Abdominal ultrasound in head and neck squamous cell carcinoma staging: yes or no?

PURPOSE: Abdominal ultrasound is a diagnostic staging procedure for distant metastases in head and neck squamous cell carcinoma (HNSCC). However, currently performed abdominal staging procedures do not follow consistent standards. Therefore, this retrospective study on 498 patients aimed at investigating on abdominal ultrasound as a staging procedure in HNSCC. MATERIALS AND METHODS: A retrospective analysis of 498 head and neck cancer patients treated in our Department of Head and Neck Surgery between 2008 and 2015 was performed. Disease-related data were collected over a mean follow-up time of 30.3 months, and results of abdominal ultrasound were analyzed. RESULTS: 426 patients received abdominal ultrasound as a staging procedure. 7% (29) were suspicious for metastases. In 19 cases (66%), the detected abnormalities were masses of the liver. In four patients, abdominal metastases were confirmed at the time of initial diagnosis. 16 patients developed abdominal metastases in the course of the disease (on average 623 days after initial diagnosis). 19 out of 20 patients with abdominal metastases had an N2/N3 cervical lymph node status. In this study, the negative predictive value of abdominal ultrasound for HNSCC staging was 99.03%, while the positive predictive value yielded 5.88% (N2/N3-patients). CONCLUSION: Only in patients with locally advanced lymph-node-status (N2/N3), abdominal ultrasound can be useful as a staging investigation to exclude abdominal metastasis in HNSCC patients. For N0/N1 patients, abdominal ultrasound might be dispensed. Of note, in case of a positive result, further diagnostic procedures are mandatory.

[Perioperative medical prophylaxis of venous thromboembolic events in head and neck surgery : A retrospective study and recommendations]. / Medikamentöse Thromboseprophylaxe bei Kopf-Hals-Operationen : Eine retrospektive Analyse und Handlungsempfehlung.

BACKGROUND: In the authors' department, a newly implemented clinical algorithm for application of perioperative thrombosis prophylaxis in head and neck surgery recommends restrictive handling of anticoagulants. This retrospective study aims to evaluate the algorithm by comparing incidences of venous thromboembolic events (VTE) and surgical revisions due to postoperative hemorrhage. MATERIALS AND METHODS: Perioperative incidences of deep vein thrombosis and pulmonary embolism as well as surgical revisions due to postoperative hemorrhage after head and neck surgery were determined based on all patients operated in the department over a period of 36 months. The incidences before (group I) and after (group II) implementation of the restrictive algorithm were compared. RESULTS: A total of 9276 patients were included. The incidences of VTE (0.12%) and surgical revisions due to postoperative hemorrhage (1.4%) were low. Incidences of VTE were non-significantly higher in group II (0.16%) than in group I (0.08%; p > 0.45, chi-square-test). Case analysis revealed that this difference was not due to implementation of the restrictive algorithm. The incidence of surgical revision due to postoperative hemorrhage was identical in the two groups (1.4%). CONCLUSION: After restricting the indication for thrombosis prophylaxis, the incidence of VTE or surgical revision due to postoperative hemorrhage did not change significantly. The provided clinical algorithm represents a low-risk and low-cost strategy of perioperative risk stratification.

[The role of surgery and salvage surgery in the era of HPV-associated oropharyngeal carcinomas]. / Rolle der Chirurgie und Salvage-Chirurgie in der Ära HPV-assoziierter Oropharynxkarzinome.

The incidence of human papillomavirus (HPV)-positive oropharyngeal carcinomas is increasing worldwide. Due to a markedly different response to treatment compared to HPV-negative oropharyngeal carcinomas, determining the ideal therapeutic approach can be challenging. Particularly in never-smokers, HPV-positive oropharyngeal carcinomas respond well to primary radiation therapy; at the same time recent studies indicate comparable survival after primary surgery. For stage I tumors according to TNM­8, retrospective analyses show very good oncologic outcomes after surgery alone, and no added benefit of adjuvant radio- or chemotherapy. Results of prospective treatment deintensification trials are expected in the coming years. Minimally invasive transoral surgical approaches for selected oropharyngeal cancers can improve preservation of postoperative function and quality of life. For both HPV-positive and HPV-negative oropharyngeal carcinomas, salvage surgery is the treatment of choice for resectable recurrent locoregional disease and resectable distant metastases.

