High-level ßIII-tubulin overexpression occurs in most head and neck cancers but is unrelated to clinical outcome.

BACKGROUND: ßIII-tubulin (TUBB3) is an isotype of microtubules, which are involved in crucial cellular roles including maintenance of cell shape, intracellular transport, and mitosis. Overexpression of TUBB3 was found to be associated with poor prognosis and resistance to tubulin-binding drugs and in several solid tumors including head and neck squamous cell carcinomas (HNSCC). Considering the potential high importance of a prognostic biomarker in these cancers, this study aimed to investigate the clinical relevance of immunohistochemical TUBB3 expression in HNSCC. METHODS: Tissue microarray (TMA) sections containing samples from 667 cancers of oral cavity, oro- and hypopharynx, and larynx for which follow-up data were available were analyzed for TUBB3 expression by immunohistochemistry. RESULTS: Over 90% of our analyzed cancers showed unequivocal cytoplasmic TUBB3 expression. Staining was considered weak in 69 (15.5%), moderate in 149 (33.5%), and strong in 188 (42.2%) of cancers. The frequent TUBB3 overexpression showed no significant correlation with pathological grading, tumor stage, nodal status, or surgical margin and had no impact on patient outcomes. CONCLUSION: Despite lacking prognostic utility in HNSCC, the remarkable high prevalence of TUBB3 expression in HNSCC emphasizes its putative relevance as a target for future drugs targeting TUBB3.

CD151 expression is frequent but unrelated to clinical outcome in head and neck cancer.

OBJECTIVES: CD151 is a plasma membrane protein belonging to the tetraspanin family. CD151 represents a putative therapeutic target and has been suggested as a prognostic marker in several cancer types. The present study aims to investigate the prognostic relevance of immunohistochemical CD151 expression in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Tissue microarray (TMA) sections containing samples from 667 cancers of oral cavity, oro- and hypopharynx and larynx, for which follow-up data were available, were analyzed for CD151 expression by immunohistochemistry. RESULTS: Membranous CD151 immunostaining was recorded in 269 (60.3 %) of 446 analyzable cases. Staining was considered weak in 129 (28.9 %), moderate in 98 (22.0 %), and strong in 42 (9.4 %) of cancers. CD151 expression was unrelated to histological grade, tumor stage, nodal status, or surgical margin. There was a tendency towards a somewhat lower prevalence of CD151 expression in tumors of the oral cavity (52.9 % positive) as compared to cancers of the oro-hypopharynx (62.1 %) and larynx (63.3 %; p = 0.0100). CD151 expression had no impact on patient survival. CLINICAL RELEVANCE: In summary, immunohistochemical analysis of CD151 lacks prognostic utility in HNSCC. The high prevalence of CD151 expression in HNSCC emphasizes its putative relevance as a therapeutic target for further development of anti-CD151 drugs.

Comparative study of wound healing in rat skin following incision with a novel picosecond infrared laser (PIRL) and different surgical modalities.

BACKGROUND AND OBJECTIVE: As a result of wound healing the original tissue is replaced by dysfunctional scar tissue. Reduced tissue damage during surgical procedures beneficially affects the size of the resulting scar and overall healing time. Thus the choice of a particular surgical instrument can have a significant influence on the postoperative wound healing. To overcome these problems of wound healing we applied a novel picosecond infrared laser (PIRL) system to surgical incisions. Previous studies indicated that negligible thermal, acoustic, or ionization stress effects to the surrounding tissue results in a superior wound healing. STUDY DESIGN/MATERIALS AND METHODS: Using the PIRL system as a surgical scalpel, we performed a prospective wound healing study on rat skin and assessed its final impact on scar formation compared to the electrosurgical device and cold steel. As for the incisions, 6 full-thickness, 1-cm long-linear skin wounds were created on the dorsum of four rats using the PIRL, an electrosurgical device, and a conventional surgical scalpel, respectively. Rats were euthanized after 21 days of wound healing. The thickness of the subepithelial fibrosis, the depth and the transverse section of the total scar area of each wound were analyzed histologically. RESULTS: After 21 days of wound healing the incisions made by PIRL showed minor scar tissue formation as compared to the electrosurgical device and the scalpel. Highly significant differences (P < 0.001) were noted by comparing the electrosurgical device with PIRL and scalpel. The transverse section of the scar area also showed significant differences (P = 0.043) when comparing PIRL (mean: 141.46 mm2; 95% CI: 105.8-189.0 mm2) with scalpel incisions (mean: 206.82 mm2; 95% CI: 154.8-276.32 mm2). The subepithelial width of the scars that resulted from using the scalpel were 1.3 times larger than those obtained by using the PIRL (95% CI: 1.0-1.6) though the difference was not significant (P < 0.083). CONCLUSIONS: The hypothesis that PIRL results in minimal scar formation with improved cosmetic outcomes was positively verified. In particular the resection of skin tumors or pathological scars, such as hypertrophic scars or keloids, are promising future fields of PIRL application.

