps anastomosed to the external jugular vein failed at a significantly higher rate than those anastomosed to the IJ system. This suggests that the IJ system should be used as a recipient vessel when feasible.

Phase I study of paclitaxel given by seven-week continuous infusion concurrent with radiation therapy for locally advanced squamous cell carcinoma of the head and neck.

PURPOSE: Paclitaxel is one of the most active agents for squamous cell carcinoma of the head and neck (SCCHN) and an in vitro radiosensitizer. The dose-response relationship for paclitaxel may depend more on exposure duration than on peak concentration. This National Cancer Institute-sponsored phase I trial was designed to determine the feasibility of combining continuous-infusion (CI) paclitaxel with concurrent radiation therapy (RT). PATIENTS AND METHODS: Patients with previously untreated stage IVA/B SCCHN were eligible. Primary end points were determination of the maximum-tolerated dose, dose-limiting toxicity, and pharmacokinetics for paclitaxel given by CI (24 hours a day, 7 days a week for 7 weeks) during RT (70 Gy/7 weeks). RESULTS: Twenty-seven patients were enrolled and assessable for toxicity. Nineteen of the patients who completed > or = 70 Gy were assessable for response. Grade 3 skin and mucosal acute reactions occurred at 10.5 mg/m(2)/d, but uninterrupted treatment was possible in five of six patients. At 17 mg/m(2)/d, skin toxicity required a 2-week treatment break for all three patients. The mean paclitaxel serum concentration at dose levels > or = 6.5 mg/m(2)/d exceeded that reported to achieve in vitro radiosensitization. Initial locoregional control was achieved in 14 (58%) of 24 of patients treated to 70 Gy, and control persisted in nine (38%). CONCLUSION: CI paclitaxel with concurrent RT is a feasible and tolerable regimen for patients with advanced SCCHN and good performance status. Preliminary response and survival data are encouraging and suggest that further study is indicated. The recommended phase II dose of paclitaxel by CI is 10.5 mg/m(2)/d with RT for SCCHN.

Radiotherapy with 6-megavolt photons for early glottic carcinoma: potential impact of extension to the posterior vocal cord.

PURPOSE: Radiation therapy has a high success rate in the treatment of early glottic carcinoma. Excellent outcomes have been reported from centers using cobalt-60 or relatively low-energy (< or = 4 MV) radiation therapy to achieve these results. Whether similar outcomes can be achieved with a 6 MV linear accelerator has been less rigorously evaluated. This study assesses the efficacy of 6 MV radiation therapy for early stage glottic cancer and identifies prognostic factors for local control and overall survival in this common disease. MATERIALS AND METHODS: One hundred twenty-eight consecutive cases of Tis, T1, and T2 squamous cell carcinomas of the glottis from 1982 to 1996 were retrospectively analyzed with regard to local control and survival. All patients were treated with definitive radiation therapy with a 6-MV linear accelerator. Potential prognostic factors for local control and survival were evaluated with univariate and multivariate models. Median follow-up of locally controlled patients was 65 months. RESULTS: The overall 3-year actuarial local control rates for T1 and T2 carcinomas were 86% and 68%, respectively. Patients with lesions involving the posterior third of the vocal cord had significantly worse 3-year local control (76% vs. 86%, P =.038). Radiation therapy technique and overall treatment time did not significantly affect local control. For patients with Tis and T1 lesions, factors associated with significantly worse local control included cordectomy-ineligible disease (P =.024), dose less than 6,600 cGy (P =.024), and lesions limited to the posterior third of the vocal cord (P =.004). Three-year local control was 76%, with doses less than 6,600 cGy and 90% with higher doses. High rates of second primary malignancies were observed and represented the major cause of death. Five-year overall survival was 84%. CONCLUSIONS: The use of 6-MV photons for treatment of early glottic cancer seems to achieve local control similar to that reported with lower-energy photons. However, patients with posterior third involvement had a poorer local control rate with standard radiation therapy, thereby suggesting that alternative approaches be considered.