[Primary cutaneous CD4+ small to medium-sized T-cell lymphoma in an adolescent patient]. / Primäres kutanes CD4+ klein- bis mittelgroßzelliges T-Zell-Lymphom bei einem Jugendlichen.

A rare finding of primary cutaneous CD4+ small to medium-sized T­cell lymphoma (SMPTCL) in a fifteen-year-old patient is reported. This is a rare tumor entity for which there is currently no standardized treatment recommendation. At the interdisciplinary tumor board, the decision was made to resect the tumor and reconstruct the defect with a nasolabial advancement flap in a two-stage process. Follow-up examinations, currently over 3 years, have shown the patient to be free of recurrences.

[Transoral resection of supraglottic laryngeal tumors with the Flex Robotic System]. / Transorale Resektion von supraglottischen Larynxkarzinomen mit dem Flex Robotic System.

The Flex Robotic System (Medrobotics, Raynham, MA, USA) allows flexible transoral endoscopic resection of head and neck tumors. The current article presents functional and first oncologic experiences with flexible transoral robot-assisted surgery for resection of supraglottic laryngeal tumors. From July 2014 to February 2020, supraglottic cancers in 32 patients (T1 = 11, T2 = 20, T3 = 1) were resected using the Flex Robotic System in the authors' clinic. Within a prospective clinical study, the feasibility, complications, and oncologic results were assessed. Tumors could be exposed, visualized, and successfully resected in all patients. In difficult-to-reach anatomic regions such as the aryepiglottic fold or petiole, the system provided a very good surgical overview. No serious adverse events occurred. Overall survival and local tumor control after 2 years were 88 and 94%, respectively. In conclusion, supraglottic tumors in difficult-to-reach areas have been successfully resected using the Flex Robotic System, with excellent local tumor control.

[The microbiome in head and neck tumors-initial findings and outlook]. / Das Mikrobiom bei Kopf-Hals-Tumoren ­ erste Erkenntnisse und Ausblick.

Technical progress in molecular biology has allowed for a more detailed analysis of the composition of the human microbiome in recent years. Inter- and intraindividual differences in microbiome composition have been demonstrated, which in part correlate with the occurrence of certain diseases. For some of the so-called oncomicrobes, a direct relationship between their effect on the host organism and carcinogenesis has been demonstrated, predominantly for gastrointestinal cancers. Initial results for head and neck cancer show inter- and intraindividual differences in the local microbiota of the tumor environment, with certain bacterial strains over- or underrepresented. Our results confirm these findings, e.g., by showing a relative abundance of fusobacteria in tumor tissue while streptococci were relatively reduced. Currently available results show a high degree of inter- and intraindividual variation, thus requiring larger patient cohorts for functional analyses.

Genetic immunization with mouse thyrotrophin hormone receptor plasmid breaks self-tolerance for a murine model of autoimmune thyroid disease and Graves' orbitopathy.

Experimental models of Graves' hyperthyroid disease accompanied by Graves' orbitopathy (GO) can be induced efficiently in susceptible inbred strains of mice by immunization by electroporation of heterologous human TSH receptor (TSHR) A-subunit plasmid. In this study, we report on the development of a bona fide murine model of autoimmune Graves' disease induced with homologous mouse TSHR A-subunit plasmid. Autoimmune thyroid disease in the self-antigen model was accompanied by GO and characterized by histopathology of hyperplastic glands with large thyroid follicular cells. Examination of orbital tissues showed significant inflammation in extra-ocular muscle with accumulation of T cells and macrophages together with substantial deposition of adipose tissue. Notably, increased levels of brown adipose tissue were present in the orbital tissue of animals undergoing experimental GO. Further analysis of inflammatory loci by 19 F-magnetic resonance imaging showed inflammation to be confined to orbital muscle and optic nerve, but orbital fat showed no difference in inflammatory signs in comparison to control ß-Gal-immunized animals. Pathogenic antibodies induced to mouse TSHR were specific for the self-antigen, with minimal cross-reactivity to human TSHR. Moreover, compared to other self-antigen models of murine Graves' disease induced in TSHR knock-out mice, the repertoire of autoantibodies to mouse TSHR generated following the breakdown of thymic self-tolerance is different to those that arise when tolerance is not breached immunologically, as in the knock-out models. Overall, we show that mouse TSHR A-subunit plasmid immunization by electroporation overcomes tolerance to self-antigen to provide a faithful model of Graves' disease and GO.

