Cross-sectional increase of adherence to multidisciplinary tumor board decisions.

BACKGROUND: Cancer research has made great progress in the recent years. With the increasing number of options in diagnosis and therapy the implementation of tumorboards (TUBs) has become standard procedure in the treatment of cancer patients. Adherence tests on tumor board decisions are intended to enable quality assurance and enhancement for work in tumor boards in order to continuously optimize treatment options for cancer patients. METHODS: Subject of this study was the adherence of the recommendations made in three of 14 tumorboards, which take place weekly in the Center for Integrated Oncology (CIO) at the University Hospital Bonn. In total, therapy recommendations of 3815 patient cases were checked on their implementation. A classification into four groups has been made according to the degree of implementation. A second classification followed regarding the reasons for differences between the recommendation and the therapy which the patient actually received. RESULTS: The study showed that 80.1% of all recommendations in the three TUBs were implemented. 8.3% of all recommendations showed a deviance. Most important reasons for the deviances were patient wish (36.5%), patient death (26%) and doctoral decision, due to the patient's comorbidities or side effects of the treatment (24.1%).Interestingly, deviance in all three tumor boards in total significantly decreased over time. CONCLUSIONS: Aim of the study was to clarify the use of tumor boards and find approaches to make them more efficient. Based on the results efficiency might be optimized by increased consideration of patients` preferences, improved presentation of patient-related data, more detailed documentation and further structuring of the tumor board meetings.

Kit transduced signals counteract erythroid maturation by MAPK-dependent modulation of erythropoietin signaling and apoptosis induction in mouse fetal liver.

Signaling by the stem cell factor receptor Kit in hematopoietic stem and progenitor cells is functionally associated with the regulation of cellular proliferation, differentiation and survival. Expression of the receptor is downregulated upon terminal differentiation in most lineages, including red blood cell terminal maturation, suggesting that omission of Kit transduced signals is a prerequisite for the differentiation process to occur. However, the molecular mechanisms by which Kit signaling preserves the undifferentiated state of progenitor cells are not yet characterized in detail. In this study, we generated a mouse model for inducible expression of a Kit receptor carrying an activating mutation and studied its effects on fetal liver hematopoiesis. We found that sustained Kit signaling leads to expansion of erythroid precursors and interferes with terminal maturation beyond the erythroblast stage. Primary KIT(D816V) erythroblasts stimulated to differentiate fail to exit cell cycle and show elevated rates of apoptosis because of insufficient induction of survival factors. They further retain expression of progenitor cell associated factors c-Myc, c-Myb and GATA-2 and inefficiently upregulate erythroid transcription factors GATA-1, Klf1 and Tal1. In KIT(D816V) erythroblasts we found constitutive activation of the mitogen-activated protein kinase (MAPK) pathway, elevated expression of the src kinase family member Lyn and impaired Akt activation in response to erythropoietin. We demonstrate that the block in differentiation is partially rescued by MAPK inhibition, and completely rescued by the multikinase inhibitor Dasatinib. These results show that a crosstalk between Kit and erythropoietin receptor signaling cascades exists and that continuous Kit signaling, partly mediated by the MAPK pathway, interferes with this crosstalk.

Treatment with lenalidomide induces immunoactivating and counter-regulatory immunosuppressive changes in myeloma patients.

Lenalidomide activates the immune system, but the exact immunomodulatory mechanisms of lenalidomide in vivo are poorly defined. In an observational study we assessed the impact of lenalidomide on different populations of immune cells in multiple myeloma patients. Lenalidomide therapy was associated with increased amounts of a CD8(+) T cell subset, phenotypically staged between classical central memory T cells (TCM) and effector memory T cells (TEM), consequently termed TCM/TEM. The moderate expression of perforin/granzyme and phenotypical profile of these cells identifies them as not yet terminally differentiated, which makes them promising candidates for the anti-tumour response. In addition, lenalidomide-treated patients showed higher abundance of CD14(+) myeloid cells co-expressing CD15. This population was able to inhibit both CD4(+) and CD8(+) T cell proliferation in vitro and could thus be defined as a so far undescribed novel myeloid-derived suppressor cell (MDSC) subtype. We observed a striking correlation between levels of TCM/TEM, mature regulatory T cells (T(regs)) and CD14(+) CD15(+) MDSCs. In summary, lenalidomide induces both activating and inhibitory components of the immune system, indicating the existence of potential counter-regulatory mechanisms. These findings provide new insights into the immunomodulatory action of lenalidomide.

Reliability of non-invasively acquired human genomic DNA as a substrate for real-time PCR-assisted analysis of genetic polymorphisms.

