[Skull base metastases with cranial nerve deficits : Clinical profile of a severe disease]. / Schädelbasismetastasen mit Hirnnervenaffektionen : Klinischer Steckbrief einer schwerwiegenden Erkrankung.

BACKGROUND AND PURPOSE: Skull base metastases are a severe complication of various malignant tumors. If cranial nerves are involved even small lesions can cause significant symptoms. Specific clinical characteristics like neurological symptoms, associated primary tumors, prognosis and optimal treatment are poorly defined and are systematically described in this article. METHODS: In a monocentric retrospective study patients with skull base metastases and cranial nerve deficits who received treatment between 2006 and 2018 were analyzed concerning clinical characteristics at initial diagnosis, treatment and course of the disease. RESULTS: In this study 45 patients with skull base metastases and cranial nerve deficits were included. The most frequent primary tumors were prostate cancer (27%), breast cancer (22%) and multiple myeloma (16%). The most involved cranial nerves were trigeminal nerve (42%), oculomomotor nerve (33%) and facial nerve (27%). Of the patients 84% had additional bone metastases outside the skull base. Dural infiltration or meningeal carcinomatosis were each observed in 13% of the patients. After radiotherapy cranial nerve deficits remained stable in 61% of all cases and in 22% symptoms improved. Median overall survival from treatment was 8 months (range 0.4-51 months). Patients with dose-escalated radiotherapy appeared to live longer (16.4 months vs. 4.7 months). This effect persisted in a multivariate analysis including the Karnofsky index, number of metastases, primary tumor and radiation dose (HR 0.37, p = 0.02). CONCLUSION: Skull base metastases with cranial nerve deficits are complex diseases with poor prognosis. Precise diagnosis and treatment are required. Further research is needed to improve treatment.

Impact of indication-shift of primary and adjuvant chemo radiation in advanced laryngeal and hypopharyngeal squamous cell carcinoma.

Based on level I evidence, postoperative platinum-based radiochemotherapy (PORCT) is the recommended standard of care in defined risk situations after resection of squamous cell carcinomas of the larynx and hypopharynx (LHSCC). The value of the addition of chemotherapy to adjuvant radiation in intermediate and high risk situations other than extracapsular spread or R1-/R2 resection is still debated. From 1993 to 2009, 555 patients (median follow-up: 24.4 months) with advanced LHSCC (UICC stages III-IVB) were treated in a curative intent. Patient data were continuously documented in the county of Leipzig cancer registry and were retrospectively analyzed as mono institutional survey. PORCT was introduced into the standard procedures in 2004, but also applied before in selected cases. Based on this paradigm shift, the patient population was divided into two comparative groups treated before and after 2004. 361 patients were treated before 2004. 43.8 % received primary surgery (OP) + postoperative radiotherapy (PORT) and 20.2 % OP + PORCT. 194 patients were treated after 2004: 21.1 % received OP + PORT and 35.6 % OP + PORCT. Regarding the PORCT groups, 20.6 % received cisplatin plus 5FU before 2004 which shifted to 59.4 % after 2004. The 3-year tumor-specific-survival rate of the whole cohort was improved from 47 to 60 % (p = 0.006). The subgroup treated with OP + PORT or PORCT improved from 56.1 to 68.5 % (p = 0.028). Localization proved to be a significant and independent factor. Only patients with advanced laryngeal cancer had significant improved survival (p < 0.01), while the improvement for hypopharyngeal cancer patients was not significant (p < 0.2). After 2004, there was a slight increase (+10.2 %) of primary radiochemotherapy (pRCT) due to stronger selection if R0 > 5 mm-resectability is unlikely. Standardised use of PORCT and pRCT considering clear indications showed to be significantly involved in improved survival in advanced LHSCC.

[Multimodal laryngeal preservation: current data-based opinion]. / Multimodaler Larynxerhalt: Wege zur besseren Patientenselektion.

This article presents the current data and discussion on multimodal laryngeal preservation strategies in advanced laryngeal/hypopharyngeal carcinoma. Principally a distinction is made between simultaneous and induction chemoradiation protocols. In terms of late toxicity and related functional limitations, induction protocols are far superior to simultaneous platinum-based chemoradiation. Currently, the individual response to the first cycle of (short) induction chemotherapy appears to be the most reliable clinical marker for making treatment decisions, and this is under clinical investigation. No standard multimodal therapeutic alternative to laryngectomy exists; therefore, at this time multimodal strategies should only be carried out within the framework of clinical trials.

