Infrasound a new weapon in cancer therapy?

BACKGROUND: Researchers take different positions when describing the effects of infrasound on the human body. Although several studies investigated the likely harmful effects of infrasound exposure from wind turbines a significant connection has not been found yet. There is evidence that infrasound interacts with cell metabolism and may disrupt cell membrane integrity. OBJECTIVES: The suggested impairment of the cells' ultrastructure by infrasound leads to the question of whether infrasound can be therapeutically used, for instance in cancer therapy. This review provides the current state of the literature. METHOD: Current literature on infrasound in cancer therapy including all studies with the search terms 'cancer' and 'infrasound' were identified and reviewed until the year 2020. RESULTS: The present state of research reveals promising effects of targeted infrasound in cancer therapy. Infrasound directly affects the tumor cells' ultrastructure and seems to sensitize several types of cancer to chemotherapy, presumably due to membrane permeabilization. The application of infrasound on tumor cells without other therapeutic agents demonstrates different effects that probably depend on the type of cells, the applied frequency and sound pressure level as well as the time of exposure. CONCLUSIONS: The mechanism of infrasound on cancer cells is not completely understood yet, hence, further studies have to be conducted to clarify the ultrastructural and metabolic changes inside the tumor cells. The development of suitable infrasound generators for the application in a clinical setting would be an important course of action.

[Hormonal influence on hearing]. / Hormonelle Beeinflussung des Hörvermögens.

BACKGROUND: Hearing loss leads to impairments in communication, social interactions, and cognitive functions. This renders early treatment particularly important. A causal therapy is not yet available. Human and animal studies have shown that certain hormones can have a positive effect on hearing. OBJECTIVE: This review provides an overview of the effects of various hormones on hearing and describes the potential benefit for future therapeutic approaches. MATERIALS AND METHODS: A systematic literature review of reviews dealing with the effects of various hormones on hearing in humans and animals published in PubMed between 2015 and 2020 was conducted. RESULTS: Hormones may mediate antiapoptotic effects on structure-relevant cells of the cochlea and auditory pathway, and may influence hair cell functionality or the electrolyte balance of the endo- and perilymph. Current research focuses on glucocorticoids; the mineral corticoid aldosterone; the sex hormones estrogen, progesterone, and testosterone; the growth hormones GH (growth hormone) and IGF­1 (insulin-like growth factor 1); thyroid hormones; and insulin. Study results are still inconsistent at this time, but various hormones appear to represent a possible future treatment option for acute hearing loss. Long-term hormone treatment, which would be necessary particularly in the case of age-related hearing loss, does not currently represent a sensible course of action due to the side effect profile of the systemic treatment/lack of practicable topical application options. CONCLUSION: The mode of action of hormones is complex. Whether they can be used in the future for individualized treatment of patients with acute hearing impairment requires further investigation.

Age-related changes in T lymphocytes of patients with head and neck squamous cell carcinoma.

INTRODUCTION: The number of aging cancer patients has increased continuously and will do so further in the future. The immune system of elderly people experiences critical changes over the time. Therefore, tumor-induced changes in the immune system are believed to differ in young and elderly cancer patients as well. METHODS: The effect of aging on the immune system was measured in peripheral blood lymphocytes (PBL) of healthy volunteers (n = 48, 21-84 yrs.) divided into three different age groups. Seventy years was set as a cut-off for defining subjects as elderly. Results were compared to two groups of adult cancer patients, which donated PBL and tumor infiltrating lymphocytes (TIL): young cancer patients (40-69 yrs.; blood: n = 13; TIL: n = 17) and elderly cancer patients (70-90 yrs.; blood: n = 20; TIL: n = 15) with head and neck squamous cell carcinoma (HNSCC). Frequencies and phenotypes of CD4+ and CD8+ T cells as well as regulatory T cells (Treg) were assessed by flow cytometry. RESULTS: We observed lower frequencies of CD8+ cytotoxic T cells during aging in both groups. Frequencies of tumor infiltrating regulatory T cells were significantly higher than in the peripheral blood but showed a significant decline in older tumor patients. With increasing age, expression of immunosuppressive CD73 and CCR7 was lower and expression of PD1 elevated on peripheral T cells in healthy volunteers and tumor patients. CONCLUSION: Immunosenescence takes place in healthy donors and cancer patients. Our results suggest that in elderly tumor patients, the immune system is impaired and the tumor-induced immune escape is less pronounced. The increased expression of PD1 implies the potential for effective immunotherapies in elderly, as treatment with checkpoint inhibitors could be more beneficial for elderly HNSCC patients.

