A comparative study of BiZact™ tonsillectomy versus cold steel dissection technique in adults: Analysis of operating time, intraoperative blood loss, postoperative bleeding rate and pain.

OBJECTIVES: To analyse operating time, intraoperative blood loss, postoperative bleeding rate and pain when using the relatively new BiZact™ tonsillectomy device compared to the commonly used cold steel dissection technique with bipolar cautery in adults. DESIGN: Retrospective case control study. Parameters analysed for significant association with technique were operating time, intraoperative blood loss, wound pain on postoperative days 1-4 and rate of post-tonsillectomy bleeding (PTB). SETTING: Monocentric study at a department of otolaryngology and head and neck surgery at a tertiary centre in Germany. PARTICIPANTS: A total of 183 patients who underwent a bilateral tonsillectomy with either the BiZact™ tonsillectomy device or the cold dissection technique with bipolar cautery for haemostasis. MAIN OUTCOME MEASURES: Operating time, intraoperative blood loss, postoperative pain on the first to fourth postoperative day (numeric rating scale: 0-10) (PTB, primary bleeding ≤24 h, secondary bleeding >24 h postoperative; Stammberger scale). RESULTS AND CONCLUSION: The BiZact™ tonsillectomy device leads to a significant shorter operating time with less intraoperative blood loss compared to cold steel dissection with bipolar haemostasis. No benefits with regards to PTB or postoperative pain could be observed. The use of the BiZact™ device provides major benefits in clinical routine and stands up to conventional tonsillectomy techniques.

Outcomes following oropharyngeal squamous cell carcinoma resection and bilateral neck dissection with or without contralateral postoperative radiotherapy of the pathologically node-negative neck.

PURPOSE: There are no consensus guidelines regarding the postoperative treatment of the contralateral pathologically node-negative neck in oropharyngeal squamous cell carcinoma. This study aimed to determine if omission of postoperative irradiation of the contralateral pathologically node-negative neck affects oncological outcomes. METHODS: We retrospectively identified 84 patients with primary surgical treatment including bilateral neck dissection and postoperative (chemo-)radiotherapy (PO(C)RT). Survival was analyzed using the log-rank test and the Kaplan-Meier method. RESULTS: Patients showed no decrease in tumor-free, cause-specific (CSS), or overall survival (OS) when PO(C)RT of the contralateral pathologically node-negative neck was omitted. Increased OS was found in patients with unilateral PO(C)RT and especially an increased OS and CSS was found in unilateral PO(C)RT and in tumors arising from lymphoepithelial tissue. CONCLUSIONS: Omitting the contralateral pathologically node-negative neck appears to be safe in terms of survival and our retrospective study advocates further prospective randomized control de-escalation trials.

The prognostic impact of B7-H3 and B7-H4 in head and neck squamous cell carcinoma.

PURPOSE: Immune checkpoint inhibition is a therapeutic option in many cancer entities. In head and neck squamous cell carcinoma (HNSCC) targeting of the PD-1/PD-L1 (B7-H1) axis is approved in recurrent/metastatic disease and is being explored in the curative setting. Here, we evaluated two related members of the B7 family, B7-H3 & B7-H4, for their prognostic impact under standard treatment. METHODS: A tissue microarray (TMA) of a single center HNSCC cohort was stained for B7-H3 and B7-H4. Staining intensity and the number of tumor cells stained were assessed, and the expression was scored according to an established algorithm. Staining scores were correlated with clinicopathological parameters and associated with patient survival. mRNA levels of both proteins were associated with patient outcome using the TCGA dataset. RESULTS: mRNA levels of B7-H3 and B7-H4 were not significantly associated with patient survival. TMA analysis revealed interpretable protein staining in 408 samples. Strong staining was the most frequent category for B7-H3 and no staining for B7-H4. In patients with p16-negative oropharyngeal SCC (OPSCC) and in a pooled cohort consisting of p16-negative OPSCC, laryngeal, hypopharyngeal and oral cavity SCC, strong B7-H3 expression was associated with better overall survival. For the latter cohort, this was in part due to reduced lymph node involvement. B7-H3 expression in p16-positive OPSCC and B7-H4 expression were not associated with outcome. CONCLUSION: Despite a possible role in tumor immune escape, B7-H3 was associated with favorable prognosis in HPV-negative HNSCC in our cohort. The underlying mechanisms and a potential impact for B7-H3 targeting remain to be elucidated.