Left hemispheric strokes in coronary surgery: implications for end-hole aortic cannulas.

BACKGROUND: Perioperative stroke (POS) is a devastating complication of coronary artery bypass grafting (CABG). Many studies have been published concerning risk factors and possible causes of POS but none have studied which side of the brain is more frequently involved. The finding of a strong preponderance of left-sided strokes calls into question some widely held theories as to the cause of POS and implicates end-hole aortic perfusion catheters as a major factor. METHODS: During a 3-year period (1996 to 1998), prospective data were collected on all 2,217 consecutive CABG patients at one hospital (with surgery by different surgeons in different groups). Strokes were classified as perioperative (within 3 days of surgery) or late (beyond 3 days but during hospitalization). RESULTS: There were a total of 51 strokes (2.3%): 21 left, 10 right, 7 bilateral, 7 lacunar, 1 brainstem, and 5 indeterminate. There were 18 major territorial perioperative strokes on the left side and 6 on the right side. Thus, 75% (18 of 24) of POS were left-sided. Stroke patients were significantly younger than nonstroke patients (66.3 +/- 10.52 versus 71.4 +/- 8.47 years, p = 0.009). Other demographic data did not differ significantly. CONCLUSIONS: If aortic clamping, cannulation, or manipulation were responsible for most strokes, then right-sided strokes should predominate, as the innominate artery is closest to the source of such emboli. In contrast, end-hole aortic cannulas direct a high-velocity jet at the left carotid orifice and may be responsible for a large proportion of POS. Side-hole aortic cannulas may reduce the incidence of this complication.

Laryngeal preservation with supracricoid partial laryngectomy results in improved quality of life when compared with total laryngectomy.

OBJECTIVES/HYPOTHESES: Study 1: To assess the oncologic outcome following supracricoid partial laryngectomy (SCPL). Study 2: To compare the quality of life (QOL) following SCPL to total laryngectomy (TL) with tracheoesophageal puncture (TEP). Study 3: To analyze whole organ TL sections to determine the percentage of lesions amenable to SCPL STUDY DESIGN: Study 1: A retrospective review of patients who underwent SCPL. Study 2: A non-randomized, prospective study using QOL instruments to compare patients who underwent either SCPL or TL Study 3: A retrospective histopathologic study of TL specimens assessed for the possibility of performing an SCPL. METHODS: Study 1: Twenty-five patients with carcinoma of the larynx underwent SCPL between June 1992 and June 1999. Various rates of oncologic outcome were calculated. Study 2: Thirty-one patients participated in the QOL assessment. This included the SF-36 general health status measure, the University of Michigan Head and Neck Quality of Life (HNQOL) instrument, and the University of Michigan Voice-Related Quality of Life (VRQOL) instrument. Study 3: Ninety surgical specimens were obtained and studied from the total laryngectomy cases in the Tucker Collection. Multiple sites were evaluated for the presence of carcinoma A computer program was written to classify whether the patient was amenable to SCPL. RESULTS: Study 1: The overall local control rate was 96% (24/25). The local control rate following SCPL with cricohyoidoepiglottopexy (CHEP) was 95% (20/21). The local control rate following SCPL with cricohyoidopexy (CHP) was 100% (4/4). Study 2: The SCPL had significantly higher domain scores than TL and TEP in the following categories for the SF-36: physical function, physical limitations, general health, vitality, social functioning, emotional limitations, and physical health summary. The significantly higher domains for the SCPL when compared with the TL and TEP for the HNQOL were eating and pain. Finally, when voice-related QOL was assessed with the V-RQOL, the domains of physical functioning and the total score were significantly better with SCPL when compared with TL and TEP. Study 3: Forty of 90 (44%) laryngeal whole organ specimens were determined to be resectable by SCPL. In 16 (18%) specimens, the patients could have undergone SCPL with CHEP and in 24 (27%) specimens the patients could have undergone SCPL with CHP. Among the 40 (44%) specimens determined to be able to have undergone SCPL, 19 were glottic (1 T1, 15 T2, 3 T3) and 21 were supraglottic (9 T2, 12 T3). CONCLUSIONS: 1) A review of the literature and an analysis of the data in this study indicate that excellent local control may be expected following SCPL. 2) The QOL following SCPL, as measured by three validated QOL instruments, is superior to TL with TEP. 3) A histologic assessment of whole organ sections of TL specimens indicates that many patients who have been subjected to TL may have been candidates for SCPL. 4) If the indications and contraindications are rigorously adhered to, SCPLs are reasonable alternatives to TL in selected cases.