Endpoints and cutpoints in head and neck oncology trials: methodical background, challenges, current practice and perspectives.

This article reviews the methodical and statistical basics of designing a trial, with a special focus on the process of defining and choosing endpoints and cutpoints as the foundations of clinical research, and ultimately that of evidence-based medicine. There has been a significant progress in the treatment of head and neck cancer in the past few decades. Currently available treatment options can have a variety of different goals, depending e.g. on tumor stage, among other factors. The outcome of a specific treatment in clinical trials is measured using endpoints. Besides classical endpoints, such as overall survival or organ preservation, other endpoints like quality of life are becoming increasingly important in designing and conducting a trial. The present work is based on electronic research and focuses on the solid methodical and statistical basics of a clinical trial, on the structure of study designs and on the presentation of various endpoints.

The impact of surgical technique on neck dissection nodal yield: making a difference.

The nodal yield of neck dissections is an independent prognostic factor in several types of head and neck cancer. The authors aimed to determine whether the applied dissection technique has a significant impact on nodal yield. This is a single-institution, prospective study with internal control group (level of evidence: 2A). Data of 150 patients undergoing 223 neck dissections between February 2011 and March 2013 have been collected in a comprehensive cancer centre. Eighty-two patients underwent neck dissection with unwrapping the cervical fascia from lateral to medial, while 68 patients were operated without specifically unwrapping the fascia, in a caudal to cranial fashion. The standardised, horizontal neck dissection technique along the fascial planes resulted in a significantly higher nodal count in Levels I, II, III and IV, as well as in terms of overall nodal yield (mean: n = 22.53) than that of the vertical dissection applied in the control group (mean: n = 15.00). This is the first publication showing a direct correlation between neck dissection nodal yield and surgical technique. Therefore, it is paramount to optimise the applied surgical concept to maximise the oncological benefit.

Perspectives in chemosensitivity and chemoresistance assays and their implementation in head and neck cancer.

Therapeutic options for patients with head and neck squamous cell carcinoma include surgery, radiation and chemotherapy. The latter plays a major role in the treatment selection of recurrent, metastatic or therapy resistant tumours, these being some of the major challenges in head and neck oncology. For these patients, chemosensitivity and chemoresistance assays would be paramount to identify their individual therapy options. In this review, seven common assays will be described and discussed in the context of several studies. Further, a new assay will also be presented, currently being validated in a European Union funded project. Comparisons will be drawn to evaluate the sensitivity and specificity of these assays in identifying individual treatment options, and their potential implementation in head and neck malignancies will be discussed. There is an unmet demand for the development of ex vivo diagnostic tools that may predict response in head and neck cancer on the way towards an individualized treatment for these patients.

Two-Year Survival Analysis of 50 Consecutive Head and Neck Cancer Patients Treated with Transoral Robotic Surgery in a Single European Centre.