A Four-Generational Report on Hereditary Head and Neck Paraganglioma.

Background This article investigates the inheritance, penetrance, clinical presentation, and therapeutic outcomes of hereditary head and neck paragangliomas (HNPGLs) by offering a four-generational report of an 18-member family affected by this rare condition. Methodology Information was compiled by examination of patients and a review of medical records and correspondence (retrospective case series). Results Six members of the 18-member family were diagnosed with HNPGL between 2002 and 2018. A known pathogenic point mutation in subunit D of the succinyl dehydrogenase complex (SDHD, c.317G>T, p.Gly106Val) was responsible for the tumor phenotype. The mutation could be revealed in seven family members, three diseased adults, one healthy adult, and three healthy children, out of the nine who consented to gene testing. The median age at diagnosis was 33.5 years (range: 22-50 years). Five of the eight primary tumors were glomus caroticum, two were glomus jugulare, and one was a glomus vagale tumor. The therapeutic approaches were multimodal and included embolization therapy, surgery, radiation, and watchful waiting. Follow-up was reported for five of the six patients (mean follow-up of 34.8 months after primary therapy); three showed no disease progression or recurrence. Conclusions This study exemplifies the autosomal dominant, parent-of-origin-dependent inheritance and the high disease penetrance in hereditary paraganglioma-pheochromocytoma syndromes. Six out of a total of eight adult descendants (75%) of the original SDHD mutation carrier developed tumors, and the morbidity associated with the disease as well as its therapy was especially high in late-diagnosed, advanced cases. This substantiates the necessity for early radiologic surveillance and genetic testing.

Tissue Microarray Analyses Suggest Axl as a Predictive Biomarker in HPV-Negative Head and Neck Cancer.

The receptor tyrosine kinase Axl is described to promote migration, metastasis and resistance against molecular targeting, radiotherapy, and chemotherapy in various tumor entities, including head and neck squamous cell carcinoma (HNSCC). Since clinical data on Axl and its ligand Gas6 in HNSCC are sparse, we assessed the association of Axl and Gas6 expression with patient survival in a single center retrospective cohort in a tissue microarray format. Expression was evaluated manually using an established algorithm and correlated with clinicopathological parameters and patient survival. A number of 362 samples yielded interpretable staining, which did not correlate with T- and N-stage. Protein expression levels were not associated with the survival of patients with p16-positive oropharyngeal SCC. In HPV-negative tumors, Axl expression did not impact patients treated with primary or adjuvant radio(chemo)therapy, but was significantly associated with inferior overall and recurrence-free survival in patients treated with surgery alone. Gas6 was a positive predictor of survival in patients whose treatment included radiotherapy. Associations remained significant in multivariable analysis. Our data question a meaningful contribution of the Axl/Gas6 pathway to radio-resistance in HNSCC and instead suggest that strong Axl expression identifies tumors requiring adjuvant radio(chemo)therapy after surgery.

Patient derived ex vivo tissue slice cultures demonstrate a profound DNA double-strand break repair defect in HPV-positive oropharyngeal head and neck cancer.