Pilot study of organ preservation multimodality therapy for locally advanced resectable oropharyngeal carcinoma.

The purpose of this study was to determine the early efficacy and toxicity of a new multimodality organ-preservation regimen for locally advanced, resectable oropharyngeal squamous cell carcinoma (SCC). Patients with T3-4N0-3M0 or T2N2-3M0 oropharyngeal SCC were eligible for this Phase II study. Patients needed the physiologic reserve for surgery and technically resectable tumors. Induction carboplatin (area under the curve = 6) and paclitaxel (200 mg/m2) x 2 cycles (q21 days) were given. Objective responders received definitive radiotherapy (XRT), 70 Gy/7 weeks with concurrent weekly paclitaxel. Initially, the dose of paclitaxel was 50 mg/m2/week; because of mucosal toxicity it was reduced to 30 mg/m2/week. Patients with N2-3 disease received post-XRT neck dissection and 2 more cycles of "adjuvant" chemotherapy. In the first 22 patients, the neutropenic fever rate was 27%. Although there has been no grade IV-V toxicity from induction therapy, grade II-III toxicity resulted in an unacceptable delay in starting XRT in 14% of patients. The response rate to induction chemotherapy was 91%. Grade III mucositis occurred in all patients during concurrent chemoradiotherapy. One patient died of pneumonia during concurrent chemoradiotherapy after receiving 26 Gy and 3 doses of paclitaxel 50 mg/m2. No dose-limiting toxicity occurred in 15 patients treated with concurrent paclitaxel 30 mg/m2/week. Actuarial overall survival at 18 months is 82%; local-regional control is 86%. To date, distant metastases have not developed in any patients. This regimen has intense but acceptable acute toxicity. The maximum tolerated dosage of weekly paclitaxel during standard continuous-course XRT is confirmed to be 30 mg/m2/week. The treatment efficacy of this regimen (response rate and short-term local-regional and distant control) is encouraging. Accrual continues to obtain long-term toxicity, efficacy, and quality-of-life data.

Morbidity after midline mandibulotomy and radiation therapy.

PURPOSE: To assess the morbidity of mandibulotomy in patients treated for neoplasms of the oropharynx and oral cavity, and to determine if postoperative radiation therapy to the mandibulotomy site carries an increased risk of complications. PATIENTS AND METHODS: The medical charts of 30 patients treated between 1992 and 1996 undergoing midline mandibulotomy for tumors of the oral cavity (7 patients) and oropharynx (23 patients) were retrospectively reviewed. Three patients presented with recurrent disease, 1 of whom was previously irradiated. Twenty-five patients received postoperative radiation after mandibulotomy to a median dose of 60 Gy to the primary tumor bed, whereas 5 patients were treated with surgery alone. The patients were separated into those whose mandibulotomy site was within the radiation treatment field (n = 9), and those whose site was shielded (n = 10). Median follow-up was 27.8 months (range 5-81 months). End points included significant pain involving the mandibulotomy site, trismus, malocclusion, wound infection, osteoradionecrosis, and time to oral intake. RESULTS: There were no postoperative deaths. Minor wound infection or breakdown occurred in 4/30 patients (13%). All of these resolved with local care and parenteral antibiotics. More serious complications involving the mandibulotomy occurred in 2 patients (7%). One patient had chronic wound drainage at the mandibular osteotomy site, which healed after plate removal. Another patient developed osteoradionecrosis. No patient developed trismus or malocclusion. With a median follow-up of 27.8 months, 4 patients have recurred locally. The complication rate was 11% for patients whose mandibulotomy site was irradiated, and 30% for those whose site was shielded. CONCLUSION: Mandibulotomy can be safely performed in patients who are likely to require postoperative external radiation.