[Laryngeal MALT lymphoma with known Sjögren syndrome]. / MALT-Lymphom des Larynx bei bekanntem Sjögren-Syndrom.

Hematopoietic neoplasms represent about 1% of all laryngeal neoplasms. MALT lymphoma arises from mucosa-associated lymphoid tissue and is associated with chronic inflammatory disease. Patients with Sjögren syndrome have a higher risk for development of non-Hodgkin lymphoma (MALT lymphoma). To date, only cases of MALT lymphoma of the salivary glands, thymus and stomach associated with Sjögren syndrome have been published. We present the case of a MALT lymphoma of the larynx associated with Sjögren syndrome. Radiation and chemotherapy are the first line of therapy as published in the literature.

[Treatment related swallowing dysfunction and the potentialities of IMRT]. / Schluckstörungen nach Kopf-Hals-Tumortherapie und die Möglichkeiten der IMRT.

Altered fractionated radiotherapy and concurrent chemoradiation could improve local control and survival for patients with locally advanced head and neck cancer. However, intensified treatment seems to increase late toxicity. Late swallowing dysfunction is common and has a large impact on quality of life and can get life-threatening character. Recent studies could show interrelations between the radiation dose to certain anatomical structures involved in the swallowing process and the risk of swallowing dysfunction. Important structures seem to be the pharyngeal constrictors and the supraglottic and glottic larynx. Further prospective clinical validations using standardized diagnostic protocols for dysphagia are necessary to establish dose constraints to anatomical structures involved in swallowing.

Intrathecal thyrotropin-releasing hormone therapy of amyotrophic lateral sclerosis.

Six patients with amyotrophic lateral sclerosis were given from 800 to 4000 micrograms of thyrotropin-releasing hormone (TRH) intrathecally for a period of 2-6 months. The progressive course of this disease, manifested by increasing atrophy, paralysis and disability score, was not altered. This supports the hypothesis that the decrease in TRH content in the anterior horn region is secondary to the cellular destruction. TRH appears to play no significant role in the pathogenesis of amyotrophic lateral sclerosis.

Molecular mechanisms of hyperthermia- and cisplatin-induced cytotoxicity in T cell leukemia.

BACKGROUND: The prognosis of early and very early relapse in acute lymphoblastic leukemia of childhood is still very poor unless a hematopoietic stem cell transplant is performed if a second remission can be achieved by induction chemotherapy. Therefore an intensification of chemotherapy is required. MATERIALS AND METHODS: In the present study the molecular mechanisms of cisplatin- and/or hyperthermia-mediated cytotoxicity in CEM cells, a human T leukemia cell line, were investigated. RESULTS: Both hyperthermia and cisplatin induced the activation of the effector caspases-3 and -6. However, caspase activation followed different time kinetics. While hyperthermia exerted maximum caspase activation immediately after application, cisplatin activated caspase-3 and -6 after 24 hours. At both time-points significant caspase-3 and -6 activation was observed when the cells were stimulated by a combination of heat and cisplatin. The application of z-VAD-fmk, a general caspase inhibitor, showed that hyperthermia mediated cytotoxicity mainly via caspase-dependent mechanisms, while cisplatin induced both caspase-dependent and -independent cytotoxicity. Time kinetic experiments revealed that hyperthermia induced cell death immediately after the heating pulse. In contrast, cisplatin-induced cell death had its maximum between 6 hours and 12 hours after the heating pulse. The combined application of heat and cisplatin induced two peaks of cytotoxicity, one immediately after the heating pulse and the other between 6 hours and 12 hours. CONCLUSION: Hyperthermia and cisplatin induced cell death in T leukemic cells by different molecular mechanisms, which might explain the enhanced cisplatin-induced cytotoxicity by hyperthermia.

Mechanisms of hyperthermia- and 4-hydroperoxy-ifosfamide-induced cytotoxicity in T cell leukemia.