[Newly developed biofeedback program for facial muscle training in patients with facial paralysis]. / Ein neu entwickeltes Biofeedbackprogramm zum Gesichtsmuskeltraining für Patienten mit Fazialisparese.

BACKGROUND: Patients with facial paralysis are significantly limited in their quality of life (QoL). If no irreversible nerve damage is apparent, intensive training of the facial muscles is recommended in addition to drug-based therapy with cortisone. In order to improve training, we have developed a digital biofeedback mirror with motion magnification to indirectly influence the vegetative nervous system. OBJECTIVE: The aim of this work was to evaluate the reliability of the biofeedback program compared to clinical examination and classification according to House-Brackmann. METHODS: Our biofeedback system is similar to a mirror with the additional advantage of increasing a patient's self-control. It not only reflects the patient's image, but also potentiates movement through video processing and a magnifying function. For this purpose, patient's facial movements are filmed and amplified in real-time. Thus, even the smallest movements can be made visible and measured so that patients receive feedback on nerve regeneration. This can increase patient's motivation for daily facial muscle training and improve compliance. RESULTS: In the present study, restriction of QoL was evaluated and objectivized with Facial Clinimetric Evaluation Scale (FaCE) and Facial Disability Index (FDI) questionnaires. It was demonstrated that the patients' self-perception was associated with poor QoL. CONCLUSION: In the current study, measurement of the facial movements showed a reliable agreement with the clinical classification according to House-Brackmann. The biofeedback system is a reliable support tool during the regeneration phase in patients with facial paralysis..

TORS in HPV-Positive Tumors-The New Standard?

In this chapter, we discuss implications of tumor site and tumor microenvironment properties of human papilloma virus (HPV)-associated cancer formation with special emphasis on the therapeutic modality of transoral robotic surgery (TORS). Over the past years, the development of robotic systems has improved, and therefore, its use in the surgical treatment of HNSCC has become a relevant treatment modality for many patients. Yet, there are limitations. Especially for endolaryngeal TORS procedures, additional technical development is mandatory, particularly with respect to visualization and manipulation. The Flex System has provided new additions that need to be further evaluated. TORS systems are going to improve technical issues and therefore reduce patient morbidity, surgical handling and treatment costs. The developed systems have to be tested and evaluated in prospective trials in order to be able to identify benefits and disadvantages in patient care. With respect to HPV-related OPSCC, TORS has become a valuable surgical alternative for an increasing number of patients.

Regional recurrence in a case series of patients with carcinoma of the nasal cavity - therapeutic implications.

INTRODUCTION: Surgery is the primary treatment option for squamous cell carcinomas of the nasal cavity (NCSCC). Nodal involvement is rare at the time of initial diagnosis, and the role of diagnostic neck dissection as well as potential adjuvant irradiation of the neck remains controversial. The objective of this study was to assess the oncologic outcomes of patients with NCSCC with special emphasis on cervical lymph node treatment and recurrence. METHODS: 37 previously untreated patients were included in this study. Demographic data, tumor characteristics, therapeutic management, and clinical outcome were analyzed. RESULTS: Patients with advanced stage tumors were slightly overrepresented in this study and overall 3-year disease-free survival was 63%. A surgical treatment approach was pursued in 89% (n=33) of patients. After total rhinectomy, there were no cases of local recurrence. Overall, 12% (n=4) of all surgically treated patients developed local recurrence. While in 45% of patients (n=15), neck dissection was performed at the time of tumor resection, initial lymph node metastasis was histologically confirmed in only 6% (n=2) of surgically treated patients. Cervical lymph node recurrence occurred in 18% (n=6) of patients, predominantly those with advanced stage tumors, despite prior treatment of the neck. CONCLUSION: Excellent local control is achievable for patients with NCSCC, especially with radical tumor resection. While cervical lymph node metastasis is rare at the time of diagnosis, regional lymph node recurrence needs to be taken into consideration when planning therapy and follow-up. Multimodal treatment of the neck may be required for patients with advanced stage tumors.

