Bone resection for facial cutaneous malignancies.

BACKGROUND AND OBJECTIVES: The aim of this study is to analyze the clinical outcomes of patients who underwent bone resection for cutaneous malignancy of the face and scalp. METHODS: We retrospectively collected patient data from 62 patients who underwent bone resection for craniofacial cutaneous malignancy of the face and scalp over the last 10 years. We investigated risk factors for disease progression and assessed the utility of pre-operative imaging to predict bone, dura, and brain infiltration. RESULTS: Out of all factors analyzed, brain invasion, surgical margin involvement, and dural margin involvement were found to significantly reduce survival. CT and MRI correctly predicted bone infiltration in 88% and 89% of cases. MRI correctly predicted dura invasion in 89% but grossly underestimated the amount of dural invasion in 23% of reports. CONCLUSIONS: Our data indicate that the resection of bone is a reasonable surgical option in the treatment of patients with advanced cutaneous malignancies of the face and scalp. Brain invasion and positive margins reduced the probability of survival.

Factors predicting poor outcomes in T1N0 oral squamous cell carcinoma: indicators for treatment intensification.

BACKGROUND: This study investigated the impact of adverse pathological features (APFs) amongst patients with T1N0 oral squamous cell carcinoma (OSCC) on both tumour control and survival. We aimed to investigate clinicopathological factors that would predict poor outcomes and determine a clinically relevant threshold for the recommendation of additional treatment. METHODS: Retrospective analysis of 121 patients from a single institution (1988-2013) who were treated with surgery only (wide local excision of the primary tumour with or without neck dissection). Only patients who are pT1cN0 or pT1pN0 were included. Patients who had received adjuvant radiotherapy were excluded from the study. RESULTS: APFs were associated with increased regional failure included tumour thickness (TT) ≥5 mm (P = 0.007), perineural invasion (PNI) (P = 0.003), infiltrative border (P = 0.030) and poor differentiation (P = 0.005). Poorly differentiated tumours were also associated with increased local failure (P = 0.03). Local control (LC), regional control (RC) and disease-specific survival (DSS) decreased with an increasing number of APFs (P = 0.009, P = <0.001 and P = 0.009, respectively). Patients with four or more APFs had significantly worse outcomes in LC (P < 0.001), RC (P < 0.001) and DSS (P < 0.001). CONCLUSION: T1N0 OSCC exhibiting four or more APFs or demonstrating poor differentiation on histology had an increased risk of locoregional failure. The presence of PNI, infiltrative border and TT ≥5 mm are associated with increased regional failure. These factors may prompt escalation of treatment for patients with T1N0 OSCC.

Perineural invasion in oral squamous cell carcinoma: quantitative subcategorisation of perineural invasion and prognostication.

BACKGROUND: Evidence regarding the prognostic value of perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) and whether PNI alone warrants consideration of adjuvant therapy is controversial. We evaluated whether histopathological sub-categorization of PNI improves risk stratification. METHODS: PNI was evaluated for nerve size, number of foci, and distance from the tumor in 318 OSCC patients. Univariable and multivariable analyses were performed, with local failure (LF) and disease-specific survival (DSS) as the primary endpoints. RESULTS: PNI did not influence prognosis when classified as absent versus present. In contrast, multifocal PNI was associated with LF (P = 0.049) and decreased DSS (P = 0.043) on multivariable analyses. The size of the involved nerve separated those with multifocal PNI into intermediate (<1 mm) and high-risk (≥1 mm) groups. Unifocal PNI and distance from the tumor did not influence prognosis. Multifocal PNI was associated with worse prognosis irrespective of post-operative radiotherapy (PORT). CONCLUSIONS: Multifocal PNI is associated with poor outcomes even with PORT suggesting consideration of therapeutic escalation, particularly with involved nerves ≥1 mm. Unifocal PNI did not affect prognosis even in the absence of PORT, which may not be required if this is the sole risk factor. Prospective validation and testing of these hypotheses is essential before implementation.

Close margin alone does not warrant postoperative adjuvant radiotherapy in oral squamous cell carcinoma.