[Oncoimmunology in old age]. / Onkoimmunologie im Alter.

Physiological aging processes of the immune system are associated with an increased susceptibility to infectious, autoimmune and tumor diseases. In accordance with the general demographic development the number of tumor patients in advanced age also increases. An end to this development is not yet foreseeable. In tumor treatment, immunotherapy with checkpoint inhibitors is becoming increasingly more important; however, only a few studies on the efficacy and side-effect profiles in older patients exist so far. In this review article the changes in the immune system in old age and the influence on carcinogenesis are discussed. In addition, the current state of research on the immunotherapy of patients in advanced age who suffer from head and neck cancer is presented.

[Otitis media: definition, pathogenesis, clinical presentation, diagnosis and therapy]. / Otitis media ­ Definition, Pathogenese, Klinik, Diagnose und Therapie.

A number of diseases of the middle ear are summed up under the term otitis media: acute otitis media, recurrent acute otitis media, otitis media with effusion, chronic suppurative otitis media and chronic otitis media epitympanalis (= cholesteatoma). Acute otitis media belongs to the most common pediatric diseases and is often caused by bacterial infection. Since the advent of pneumococcal vaccines the quantity of AOM caused by pneumococci has declined; vaccination against NTHi and Moraxella catarrhalis are being developed. Main pillar of conservative treatment of AOM is symptomatic therapy of otalgia and fever as well as restoring the Eustachian tubal function. When indicated, amoxicillin represents antibiotic medication of choice. Acute mastoiditis, facial nerve paresis, labyrinthitis, Gradenigo syndrome, sinus vein thrombosis, meningitis and brain abscess belong to the complications of AOM among others. Both innate and adaptive immune system are involved in recovery of OM with innate immunity playing a critical role. Dysfunction of the Eustachian tube often underlies OM. Manometric measurement of Eustachian tube function may be useful for indication of balloon Eustachian tuboplasty. Several theories explain pathogenesis of cholesteatoma and multiple pro-inflammatory processes promote its progress in the course of the disease.

[The role of innate immunity in otitis media]. / Rolle des angeborenen Immunsystems bei Otitis media.

Otitis media (OM) belongs to the most common pediatric diseases and causes more medical contacts, surgical interventions, and drug prescriptions than any other infectious disease. Recent findings have identified a critical role of innate immunity in recovery from OM. The middle ear mucosa identifies invading pathogens by sensing pathogen-associated molecule patterns (PAMPs) via pattern recognition receptors such as the Toll-like receptors (TLRs). They generate immediate antimicrobial responses and cytokine release, leading to an inflammatory reaction as seen in acute or chronic OM. Cross-talk between TLRs can enhance or suppress the healing process in the middle ear. In order to prevent over-activation on the one hand and insufficient immune response on the other, the signaling network between different TLRs must be integrated and controlled by positive and negative feedback loops. This guarantees a proper immune response in the middle ear after infection. In this review, we focus on the involvement of the innate immune system and TLRs in OM, as well on their relevance for new vaccination strategies and immunotherapies.

[Hebephrenia - a viable psychopathological construct?] / Hebephrenie ­ ein brauchbares psychopathologisches Konstrukt?

Ewald Hecker was the first psychiatrist to describe the disease entity of hebephrenia in some detail, focusing mainly on disturbances of affect. Later Emil Kraepelin and Eugen Bleuler saw hebephrenia as a subtype of dementia praecox or schizophrenia. Willy Mayer-Gross and Karl Leonhard characterized hebephrenia with highly differentiated psychopathological descriptions, whereas this construct only played a minor role in the works of Klaus Conrad and Kurt Schneider. The International Classification of Diseases (ICD-10) lists hebephrenia as a subtype of schizophrenia but in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) no subtypes of schizophrenia are mentioned and the concept of hebephrenia is thus lost. Hebephrenia can be seen as an ideal type describing a psychopathological course pattern. This construct can be useful to conceptualize a group of disorders of affect which otherwise escape description, especially since these psychopathological alterations of affect are difficult to operationalize. To have a viable concept of these disorders is relevant for the prognosis and therapy planning. If the concept of hebephrenia is abolished, important psychopathological knowledge might be lost for future generations of psychiatrists.

[Psychiatry as a practical science : Considerations following Wolfgang Wieland (1933-2015)]. / Psychiatrie als praktische Wissenschaft : Überlegungen nach Wolfgang Wieland (1933­2015).

