Search

Supplementary Table S4. Focal copy number aberrations detected in the relapse samples

Supplementary Fig. S1: Stepwise accumulation of segmental chromosomal aberrations (SCAs) in chromosome 7 of the case study. Supplementary Fig. S2: Whole genome views of 10 different samples of a single stage 4 neuroblastoma patient. Supplementary Fig: S3: Allele difference tracks and smooth signals of chromosome 1q of four different samples of the case study. Supplementary Fig. S4: I-FISH for visualization of 1q deletion in the DTCs at diagnosis and tumor 6 at diagnosis. Supplementary Fig. S5: Frequencies of common segmental chromosomal aberrations in the DTCs with and without 1q deletions at diagnosis and relapse. Supplementary Fig. S6: Deleted regions of 19q in different patients. Supplementary Fig. S7: Event-free and overall survival curves for patients with and without 1q, 19q, or ATRX deletions in the primary tumors. Supplementary Fig. S8: Event-free and overall survival curves for patients with and without 1q, 19q, or ATRX deletions in the diagnostic DTCs.

Purpose: Tumor relapse is the most frequent cause of death in stage 4 neuroblastomas. Since genomic information on the relapse precursor cells could guide targeted therapy, our aim was to find the most appropriate tissue for identifying relapse-seeding clones.Experimental design: We analyzed 10 geographically and temporally separated samples of a single patient by SNP array and validated the data in 154 stage 4 patients.Results: In the case study, aberrations unique to certain tissues and time points were evident besides concordant aberrations shared by all samples. Diagnostic bone marrow–derived disseminated tumor cells (DTCs) as well as the metastatic tumor and DTCs at relapse displayed a 1q deletion, not detected in any of the seven primary tumor samples. In the validation cohort, the frequency of 1q deletion was 17.8%, 10%, and 27.5% in the diagnostic DTCs, diagnostic tumors, and DTCs at relapse, respectively. This aberration was significantly associated with 19q and ATRX deletions. We observed a significant increased likelihood of an adverse event in the presence of 19q deletion in the diagnostic DTCs.Conclusions: Different frequencies of 1q and 19q deletions in the primary tumors as compared with DTCs, their relatively high frequency at relapse, and their effect on event-free survival (19q deletion) indicate the relevance of analyzing diagnostic DTCs. Our data support the hypothesis of a branched clonal evolution and a parallel progression of primary and metastatic tumor cells. Therefore, searching for biomarkers to identify the relapse-seeding clone should involve diagnostic DTCs alongside the tumor tissue. Clin Cancer Res; 23(15); 4224–32. ©2017 AACR.

To evaluate the effect of histopathologic skin invasion on 2- and 5-year disease-free survival (DFS) and overall survival (OS) in patients treated with primary surgery for locally advanced oral cavity squamous cell carcinoma (OCSCC).A retrospective case-control study was performed comparing previously untreated patients with pT4a OCSCC with and without skin invasion.Academic medical center.Propensity score-matched cohorts were derived by age, sex, surgical margins, pathologic N classification, adjuvant treatment, and primary tumor site. The Kaplan-Meier method was used to evaluate 2- and 5-year OS and DFS, which were compared between cohorts via the log rank (Mantel-Cox) test statistic.Overall 25 patients were identified to have pathologic skin invasion, and 50 were selected for the matched control group. OS was significantly lower for patients with skin invasion as compared with controls at 2 years (30.8% vs 53.3%,Histopathologic skin invasion in OCSCC is associated with dismal prognosis in patients who underwent primary surgical treatment. OS outcomes for patients with skin invasion are comparable to survival of patients with recurrent/metastatic disease and T4N2 disease.

Introduction: Vaccine hesitancy has historically played a large role in the low rate of the human papillomavirus (HPV) vaccine coverage in the United States and has further surfaced to the forefront of public discourse since the start of the COVID-19 pandemic. This study aims to determine how HPV vaccination attitudes and trends among primary care physicians and patients have changed since the COVID-19 pandemic. Design: Physicians and patients (aged 9-45) participated in a voluntary survey regarding HPV vaccination. In patients under 18 years of age, the survey was completed by the patient’s parent or guardian. Results: Of the 27 healthcare providers surveyed, 22.2% agreed that there has been an increase in misinformation about the HPV vaccine since the COVID-19 pandemic and 7.4% of providers believed that patients were less willing to discuss or receive the HPV vaccine. A majority of patients surveyed (87.7%) were aware of the HPV vaccine but only about a third of those patients had received all three doses of the vaccine (28.1%). Conclusion: Recent trends in receiving the HPV vaccine may be associated with the polarizing climate during the COVID-19 pandemic. Understanding how trends in vaccine hesitancy have changed since the pandemic will allow further and more targeted efforts to increase HPV vaccine uptake.