Molecular epidemiological studies require high numbers of participants. The combination of an non-invasive access to human DNA with a rapid genotyping analysis, e.g. by use of LightCycler assisted real-time polymerase chain reaction (PCR), can be helpful in conducting such trials. The aim of our study was to define, for the first time, the use of LightCycler technology in analysis of non-invasively derived DNA. DNA extracted from blood, mouthwash and buccal cytobrush samples from 100 volunteers was analyzed for the genotypes of cytochrome P450 CYP1B1, and glutathione S-transferases GSTT1, GSTM1 and GSTP1. The median amounts of DNA isolated from blood, mouthwash and buccal cytobrush samples were 95, 11 and 8 microg, respectively. While genotyping for CYP1B1 codon 432 polymorphism and GSTP1 codon 105 polymorphism resulted in a complete correspondence for all three modes of sampling, the identification of individuals with null-genotype for GSTT1 or GSTM1 failed in some cases due to atypical courses of the corresponding melting curves, leading to high false-positive rates in the group of non-invasively derived samples. Thus, the results presented here call for caution in using LightCycler assisted real-time PCR in non-invasively collected samples, at least when appropriate control strategies are not implemented.

Anesthesia for intranasal surgery: a comparison between tracheal intubation and the flexible reinforced laryngeal mask airway.

UNLABELLED: The purpose of the study was to assess the suitability and safety of the flexible reinforced laryngeal mask airway (FRLMA) for intranasal surgery (INS) anesthesia. A secondary objective was to compare the incidence of complications of removal of the FRLMA with tracheal extubation in awake and anesthetized patients. One hundred fourteen ASA physical status I and II patients requiring INS were randomly assigned into three groups: Group I = FRLMA, Group II = endotracheal tube (ET) extubated awake, and Group II = ET extubated deeply anesthetized. In Group I, the incidence of coughing and oxyhemoglobin desaturation at removal was significantly reduced compared with that in Groups II and III (P < 0.05). There were no episodes of postremoval laryngospasm in Group I; in Group III, the incidence was 19% (P < 0.05), whereas in Group II, it was 6% (not significantly different). The number of patients with oxyhemoglobin desaturation < or = 92% on admission to the postanesthesia care unit was 0% in Group I, 26% in Group II (P < 0.05), and 16% in Group III (not significantly different). At bronchoscopy, the incidence of blood visible in the airway was low and similar among the three groups (3%, 6%, and 3%, respectively). There were no significant differences in the incidence of airway complications between Groups II and III. IMPLICATIONS: We compared airway management for intranasal surgery anesthesia using a new device, the flexible reinforced laryngeal mask airway, with the current standard of tracheal intubation. The study demonstrates that the flexible reinforced laryngeal mask airway can provide a safe, protected airway with a smoother emergence from anesthesia than tracheal intubation.

Sphenopalatine blocks in the treatment of pain in fibromyalgia and myofascial pain syndrome.

Sphenopalatine blocks have been used to treat pain for more than 80 years. Anecdotal support for sphenopalatine ganglion blocks has been very strong in those who believe in the technique, but the research results have been inconclusive. Therefore, a double blind, placebo-controlled study was performed on 61 patients, 42 with fibromyalgia and 19 with myofascial pain syndrome. Pain was measured using visual analogue scales prior to treatment, during treatment, and 28 days after the treatment. Headaches were evaluated in frequency and location prior to and after treatment. Sphenopalatine ganglion blocks were performed under direct vision using 4% lidocaine and sterile water as a placebo. Analysis of the results showed no statistical differences between the lidocaine and the placebo groups.

Technique for assessing nasal airway resistance in patients treated prosthetically.

This investigation was designed to compare nasal airway resistance (Rnaw) values by use of "head-out" plethysmography and standard posterior pressure-flow rhinometry. Fourteen adults who had prostheses because of velopharyngeal inadequacy caused by a variety of etiologic conditions were examined. Each patient performed rest breathing and sustained /m/ productions to develop Rnaw values for comparison. The results revealed increased Rnaw and decreased cross-sectional nasal airway area and derived velopharyngeal orifice area when the appliances were in place. The two techniques for assessing Rnaw produced comparable results when certain conditions were met. Clinical implications for team assessment of patients involved with prosthetic management are discussed.

Medial meatal fibrosis: the University of Western Ontario experience.

