[Thyroid medicine for ENT physicians]. / Schilddrüsenmedizin für HNO­Ärzte.

Diseases of the thyroid gland are frequent incidental findings during ultrasound examination of the neck. They affect nearly one third of the normal population. Treatment is not always indicated; however, laboratory diagnostic measures must be initiated to specify the disease. The primary indications for consulting a thyroid specialist are thyroid nodules, goiters, autonomy of the thyroid gland, autoimmune diseases, Graves' disease, and Hashimoto thyroiditis. The aim of this review is to provide an overview of the most important thyroid diseases and their treatment options.

Differential chemokine expression patterns in tonsillar disease.

Expression profiles of CXC- and CC-chemokines in various forms of tonsillar disease were studied to evaluate whether certain chemokines play a predominant role in a specific subset of tonsillar disease. Total RNA was isolated from 89 biopsies (21 hyperplastic palatine tonsils, 25 adenoids, 16 chronic inflammatory palatine tonsils and 27 chronic inflammatory palatine tonsils with histological prove of acute inflammation), reverse transcribed and subjected to PCR amplifying IL-8, Gro-alpha, eotaxin-1, eotaxin-2, MCP-3, MCP-4 and RANTES. 2% agarose gel electrophoresis revealed a predominance of IL-8 in the chronic inflammatory palatine tonsil group compared to tonsillar hyperplasia. Furthermore, eotaxin-2 was strongly overexpressed in adenoid samples compared to chronic inflammatory specimens. Our data suggest that the majority of diseases related to adenoid formation are mediated via an eotaxin-2 expression, whereas chronic inflammatory tonsillitis is associated with IL-8 upregulation. These data imply that adenoids are related to a Th-2, and chronic inflammatory tonsillitis to a Th-1 based immune response.

Indications of cone beam CT in head and neck imaging in children.

For imaging of bony structures, especially for the anterior and lateral skull base in ORL medicine, cone beam computed tomography (CBCT) is an increasingly used alternative to CT, with a lower exposition to plain radiography that makes its use for imaging, particularly in children, very interesting. The aim of this study was to analyse possible indications and settings for CBCT in children and compare them to those of adults. A total of 554 patients (age range 0-18 years, mean age 10.36 years), who underwent CBCT between 01/2004-06/2013 in the ENT department at the university clinic of Marburg were enrolled in this retrospective analysis to evaluate technical parameters and indications. Data on CBCT of all children were compared with previously published data collected from 1730 adults who were diagnosed with the help of CBCT in the ENT department at the university clinic of Marburg, during the years 2012-2013. The most frequent indications of CBCT in children vs. adults were in the anterior skull base region: mid-facial trauma (60.4%) vs. chronic rhinosinusitis (54.8%), disturbed nasal breathing (13.9% vs. 13.0%) and chronic rhinosinusitis (12%) vs. mid-facial trauma (10.8%). For the lateral skull base the main indications were cholesteatoma (20.3%) vs. position control of cochlear implant (CI) electrode (31.2%), chronic otorrhoea (17.5%) vs. cholesteatoma (20.9%), and position control of CI electrode (11.8%) vs. chronic otitis media mesotympanalis (6.8%). CBCT is a suitable imaging modality for bony structures in adults and children. Settings mainly depend on the region of interest. One aim should also be to reduce exposure to radiation in both adults and children.

Evaluation of different time schedules in training with the Da Vinci simulator.