BACKGROUND: There are major variations between institutions regarding postoperative adjuvant therapy for adverse features in patients with oral squamous cell carcinoma (SCC). The authors' practice has been to not recommend any adjuvant therapy on the basis of close (<5 mm but uninvolved) margins unless there are additional adverse features. The primary objective of this study was to assess whether the local control achieved in this patient cohort was acceptable. METHODS: In this single-institution, retrospective analysis, local control was the primary endpoint, and disease-specific survival (DSS) was the secondary endpoint. Differences in survival were determined using the log-rank test, and survival curves were generated using the Kaplan-Meier method. RESULTS: One hundred forty-four patients (79 men and 65 women; median age, 64.1 years; mean follow-up, 3.3 years) underwent surgery alone for oral SCC with curative intent and were recorded as having close tumor margins on histology. The local control rate for all patients who underwent surgery alone was 91% (95% confidence interval, 81.9%-95.2%), and the DSS rate was 84% (95% confidence interval, 74.0%-89.9%) at 5 years. There was no pattern of worse local control or DSS rates with the ordered stratification of close margins. The 5-year local control rates for having 0, 1, 2, and 3 additional adverse features were 100%, 96%, 83%, and 71%, respectively (P = .004; trend test). CONCLUSIONS: Surgery alone without postoperative adjuvant therapy offered acceptable local control in patients who had close margin status as their only adverse feature and may be reasonable in the presence of 1 other adverse clinicopathologic feature.

Assessment of second tier lymph nodes in melanoma and implications for extent of elective neck dissection in metastatic cutaneous malignancy of the parotid.

BACKGROUND: The parotid is the commonest site of cutaneous metastases in the head and neck. The role and extent of neck dissection in patients with parotid metastatic cutaneous malignancy remains controversial. METHODS: We reviewed the lymphoscintigraphy and single photon emission CT (SPECT) of patients with melanoma who had a sentinel node in the parotid to determine the second tier cervical lymph nodes. RESULTS: Levels II and III cervical nodes make up 82% of second tier lymph nodes for the parotid, and levels IV and V, 12% and 4%, respectively. Second tier lymph nodes isolated to levels I, IV, or V, bypassing levels II and III, occurred in only 2% of cases. CONCLUSION: The risk of harboring occult metastasis in levels I, IV, and V when levels II and III are negative is low. Levels II and III neck dissection is likely to be an effective staging procedure in patients with isolated parotid metastases.

Imprinted polymers for chiral resolution of (±)-ephedrine, 4: packed column supercritical fluid chromatography using molecularly imprinted chiral stationary phases.

(-)-Ephedrine-molecularly imprinted polymers (MIPs) have been successfully used as stationary phases in supercritical fluid chromatography for the separation of (±)-ephedrine enantiomers. This approach combines the simple preparation and predictable elution order of MIP stationary phases with the superior mobile phase diffusivity and low viscosity of supercritical fluid mobile phases. The optimised mobile phase comprised supercritical carbon dioxide with a modifier consisting of MeOH/isopropylamine/H(2)O 93:5:2 (v/v/v). In many cases, better resolution separations were observed compared to when liquid mobile phases were used, and better separations achieved at high sample loads, although interestingly the MIPs which work best in SFC are different from the MIPs that work best in HPLC with an amine modifier. The MIP stationary phases were stable under the conditions employed and the chromatography was reproducible. This work opens the door to exploiting MIP stationary phases in preparative SFC.

Orbital exenterations: an 18-year experience from a single head and neck unit.

BACKGROUND: To review the outcomes of the patients who undergo orbital exenteration for malignancy. METHODS: A retrospective review of patients who underwent orbital exenteration performed at Royal Prince Alfred and Concord Hospitals between 1990 and 2008. RESULTS: A total of 38 patients were identified. The most common malignancies were squamous cell carcinoma (14 cutaneous and five mucosal origin), basal cell carcinoma (12 cutaneous) and melanoma (five patients). Orbital invasion was the main indication for orbital exenteration. Additional procedures were performed in 29 (76%) patients at the time of exenteration, including craniotomies in eight patients and maxillectomy in 15 patients. Flap reconstructions were required in 35 (92%) patients, including 33 free flap repairs and two local flap repairs. Post-operative complications included cerebrospinal fluid leak (16%) and wound-related complications (13%). The disease-specific survival rate was 97% at 1 year and 92% at 5 years. The local control rate was 83% at 1 year and 55% at 5 years. Fifty per cent of patient mortality and 63% of local recurrence occurred within the first post-operative year. CONCLUSIONS: In this series, locoregional control and survival were high, suggesting that aggressive surgical measures such as orbital exenteration are not unreasonable in well-selected patients. Free flap reconstruction is a reliable reconstructive technique which may reduce major complications. The first post-operative year is the most important period when monitoring for recurrence.