BACKGROUND: HPV-positive head and neck squamous cell carcinoma of the oropharynx (OPSCC) are more sensitive towards radiation than HPV-negative OPSCC. Two main theories exist regarding the underlying mechanism. Stronger lymphocyte infiltration points to an enhanced immunogenicity, whereas data from HPV-positive HNSCC cell lines suggest an enhanced cellular radiosensitivity based on a defect in DNA double-strand break (DSB) repair. The critical limitation of the latter theory is that the evidence was largely derived from a small number of established HPV-positive HNSCC cell lines. METHODS AND MATERIALS: Fresh patient-derived OPSCC samples were cut in 400 µm sections and cultured on cell culture inserts. Slice cultures were irradiated, in part combined with ATM inhibition, and fixed and frozen after 2 and 24 h. DSBs were analyzed by quantification of 53BP1 foci in nuclei co-stained with the SCC marker p63 via immunofluorescence microscopy. RESULTS: Ex vivo OPSCC tumor slice cultures maintained stable oxygenation and proliferation characteristics for at least 3 days. Areas of p63-positivity in immunofluorescence microscopy matched histologically confirmed tumor cell areas in serial sections, indicating the suitability of p63 as a tumor cell marker. p63-positive nuclei in HPV-positive OPSCC tissues (n = 14) showed profoundly elevated numbers of residual radiation-induced DSBs as compared to those from HPV-negative OPSCC (n = 12) (3 Gy: on average 4.9 vs. 1.2 foci per nucleus; p < 0.0001). Within the HPV-positive subgroup, samples derived from patients with a smoking history of less than 10 pack years demonstrated higher residual DSBs as compared to those derived from patients with 10 or more pack years (3 Gy: on average 6.5 vs. 3.2 foci per nucleus; p = 0.0105). Additional ATM inhibition resulted in a substantial increase in residual foci in all 4 HPV-negative samples tested but strikingly only in 2 out of 11 HPV-positive samples. CONCLUSIONS: In summary, our data provide robust, cell line-independent experimental evidence for an intrinsic DSB repair deficiency in HPV-positive OPSCC, strongly suggesting a meaningful contribution to the enhanced clinical radiosensitivity. The reduced effectiveness of ATM inhibition indicates a defect in the ATM-orchestrated DNA damage response. Lower numbers of residual 53BP1 nuclear foci in the ex vivo assay may identify HPV-positive patients with effective DSB repair who should potentially be excluded from de-intensification approaches.

Analyzing tyrosine kinase activity in head and neck cancer by functional kinomics: Identification of hyperactivated Src family kinases as prognostic markers and potential targets.

Signal transduction via protein kinases is of central importance in cancer biology and treatment. However, the clinical success of kinase inhibitors is often hampered by a lack of robust predictive biomarkers, which is also caused by the discrepancy between kinase expression and activity. Therefore, there is a need for functional tests to identify aberrantly activated kinases in individual patients. Here we present a systematic analysis of the tyrosine kinases in head and neck cancer using such a test-functional kinome profiling. We detected increased tyrosine kinase activity in tumors compared with their corresponding normal tissue. Moreover, we identified members of the family of Src kinases (Src family kinases [SFK]) to be aberrantly activated in the majority of the tumors, which was confirmed by additional methods. We could also show that SFK hyperphosphorylation is associated with poor prognosis, while inhibition of SFK impaired cell proliferation, especially in cells with hyperactive SFK. In summary, functional kinome profiling identified SFK to be frequently hyperactivated in head and neck squamous cell carcinoma. SFK may therefore be potential therapeutic targets. These results furthermore demonstrate how functional tests help to increase our understanding of cancer biology and support the expansion of precision oncology.

Rational surgical neck management in total laryngectomy for advanced stage laryngeal squamous cell carcinomas.

PURPOSE: Controversies exist in regard to surgical neck management in total laryngectomies (TL). International guidelines do not sufficiently discriminate neck sides and sublevels, or minimal neck-dissection nodal yield (NY). METHODS: Thirty-seven consecutive primary TL cases from 2009 to 2019 were retrospectively analyzed in terms of local tumor growth using a previously established imaging scheme, metastatic neck involvement, and NY impact on survival. RESULTS: There was no case of level IIB involvement on any side. For type A and B tumor midline involvement, no positive contralateral lymph nodes were found. Craniocaudal tumor extension correlated with contralateral neck involvement (OR: 1.098, p = 0.0493) and showed increased involvement when extending 33 mm (p = 0.0134). Using a bilateral NY of ≥ 24 for 5-year overall survival (OS) and ≥ 26 for 5-year disease-free survival (DFS) gave significantly increased rate advantages of 64 and 56%, respectively (both p < 0.0001). CONCLUSIONS: This work sheds light on regional metastatic distribution pattern and its influence on TL cases. An NY of n ≥ 26 can be considered a desirable benchmark for bilateral selective neck dissections as it leads to improved OS and DFS. Therefore, an omission of distinct neck levels cannot be promoted at this time.

Comparative effectiveness trial of transoral head and neck surgery followed by adjuvant radio(chemo)therapy versus primary radiochemotherapy for oropharyngeal cancer (TopROC).