BACKGROUND: To date, this prospective cohort study is the largest of its kind from a single European academic tertiary care center to report 2-year survival outcomes for head and neck squamous cell carcinoma treated primarily with transoral robotic-assisted resection. PATIENTS AND METHODS: Fifty consecutive, appropriately staged patients were enrolled prospectively, and underwent transoral robotic surgery (TORS) between September 2011 and August 2013. Overall, 24 patients had a T1 primary tumor, 23 had a T2 primary tumor, 2 had a T3 primary tumor, and 1 had a T4a primary tumor. Eighteen patients had overall stage I-II disease, and 32 patients had stage III-IV disease. Following transoral robotic resection of their primaries and appropriate neck dissection(s) as indicated, adjuvant treatment could be spared for 20 patients; another 5 patients refused the recommended adjuvant treatment. Seventeen patients received 60 Gy adjuvant radiotherapy and 8 patients underwent 66 Gy adjuvant chemoradiotherapy. RESULTS: At the time of the last follow-up visit (median 27 months), overall survival was 94 %, with two disease-specific deaths and one unrelated death (heart attack). The 2-year disease-free and recurrence-free survival rates were 88 and 80 %, respectively; however, the local recurrence rate was only 10 % after 2 years. CONCLUSION: Using TORS as their primary modality, 40 % of patients did not need adjuvant treatment and showed similar survival rates to that of conventional surgery or primary chemoradiotherapy. In another 34 % of patients, adjuvant chemotherapy could be spared and adjuvant radiotherapy could be reduced by 10 Gy compared with primary chemoradiotherapy of 70 Gy. Further studies are warranted with respect to long-term survival.

Feasibility and safety of transoral robotic surgery (TORS) for early hypopharyngeal cancer: a subset analysis of the Hamburg University TORS-trial.

Over the past 5 years, transoral robotic surgery (TORS) has become well established as one of the standard treatment options for T1 and T2 oropharyngeal squamous cell carcinoma. Besides this main indication, TORS can provide with improved access to other subsites of the upper aerodigestive tract as well, such as the supraglottic larynx and the hypopharynx, with superior visibility and maneuverability to that of transoral laser microsurgery (TOLM). Since September 2011, over one hundred TORS procedures have been performed at our institution, predominantly for oropharyngeal cancer. As part of our first 50 transoral robotic cases making up our initial TORS-trial, five patients underwent TORS for early hypopharyngeal carcinoma. The present case series evaluates its feasibility, safety and the completeness of resection in this well-defined subgroup of patients. Main outcome measures were completeness of resection, the presence or lack of postoperative bleeding, number of days intubated, rate of elective tracheotomy, duration of intensive care and/or intermediate care, speech and swallowing function, and duration of nasogastric and/or gastrostomy tube dependency. All patients have been free of recurrence to date. One patient died of other disease. Four patients are alive and free of tumour, three of them did not need adjuvant therapy. Transoral robotic surgery with appropriate neck dissection is a valid primary treatment option for select early hypopharyngeal carcinoma, especially in cases that did not require adjuvant treatment. In contrast to TOLM, TORS allows a multi-planar en bloc resection in the hypopharynx which makes histopathological evaluation more reliable. In addition to this, its faster learning curve makes the results less dependent on the individual surgeons' capabilities.

A comparison of hearing results following stapedotomy under local versus general anesthesia.

Advances in operative technique, instrumentation, and prosthesis design in otosclerosis surgery continue since Shea performed the first successful surgery. This is the first analysis to specifically compare post-operative hearing outcomes following stapedotomy surgery performed under local versus general anesthesia. Hearing outcomes were further stratified by comparing conventional perforator and Er:YAG laser ablation perforation techniques. Pre- and post-operative audiograms were retrospectively analyzed together with the method of anesthesia and the perforation technique for all patients with otosclerosis who underwent stapedotomy between 1998 and 2007. Pre-operative individual standard audiometry frequency thresholds (IFTs), air (AC) and bone conduction pure tone averages (PTA), and air bone gaps (ABG) were compared against post-operative results. Differences between pre- and post-operative PTAs and ABGs were compared between patients who received stapedotomy under local versus general anesthesia, as well as for patients who underwent conventional versus Er:YAG laser ablation perforations. Eighty-six patients were identified of which 24 % (n = 21) received local and 76 % (n = 65) received general anesthesia. Post-operative audiograms were available for 84 and 48 patients, respectively. Significant improvements were seen across all groups for standard 4-frequency AC-PTA and ABG and for IFTs up to 3 kHz. No significant difference was seen for IFTs between 4 and 6 kHz. A significant decline in post-operative hearing thresholds was seen at 8 kHz. Significant improvements in PTA and ABG were seen for all groups. There was a trend toward general compared to local anesthesia post-operative hearing results furthermore in combination with conventional perforation technique then with laser technique.