Chromatographic determination of solubilities in superheated water.

Superheated water (SHW) is an effective solvent for the extraction of a variety of environmental pollutants, but knowledge of the solubilities in water at elevated temperatures necessary to maximise the efficiency of the process is often lacking. Ambient temperature aqueous solubilities have been measured by reverse-phase HPLC from correlations with retention factors, k, but for poorly soluble organics the eluent must contain a proportion of organic modifier followed by extrapolation to pure water. The use of SHW as mobile phase allows direct determination of aqueous solubility from measurement of k on a modified HPLC system in which the eluent is cooled before detection to improve baseline stability. Alumina-bonded octadecylsilane columns were found to be more stable in SHW chromatography than their silica-bonded counterparts. To validate the procedure, measurements of k were made between 100 and 200°C for toluene and correlated with literature solubilities; the solubilities at 170°C of a number of related aromatics were then determined from their k-values.

Free flap reconstruction for melanoma of the head and neck: indications and outcomes.

INTRODUCTION: Occasionally, patients present with locally advanced melanoma of the head and neck involving deeper structures or with bulky local recurrence in regions with pre-existing surgical scars or previous irradiation. In these circumstances surgery may offer the only likely chance of local disease control and reconstruction of the ablation defect may require microvascular reconstruction. The primary aim of this study was to assess whether there was any evidence that adopting an aggressive surgical approach provided a survival benefit for these patients. METHODS: A retrospective analysis of 16 patients from the Sydney Head & Neck Cancer Institute database was performed. A matched pair analysis using patients from the Sydney Melanoma Unit database comparing disease-specific survival was performed. RESULTS: There were thirteen patients with cutaneous melanoma and three with mucosal melanoma. Thirteen patients (82%) required a bone resection and nine of these (70%) required skull base resections. Seven muscle flaps and nine fasciocutaneous flaps were performed. The free flap success rate was 94% (15/16). The overall survival was 69% and the disease free survival was 46% (median follow-up: 16 months). There was a 44% (71% v 27%) increase in stage-matched, disease-specific survival of the free flap group compared to the control group at three years (p=0.06: hazard ratio for death 0.26 (0.08-1.0)). CONCLUSIONS: For carefully selected patients with locally advanced melanoma of the head and neck an aggressive surgical approach, including radical resection and reconstruction with free tissue transfer, may be indicated to provide disease control and short-term survival benefit.

Outcomes of primary surgical treatment of T1 and T2 carcinomas of the oropharynx.

OBJECTIVES: Oropharyngeal cancers represent 10%-15% of all head and neck cancers. At presentation 60%-70% will have advanced-stage disease with a high incidence of neck metastases. Primary treatment employing radiotherapy, with or without chemotherapy, is widely prescribed. The aim of this study is to analyze the outcome of definitive surgical management of T1-T2 cancers of the oropharynx. METHODS: We conducted a retrospective cohort study of patients treated at the Sydney Head and Neck Cancer Institute. Patients with previously untreated squamous cell carcinoma (SCC) of the oropharynx were included according to the TNM stage of the disease as follows: T1 or T2, any N-stage, and M0. All patients underwent definitive primary surgical management. Primary analysis endpoints were locoregional control rates and disease-specific survival. RESULTS: Ninety-two patients were identified, of which 26 were T1 and 66 were T2. Forty-four patients had clinical neck disease, and 57 had postoperative radiotherapy. The results showed no significant difference between the T1 and T2 groups with respect to local control or treatment type; however, advanced-stage neck disease was associated with a worse prognosis. The 5-year disease-specific survival was 83% and local control rate was 87%. Ultimately, 25 of the 92 patients had treatment failure (27%). CONCLUSIONS: Selected patients with early-stage primary cancers of the oropharynx may be effectively treated with definitive primary surgery.