Glomus tumors are mesenchymal tumors that arise from glomus bodies and most frequently occur in the distal extremities. These tumors can occur throughout the body and are typically benign. However, a very small fraction of glomus tumors displays aggressive features and are considered atypical or malignant. We report on our experience and management of the first case in the literature of a malignant glomus tumor in a child originating in the paraspinal region with involvement of the cervical spine. Malignant glomus tumors tend to be locally aggressive, and en bloc resection is difficult, especially when the tumors occur in the head and neck. Additional studies on disease progression and adjuvant treatment outcomes are necessary to determine the best treatment approach and long-term outcomes in patients with malignant glomus tumors.

Introduction Glioblastoma multiforme (GBM) is the most common primary brain malignancy in adults and is typically in the supratentorial cerebral hemispheres. It has been reported to occur in the posterior fossa at the cerebellopontine angle (CPA), but the incidence is extremely rare. Case Report We report a case of a patient with a history of neurofibromatosis type I (NFI) diagnosed with a GBM arising in the CPA after presenting with facial numbness and pain. Patients with NFI are known to have an increased risk of developing both benign and malignant tumors, including a propensity for brainstem gliomas. However, there is no known association between NFI and tumors of the CPA. We believe this is the first reported case of a GBM of the CPA in a patient with NFI. Conclusion Although rare, GBM should be included in the differential diagnosis of a patient with a CPA tumor, especially in patients with increased risk of malignant pathology.

The goal of this study was to determine the incidence of postoperative tachycardia and its predictive value of complications in patients following microvascular free flap surgery in the head and neck.Retrospective chart review.Single tertiary care academic medical center.All patients who underwent a microvascular free flap of the head and neck by surgeons in the department of otolaryngology from 2013 to 2017 were included in this study.Of the 344 who patients met inclusion criteria, 40.4% had a maximum heart rate (HR) of the hospitalization over 110 beats per minute (bpm). Patients with a maximum HR greater than 110 bpm were 19 times more likely to experience a composite vascular complication (myocardial infarction, myocardial necrosis, or pulmonary embolism) than patients with a maximum HR110 bpm ( P = .0063). Patients with a history of chronic kidney disease were also noted to have an increased risk of experiencing a postoperative composite vascular event.Postoperative tachycardia is significantly associated with adverse outcomes and should not be dismissed as a normal variant. Identifying patients at an increased risk of having an underlying complication can help guide interpretation, workup, and management of postoperative patients in the head and neck population.

Head and neck cancer patients require close clinical follow up to monitor and address sequelae of treatment and for adequate cancer surveillance. The goal of this study is to determine barriers and risk factors for head and neck cancer patients who are lost-to-follow-up.A chart review of the Head and Neck Cancer Registry was performed to identify patients who were lost-to-follow-up (LTF). LTF was defined as missing two consecutive appointments as recommended by their oncologic surgeon. Those identified as LTF were contacted via email and phone to complete a 16-question survey addressing possible barriers to follow up.Of the 353 patients reviewed, 53 met the criteria for LTF (15%). Forty-eight participants were contacted, and 23 surveys were completed (48%). Of the 23 patients that responded, 22% reported difficulty scheduling an appointment, 30% had transportation barriers, 22% had personal or work obligations that prevented follow up, 17% did not follow up because they "felt better," and 39% were following up with an otolaryngologist or oncologist closer to home. Only three participants (13%) were aware of the recommended 5-year surveillance period.Head and neck cancer patients have a variety of reasons they are lost to follow-up. Understanding these barriers is critical to creating a patient-centered model that balances both clinical surveillance needs and reasonable expectations for patients. Improvements can be made to educate patients on the recommended length of follow-up and its importance.

We evaluated long-term outcome and genomic profiles in the Austrian Neuroblastoma Trial A-NB94 which applied a risk-adapted strategy of treatment (RAST) using stage, age and MYCN amplification (MNA) status for stratification. RAST ranged from surgery only to intensity-adjusted chemotherapy, single or multiple courses of high-dose chemotherapy (HDT) followed by autologous stem cell rescue depending on response to induction chemotherapy, and irradiation to the primary tumor site. Segmental chromosomal alterations (SCAs) were investigated retrospectively using multi- and pan-genomic techniques. The A-NB94 trial enrolled 163 patients. Patients with localized disease had an excellent ten-year (10y) event free survival (EFS) and overall survival (OS) of 99 ± 1% and 93 ± 2% whilst it was 80 ± 13% and 90 ± 9% for infants with stage 4S and for infants with stage 4 non-MNA disease both 83 ± 15%. Stage 4 patients either &gt, 12 months or ≤12 months but with MNA had a 10y-EFS and OS of 45 ± 8% and 47 ± 8%, respectively. SCAs were present in increasing frequencies according to stage and age: in 29% of localized tumors but in 92% of stage 4 tumors (p &lt, 0.001), and in 39% of patients ≤ 12 months but in 63% of patients &gt, 12 months (p &lt, 0.001). RAST successfully reduced chemotherapy exposure in low- and intermediate-risk patients with excellent long-term results while the outcome of high-risk disease met contemporary trials.