Endonasal dilatation of the Eustachian tube (EET) in children: feasibility and the role of tubomanometry (Estève) in outcomes measurement.

Studies on endonasal dilatation of the Eustachian tube (EET) utilizing a balloon catheter have shown encouraging results over the last years. This retrospective analysis presents our outcomes with EET in children with chronic obstructive dysfunction of the Eustachian tube, as well as the role of tubomanometry (TMM, Estève) as a diagnostic tool in the pre- and postoperative assessment of the Eustachian tube (ET) dysfunction. The data of 33 children, having undergone EET between September 2010 and March 2014, were retrospectively evaluated. They were assessed using tubomanometry before and after the EET. The R-data as the rate of Eustachian tube function in tubomanometry (TMM) were pre- and postoperatively matched with the clinical outcomes. Moreover, the patients' complaints before and after the procedure were analyzed. We did not see any EET-related complications in children. Most patients noticed a relief of their complaints. In the same time, tubomanometry was not able to show improved tube function or favorable postoperative changes in the R-data. Ear-related symptoms (e.g. otorrhea, otalgia, hearing loss) have been improved. EET is a feasible method in adults as well as in children to treat chronic tube dysfunction. However, tubomanometry does not seem to be the adequate tool to evaluate the tube function and thus the success rate of EET in children with chronic dysfunction of the Eustachian tube.

Reduction of thermocoagulative injury via use of a picosecond infrared laser (PIRL) in laryngeal tissues.

The carbon dioxide (CO2) laser is routinely used in glottic microsurgery for the treatment of benign and malignant disease, despite significant collateral thermal damage secondary to photothermal vaporization without thermal confinement. Subsequent tissue response to thermal injury involves excess collagen deposition resulting in scarring and functional impairment. To minimize collateral thermal injury, short-pulse laser systems such as the microsecond pulsed erbium:yttrium-aluminium-garnet (Er:YAG) laser and picosecond infrared laser (PIRL) have been developed. This study compares incisions made in ex vivo human laryngeal tissues by CO2 and Er:YAG lasers versus PIRL using light microscopy, environmental scanning electron microscopy (ESEM), and infrared thermography (IRT). In comparison to the CO2 and Er:YAG lasers, PIRL incisions showed significantly decreased mean epithelial (59.70 µm) and subepithelial (22.15 µm) damage zones (p < 0.05). Cutting gaps were significantly narrower for PIRL (133.70 µm) compared to Er:YAG and CO2 lasers (p < 0.05), which were more than 5 times larger. ESEM revealed intact collagen fibers along PIRL cutting edges without obvious carbonization, in comparison to diffuse carbonization and tissue melting seen for CO2 and Er:YAG laser incisions. IRT demonstrated median temperature rise of 4.1 K in PIRL vocal fold incisions, significantly less than for Er:YAG laser cuts (171.85 K; p < 0.001). This study has shown increased cutting precision and reduced lateral thermal damage zones for PIRL ablation in comparison to conventional CO2 and Er:YAG lasers in human glottis and supraglottic tissues.

Role of panendoscopy in identifying and managing risk of head and neck squamous cell carcinoma in routine follow-up: a retrospective clinical evaluation.