Accuracy of positron emission tomography in the evaluation of patients treated with chemoradiotherapy for mucosal head and neck cancer.

BACKGROUND: The aim of this study was to evaluate the accuracy of positron emission tomography (PET) in assessing the patients treated with primary chemoradiotherapy for mucosal carcinoma of the head and neck. METHODS: A retrospective review of patients with biopsy-proven cancer of mucosal head and neck sites receiving chemoradiotherapy with curative intent was undertaken. RESULTS: Seventy-eight patients met the study criteria. Staging PET identified unsuspected distant metastatic disease in 11% of patients. Sixty-one patients (78%) had a complete metabolic response on PET, with 17 showing residual disease. Sensitivity of PET was 82% (positive predictive value: 82%) and specificity was 95% (negative predictive value: 95%). Accuracy of PET response was significantly better than clinical assessment and conventional imaging (p < .002, p < .001, respectively). CONCLUSION: PET has been found to be significantly better than clinical examination or conventional imaging in restaging patients after chemoradiotherapy. Patients with a complete response on posttreatment PET have a significant survival advantage and can be safely observed.

Interaction of soil, water and TNT during degradation of TNT on contaminated soil using subcritical water.

Subcritical water was used at laboratory scale to reveal information with respect to the degradation mechanism of TNT on contaminated soil. Highly contaminated soil (12% TNT) was heated with water at four different temperatures, 150, 175, 200 and 225 degrees C and samples were obtained at appropriate time intervals. At the same time, similar experiments were performed with TNT spiked on to clean soil, sand and pure water in order to compare and eliminate various factors that may be present in the more complex contaminated soil system. Subcritical water was successful at remediating TNT-contaminated soil. TNT destruction percentages ranged between 98 and 100%. The aim of this work was to study the soil-water-contaminant interaction and determine the main physical parameters that affect TNT degradation. It was shown that the rate-limiting step of the process is the extraction/diffusion of TNT molecules from the soil core to the soil surface, where they degrade. Additionally, it was determined that the soil matrix also catalyses degradation to a lesser extent. Autocatalytic effects were not clearly observed.

Implications for clinical staging of metastatic cutaneous squamous carcinoma of the head and neck based on a multicenter study of treatment outcomes.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) of the head and neck is a common cancer that has the potential to metastasize to lymph nodes in the parotid gland and neck. Previous studies have highlighted limitations with the current TNM staging system for metastatic skin carcinoma. The aim of this study was to test a new staging system that may provide better discrimination between patient groups. METHODS: A retrospective multicenter study was conducted on 322 patients from three Australian and three North American institutions. All had metastatic cutaneous SCC involving the parotid gland and/or neck and all were treated for cure with a minimum followup time of 2 years. These patients were restaged using a newly proposed system that separated parotid disease (P stage) from neck disease (N stage) and included subgroups of P and N stage. Metastases involved the parotid in 260 patients (149 P1; 78 P2; 33 P3) and 43 of these had clinical neck disease also (22 N1; 21 N2). Neck metastases alone occurred in 62 patients (26 N1; 36 N2). Ninety percent of patients were treated surgically and 267 of 322 received radiotherapy. RESULTS: Neck nodes were pathologically involved in 32% of patients with parotid metastases. Disease recurred in 105 (33%) of the 322 patients, involving the parotid in 42, neck in 33, and distant sites in 30. Parotid recurrence did not vary significantly with P stage. Disease-specific survival was 74% at 5 years. Survival was significantly worse for patients with advanced P stage: 69% survival at 5 years compared with 82% for those with early P stage (P = 0.02) and for those with both parotid and neck node involvement pathologically: 61% survival compared with 79% for those with parotid disease alone (P = 0.027). Both univariate and multivariate analysis confirmed these findings. Clinical neck involvement among patients with parotid metastases did not significantly worsen survival (P = 0.1). CONCLUSIONS: This study, which included a mixed cohort of patients from six different institutions, provides further information about the clinical behavior of metastatic cutaneous SCC of the head and neck. The hypothesis that separation of parotid and neck disease in a new staging system is supported by the results. The benefit of having subgroups of P and N stage is uncertain, but it is likely to identify patients with unfavorable characteristics that may benefit from further research.