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.

[The Current Role of Salvage-Surgery of Recurrent Tumors in the Larynx and Pharynx]. / Aktueller Stand Salvage-chirurgischer Therapiekonzepte bei Rezidivtumoren des Larynx und Pharynx.

Over the past 20 years, the therapeutic concepts for the treatment of head and neck cancer have evolved and non-surgical treatment strategies have gained in importance. However, despite improved organ preservation protocols and primary chemoradiation, tumor recurrence is still frequent. Under these conditions, salvage surgery if often the only remaining curative treatment option. Over the past 30 years, advancements in plastic-reconstructive surgery have broadened the surgical spectrum in the head and neck area, offering new treatment options for salvage surgery in recurrent cancer of the pharynx and larynx. Survival after salvage surgery mainly depends on the primary treatment modality as well as the localization and tumor stage at the time of initial diagnosis and local recurrence. For the reconstruction of defects after salvage surgery, pedicled flaps and microvascular free flaps may be utilized. The most frequently used flaps in these situations are the pectoralis major island- or the myocutaneous latissimus dorsi island flap. The radial forearm and the ALT-flap are potentially applicable free flaps. With the use of these flaps, vital tissue is transferred into the previously irradiated area, hereby allowing for reconstruction and functional preservation of the resected area and preventing complications such as fistulas. The expected morbidity and the likelihood of surgical success must be assessed thoroughly in every individual case prior to performing salvage surgery. This review aims to support decision making in these situations.

[Advances in transoral robotic surgery]. / Fortschritte in der transoralen roboterassistierten Chirurgie.

BACKGROUND: The role of transoral robotic surgery (TORS) in the treatment of head and neck tumors has expanded in the last decade. OBJECTIVES: We present the development and current advances in TORS along with the current indications and contraindications, and describe future developments. METHODS: We present our own studies and review those in the literature. RESULTS: Since approval of the da Vinci® system, the number of TORS cases has increased significantly. The main indications are tumors of the oropharynx and supraglottis. Most published studies are retrospective case series with no control group. In addition to the further development of the da Vinci® system, the introduction of the Flex®-system is a significant progression. The costs of using robotic systems are high. CONCLUSIONS: Technical improvement of robotic systems and the development of new surgical techniques will further expand the indications for TORS. The value of TORS needs to be assessed in prospective controlled studies.

[Immunotherapy in head and neck cancer]. / Immuntherapie bei Kopf-Hals-Karzinomen.

The physiological immune response to malignant cells is based on the interaction of antigen-presenting cells, such as dendritic cells and macrophages, with T and B lymphocytes. CD8(+) effector and natural killer cells are primarily responsible for tumor cell lysis. Tumor cells exploit several mechanisms to influence the body's immune system and promote development and progress of solid head and neck malignancies. Via regulatory T cells, myeloid-derived suppressor cells, tumor-associated macrophages, and cancer-associated fibroblasts, tumor cells promote development of suppressive signaling pathways that enable tumor progression. Novel immune therapeutics aim to influence these signaling pathways. Current studies are investigating agents which influence immune-stimulating or immune-suppressive cytokines, as well as drug-based Toll-like receptor activation and vaccination in head and neck cancer. Development of monoclonal antibodies allows for direct and highly specific binding of therapeutics to cell receptors - recently discovered immune checkpoint receptors are particularly intriguing targets. Monoclonal antibodies directed specifically toward T cell-stimulating receptors such as CD28 and CD134, or immunosuppressive receptors CTLA-4 and PD-1, are currently under investigation and have shown promising results.

[A new flexible endoscopy-system for the transoral resection of head and neck tumors]. / Ein neuartiges flexibles Endoskopie-System zur transoralen Resektion von Kopf-Hals-Tumoren.