In the light of historical and modern criticism of the discipline of psychiatry and psychotherapy as a medical subspecialty, this paper deals with aspects of the theory of medicine as postulated by the physician and philosopher Wolfgang Wieland. According to his contributions medicine is a practical science aiming at establishing rational action. Central to this model is a diagnosis, which helps to subsume individual cases under general principles from which essential therapeutic options can be derived. Hence, psychiatry and psychotherapy become a medical subspecialty by adopting the basic model of medical reasoning and action as described by Wieland. Nevertheless, the limits of such an approach must be taken into consideration. Especially in a psychiatric and psychotherapeutic context it is of particular importance that even when being guided by general principles the responsibility for the personality of each individual patient should be adequately met. Furthermore, attention should be paid to the limits of the subspecialty of psychiatry and psychotherapy as a medical discipline, which also requires a critical analysis of the concept of psychiatric illness.

[The Concept of Typology in Psychiatry in the Context of Historical Contributions of Max Weber and Karl Jaspers]. / Das Typuskonzept in der Psychiatrie - Überlegungen nach Max Weber und Karl Jaspers.

Against the background of Max Weber's and Karl Jaspers' outstanding historical contributions to the conceptual development of different typologies, the importance of a psychiatric typology is examined. The term "ideal type" was introduced into social science by Weber as an analytical construct to describe and classify cultural phenomena. This concept was adopted for the psychiatric context by Jaspers who proposed to establish a typological system in the field of psychotic disturbances without an organic correlate. He emphasized the importance of the course of psychopathological symptoms for such a typological system. The concept of typology can be regarded as a promising heuristic approach in psychiatry, providing a classification system for complex psychopathological symptoms. Even though several historic typologies exist in psychopathology, their usefulness in the fields of therapy and prognosis needs to be critically assessed. Also, new typologies will have to be developed, taking into account neurobiological knowledge now available.

[Facial nerve schwannoma in the inner auditory canal and geniculate ganglion]. / Schwannome des N. facialis im inneren Gehörgang und am Ganglion geniculi.

BACKGROUND: Schwannoma of the vestibular nerve is the most common tumor found in the inner auditory canal. If a schwannoma of the facial nerve is found unexpectedly during surgery, the original surgical plan may have to be changed. In our series, we describe the symptoms, diagnostic procedures and therapy of this infrequent, benign tumor. In particular, we want to analyse the influence of diagnostic techniques, such as magnetic resonance tomography and electrophysiology, on the diagnosis of these tumors. PATIENTS: Between 1975 and 2001, we diagnosed 17 cases of facial nerve schwannoma in the inner auditory canal or the geniculate ganglion. All patients were treated surgically. In 16 cases, we used the enlarged middle fossa approach and in the remaining patient the translabyrinthine approach was used. RESULTS: In 11 cases, the facial nerve could be saved but in six the nerve had to be rebuilt with a transplant. During the first years of our study, palsy of the facial nerve was a frequent finding. In the later years, a hearing impairment and tinnitus became the most frequent symptoms. CONCLUSIONS: Advances in magnetic resonance imaging have, in many cases, facilitated the differentiation between schwannomas of the facial nerve and the vestibular nerve over the last years. Signal enhancement at the geniculate ganglion is important for the diagnosis of facial nerve schwannoma. In individual cases, we found significant findings using electrophysiological procedures. In three cases, the temporal delay was elongated. Based on these findings, the therapeutic procedures can be discussed together with the patients.

Nasal airway changes after Le Fort I--impaction and advancement: anatomical and functional findings.

Twenty patients were studied prospectively to assess intranasal anatomical changes and functional changes resulting from a one-piece Le Fort I-osteotomy with anterior and superior positioning of the maxilla. Presurgical and 3 months postsurgical rhinological inspection, anterior rhinomanometry and acoustic rhinometry were performed. Interalar width was measured and cephalograms were used to assess maxillary movement. Rhinoscopically, three septal perforations (15%) were noticed. Turbinate enlargement was less common postoperatively. Interalar width increased significantly. These findings correlate with a significant increase in cross-sectional diameter at the Isthmus nasi revealed by acoustic rhinometry 3 months postoperatively. The mean total nasal airflow measured by anterior rhinomanometry was unchanged indicating no increase in resistance despite decreased intranasal dimensions in cases where the impaction is not higher than 5 mm.

Enlarged middle fossa vestibular schwannoma surgery: experience with 735 cases.