BACKGROUND: This prospective study analyzed the effect of different time schedules in training on the main performance outcomes: overall score, time to complete, and economy of motion. METHODS: The study was performed on the da Vinci Skills Simulator from December 2014 to April 2016. Forty robotic novices were randomized into two groups of 20 participants, which trained in the same three exercises but with different intervals between their training sessions. Each group performed training in Peg Board 1 in their first week, Match Board 2 in their second week, and Ring and Rail 2 in their third week. On their last day, Needle Targeting and Energy Dissection 2, for which no previous training had been received, were performed. Regarding the different training intervals, group 1 trained each exercise six times in a row once a week. Group 2 performed their training once a day for 5 days. Technical performance parameters were recorded by the Mimics simulator software for further analysis. In addition, the participants were asked to fill out a questionnaire concerning the robotics training. RESULTS: Group 2 performed significantly better compared to group 1 in the main metrics in the more advanced exercises. For the easier exercises, the training frequency did not lead to significant differences in performance outcome. A significant skills gain was seen between the first and last training sessions for all exercises in both groups. CONCLUSIONS: Performance in the final exercise NT was significantly better in group 2 than group 1. Regarding ED 2, no difference was found between the two groups. As the training of group 2 led to significantly better outcomes, we suggest that, especially for advanced exercises, it seems to be more favorable to perform training every day for a short period than to train once a week six times in a row.

Structured training on the da Vinci Skills Simulator leads to improvement in technical performance of robotic novices.

BACKGROUND: The increasing use of minimally invasive techniques such as robotic-assisted devices raises the question of how to acquire robotic surgery skills. The da Vinci Skills Simulator has been demonstrated to be an effective training tool in previous reports. To date, little data are available on how to acquire proficiency through simulator training. We investigated the outcome of a structured training programme for robotic surgical skills by robotic novices. METHODS: This prospective study was conducted from January to December 2013 using the da Vinci Skills Simulator. Twenty participants, all robotic novices, were enrolled in a 4-week training curriculum. After a brief introduction to the simulator system, three consecutive repetitions of five selected exercises (Match Board 1, 2, 3 and Ring and Rail 1, 2) were performed in a defined order on days 1, 8, 15 and 22. On day 22, one repetition of a previously unpractised more advanced module (Needle Targeting) was also performed. After completion of each study day, the overall performance, time to completion, economy in motion, instrument collisions, excessive instrument force, instruments out of view, master workspace range and number of drops were analysed. RESULTS: Comparing the first and final repetition, overall score and time needed to complete all exercises, economy of motion and instrument collisions were significantly improved in nearly all exercises. Regarding the new exercise, a positive training effect could be demonstrated. While its overall entry score was significantly higher, the time to completion and economy of motion were significantly lower than the scores on the first repetition of the previous 5 exercises. CONCLUSIONS: It could be shown that training on the da Vinci Skills Simulator led to an improvement in technical performance of robotic novices. With regard to a new exercise, the training had a positive effect on the technical performance.

The effect of different training exercises on the performance outcome on the da Vinci Skills Simulator.

BACKGROUND: Increasing usage of robotic surgery presents surgeons with the question of how to acquire the special skills required. This study aimed to analyze the effect of different exercises on their performance outcomes. METHODS: This prospective study was conducted on the da Vinci Skills Simulator from December 2014 till August 2015. Sixty robotic novices were included and randomized to three groups of 20 participants each. Each group performed three different exercises with comparable difficulty levels. The exercises were performed three times in a row within two training sessions, with an interval of 1 week in between. On the final training day, two new exercises were added and a questionnaire was completed. Technical metrics of performance (overall score, time to complete, economy of motion, instrument collisions, excessive instrument force, instruments out of view, master work space range, drops, missed targets, misapplied energy time, blood loss and broken vessels) were recorded by the simulator software for further analysis. RESULTS: Training with different exercises led to comparable results in performance metrics for the final exercises among the three groups. A significant skills gain was recorded between the first and last exercises, with improved performance in overall score, time to complete and economy of motion for all exercises in all three groups. CONCLUSIONS: As training with different exercises led to comparable results in robotic training, the type of exercise seems to play a minor role in the outcome. For a robotic training curriculum, it might be important to choose exercises with comparable difficulty levels. In addition, it seems to be advantageous to limit the duration of the training to maintain the concentration throughout the entire session.

Adenosine-mediated immunosuppression in patients with squamous cell carcinoma of the head and neck.