BACKGROUND: For loco-regionally advanced, but transorally resectable oropharyngeal cancer (OPSCC), the current standard of care includes surgical resection and risk-adapted adjuvant (chemo) radiotherapy, or definite chemoradiation with or without salvage surgery. While transoral surgery for OPSCC has increased over the last decade for example in the United States due to transoral robotic surgery, this treatment approach has a long history in Germany. In contrast to Anglo-Saxon countries, transoral surgical approaches have been used frequently in Germany to treat patients with oro-, hypopharyngeal and laryngeal cancer. Transoral laser microsurgery (TLM) has had a long tradition since its introduction in the early 70s. To date, the different therapeutic approaches to transorally resectable OPSCC have not been directly compared to each other in a randomized trial concerning disease control and survival. The goal of this study is to compare initial transoral surgery to definitive chemoradiation for resectable OPSCC, especially with regards to local and regional control. METHODS: TopROC is a prospective, two-arm, open label, multicenter, randomized, and controlled comparative effectiveness study. Eligible patients are ≥18 years old with treatment-naïve, histologically proven OPSCC (T1, N2a-c, M0; T2, N1-2c, M0; T3, N0-2c, M0 UICC vers. 7) which are amenable to transoral resection. Two hundred eighty patients will be randomly assigned (1:1) to surgical treatment (arm A) or chemoradiation (arm B). Standard of care treatment will be performed according to daily routine practice. Arm A consists of transoral surgical resection with neck dissection followed by risk-adapted adjuvant therapy. Patients treated in arm B receive standard chemoradiation, residual tumor may be subject to salvage surgery. Follow-up visits for 3 years are planned. Primary endpoint is time to local or locoregional failure (LRF). Secondary endpoints include overall and disease free survival, toxicity, and patient reported outcomes. Approximately 20 centers will be involved in Germany. This trial is supported by the German Cancer Aid and accompanied by a scientific support program. DISCUSSION: This study will shed light on an urgently-needed randomized comparison of the strategy of primary chemoradiation vs. primary surgical approach. As a comparative effectiveness trial, it is designed to provide data based on two established regimens in daily clinical routine. TRIAL REGISTRATION: NCT03691441 Registered 1 October 2018 - Retrospectively registered.

Mass Spectrometric Comparison of HPV-Positive and HPV-Negative Oropharyngeal Cancer.

Squamous cell carcinoma of the head and neck (HNSCC) consist of two distinct biological entities. While the numbers of classical, tobacco-induced HNSCC are declining, tumors caused by human papillomavirus (HPV) infection are increasing in many countries. HPV-positive HNSCC mostly arise in the oropharynx and are characterized by an enhanced sensitivity towards radiotherapy and a favorable prognosis. To identify molecular differences between both entities on the protein level, we conducted a mass spectrometric comparison of eight HPV-positive and nine HPV-negative oropharyngeal tumors (OPSCC). Overall, we identified 2051 proteins, of which 31 were found to be differentially expressed. Seventeen of these can be assorted to three functional groups, namely DNA replication, nuclear architecture and cytoskeleton regulation, with the differences in the last group potentially reflecting an enhanced migratory and invasive capacity. Furthermore, a number of identified proteins have been described to directly impact on DNA double-strand break repair or radiation sensitivity (e.g., SLC3A2, cortactin, RBBP4, Numa1), offering explanations for the differential prognosis. The unequal expression of three proteins (SLC3A2, MCM2 and lamin B1) was confirmed by immunohistochemical staining using a tissue microarray containing 205 OPSCC samples. The expression levels of SLC3A2 and lamin B1 were found be of prognostic relevance in patients with HPV-positive and HPV-negative OPSCC, respectively.

Receptor tyrosine kinase MET as potential target of multi-kinase inhibitor and radiosensitizer sorafenib in HNSCC.

BACKGROUND: The multi-kinase inhibitor sorafenib displays antitumoral effects in head and neck squamous cell carcinoma (HNSCC); however, the targeted kinases are unknown. Here we aimed to identify those kinases to determine the mechanism of sorafenib-mediated effects and establish candidate biomarkers for patient stratification. METHODS: The effects of sorafenib and MET inhibitors crizotinib and SU11274 were analyzed using a slide-based antibody array, Western blotting, proliferation, and survival assays. X-rays were used for irradiations. RESULTS: Sorafenib inhibited auto-phosphorylation of epidermal growth factor receptor and MET, which has not been described previously. MET expression in HNSCC cells was not always associated with activity/phosphorylation. Furthermore, sorafenib-dependent cell kill and radiosensitization was not associated with MET level. Although MET inhibitors blocked proliferation, they caused only mild cytotoxicity and no radiosensitization. CONCLUSION: We identified MET as a new potential target of sorafenib. However, MET inhibition is not the cause for sorafenib-mediated cytotoxicity or radiosensitization.