INTRODUCTION: Within the last years transoral robotic surgery (TORS) with endoscopic visualization and surgery has gained importance in the resection of head and neck tumors and is an alternative to transoral laser microsurgery. The further development of transoral endoscopic systems should enhance the surgical options and reduce the surgery related morbidity. Thus, we evaluated a new flexible endoscopy system in cadaver -dissections. METHODS: In March 2014 we performed all standard procedures of transoral tumor surgery in the oropharynx, hypopharynx and larynx in 3 fresh cadaveric specimens using the Medrobotics Flex(®) System. In a prospective study we analyzed exposure, -visualization, accessibility and resectability of the respective -anatomic regions. RESULTS: All relevant anatomic structures of the pharynx and supraglottic region could be well exposed, visualized and accessed. Tonsillectomies and resections of the soft palate as well as the base of tongue could be performed easily. Supraglottic resections were possible with a good visualization. The piriform sinus could be exposed, and controlled tissue resections were possible-. The vocal cords were accessible and cordectomies could be performed. CONCLUSION: By combining a robot assisted flexible endoscope with flexible instruments the Flex system facilitates the visualization and accessibility of all relevant anatomic structures of pharynx and larynx. It is a promising system which now has to be further evaluated in clinical trials.

[The primary use of pectoralis myofascial flap in salvage laryngectomy]. / Die primäre Verwendung des myofaszialen M. pectoralis-major-Lappens bei der Salvage-Laryngektomie.

BACKGROUND: The salvage laryngectomy (SLE) is very often the only curative option in recurrent laryngeal or hypopharyngeal carcinomas. But the SLE is associated with an increased risk of complications such as the formation of salivary fistulas. To reduce the rate of fistulas a simultaneous elevation of the myofascial pectoralis major flap (PMML) is described. The aim of this study was to compare the SLE with and without the use of the PMML for prophylaxis of salivary fistulas. PATIENTS AND METHOD: 9 patients were included, suffering from a T4a larynx or hypopharynx carcinoma recurrence after RCT in the years 2012 and 2013 and subsequently treated by a SLE. An additional elevation of PMML was indicated due to the following criteria: end of RCT less than one year ago, tumor localization outside the glottis, infiltration of thyroid cartilage and prelaryngeal muscles. After PMML elevation the flap was sewed onto a primary closed pharynx. RESULTS: 6 out of 9 patients (2/3) received an additional covering of the pharynx by the PMML during SLE. In no case a postoperative salivary fistula was seen. In the remaining 3 patients (1/3) the pharynx was primarily closed without an additional covering by the PMML. In this group of patients one postoperative salivary fistula was seen. CONCLUSION: Due to the simultaneous application of the PMML in the context of SLE the rate of postoperative salivary fistula could be effectively reduced in our own patients. The PMML is suitable due to its safe elevation technique, the missing secondary thoracal cutaneous defect, and a good modelling possibility in the recipient area.

[The use of a flexible CO2-laser fiber in transoral robotic surgery (TORS)]. / Der Einsatz einer flexiblen CO2-Laser-Faser in der transoralen Roboter-assistierten Chirurgie (TORS).

BACKGROUND: Recently transoral robotic surgery has gained importance in the resection of head and neck tumors, especially in North America. The available resection tools are a fiber guided Tm:YAG-laser and a monopolar cautery, both causing wide coagulation and vaporization zones in healthy tissue. In order to improve the cutting properties we combined the system with a flexible CO2-laser fiber. MATERIAL AND METHODS: 6 patients suffering from T1 and T2 oropharyngeal carcinomas were treated between July 2012 and September 2012. In a prospective study we analyzed the feasibility, cutting properties, speed of resection as well as hemostasis and compared those with the monopolar cautery and the Tm:YAG laser which were recently examined in a series of 17 patients. RESULTS: The application of a CO2-laser fiber with the da Vinci system was feasible and showed good cutting properties. Using a 15 watts energy level resulted in a favourable cutting depth and adequate hemostasis. In comparison to the monopolar cautery or the Tm:YAG laser, smaller coagulation and vaporization zones could be achieved. CONCLUSION: Cutting properties of the da Vinci system can be improved by using a flexible CO2-laser fiber. Further prospective evaluations will follow.