This review article describes the potential role of ectonucleotidase activity, adenosine metabolism, and the adenosinergic signaling pathway in the suppression of the host immune system in patients with head and neck cancer. Identifying such mechanisms leads to a better understanding of immunosuppressive mechanisms in this patient population. Further, potential targets for immunotherapy in an adjuvant approach to treating squamous cell carcinoma of the head and neck in the future might be identified and improve the prognosis of these patients.

[Penetrating injuries of the head and neck region - a potentially life threatening situation]. / Penetrierende Verletzungen der Kopf-Hals-Region - Eine Potentiell Lebensbedrohliche Situation.

UNLABELLED: Penetrating Injuries of the Head and Neck Region - A Potentially Life Threatening Situation Background: Cuts, stabs and gunshot wounds in the head and neck region are potentially life-threatening because of the high risk of vascular lesions. A consistent emergency management is usually based on an operative exploration of the wound with effective reconstruction of viable structures. PATIENTS AND METHODS: Various penetrating injuries of the head and neck region are described in 11 cases with respect of age, gender, course of events of injury, type of injury, involved structures, diagnostic and operative procedures and outcome and compared with current literature and guidelines. RESULTS: In 10 of 11 patients, in the context of an interdisciplinary emergency room management, CT angiography was performed following clinical examination. A surgical exploration and wound treatment was performed in 9 of these patients. The common carotid artery, the external carotid artery and large venous blood vessels of the neck were injured in 2 cases respectively. None of the patients deceased or suffered permanent damage. CONCLUSION: The outcome of deep head and neck lesions with relevant vascular trauma is determined by a rapid and interdisciplinary approach. A rapid, systematic and interdisciplinary approach in specialized trauma centers has a significant role in ensuring that patients with penetrating wounds in the head and neck -region rarely die due to their serious injury or their consequences.

Indications for reconstruction of mucosal defects in oropharyngeal cancer using a supraclavicular island flap.

The use of the supraclavicular island flap (SCIF) for the reconstruction of facial and neck skin defects is increasing. The value of this fasciocutaneous flap as a reconstructive modality for oropharyngeal defects in cancer patients is unclear. In the present study, a SCIF was used for reconstruction of mucosal defects following resection of the tumour in a group of four patients with T2 squamous cell carcinoma of the oropharynx and a clinical N0 neck. Reconstruction was performed following transoral tumour resection and selective neck dissection at levels I-III in the same session. Intraoperative and postoperative complications were analyzed, and functional and aesthetic results for the neck and shoulder region were evaluated in follow-up examinations. In addition, sensation to the flap was evaluated. No flap failures were observed. Only minor surgical complications were evident, which did not cause any relevant functional or aesthetic impairments. Sensation to the flap was observed in all cases. The SCIF appears to be a good and time-saving alternative to free flaps for oropharyngeal reconstruction following oncological resection in selected patients.

Human CD4+ CD39+ regulatory T cells produce adenosine upon co-expression of surface CD73 or contact with CD73+ exosomes or CD73+ cells.