Expression of Epithelial-Mesenchymal Transition Regulating Transcription Factors in Head and Neck Squamous Cell Carcinomas.

BACKGROUND/AIM: The transcription factors Twist, Snail, Slug, ZEB1 and ZEB2 regulate epithelial-mesenchymal transition (EMT) and their expression has been associated with a poor prognosis in several cancer entities. The aim of this analysis was to investigate in parallel the expression of all of these transcription factors in head and neck squamous cell carcinomas (HNSCCs) in order to gain insight into their possible co-expression. MATERIALS AND METHODS: Tumor tissue samples were immunohistochemically stained using antibodies against these transcription factors. The staining intensity and cellular distribution of the immunoreactivity was recorded. RESULTS: In general, transcription factor immunoreactivity was noted in the nucleus of both cancer and stromal cells. The highest immunoreactivity was observed for Twist. Snail, Slug, ZEB1 and ZEB2 showed a much lesser immunoreactivity in cancer cells and they were expressed independently from each other. CONCLUSION: Twist is the major transcription factor active in HNSCC; the other transcription factors of EMT seem to be of less importance in this tumor entity.

Similar cisplatin sensitivity of HPV-positive and -negative HNSCC cell lines.

Patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) show better survival rates than those with HPV-negative HNSCC. While an enhanced radiosensitivity of HPV-positive tumors is clearly evident from single modality treatment, cisplatin is never administered as monotherapy and therefore its contribution to the enhanced cure rates of HPV-positive HNSCC is not known. Both cisplatin and radiotherapy can cause severe irreversible side effects and therefore various clinical studies are currently testing deintensified regimes for patients with HPV-positive HNSCC. One strategy is to omit cisplatin-based chemotherapy or replace it by less toxic treatments but the risk assessment of these approaches remains difficult. In this study we have compared the cytotoxic effects of cisplatin in a panel of HPV-positive and -negative HNSCC cell lines alone and when combined with radiation.While cisplatin-treated HPV-positive strains showed a slightly stronger inhibition of proliferation, there was no difference regarding colony formation. Cellular responses to the drug, namely cell cycle distribution, apoptosis and γH2AX-induction did not differ between the two entities but assessment of cisplatin-DNA-adducts suggests differences regarding the mechanisms that determine cisplatin sensitivity. Combining cisplatin with radiation, we generally observed an additive but only in a minority of strains from both entities a clear synergistic effect on colony formation. In summary, HPV-positive and -negative HNSCC cells were equally sensitive to cisplatin. Therefore replacing cisplatin may be feasible but the substituting agent should be of similar efficacy in order not to jeopardize the high cure rates for HPV-positive HNSCC.

Effect of sorafenib on cisplatin-based chemoradiation in head and neck cancer cells.

Despite aggressive chemoradiation (CRT) protocols in the treatment of patients with head and neck squamous cell carcinomas (HNSCC), the outcome is still unfavorable. To improve therapy efficacy we had already successfully tested the multikinase inhibitor sorafenib in combination with irradiation (IR) in previous studies on HNSCC cell lines. In this study we investigated its effect on combined CRT treatment using cisplatin.Radio- and chemosensitivity with and without sorafenib was measured in four HNSCC cell lines and normal fibroblasts (NF) by colony formation assay. Apoptosis and cell cycle analysis were performed by flow cytometry.In HNSCC cells, sorafenib enhanced the antiproliferative effect of cisplatin without affecting apoptosis induction and with only minor effects on cell inactivation. Sorafenib added prior to irradiation enhanced cellular radiosensitivity in three of the tested HNSCC cell lines and caused massive overall cell inactivation when combined with CRT. In contrast, sorafenib did not radiosensitize NF and reduced cisplatin-induced cell inactivation. Cell inactivation by IR and cisplatin is further increased by the addition of sorafenib in HNSCC, but not in NF cells. Therefore, sorafenib is a promising candidate to improve therapy efficacy for HNSCC.

Automatic periodic stimulation of the vagus nerve during single-incision transaxillary robotic thyroidectomy: Feasibility, safety, and first cases.