The prognosis of patients with early ALL (acute lymphoblastic leukaemia) relapse is poor with conventional chemotherapy alone. Thus, intensified chemotherapy strategies are required. The application of hyperthermia enhances the efficacy of certain antineoplastic drugs such as ifosfamide. In this study, the effects and molecular mechanisms of ifosfamide (4hydroperoxy-ifosfamide = 4OOH-IFA)- and/or hyperthermia-induced cell death are investigated in CEM cells. Hyperthermia enhanced the efficacy of 4OOH-IFA in a subaddictive manner. Analysis of caspase activation revealed an early hyperthermia-induced stimulation of caspase-3 and -6 directly after the heating pulse, while maximum activation following stimulation with 4OOH-IFA was obtained after 24 hours of culture. The combination of 4OOH-IFA and hyperthermia mediated an overaddictive caspase stimulation directly following the heating phase. At this time also an overaddictive cytotoxic effect was noticed, being mainly responsible for the enhancing effects of hyperthermia on 4OOH-IFA cytotoxicity. In conclusion, hyperthermia enhanced the cytotoxic effect of 4OOH-IFA on CEM cells by stimulation of an early 4OOH-IFA effect. Thus, thermochemotherapy might be considered as an intensifying treatment option in relapsed T cell leukemias.

[Activity of the psychologist within the inpatient psychotherapy of behavior disordered children and adolescents]. / Zur Tätigkeit des Psychologen innerhalb der stationären Psychotherapie verhaltensgestörter Kinder und Jugendlicher.

The author, after discussing the problem of cooperation between the physician and psychologist within the framework of psychotherapeutic activity, deals with the special functions of psychologists. Work done in this respect at the Dresden Medical Academy's department for psychotherapy of malbehaving children and juveniles of normal intelligence is described. Also outlined in this paper are the role played by the psychologist in the use of various methods of therapy and his cooperation in the continuing education and training of nurses, the psychometric control of the course of therapy, and the rehabilitation of children and juveniles.

["Parent centered" group work as a possibility in parent counseling in child psychotherapy]. / "Elternzentrierte" Gruppenarbeit als Möglichkeit der Elternberatung in der Kinderpsychotherapie.

Neurotic disturbances in children can be largely explained by pathogenic attitudes of the parents. Disappointment, guilt and helplessness are neutralised or denied by a multitude of defence mechanisms. The advisory service for parents is concerned with the task to dissolve these defence mechanism and to relieve the disturbed parents-child relations. According to the authors' opinion, parents can arrive at a "child-centred" attitude when the therapist, too, is experienced in his attitude as "child-and-parents-centred". In the group work with parents, a combination of talk groups with "supplementary methods" after Brocher and training groups according to the "defeatless method of conflict overcoming" after Gordon has proved to be suitable. Practical approach and experiences are described.

Heat- and 4-hydroperoxy-ifosfamide-induced apoptosis in B cell precursor leukaemias.

In the group of high risk childhood acute lymphoblastic leukaemia (ALL), very early and early relapses have a very poor prognosis with conventional chemotherapy alone. Remission induction in these patients is often hindered by drug resistance. Thus, intensifying chemotherapy strategies are required. Application of hyperthermia enhances efficacy of certain anti-neoplastic drugs such as ifosfamide. In this study, effects and molecular mechanisms of ifosfamide - and hyperthermia-induced apoptosis are investigated in a B cell precursor leukaemia cell line (REH) and in primary patient-derived B cell progenitor leukaemic blasts. Both 4OOH-IFA and hyperthermia are able to induce cell death in leukaemic cells, mainly by induction of caspase-dependent apoptosis. However, completely different kinetics of caspase-3, -8 and -9 activation are found for both stimuli. In addition, activation of caspase-1 is only observed following stimulation with hyperthermia. Combined application of ifosfamide and hyperthermia reveals increased cytotoxicity in both the leukaemia cell line and in 5/8 of the patient-derived leukaemic blast samples. In conclusion, hyperthermia and ifosfamide mediate cytotoxicity in B precursor leukaemic blasts by different kinetics of caspase activation. This might explain the additive effects of 4OOH-IFA and heat on leukaemic cell death. Therefore, whole body thermochemotherapy could be considered as a treatment option in relapsed leukaemic patients.