We discuss the clinical effectiveness and predictive value of routine panendoscopy for surveillance and follow-up of head and neck squamous cell carcinoma (HNSCC). Retrospective comparative study. Department of Otolaryngology-Head and Neck Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Two hundred and four HNSCC patients (follow-up between 2004 and 2007) were retrospectively evaluated. During follow-up, panendoscopy was performed routinely once a year. To avoid unnecessary procedures, we evaluated the value of radiological and clinical parameters in follow-up. On comparing normal-computerized tomography (CT) vs. abnormal CT results, a 13-fold higher frequency of recurrence (odds ratio 12.74; 95% CI 4.22, 38.48; p < 0.001) was found. Additionally, patient medical history, clinical investigation, and recurrence pattern were significant parameters when detecting a possible recurrence. Panendoscopy could have been avoided in 40% of patients with HNSCC (173/432). A follow-up schedule avoiding routine panendoscopy in HNSCC follow-up when the combination of diagnostic parameters is satisfactory does not influence the sensitivity or specificity of the test.

Continuous tissue microarray based identification of cancers with homogeneous target expression for successful targeted therapy in clinical routine practice.

In cancer therapy, the number of drugs targeting cells with characteristic molecular aberrations is continuously rising. However, application of these new drugs still is limited to a few tumor entities. The aim of this study was to test the concept of routinely identifying all possible cancer patients who might eventually benefit from targeted therapy. Therefore, all malignant tumors routinely submitted to our Institute of Pathology over a period of 4 months were brought into a tissue microarray format. Using "in situ" methods, tumors were analyzed for HER2, EGFR, and KIT status as examples for potential therapeutic target genes. In positive cases, target heterogeneity was excluded by analyzing all available large sections. Outside of tumor entities for which targeted drugs are already approved, the study revealed six tumors with homogeneously distributed HER2 overexpression/amplification (bladder, esophageal and colorectal) and seven tumors with homogeneous EGFR amplification (vulvar, ovarian, breast, esophageal and laryngeal, and adenocarcinoma of unknown primary). A total of 151 tumors showed KIT overexpression but none of seven sequenced cases showed KIT mutations. We furthermore report on a 69-year-old patient with homogeneously HER2-amplified metastatic colorectal cancer who is successfully treated by trastuzumab monotherapy. This study demonstrates that tissue microarray based screening for therapeutic target genes in tumors outside established indications represents a feasible approach suitable for routine application. The successful treatment of one patient with homogeneously HER2 positive metastatic colorectal cancer argues for the clinical utility of this approach at least in carefully selected, homogeneous cancers.

Simultaneous cytoplasmic and nuclear protein expression of melanoma antigen-A family and NY-ESO-1 cancer-testis antigens represents an independent marker for poor survival in head and neck cancer.

The prognosis of head and neck squamous cell carcinoma (HNSCC) patients remains poor. The identification of high-risk subgroups is needed for the development of custom-tailored therapies. The expression of cancer-testis antigens (CTAs) has been linked to a worse prognosis in other cancer types; however, their prognostic value in HNSCC is unclear because only few patients have been examined and data on CTA protein expression are sparse. A tissue microarray consisting of tumor samples from 453 HNSCC patients was evaluated for the expression of CTA proteins using immunohistochemistry. Frequency of expression and the subcellular expression pattern (nuclear, cytoplasmic, or both) was recorded. Protein expression of melanoma antigen (MAGE)-A family CTA, MAGE-C family CTA and NY-ESO-1 was found in approximately 30, 7 and 4% of tumors, respectively. The subcellular expression pattern in particular had a marked impact on the patients' prognosis. Median overall survival (OS) of patients with (i) simultaneous cytoplasmic and nuclear expression compared to (ii) either cytoplasmic or nuclear expression and (iii) negative patients was 23.0 versus 109.0 versus 102.5 months, for pan-MAGE (p < 0.0001), 46.6 versus 50.0 versus 109.0 for MAGE-A3/A4 (p = 0.0074) and 13.3 versus 50.0 versus 100.2 months for NY-ESO-1 (p = 0.0019). By multivariate analysis, these factors were confirmed as independent markers for poor survival. HNSCC patients showing protein expression of MAGE-A family members or NY-ESO-1 represent a subgroup with an extraordinarily poor survival. The development of immunotherapeutic strategies targeting these CTA may, therefore, be a promising approach to improve the outcome of HNSCC patients.

Single-incision transaxillary robotic total thyroidectomy for Graves' disease: improved feasibility and safety with novel robotic instrumentation.