[The treatment of chronic wounds in the head and neck area after radiotherapy with medical honey]. / Die Behandlung chronischer Wunden im Kopf-Hals-Bereich nach Radiatio mit medizinischem Honig.

BACKGROUND: Wound healing problems and chronic wounds can be a therapeutic challenge are a frequent problem after radiotherapy. They can appear spontaneously or after further surgery. The permanently altered tissue is associated with recurrent bacterial infections with weeping wounds, which cannot be treated sufficiently by conventional conservative wound care. The topical application of medical honey seems to have a positive effect in such cases. The aim of this prospectively study is to check this effectiveness in the treatment of wound healing problems and chronic wounds in the head and neck area of irradiated patients. PATIENTS AND METHODS: In the period of July 2012 until August 2013 nine patients were treated with medical honey. All pa-tients had previously radiotherapy in the head and neck area. 5 patients had protracted wound healing problems after salvage surgery. The remaining 4 cases had spontaneously dehiscenced wounds at the beginning of the study. The wound healing was confirmed by measurement of the wound edges and depth and by adequate photo documentation. RESULTS: In all cases, the conventional wound care was unsuccessfully. In 8 of 9 cases, the wounds could be brought to cure by the application of medical honey over 3-8 weeks. Side effects or allergic reactions to the medical honey were not seen in any -cases. CONCLUSION: Based on our clinical experience we believe that the topical application of medical honey in non-healing or recurrent wounds in the head and neck area after radiotherapy is a reason-able and successful alternative therapy.

Prospects for online adaptive radiation therapy (ART) for head and neck cancer.

BACKGROUND: The aim of the present study is to examine the impact of kV-CBCT-based online adaptive radiation therapy (ART) on dosimetric parameters in comparison to image-guided-radiotherapy (IGRT) in consecutive patients with tumors in the head and neck region from a prospective registry. METHODS: The study comprises all consecutive patients with tumors in the head and neck area who were treated with kV-CBCT-based online ART or IGRT-modus at the linear-accelerator ETHOS™. As a measure of effectiveness, the equivalent-uniform-dose was calculated for the CTV (EUDCTV) and organs-at-risk (EUDOAR) and normalized to the prescribed dose. As an important determinant for the need of ART the interfractional shifts of anatomic landmarks related to the tongue were analyzed and compared to the intrafractional shifts. The latter determine the performance of the adapted dose distribution on the verification CBCT2 postadaptation. RESULTS: Altogether 59 consecutive patients with tumors in the head-and-neck-area were treated from 01.12.2021 to 31.01.2023. Ten of all 59 patients (10/59; 16.9%) received at least one phase within a treatment course with ART. Of 46 fractions in the adaptive mode, irradiation was conducted in 65.2% of fractions with the adaptive-plan, the scheduled-plan in the remaining. The dispersion of the distributions of EUDCTV-values from the 46 dose fractions differed significantly between the scheduled and adaptive plans (Ansari-Bradley-Test, p = 0.0158). Thus, the 2.5th percentile of the EUDCTV-values by the adaptive plans amounted 97.1% (95% CI 96.6-99.5%) and by the scheduled plans 78.1% (95% CI 61.8-88.7%). While the EUDCTV for the accumulated dose distributions stayed above 95% at PTV-margins of ≥ 3 mm for all 8 analyzed treatment phases the scheduled plans did for margins ≥ 5 mm. The intrafractional anatomic shifts of all 8 measured anatomic landmarks were smaller than the interfractional with overall median values of 8.5 mm and 5.5 mm (p < 0.0001 for five and p < 0.05 for all parameters, pairwise comparisons, signed-rank-test). The EUDOAR-values for the larynx and the parotid gland were significantly lower for the adaptive compared with the scheduled plans (Wilcoxon-test, p < 0.001). CONCLUSIONS: The mobile tongue and tongue base showed considerable interfractional variations. While PTV-margins of 5 mm were sufficient for IGRT, ART showed the potential of decreasing PTV-margins and spare dose to the organs-at-risk.