BACKGROUND: Automatic periodic stimulation (APS) of the vagus nerve during thyroid surgery may provide the patient with increased safety to prevent impending thermal or stretch-related injury to the recurrent laryngeal nerve (RLN). METHODS: Vagal stimulation would be of particular interest in remote access robotic thyroid surgery, where the RLN may be exposed to more conducted heat because of the exclusive use of the Harmonic scalpel. Using APS, the console surgeon may adjust the dissection technique according to the signal changes to avoid impending thermal damage to the nerve. RESULTS: In 2 transaxillary robotic thyroidectomy cases, we placed the vagus electrode onto the ipsilateral vagus trunk through the single-incision transaxillary access before docking the da Vinci robot. APS of the ipsilateral nerve has been conducted without complications. CONCLUSION: APS of the ipsilateral vagus is feasible and safe during transaxillary robotic thyroidectomy, and may contribute to prevent impending thermal injury to the RLN.

Molecular targeting in combination with platinum-based chemoradiotherapy in head and neck cancer treatment.

BACKGROUND: Significant evidence exists supporting the use of platinum-based chemoradiotherapy (CRT) as a primary curative approach in locoregionally advanced head and neck cancer (HNSCC). Despite these aggressive protocols, 70% of patients die within 5 years because of locoregional recurrence or distant metastasis. To increase the response and survival of patients with HNSCC, CRT has been combined with molecular agents targeting distinct kinases. METHODS: This study was performed using a systematic literature review. RESULTS: The effect of targeted therapy on patient survival in the context of CRT remains controversial, with toxicities tending to be more severe but still acceptable. CONCLUSION: Supplementing CRT with target therapeutics might only improve survival in some patients with locally advanced HNSCC. Therefore, future studies must address the underlying biological mechanisms that can have an impact on treatment response. Such knowledge is essential in order to facilitate the effective and personalized treatment of patients with locally advanced HNSCC by combining CRT and targeted therapy. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2173-E2181, 2016.

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.

Robotic-assisted selective and modified radical neck dissection in head and neck cancer patients.

INTRODUCTION: Recently, several authors introduced various methods and published feasibility studies on novel robotic-assisted neck dissection techniques for head and neck cancer patients. Cosmesis and general appearance have become important concerns of cancer patients today. Especially in the head and neck area, a conspicuous scar can reduce patient satisfaction after surgery. With conventional neck dissection techniques, a long scar in the neck is unavoidable. Therefore, the development of robotic assisted neck dissection provides the patients with a scarless neck in these situations. However, there are some limitations of the application of these techniques in their current stage of development. METHODS: This study was performed using a systematic literature review. RESULTS: The reviewed clinical studies show that robotic-assisted neck dissection yields similar functional and early oncologic outcomes to that of conventional neck dissection, as well as excellent cosmetic satisfaction of patients. Despite these benefits, some disadvantages can be observed, in terms of longer operation times as well as higher procedure costs. CONCLUSION: Besides the similar oncologic and functional outcomes compared with the open procedure so far, more prospective, controlled, multicenter studies are required to establish robotic-assisted neck dissection as an alternative standard and to justify its added costs beyond the cosmetic advantages.

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.

Initial learning curve of single-incision transaxillary robotic hemi- and total thyroidectomy--A single team experience from Europe.

INTRODUCTION: The primary advantage of robotic thyroidectomy is to avoid a neck scar. On the other hand, this sophisticated technique implies some potential risks otherwise not associated with conventional thyroidectomy, increased costs, and prolonged operating times. With all these factors being an important issue, we analysed the data of our initial European series in order to understand the nature of the learning curve for this technique. METHODS: Ten patients underwent transaxillary robotic thyroidectomy for benign disease, performed consistently by the same surgeon with the same team, within a timeframe of 12 months. There were four total thyroidectomies and six hemithyroidectomies. Operating times broken down into creating the working space, docking the robot, and console work (including wound closure), were prospectively recorded and evaluated. RESULTS: By the end of the initial learning curve comprising ten patients, the total operating time for a robotic hemithyroidectomy and for a total thyroidectomy has decreased by 49% to 190 min, and by 31% to 229 min, respectively. Intraoperative complications were successfully managed without conversion to open access surgery. CONCLUSION: The learning curve for transaxillary robotic thyroidectomy is rather steep; reasonable progress in terms of operating times can be achieved within the first ten cases. Consistency in the team and careful patient selection are paramount factors for success.