BACKGROUND: Graves' disease represents a relative contraindication for robotic thyroidectomy due to increased vascularity with a higher risk of intraoperative bleeding. With a novel robotic instrumentation, however, it is possible to reduce this risk considerably. METHODS: A 30-year-old female patient with Graves' disease and keloid-prone olive skin underwent a single-incision transaxillary robotic total thyroidectomy through the left axilla using an 8-mm Fenestrated bipolar forceps instead of the standard 8-mm ProGrasp forceps. RESULTS: Total blood loss was 25 ml, and robotic console time was 132 min. There was no postoperative recurrent palsy. Postoperative parathormone level was 47 ng/l (preop.: 56 ng/l), and serum calcium level was normal at 2,17 mmol/l (preop.: 2,23 mmol/l). CONCLUSION: Transaxillary robotic surgery (TARS) with unilateral single-incision access is feasible and safe for Graves' disease with minimal blood loss and reduced risk of conversion thanks to the bipolar capability of the 8-mm Fenestrated bipolar forceps.

Use of a microsecond Er:YAG laser in laryngeal surgery reduces collateral thermal injury in comparison to superpulsed CO2 laser.

Despite causing significant thermocoagulative insult, use of the carbon dioxide (CO2) laser is considered gold standard in surgery for early stage larynx carcinoma. Limited attention has been paid to the use of the erbium:yttrium-aluminium-garnet (Er:YAG) laser in laryngeal surgery as a means to reduce thermal tissue injury. The objective of this study is to compare the extent of thermal injury and precision of vocal fold incisions made using microsecond Er:YAG and superpulsed CO2 lasers. In the optics laboratory ex vivo porcine vocal folds were incised using Er:YAG and CO2 lasers. Lateral epithelial and subepithelial thermal damage zones and cutting gap widths were histologically determined. Environmental scanning electron microscopy (ESEM) images were examined for signs of carbonization. Temperature rise during Er:YAG laser incisions was determined using infrared thermography (IRT). In comparison to the CO2 laser, Er:YAG laser incisions showed significantly decreased epithelial (236.44 µm) and subepithelial (72.91 µm) damage zones (p < 0.001). Cutting gaps were significantly narrower for CO2 (878.72 µm) compared to Er:YAG (1090.78 µm; p = 0.027) laser. ESEM revealed intact collagen fibres along Er:YAG laser cutting edges without obvious carbonization, in comparison to diffuse carbonization and tissue melting seen for CO2 laser incisions. IRT demonstrated absolute temperature rise below 70 °C for Er:YAG laser incisions. This study has demonstrated significantly reduced lateral thermal damage zones with wider basal cutting gaps for vocal fold incisions made using Er:YAG laser in comparison to those made using CO2 laser.

Laryngeal injuries following endotracheal intubation in ENT surgery: predictive value of anatomical scores.

Endotracheal intubation has been associated with a threefold higher incidence of laryngopharyngeal complaints following anesthesia in comparison to laryngeal mask airway. Such complaints, including hoarseness and sore throat, have been reported in up to 90% of patients within 24 h of extubation. The purpose of this study was to determine which preoperatively documented clinical and anatomic parameters are predictive of laryngo-pharyngeal trauma resulting from elective endotracheal intubation. Fifty-three patients undergoing ENT procedures requiring general anesthesia with endotracheal intubation were recruited. Pre and postoperative laryngostroboscopic examination was performed and findings correlated to preoperative clinical and anatomic parameters. Readily assessed anatomic parameters including height (>180 cm) and weight (>80 kg) correlated significantly to the Eckerbom grade of intubation-associated acute laryngeal injury (rs = 0.374; p = 0.006 and rs = 0.278; p = 0.044, respectively). The mandibular protrusion test also correlated significantly to the Eckerbom grade (rs = 0.462, p = 0.001) while the upper-lip-bite test showed significant correlation to impaired vocal fold oscillation (rs = 0.288, p = 0.036), with injury prediction sensitivities of 37.5 and 39.4%, respectively. No parameters correlated to subjective complaints (n = 5, 9.2%). This study provides suggestions on how to improve the classification of intubation-associated laryngeal injuries as well as providing the basis for larger clinical trials in other surgical subspecialties.