Clinical care pathways: decreasing resource utilization in head and neck surgical patients.

In this era of decreasing reimbursement, health systems have been forced to become more efficient and decrease resource utilization to remain financially viable. One of the methods of internal cost control has been the use of clinical pathways. Given the complexity of treatment of head and neck cancer patients, clinical pathways can help to standardize decision making and introduce uniformity in resource utilization. The objective of this study is to compare resource utilization and outcomes before and after implementation of a clinical pathway for head and neck surgical patients. We observed significant decreases in hospital costs as well as shorter lengths of stay after pathway implementation. It is our belief that a uniform management tool is beneficial in this complex disease.

Detection of recurrent head and neck squamous cell carcinomas after radiation therapy with 2-18F-fluoro-2-deoxy-D-glucose positron emission tomography.

OBJECTIVES/HYPOTHESIS: Fluorodeoxyglucose positron emission tomography (FDG-PET) has been proposed as a sensitive method to diagnose and stage various malignancies. We assessed the efficacy of FDG-PET imaging in distinguishing tumor persistence/recurrence from posttreatment changes following radiation therapy for squamous carcinomas of the head and neck STUDY DESIGN: Retrospective analysis of FDG-PET results compared with biopsy results or outcome, or both. METHODS: Twenty-eight patients who had undergone radiation therapy with or without surgery for treatment of squamous cell carcinoma were studied with FDG-PET imaging. There was clinical suspicion for recurrence in each patient, but no obvious mass or lesion to biopsy was found on physical examination or anatomic imaging. The results of FDG-PET imaging were compared with those of biopsy or clinical follow-up of at least 6 months, or both. RESULTS: FDG-PET imaging was positive in 13 patients, and the presence of active disease was confirmed in 12. Two thirds of the 12 received further cancer treatment. There were 15 negative FDG-PET images. Thirteen of these were confirmed true-negative images, but two studies were false-negative images. The sensitivity and specificity of FDG-PET were 86% and 93%, respectively, with positive and negative predictive values of 92% and 87%, respectively. The overall accuracy was 89%. CONCLUSION: FDG-PET imaging is a useful modality to distinguish tumor persistence/recurrence from radiation-induced tissue changes in the neck following treatment for head and neck cancer. FDG-PET can identify patients who may benefit from further treatment, and may lead to improved outcome for individual patients.

Nerve cell adhesion molecule expression in squamous cell carcinoma of the head and neck: a predictor of propensity toward perineural spread.

OBJECTIVE: To evaluate head and neck squamous cell carcinomas (SCCAs) for the expression of nerve cell adhesion molecule (N-CAM). We propose that expression of N-CAM by tumor cells may be associated with perineural invasion in SCCA of the head and neck. METHODS: Seventy-six archived specimens of histologically proven SCCA were analyzed by immunohistochemistry for the expression of N-CAM. Positive and negative controls were used to assess staining. Two sections of each specimen were reviewed for the presence of perineural invasion. A retrospective chart review was performed for each patient that corresponded to the above specimens. RESULTS: Perineural invasion was present in 28 (37%) of the 76 patients evaluated for the expression of N-CAM. N-CAM expression was demonstrated in 38 (50%) of the 76 specimens. The incidence of N-CAM expression was significantly associated with perineural invasion (P = .002). There was no significant association between the presence of staining or the presence of perineural invasion and the incidence of locoregional recurrence, distant metastasis, or survival status; however, the mean follow-up was only 13.6 months (range, 1-49 mo). CONCLUSION: There is a positive correlation between the presence of N-CAM expression and perineural invasion in SCCA of the head and neck. The expression of this adhesion molecule by tumor cells may facilitate both homophilic cell-to-cell and heterophilic cell-to-substrate adhesion, thereby enabling the tumor cells to use the perineural tissues or neural cells, or both as a conduit for perineural spread.