Medial meatal fibrosis is an uncommon but surgically treatable cause of conductive hearing loss. A review of 10 years experience with this entity at The University of Western Ontario revealed a total of 15 cases involving nine patients. Each of them was treated by one of four otologists. This disease may arise from either recurring or chronic infection or from chronic dermatitis, and it frequently presents with bilateral involvement. It may occur at virtually any age, and to our knowledge, this series includes the first cases of this disease to be described in children. The medical and surgical management of this condition is described in detail and the results are summarized.

Conservative management of Tumarkin's otolithic crisis.

Tumarkin's otolithic crisis (TOC), characterized by a sudden drop attack without accompanying loss of consciousness, vertigo or autonomic signs, is a rare phenomenon thought to be of peripheral origin and associated with late-stage Meniere's disease. The purpose of this paper is to describe the clinical course of TOC in our series; to discuss the relationship between TOC and the onset and symptomatology of pre-existent Meniere's disease, and to determine the management of patients with TOC.

Epiglottitis: adult and pediatric comparisons.

All cases of epiglottitis admitted to the three affiliated teaching hospitals of the University of Western Ontario over the ten year period prior to December 1986, were subjected to a retrospective chart review. The findings confirmed the suspicion of the senior authors that adult epiglottitis is almost as frequent an entity as epiglottitis in children. This probably results from an increased awareness of the disease process rather than an actual increase in incidence. Also of note is the bimodal age distribution of 0-8 years in children and 20-40 years in adults. As well, clinical presentation, causative organisms, treatment modalities and complications between adults and pediatric age groups are compared and contrasted.

Otolaryngologic manifestations of amyotrophic lateral sclerosis.

Otolaryngological manifestations were examined in a series of 250 patients diagnosed as having ALS between 1976 and 1986. Surgical intervention was only required in 10 cases due to excessive drooling and aspiration. Five patients had submandibular gland excisions with only limited improvement in respect to drooling. One case having a unilateral tympanic neurectomy had significantly better drooling control. Cricopharyngeal myotomy is helpful when dysphagia is predominantly due to cricopharyngeal spasm. In our series, tympanic neurectomy and chorda tympanectomy provide the better control of drooling for these patients and has the added advantage of being performed under local anesthesia.

Rhinological disorders in the elderly.

Aging in the nasal tissues produces anatomical and physiological changes in the elderly. The elderly have a generalized decrease in body water content of 7%, and with the degeneration of mucus-secreting cells, the effectiveness of the mucociliary system is reduced with frequent symptoms of nasal stuffiness. The fragmentation and weakening of the cartilage of the septum also causes airflow changes contributing to nasal stuffiness. The elderly also experience hormonal and metabolic changes which affect the physiologic nasal function. Epistaxis is relatively common in the elderly, and aging changes in the vascular system such as atherosclerosis contribute to the severity of epistaxis. The majority of nosebleeds in the elderly originate anteriorly due to dryness and local trauma.

Malleus to stapes assembly.

The malleus to stapes assembly is the ideal ossicular reconstruction because of its high degree of success. Unfortunately, both the malleus and the stapes have to be in good position to use this type of reconstruction making it much less common than other forms of ossiculoplasty. Over a six year period, 1976-1982, there were 20 such procedures performed, as compared to 85 cases of hemi-incus interposition ossiculoplasty in the same period. The malleus to stapes assembly technique and indications are described in this report. Reconstruction results show an 80% air-bone gap closure within 10 dB with an average improved speech reception threshold of 18 dB.

The changing nature of otological practice in a teaching centre.

The impression that otologic surgical practice is a declining segment of the specialty of otolaryngology is widespread. In an attempt to assess objectively the validity of that assumption, the authors reviewed their own experience over the 12 years 1971-82 inclusive. Five representative years out of the 12 were examined--1971, 1974, 1977, 1979, and 1982. In each of these years, the relative and absolute frequency with which six common otological procedures were performed was determined. The procedures selected for study included myringoplasty, tympanoplasty Type I, II, III and IV, and stapedectomy. In addition the relative frequency of primary vs. revision operations was assessed. The data indicate a change in the pattern of otologic surgical practice over the period, most noticeably in the ratio of primary to revision procedures. These changes have significant implications for the teaching and practice of otology in the future.

Ossiculoplasty using a hemi-incus interposition.

A damaged incus is one of the common reconstruction problems encountered by the otologic surgeon. Eighty-five hemi-incus interposition reconstructive procedures performed between 1976 and 1982 were reviewed. Reconstruction consisted of an autogenous or homologous incus bone graft interposed between the tympanic membrane and the mobile stapes superstructure. Air bone gap closure to within 20 dB was obtained in 77% of cases. Reconstruction using bone graft is better tolerated by the middle ear and the extrusion rate less than that of the biocompatible implants.