Abundant expression of mTOR kinase in salivary gland tumors - potentials as therapy target?

BACKGROUND: Salivary gland tumors constitute 3-6% of all head and neck neoplasms in adults. Because of limited advances made in the treatment of metastatic disease, the more important is the role of new therapeutic strategies, including molecular therapy. The mammalian target of rapamycin (mTOR) has recently been established as a therapeutic target for several drugs. MATERIAL: Evaluation of phospho-mTOR as a possible therapy target by patients with salivary gland tumors. Immunohistochemical semi-quantitative analyses of the expression of phospho-mTOR(Ser2448) were processed on a tissue microarray containing samples from more than 900 patients. For statistical analysis, contingency table and chi-squared test (likelihood) were used. RESULTS: We observed at least weak phospho-mTOR expression in 25.6-41.2% of all 4 histological adenoma and in 36.8-61.6% of all 11 histological carcinoma subtypes analyzed. No association was seen between phospho-mTOR expression and tumor grade in mucoepidermoid carcinomas. CONCLUSION: In conjunction with literature data providing the evidence for a functional role of mTOR in salivary gland tumors, we conclude that treatment with mTOR-antagonists might potentially also be efficient in wide variety of salivary gland carcinomas.

Direct quantification of polo-like kinase 1 activity in cells and tissues using a highly sensitive and specific ELISA assay.

Polo-like kinase 1 (Plk1) plays a pivotal role in the regulation of cellular proliferation. Plk1 is overexpressed in approximately 80% of human tumors of diverse origins, and overexpression of Plk1 promotes neoplastic transformation of human cells. A growing body of evidence suggests that deregulation of Plk1 closely correlates with prognosis of various cancers in humans. Thus, accurate assessment of Plk1 deregulation would provide clear clinical advantages. However, because of the limited amount of cancer tissues available, quantification of the Plk1 activity has not been feasible. Here, we report the development of a rapid, highly sensitive, and specific ELISA-based Plk1 assay that can quantify the level of Plk1 activity with a small amount (2-20 microg) of total cellular proteins. Unlike the conventional immunocomplex kinase assay, this assay directly utilizes total cellular lysates and does not require a Plk1 enrichment step such as immunoprecipitation or affinity purification. Using this assay, we demonstrated that Plk1 activity is elevated in tumors but not in the surrounding normal tissues and that the level of Plk1 activity significantly diminishes after an antiproliferative chemotherapy. The method described here may provide an innovative tool for assessing the predisposition for cancer development, monitoring early tumor response after therapy, and estimating the prognosis of patients with cancers from multiple organ sites.

The endoscopic approach to the neck: a review of the literature, and overview of the various techniques.

BACKGROUND: The endoscopic surgical approach to the neck has reached the head and neck surgeons' view with a certain delay, compared to other fields of endoscopic procedures. This may be attributed to the tight work space and plenty of vital structures in the operating field. Since study groups described first attempts with endoscopic or video assisted removals of thyroid glands in the late nineties, selective neck dissections on animal models or cadaveric dissections were performed in 2003. METHOD: The review consists of a Medline Search regarding the terms of endoscopic, video- assisted neck dissections, excision of neck lesions, thyroidectomy and submandibular resection and minimal access surgery. The three main procedures (selective neck dissection, submandibular resection and thyroidectomy) are described and reviewed in the following test. RESULTS: Various techniques have been performed successfully and led to good clinical results. The studies described in literature other than for thyroidectomy often do not exceed the level of small series or case-reports. CONCLUSION: With a good proof of indication gasless lifting techniques, video assisted endoscopical techniques and subcutaneous approaches with gas filling procedures are feasible in neck surgery. All methods depending on the surgeons' experience describe no significantly extended operation times, a better and faster wound-healing and an optimized cosmetic outcome, compared to open approaches. Surgeons should always be aware of the limitations of the minimal invasive techniques regarding the complications or modifications during neck dissection/thyroidectomy.