While murine CD4(+) CD39(+) regulatory T cells (T(reg)) co-express CD73 and hydrolyze exogenous (e) adenosine triphosphate (ATP) to immunosuppressive adenosine (ADO), surface co-expression of CD73 on human circulating CD4(+) CD39(+) T(reg) is rare. Therefore, the ability of human T(reg) to produce and utilize ADO for suppression remains unclear. Using mass spectrometry, we measured nucleoside production by subsets of human CD4(+) CD39(+) and CD4(+) CD39(-)CD73(+) T cells or CD19(+) B cells isolated from blood of 30 volunteers and 14 cancer patients. CD39 and CD73 expression was evaluated by flow cytometry, Western blots, confocal microscopy or reverse transcription-polymerase chain reaction (RT-PCR). Circulating CD4(+) CD39(+) T(reg) which hydrolyzed eATP to 5'-AMP contained few intracytoplasmic granules and had low CD73 mRNA levels. Only ∼1% of these T(reg) were CD39(+) CD73(+) . In contrast, CD4(+) CD39(neg) CD73(+) T cells contained numerous CD73(+) granules in the cytoplasm and strongly expressed surface CD73. In vitro-generated T(reg) (Tr1) and most B cells were CD39(+) CD73(+) . All these CD73(+) T cell subsets and B cells hydrolyzed 5'-AMP to ADO. Exosomes isolated from plasma of normal control (NC) or cancer patients carried enzymatically active CD39 and CD73(+) and, when supplied with eATP, hydrolyzed it to ADO. Only CD4(+) CD39(+) T(reg) co-incubated with CD4(+) CD73(+) T cells, B cells or CD39(+) CD73(+) exosomes produced ADO. Thus, contact with membrane-tethered CD73 was sufficient for ADO production by CD4(+) CD39(+) T(reg). In microenvironments containing CD4(+) CD73(+) T cells, B cells or CD39(+) CD73(+) exosomes, CD73 is readily available to CD4(+) CD39(+) CD73(neg) T(reg) for the production of immunosuppressive ADO.

[Successful treatment of subglottic tracheal stenosis with a mucosa-lined radial forearm fascia flap]. / Erfolgreiche Behandlung einer subglottischen Trachealstenose mittels Mukosa-Radialisfaszien-Lappen.

Short-segment tracheal stenosis is often treated by segmental resection and end-to-end anastomosis. Longer-segment stenosis can sometimes be treated using dilation, laser therapy, bronchoscopic stent insertion and segmental resection and reconstruction. Long-segment restenosis with a buildup of scar tissue due to successful resection surgery in the past represents a particular therapeutic challenge and a sufficiently vascularized transplant may be the only option. We describe the case of a 37-year-old patient who underwent a tracheal reconstruction using a mucosa-lined radial forearm flap. Subsequent to a traumatic laryngotracheal fracture, long-term ventilation and multiple surgical interventions, the patient had developed a functionally relevant subglottic stenosis (5.5 cm). Following longitudinal anterior resection of the trachea 1 cm above and below the stenosis, a Dumon® stent was inserted. Simultaneously, a radial forearm fascia flap was harvested, as were two full-thickness buccal mucosa grafts, which were sutured onto the subcutaneous tissue and fascia of the forearm flap. Beginning caudally, the mucosa-lined flap was then sutured, air-tight, into the anterior tracheal defect with the mucosa facing the lumen. Finally, end-to-end anastomosis connected the blood vessels of the radial forearm flap to the recipient blood vessels in the neck. The patient was successfully extubated after 24 h and discharged after 5 days. A postoperative CT scan revealed optimal placement of the stent and the patient's speech and breathing were sufficiently re-established. The stent was removed bronchoscopically 6 weeks after surgery. Examinations during the 6-month follow-up period showed that the diameter of the reconstructed airway was retained and the patient remained symptom-free.

[Transoral robotic surgery for head and neck tumors: a series of 17 patients]. / Transorale Roboter-assistierte Chirurgie von Kopf-Hals-Tumoren: Eine Fallserie mit 17 Patienten.

BACKGROUND: Within the last years transoral robotic surgery (TORS) has gained importance in the resection of head and neck tumors, especially in North America. In contrast only few groups in Germany have studied this system so far. In respect to potential future developments in surgical robotic systems it seems reasonable to deal with this system. MATERIAL AND METHODS: 17 patients with tumors of the oropharynx, the base of tongue or the supraglottic area were treated with TORS in our clinic, between May 2011 and June 2012. In a prospective study we analyzed the exposure, visualization and resectability of these tumors using the da Vinci-system. In addition, set up and operation time, as well as costs were evaluated. RESULTS: All neoplasms of the oropharynx (n=9) and the tongue base (n=5) could be well exposed, visualized and resected. In the supraglottic area (n=3) 2 tumors could not be properly exposed and therefore resection was converted to a transoral microscopic laser approach. Resection with the cautery spatula tip or the Tm:YAG-laser fibre caused wide coagulation zones, but resulted in good hemostasis. The costs for the medical equipment and the leasing rate were 6280 € per case at our institution. CONCLUSION: Tumors of the tongue base and oropharynx could be easily visualized with help of the da Vinci-system. The resection of supraglottic tumors can be challenging, due to the arrangement of the robotic-arms and the narrow anatomic conditions. Despite its high costs, the da Vinci-system is a potentially interesting supplementation to existing surgical techniques.