Outcome of treatment for advanced cervical metastatic squamous cell carcinoma.

BACKGROUND: Patients with advanced cervical metastases from mucosal squamous cell carcinoma have a poor prognosis because of their high risk of regional and distal failure. This study aims to evaluate the outcomes of patients with clinical N2 or N3 disease managed with surgery and postoperative radiotherapy. METHODS: From a comprehensive computerized database, 181 entered patients who had neck dissection for N2 or N3 disease between 1988 and 1999 were evaluated. The mean age was 62 years, and minimum follow-up was 3 years. RESULTS: A total of 233 neck dissections were performed in 181 patients, including 163 comprehensive and 70 selective dissections. Postoperative radiotherapy was given in 82% of cases. The local control rate was 75% at 5 years, and control of disease in the treated neck was achieved in 86%. Macroscopic extracapsular spread (ECS) significantly increased regional recurrence (p = .001). Adjuvant radiotherapy significantly improved neck control (p = .004) but did not alter survival. Patients with ECS (both microscopic and macroscopic) who received radiotherapy had a significantly better survival than did patients with ECS who did not receive radiotherapy. Disease-specific survival for the entire group was 39% at 5 years. By use of multivariate analysis, macroscopic ECS and N2c neck disease were independent adverse prognostic factors for survival (p = .001). CONCLUSIONS: Despite a high rate of control in the treated neck, the poor survival (39%) in this patient group indicates that adjuvant therapeutic strategies need to be considered.

Manipulation of the stereochemical outcome and product distribution in the Henry reaction using CO2 pressure.

The rate and stereocontrol of the Henry reaction in the presence of CO(2) can be controlled simply by manipulation of CO(2) pressure, and can be understood by consideration of the kinetic and thermodynamic aspects of the reaction.

Treatment of advanced cancer of the larynx and hypopharynx with chemoradiation.

AIM: To analyze the outcome of patients diagnosed with advanced cancer of the larynx and hypopharynx treated with combined chemotherapy and radiotherapy at Sydney Cancer Centre, Royal Prince Alfred Hospital, Sydney, Australia. METHODS: Analysis of prospectively gathered data concerning patients treated between 1994 and 2000 in a multidisciplinary, tertiary referral head and neck service. Outcome measures were: treatment toxicity, locoregional tumour control, and disease specific survival. RESULTS: Among 54 eligible patients, cancer involved the larynx in 31 patients and hypopharynx in 23 and, of these, 38 (70%) completed all the scheduled treatment. Chemotherapy and radiotherapy were given sequentially in 39 patients and concurrently in 15. The median age of patients was 63 years (range 35-79 years) and all but three had clinical stage III or IV disease. There were two treatment related deaths. Disease persisted in five patients and 14 others relapsed. Overall, 11 (24%) patients have had a laryngectomy; five for persistent disease, three for local recurrence and three for treatment related complications in the absence of disease. There were 15 cancer-related deaths. Cumulative disease specific survival at 2 years was 77% for the larynx cancer group and 72% for hypopharynx. The larynx was preserved in 26 of 30 patients alive at follow up. CONCLUSIONS: Patients diagnosed with advanced cancer of the larynx and hypopharynx may be considered for organ preservation treatment with chemoradiation, reserving surgery for persistent or recurrent disease. Careful patient selection is recommended because of the potential for significant treatment related toxicity.

Reactions in unusual media.

This review provides an introduction to three of the most well-developed solvent replacement strategies currently under investigation for synthetic chemistry: Ionic liquids, fluorous phase techniques, and supercritical carbon dioxide. They are all fascinating reaction media, and have considerable potential for use in pharmaceutical synthesis. However, this has to be balanced with problems and limitations of the new methods. This review aims to provide an overall account of recent advances in the use of unusual media for synthetic chemistry, with an emphasis on highlighting potential benefits, but also limitations, of each of the methods described.

Tumor thickness influences prognosis of T1 and T2 oral cavity cancer--but what thickness?