Introduction The treatment options for acoustic neuromas are observation with serial imaging, stereotactic radiation, or surgical resection. The most common surgical approaches are the translabyrinthine (TL), the retrosigmoid (RS), and the middle cranial fossa. During the TL approach the sigmoid sinus is decompressed with bipolar cautery to allow greater medial exposure. It is unknown if this causes any long-term narrowing or thrombus of the sigmoid sinus. Methods We performed a retrospective review of patients who underwent acoustic neuroma resection to determine if patients undergoing a TL approach for acoustic neuroma resection develop radiographic evidence of sigmoid sinus stenosis or thrombosis compared with patients undergoing a RS approach. Results A total of 128 patients were included in this study, 56 patients underwent a TL approach and 72 patients underwent a RS approach. We compared the preoperative and postoperative diameter of the ipsilateral and contralateral sigmoid sinus at proximal, midpoint, and distal locations on magnetic resonance imaging examinations. There was no significant difference between the preoperative and postoperative diameter of the ipsilateral or contralateral sigmoid sinus based on surgical approach. Conclusion Decompression of the sigmoid sinus during the TL approach does not have a significant postoperative effect on the dural venous sinus patency.

Background Postoperative blindness is a devastating surgical complication. Although usually associated with prolonged cardiac and prone spinal operations, it may follow other procedures as well. Postoperative blindness is most commonly caused by a vascular etiology, but it can more rarely be caused by status epilepticus. We have previously reported a case of this phenomenon following a staged spinal deformity surgery. Case Description Here we report 2 additional cases following a skull base procedure and a single stage lumbar spine surgery. In all instances, rapid recognition that the patients' blindness was due to occipital seizures resulted in acute antiepileptiform treatment and full restoration of vision. Conclusions Although a rare phenomenon, this syndrome, first recognized and described by Tarik F. Ibrahim, should be considered in any patient with postoperative visual impairment.

Amplification of MYCN is the signature genetic aberration of 20–25% of neuroblastoma and a stratifying marker associated with aggressive tumor behavior. The detection of heterogeneous MYCN amplification (hetMNA) poses a diagnostic dilemma due to the uncertainty of its relevance to tumor behavior. Here, we aimed to shed light on the genomic background which permits hetMNA in neuroblastoma and tied the occurrence to other stratifying markers and disease outcome. We performed SNP analysis using Affymetrix Cytoscan HD arrays on 63 samples including constitutional DNA, tumor, bone marrow and relapse samples of 26 patients with confirmed hetMNA by MYCN‐FISH. Tumors of patients ≤18m were mostly aneuploid with numeric chromosomal aberrations (NCAs), presented a prominent MNA subclone and carried none or a few segmental chromosomal aberrations (SCAs). In older patients, tumors were mostly di‐ or tetraploid, contained a lower number of MNA cells and displayed a multitude of SCAs including concomitant 11q deletions. These patients often suffered disease progression, tumor dissemination and relapse. Restricted to aneuploid tumors, we detected chromosomes with uniparental di‐ or trisomy (UPD/UPT) in almost every sample. UPD11 was exclusive to tumors of younger patients whereas older patients featured UPD14. In this study, the MNA subclone appears to be constraint by the tumor environment and thus less relevant for tumor behavior in aggressive tumors with a high genomic instability and many segmental aberrations. A more benign tumor background and lower tumor stage may favor an outgrowth of the MNA clone but tumors generally responded better to treatment., What's new? MYCN amplification (MNA) in neuroblastoma (NB) generally associates with an aggressive tumor behavior and detection of MNA leads to an automatic upstaging of the tumor in non‐stage 1 tumors. But what if only a fraction of the tumor cells is MYCN‐amplified? To investigate the diagnostic importance of heterogeneous MNA, the authors conducted a genetic analysis of samples from 26 NB patients with a particular focus on accompanying genetic aberrations. They concluded that tumor behavior is largely dependent on patient age and other chromosomal alterations in the genetic tumor background rather than the mere presence of the MNA clone.