OBJECTIVE: To show the clinical outcome in patients with sporadic vestibular schwannoma (VS) operated on by the enlarged middle cranial fossa approach (EMFA). STUDY DESIGN: Retrospective case review. SETTING: A tertiary referral center with four neurotologists experienced in EMFA surgery. PATIENTS: There were 376 women and 359 men, with a mean age of 51.1 years (range, 12-77). INTERVENTION: Enlarged middle cranial fossa approach surgery. MAIN OUTCOME MEASURES: Magnetic resonance imaging and computed tomography scans were used for follow-up and re-evaluation of the operative sites. Facial nerve function and hearing were tested. RESULTS: Overall complete VS removal was achieved in 97.1% of patients. There were two recurrences (0.3%) after microscopically complete tumor removal. Depending on the tumor size, postoperative normal and near-normal facial outcome ranged from 83% to 99% (average, 92%), and hearing at or near the preoperative level (+/-15 dB pure-tone average or +/-15% speech discrimination) was preserved in 60.2%, 48.2%, 23.9%, and 17.6%, respectively. CONCLUSIONS: The EMFA is an excellent low-morbidity approach for VS removal with limited cerebellopontine angle extension (2 cm). Specific advantages of the EMFA are the superior internal auditory canal exposure, resulting in an extremely low tumor recurrence rate; best capability for hearing preservation; and minimal incidence of cerebrospinal fluid leaks. Postoperative facial function outcome compares with that of other surgical approaches. The best results are achieved in subjects with small tumors and good hearing, advocating early diagnosis and treatment.

Extended middle fossa surgery for meningiomas within or at the internal auditory canal.

OBJECTIVE: To show the clinical outcome in patients with meningioma within or at the internal auditory canal (IAC) operated on by the extended middle cranial fossa approach. STUDY DESIGN: Retrospective case review. SETTING: A tertiary referral center. PATIENTS: Twelve patients, 9 women and 3 men, whose ages ranged from 37 to 70 years (mean 57 years). One tumor was entirely intracanalicular, 5 had an intra-extracanalicular growth, 3 were centered at the posterior porus lip, and 3 tumors were localized in the midpetrosal region with spread into the IAC. INTERVENTION: Extended middle cranial fossa approach. MAIN OUTCOME MEASURES: Magnetic resonance imaging and computed tomography were used for follow-up and reevaluation of the operative sites. Facial nerve function and hearing were examined. RESULTS: Complete resection was achieved in 10 (83%) of 12 patients. The retrosigmoid approach was necessary to complete tumor resection in one patient, and in another, partial resection was done because of the en plaque type of tumor growth. There was one unexpected recurrence. All patients retained normal or near-normal facial nerve function postoperatively. Three patients were deaf before surgery, and preoperative hearing level was preserved in 42%. CONCLUSIONS: Attempted hearing preservation surgery is justified in patients with small tumors and preserved hearing, because tumor exposure and safety of resection are comparable with that of hearing-destructive procedures. Lateral extension of the tumor to the fundus does not prevent complete resection with preservation of function, and elective bone resections beyond the visible tumor margins seem not to substantially influence the tumor recurrence rates.

[Inverted papilloma of the nose and paranasal sinuses. Long-term outcome of endoscopic endonasal resection]. / Invertierte Papillome der Nase und ihrer Nebenhöhlen. Langzeitergebnisse nach endoskopischer endonasaler Resektion.

There is still some skepticism about endoscopic endonasal resection of inverted papillomas. We conducted a long-term retrospective study and examined 104 patients (82 male, 22 female) with inverted papilloma who were operated at the ENT-Department of the University of Erlangen between 1974 and 1997. The endoscopic approach was chosen in each case, either alone or in combination with external approaches. In 64.4% (67 cases), tumors of all T-classes were resected by endoscopic approach alone (T1:17.9%, T2:23.9%, T3:41.8%, T4:16.4%). For the rest of the patients an additional transoral and transfacial approach was necessary due to difficult tumor localization (T2:24.3%, T3:29.7%, T4:45.9%). The mean age of the patients was 55 years. The recurrence rate after primary endoscopic endonasal sinus surgery was 22.4% (15/67) and after combined endoscopic and external surgery 16.2% (6/37). Second salvage surgery after endoscopic sinus surgery was performed again endonasally in 46% (7/15) and externally in 53.3% (8/15). The recurrence rate after the endonasal approach was now 57.1% (4/7) and 50% (4/8) after external surgery. Third salvage surgery was performed again endoscopically in four cases and externally in four cases. The recurrence rate in both groups was 50% each, so that up to six operations, either endoscopically or externally, were necessary for complete tumor resection. The longest period for a tumor recurrence was 3.4 years after endoscopic sinus surgery and 9 years after combined endoscopic and external surgery. A tumor recurrence after endoscopic endonasal sinus surgery that could not be managed endoscopically again occurred in 12%. Tumor localization is the limiting factor for endoscopic endonasal sinus surgery of inverted papilloma. However, in 64.4% of cases, endoscopic endonasal sinus surgery alone was performed successfully without any loss of one patient. Long-term follow-up is necessary since the recurrence of tumor can happen after a long time. Endoscopic endonasal sinus surgery of inverted papilloma is safe and should be preferred due to its minimal invasive character.