BACKGROUND: Previous studies have demonstrated that tumor thickness might influence prognosis in oral cancer, but the significant point at which outcome changes has varied from 1.5 mm to 6 mm. The clinical relevance of thickness remains unclear, and a reproducible prognostic "breakpoint" needs to be defined. METHODS: Tumor thickness was measured in 145 oral cavity squamous cancers, clinically staged T1 (n = 62) or T2 (n = 83). Clinical and pathologic data were collected prospectively between 1988 and 2000, but thickness was measured on paraffin sections for this study. Minimum follow-up was 2 years, and thickness was correlated with local control, cervical node involvement, and survival. Patients with clinically positive nodes (n = 21) were not excluded. Overall, 55 patients had pathologic node involvement at some time in their disease. RESULTS: Median tumor thickness was 6.2 mm, and there was little variation between sites: tongue, 6.4 mm; floor of mouth, 6.6 mm; and other sites, 5.7 mm. Median thickness for T1 tumors was 4.3 mm, significantly less than the T2 group, 8 mm (p <.01). Median thickness also varied significantly for tumors with associated nodal disease (8.5 mm) and without nodal disease (5.8 mm) (p <.01). Prognosis changed significantly at a cutoff of 4 mm with local control, nodal disease, and survival rates of 91%, 8%, and 100%, respectively, for tumors <4 mm compared with 84%, 48%, and 74% for those 4 mm or more thick (p <.01). Subgrouping greater than and less than 3 mm and 5 mm also showed a difference but with poorer discrimination. Thickness and pathologic nodal involvement were highly significant independent prognostic factors. CONCLUSIONS: Tumor thickness is a highly significant, objectively measurable prognostic factor in early stage oral cancers. There is a need to standardize techniques of measurement to allow a multi-institutional study to be carried out. This will facilitate the development of strategies aimed at improving the outcome of higher risk patients.

Clinical outcome following total laryngectomy for cancer.

BACKGROUND: Patients with advanced cancers of the larynx and hypopharynx have been treated with total laryngectomy at the Department of Head and Neck Surgery, Royal Prince Alfred Hospital, Sydney in the past. Increasingly, these patients are being managed with organ-sparing protocols using chemo-therapy and radiotherapy. The aim of the present study was to review complication, recurrence and survival rates following total laryngectomy. METHODS: Patients who had total laryngectomy for squamous carcinomas of the larynx or hypopharynx between 1987 and 1998 and whose clinicopathological data had been prospectively accessioned onto the computerized database of the Department of Head and Neck Surgery, Royal Prince Alfred Hospital, were reviewed. Patients whose laryngectomy was a salvage procedure for failed previous treatment were included. RESULTS: A total of 147 patients met the inclusion criteria for the study, including 128 men and 19 women with a median age of 63 years. Primary cancers involved the larynx in 90 patients and hypopharynx in 57. There were 30 patients who had recurrent (n = 24) or persistent disease (n = 6) after previous treatment with radiotherapy (26 larynx cases and four hypopharynx cases). Pharyngo-cutaneous fistulas occurred in 26 cases (17.7%) and, using multivariate analysis, the incidence did not correlate with T stage, previous treatment or concomitant neck dissection. Local control rates were 86% for the larynx and 77% for the hypo-pharynx groups and neck control was 84% and 75%, respectively. Five-year survival for the larynx cancer group was 67% and this was significantly influenced by T stage and clinical and pathological N stage. Survival in the hypopharynx group was 37% at 5 years and this did not significantly correlate with T or N stage. There was a non-significant trend to improved survival among previously treated patients whose laryngectomy was a salvage procedure. CONCLUSION: Patients with cancer of the larynx had a significantly better survival following total laryngectomy than patients with hypopharyngeal cancer. Those whose laryngectomy was carried out as a salvage procedure following failed previous treatment did not have a worse outcome than previously untreated patients.

Supercritical fluids and their applications in biotechnology and related areas.

This article serves as an overview, introducing the currently popular area of supercritical fluids (SFs) and their uses in biotechnology and related areas. It covers the fundamentals of supercritical science and moves on to the biotechnological and associated applications of these fluids. Subject areas covered include pure substances as supercritical fluids, the properties of supercritical fluids, organic cosolvents, solubility, and the following applications: extraction, chromatography, reactions, particle production, deposition, and the drying of biological specimens. Within each application, and where possible, the basic principles of the technique are given, as well as a description of the history, instrumentation, methodology, uses, problems encountered, and advantages over the traditional, nonsupercritical methods.