Stefan Mattheis

HMGB1 is overexpressed in tumor cells and promotes activity of regulatory T cells in patients with head and neck cancer

HMGB1 has gained a prominent role in cancer development and is implicated in tumor escape phenomena. To date, only few data are available on effects of HMGB1 on regulatory T cells (Treg) in cancer patients. This study evaluates the prevalence of HMGB1 and its effects on Treg in patients with head and neck squamous cell carcinoma (HNSCC). Sixty-seven patients with HNSCC and seventeen healthy donors were included in this study. Tumor tissues of patients were analyzed for expression of HMGB1 employing immunofluorescence and qRT-PCR. HMGB1 serum levels were assessed using ELISA. Tumor-infiltration and Treg from peripheral blood were phenotyped with flow cytometry and immunofluorescence microscopy. Migration and suppressive function of Treg upon HMGB1 stimulation was analyzed in chemotaxis assays and CFSE assays. HMGB1 is overexpressed in tumor cells of HNSCC, and serum levels are significantly elevated. Tumor-infiltrating Treg express HMGB1-recognizing receptors, TLR4 and RAGE. HMGB1 is a chemoattractant for Treg and promotes their suppressive function. Our data provide new aspects how the HMGB1 tumor-derived danger signal augments function of Treg in patients with HNSCC.

Comparative analysis of resection tools suited for transoral robot-assisted surgery

Introduction of transoral robot-assisted surgery (TORS) has a strong potential to facilitate surgical therapy of head and neck squamous cell cancer (HNSCC) by decreasing the indication for an external surgical approach. However, the availability of resection tools is limited and comparative studies in the context of TORS are not available. In the context of the newest da Vinci Si HD® robotic system, various dissection methods were compared in a surgical animal model using porcine tongue at three different sites representing mucosal, muscular and lymphatic tissue. Resection methods included (a) CO2 laser tube, (b) flexible fiber Tm:YAG laser, (c) monopolar blade, and (d) radio frequency (RF) needle. Specimens were formalin-fixed, paraffin-embedded, cut, and stained with haematoxylin–eosin. Dissected tissue was examined for the width of the incision as well as the individual coagulation zone of each tool at various tissue sites. In addition, instrument costs and performance were determined. The incisions made by the RF needle had the most favourable cutting width and also smaller coagulation defects, as opposed to other tools, granting the best preservation of tumour-adjacent structures and improved pathological assessment. Instrument performance was best evaluated for CO2 laser and RF needle, whereas financial expenses were lowest for RF needle and monopolar blade. Improvement and modification of resection tools for TORS become a relevant criterion in order to facilitate routine usage in the surgical therapy of HNSCC. A consequent decrease in surgical mortality and improved precision of surgical tumour resection could lead to a significant clinical growth potential of TORS.

A european multicenter study evaluating the flex robotic system in transoral robotic surgery.

To evaluate the application of the Flex Robotic System in transoral robotic surgery (TORS).

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.

Flex Robotic System in transoral robotic surgery: The first 40 patients

The Flex Robotic System is a new robotic device specifically developed for transoral robotic surgery (TORS).

In vitro chemosensitivity of head and neck cancer cell lines

BackgroundSystemic treatment of head and neck squamous cell carcinoma (HNSCC) includes a variety of antineoplastic drugs. However, drug-resistance interferes with the effectiveness of chemotherapy. Preclinical testing models are needed in order to develop approaches to overcome chemoresistance.MethodsTen human cell lines were obtained from HNSCC, including one with experimentally-induced cisplatin resistance. Inhibition of cell growth by seven chemotherapeutic agents (cisplatin, carboplatin, 5- fluorouracil, methotrexate, bleomycin, vincristin, and paclitaxel) was measured using metabolic MTT-uptake assay and correlated to clinically-achievable plasma concentrations.ResultsAll drugs inhibited cell growth in a concentration-dependent manner with an IC50 comparable to that achievable in vivo. However, response curves for methotrexate were unsatisfactory and for paclitaxel, the solubilizer cremophor EL was toxic. Cross-resistance was observed between cisplatin and carboplatin.ConclusionChemosensitivity of HNSCC cell lines can be determined using the MTT-uptake assay. For DNA-interfering cytostatics and vinca alkaloids this is a simple and reproducible procedure. Determined in vitro chemosensitivity serves as a baseline for further experimental approaches aiming to modulate chemoresistance in HNSCC with potential clinical significance.

Acute Arterial Hemorrhage Following Radiotherapy of Oropharyngeal Squamous Cell Carcinoma