The role of the adenosinergic pathway in immunosuppression mediated by human regulatory T cells (Treg).

Tumor-induced dysfunction of immune cells is a common problem in cancer. Tumors induce immune suppression by many different mechanisms, including accumulation of regulatory T cells (Treg). Adaptive Treg (Tr1) generated in the tumor microenvironment express CD39 and CD73 ectonucleotidases, produce adenosine and are COX2+PGE2+. Adenosine and PGE2 produced by Tr1 or tumor cells bind to their respective receptors on the surface of T effector cells (Teff) and cooperate in up-regulating cytosolic 3'5'-cAMP levels utilizing adenylyl cyclase isoform 7 (AC-7). In Teff, increased cAMP mediates suppression of anti-tumor functions. Treg, in contrast to Teff, seem to require high cAMP levels for mediating suppression. This differential requirement of Treg and Teff for cAMP offers an opportunity for pharmacologic interventions using selected inhibitors of the adenosine/PGE2 pathways. Blocking of adenosine/PGE2 production by Tr1 or blocking binding of these factors to their receptors on T cells or inhibition of cAMP synthesis in Teff all represent novel therapeutic strategies that used in combination with conventional therapies could restore anti-tumor functions of Teff . At the same time, these inhibitors could disarm Tr1 cells by depriving them of the factors promoting their generation and activity or by down-regulating 3'5'-cAMP levels. Thus, the pharmacologic control of Treg-Teff interactions offers a novel strategy for restoration of anti-tumor Teff functions and silencing of Treg. Used in conjunction with anti-cancer drugs or with immune therapies, this strategy has a potential to improve therapeutic effects by preventing or reversing tumor-induced immune suppression.

TLR4 signaling induced by lipopolysaccharide or paclitaxel regulates tumor survival and chemoresistance in ovarian cancer.

Toll-like receptors (TLRs) expressed on immune cells trigger inflammatory responses. TLRs are also expressed on ovarian cancer (OvCa) cells, but the consequences of signaling by the TLR4/MyD88 pathway in these cells are unclear. Here, TLR4 and MyD88 expression in OvCa tissues (n=20) and cell lines (OVCAR3, SKOV3, AD10, A2780 and CP70) was evaluated by reverse transcriptase-PCR, western blots and immunohistochemistry. Cell growth, apoptosis, nuclear factor-kappaB (NF-kappaB) translocation, IRAK4 and TRIF expression and cJun phosphorylation were measured following tumor cell exposure to the TLR4 ligands, lipopolysaccharide (LPS) or paclitaxel (PTX). Culture supernatants were tested for cytokine levels. TLR4 was expressed in all tumors, tumor cell lines and normal epithelium. MyD88 was detectable in tumor tissues and in 3/5 OvCa lines but not in normal cells. In MyD88(+) SCOV3 cells, LPS or PTX binding to TLR4 induced IRAK4 activation and cJun phosphorylation, activated the NF-kappaB pathway and promoted interleukin (IL)-8, IL-6, vascular endothelial growth factor and monocyte chemotactic protein-1 production and resistance to drug-induced apoptosis. Silencing of TLR4 in SCOV3 cells with small interference RNA resulted in phosphorylated-cJun (p-cJun) downregulation and a loss of PTX resistance. In PTX-sensitive, MyD88(neg) A2780 cells, TLR4 stimulation upregulated TRIF, and TLR4 silencing eliminated this effect. Thus, TLR4/MyD88 signaling supports OvCa progression and chemoresistance, promoting immune escape.