Arachidonic acid metabolism in nasal tissue and peripheral blood cells in aspirin intolerant asthmatics.

Aspirin intolerance (AI) is characterized by polypous rhinosinusitis, bronchial asthma and adverse reactions to aspirin. The common intolerance to all cyclo-oxygenase inhibitors allows us to focus study of the pathogenesis of AI on the metabolism of arachidonic acid (AA). We studied the metabolism of AA in nine aspirin intolerant asthmatics (AIA) and eight healthy volunteers (controls) by measuring prostaglandin E2 (PGE2) and peptido-leukotrienes (pLT = LTC4/D4/E4) in nasal tissue and peripheral blood cells (PBCs) using a specific immunoassay. In all patients with AI the tests were performed before and after bronchial provocation with lysine-ASA. In the control group the tests were done before and after 500 mg ASA p.o. The release of pLT in nasal polyps of AIA was found to be significantly higher than in normal mucosa of AIAs and controls. In every tissue a significant increase of pLT after aspirin challenge was observed. Nasal polyps of AIA show a significantly lower release of PGE2 than normal mucosa of AIAs and controls. Peripheral blood cells of AIA show a significantly higher release of pLT and a significantly lower release of PGE2 than PBCs of controls. Therefore clinical manifestations of AI may be based on an alteration of AA metabolism in AIA.

[Enlarged middle fossa approach to the cerebello-pontine angle. Technique and indications]. / Voie d'abord sus-pétreuse élargie à l'angle ponto-cérébelleux. La technique et les indications.

Our enlarged middle fossa approach, first published in 1982, aims to expose the internal auditory meatus and cerebello-pontine angle from above, with preservation of the cochlea and labyrinth. The steps of the operation are described, especially certain technical details: the skin incision, resection of the squamous temporal bone, extradural exposure of the petrous temporal bone, subsequent resection of the middle meningeal artery and superior petrosal sinus, extensive bone removal behind and in front of the internal auditory meatus, opening of the dura mater to expose the brain stem, and plastic closure of the defects. Believing in the advantages of this approach, we have modified the technique for various indications, including decompression of the facial and cochleovestibular nerves for cases of vascular compression and Menière's disease; management of temporal bone fractures with CSF leak of facial nerve damage; extensive cholesteatoma of the petrous bone; meningiomas or other tumours of the petrous bone; neuromas of the facial or vestibular nerve. It should be emphasised that the middle fossa approach may be combined with other approaches in the resection of lateral skull base tumours with preservation of the inner and middle ear.

Experimental sensorineural hearing loss following drill-induced ossicular chain injury.

In a guinea pig model, a standardized drill-induced injury to the body of the incus was applied, and the effects on hearing were characterized by electrocochleography. Drilling resulted in a threshold shift within seconds, and after 15 min it averaged 35.7 dB for clicks, 35 dB nHL for 4 kHz bursts, 36.7 dB nHL for 6 kHz bursts and 39 dB nHL for 8 kHz bursts. The deterioration of the threshold shift remained stable throughout the 5-week post-operative observation period. In five animals a disarticulation of the incudostapedial joint was performed prior to drilling, but this did not reduce the threshold shift. Caution is mandatory during drilling around an intact ossicular chain to avoid a permanent sensorineural hearing loss, and disarticulation of the incudostapedial joint prior to drilling has no protective value.

[Function preserving surgery of glomus jugulare tumors. An achievable goal?]. / Funktionserhaltende Chirurgie von Glomus-jugulare-Tumoren. Ein realisierbares Ziel?

In this retrospective study, oncologic and functional results of 24 patients treated for glomus jugulare tumor stages C and D are reported. The surgical approach used was a combined transmastoid-transcervical approach, which was modified according to individual tumor growth. As needed, this was combined with a transtemporal or retrosigmoid approach. Complete tumor removal resulted in a cure rate of 100%. Surgically induced cranial nerve palsies developed in 38% of the patients. In 54% of cases it was possible to retain middle ear function. Seven patients had incomplete tumor removal requiring postoperative irradiation, with tumor progression occurring in 2 patients. Radical tumor removal was modified by efforts to reduce mutilating resections. These results show that individually tailored and combined multidirectional surgical approaches can allow total tumor removal to be performed with lower morbidity.