Background and Purpose:Vascular erosion is a rare but life-threatening complication after radiotherapy. The authors report on acute arterial bleeding and its therapy following radiotherapy of oropharyngeal tumors.Patients and Methods:Ten patients with oropharyngeal squamous cell carcinoma of any stage developed foudroyant acute arterial hemorrhage 3–46 months (14.4 ± 5.1 months) after primary (5/10) or adjuvant radio(chemo)therapy (R[C]T).Results:All patients had a history of recurrent minor bleeding episodes and showed deep mucosal ulcerations also outside the primary tumor region. A life-threatening arterial hemorrhage appeared in the area of these mucosal defects in the pharyngeal region. Affected vessels were the common carotid artery as well as the internal and the external portion with branches like the ascending pharyngeal and superior thyroid arteries. Treatment consisted of emergency intubation or tracheotomy followed by exposure and package of the pharynx and surgical ligature and/or embolization. 6/10 patients (all hospitalized) survived the episode, however, lethal outcome in 4/10 patients (outpatients) was related to asphyxia as a result of blood aspiration or exsanguination. None of the patients revealed evidence of persistent or recurrent tumor disease as proven by biopsy/autopsy and imaging technique.Conclusion:Vascular erosion following primary or adjuvant R(C)T represents a rare and potentially life-threatening complication requiring immediate emergency treatment involving head and neck surgeons, anesthesiologists and neuroradiologists. For patients with oropharyngeal neoplasms treated by R(C)T and showing recurrent bleeding episodes and mucosal ulceration particularly after the acute treatment phase, hospitalization with prophylactic surgical ligature or embolization of affected arteries is recommended.ZusammenfassungHintergrund und Ziel:Schädigungen von Blutgefäßen stellen eine seltene, jedoch potentiell lebensbedrohliche Komplikation nach Strahlentherapie dar. Die Autoren berichten über akute arterielle Blutungen und deren Therapie nach Strahlentherapie von oropharyngealen Tumoren.Patienten und Methodik:Zehn Patienten mit einem oropharyngealen Plattenepithelkarzinom jeglichen Tumorstadiums entwickelten 3–46 Monate (14,4 ± 5,1 Monate) nach primärer (5/10) oder adjuvanter Radio(chemo)therapie (R[C]T) eine akute arterielle Blutung (Tabelle 1).Ergebnisse:Alle Patienten zeigten in ihrer Vorgeschichte kleinere Blutungsepisoden und litten unter tiefen Schleimhautulzerationen im Pharynx auch außerhalb der Primärtumorregion (Abbildung 1). Die lebensbedrohlichen Blutungen traten im Bereich dieser Schleimhautdefekte auf. Betroffene Gefäße waren die Arteriae carotis communis, carotis interna und carotis externa mit ihren Ästen, Arteria pharyngea ascendens und Arteria thyroidea superior. Die Therapie umfasste die notfallmäßige Intubation oder Tracheotomie und Tamponade des Rachens, gefolgt entweder von einer Ligatur (Abbildung 2) und/oder Embolisation des betroffenen Gefäßes. 6/10 Patienten überlebten dieses Ereignis, 4/10 Patienten verstarben vor Erreichen der Klinik infolge des hohen Blutverlusts oder Aspiration. Keiner der Patienten zeigte zum Zeitpunkt der Blutung bildmorphologisch oder histologisch einen Residual- oder Rezidivtumor.Schlussfolgerung:Gefäßschädigungen infolge primärer oder adjuvanter R(C)T stellen eine potentiell lebensbedrohliche Komplikation dar, die einer unmittelbaren notfallmäßigen interdisziplinären Behandlung durch Kopf-Hals-Chirurgen, Anästhesisten und Neuroradiologen bedarf. Bei Patienten mit oropharyngealen Karzinomen, die nach einer R(C)T unter wiederkehrenden pharyngealen Blutungsepisoden und Schleimhautulzerationen leiden, sollte eine stationäre Überwachung mit einer eventuellen prophylaktischen Unterbindung oder einem neuroradiologisch-interventionellen Verschluss (Abbildung 3) der betroffenen Gefäße in Erwägung gezogen werden.

First use of a new retractor in transoral robotic surgery (TORS)

Transoral robotic surgery (TORS) has gained importance in head and neck surgery due to the possibility to visualize regions within the pharynx and larynx which are difficult to access. The success of transoral surgery depends on the exposure of the region of interest in order to allow visualization using a camera system. The Medrobotics Flex® Robotic System is a new flexible endoscopic system designed to overcome difficulties experienced in transoral surgery using other robotic systems with rigid endoscopes and instruments. In this article, we describe the first use of the Medrobotics Flex® Retractor in humans, a retractor designed for advanced transoral procedures. We report our experience in 11 patients requiring surgery of the oropharynx, hypopharynx, and supraglottic larynx. In all cases, we successfully exposed all targeted surgical regions. We experienced easy handling of the retractor alongside comparable positioning times and no observed mucosal damage.

Chirurgisches Management der persistierenden Speichelfistel nach Salvage-Laryngektomie

Erratum. Laryngo-Rhino-Otol 2013; 92: e1 Erratum N. Rothmeier, T. K. Hoff mann, G. K. Lehnerdt, S. Lang, S. Mattheis Laryngo-Rhino-Otol 2013; 92 (04): 236–243 DOI: 10.1055/s-0033-1333721 Chirurgisches Management der persistierenden Speichelfi stel nach Salvage-Laryngektomie In Heft 4/13 der Laryngo-Rhino-Otol wurde in der Originalarbeit Chirurgisches Management der persistierenden Speichelfi stel nach Salvage-Laryngektomie ein Mitautor falsch benannt. Korrekt muss die Autorenliste lauten: N. Rothmeier, T. K. Hoff mann, G. Lehnerdt, S. Lang, S. Mattheis Dieser Artikel ist ein Erratum zum Beitrag: „Chirurgisches Management der persistierenden Speichelfi stel nach SalvageLaryngektomiein“ der Laryngo-Rhino-Otol 2013; 92 (04): 236–243.

[Bipedicled flap technique according to Schultz-Coulon using open approach for septal defect repair].

BACKGROUND The successful closure of a nasal septal perforation is a surgical challenge, which applies especially to large defects with a diameter exceeding 2.0 × 2.0 cm. This retrospective study presents results using open septoplasty via a transcolumellar approach and bipedicled flaps according to Schultz-Coulon for closure. RESULTS In 45/50 patients the perforation was closed successfully (90%) (CI 0.82-0.98). The survey of patients showed significant improvement rates for all questioned parameters. CONCLUSIONS In our hands the bipedicled flap technique combined with open access to the nasal septum yields good success rates for closure and consecutive improvement of life quality, also for large defects exceeding 2.0 × 3.0 cm. The open approach provides cosmetically excellent results based on the appropriate suture techniques and is advantageous concerning intraoperative overview and suture of the mucosal flaps. Additionally it can be easily combined with an open septorhinoplasty.