Follicular thyroid cancer (FTC) is the second most common type of thyroid cancers. In order to develop more effective personalized therapies, it is necessary to thoroughly evaluate patient-derived cell lines in in vivo preclinical models before using them to test new, targeted therapies. This study evaluates the tumorigenic and metastatic potential of a panel of three human FTC cell lines (WRO, FTC-238, and TT1609-CO2) with defined genetic mutations in two in vivo murine models: an orthotopic thyroid cancer model to study tumor progression and a tail vein injection model to study metastasis. All cell lines developed tumors in the orthotopic model, with take rates of 100%. Notably, WRO-derived tumors grew two to four times faster than tumors arising from the FTC-238 and TT2609-CO2 cell lines. These results mirrored those of a tail vein injection model for lung metastasis: one hundred percent of mice injected with WRO cells in the tail vein exhibited aggressive growth of bilateral lung metastases within 35 days. In contrast, tail vein injection of FTC-238 or TT2609-CO2 cells did not result in lung metastasis. Together, our work demonstrates that these human FTC cell lines display highly varied tumorigenic and metastatic potential in vivo with WRO being the most aggressive cell line in both orthotopic and lung metastasis models. This information will be valuable when selecting cell lines for preclinical drug testing.

Multiple specialties have demonstrated increased risk of certain postoperative complications in patients with an increased body mass index (BMI). The goal of this study was to understand the outcomes of patients undergoing parotidectomy with an increased BMI and to identify any other patient risk factors for postoperative complications. This study was a retrospective chart review of 432 patients. Patient variables collected included BMI, age, gender, history of diabetes mellitus, type of parotidectomy, and pathology. Outcomes reviewed included facial nerve weakness, hematoma or seroma formation, and wound infection. The results showed that BMI had no statistically significant effect on complications. However, patients undergoing a total parotidectomy, malignant pathology, and patients with a history of diabetes mellitus had significantly more postoperative facial weakness. In conclusion, BMI does not influence postoperative complications in patients undergoing parotidectomy. Patients with diabetes, those undergoing total parotidectomies, and patients with malignant pathology have significantly more facial weakness and should be counseled accordingly.

Purpose Given the increasing costs of medical care, there has been a shift to outpatient elective surgeries in certain patient populations among all surgical specialties. The goal of this study was to compare the safety and efficacy of outpatient parotidectomy with traditional inpatient parotidectomy. Materials and Methods This is a retrospective chart review of all patients who underwent a parotidectomy at a single tertiary academic center from 2007 through 2017. Results There were 568 patients who met the inclusion criteria. There was no difference in demographics or patient comorbidities between the inpatient and outpatient groups. There was no increased incidence of postoperative complications or extent of postoperative care in patients who underwent outpatient parotidectomy. On average at the authors' institution, the direct outpatient parotidectomy cost was $1,200 less than the inpatient equivalent. Conclusion Outpatient parotidectomy can be performed safely and cost effectively with no increased risk of complications.

Acute and chronic sinusitis can give rise to a wide array of intracranial and orbital complications. These complications include brain abscess, subdural empyema, epidural abscess, meningitis, venous sinus thrombosis, frontal bone osteomyelitis, and orbital cellulitis and abscess. Despite numerous medical advances, these complications carry a risk of mortality and significant morbidity. Recent studies have shown improvement in both the mortality and the morbidity associated with the neurologic complications of acute and chronic sinusitis. However, there are still a large portion of patients with long-term sequelae, and the literature reports a morbidity rate of approximately 30%. The most common post-treatment morbidities include permanent changes in vision, seizures, and hemiparesis. Although the overall incidence of neurologic complications from a sinogenic source are rare, the potential long-term complications can be devastating making prompt diagnosis and treatment vital to improving outcomes.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by mutations of mismatch repair genes leading to the early development of multiple malignancies. The most common malignancy is colorectal cancer but there is a strong association with malignancies of the ovary, endometrium, small intestine, stomach, skin, brain, and pancreas. We report a case of a 35-year-old female with a history of known HNPCC who presented with adenocarcinoma of the small intestine as well as a synchronous oral tongue squamous cell carcinoma. The patient underwent a combined oncologic surgery involving a hemiglossectomy, selective neck dissection, and partial small bowel resection. Despite the wide range of malignancies seen in patients with HNPCC, no cases of oral cavity cancer have previously been reported. This represents the first case in the literature of oral cavity cancer in a patient with HNPCC.

Objectives To identify the recurrence rates and survival outcomes of patients with invasive squamous cell carcinoma of the scalp. Methods This study was a retrospective chart review of eight patients that had squamous cell carcinoma of the scalp with either periosteal or skull invasion on clinical and/or radiographic evaluation. Results The disease-free survival was 62.5% (5/8 patients) with a local control rate of 75% (6/8 patients) for the entire group. The two patients with full-thickness craniectomy had a local control rate of 100% (2/2 patients); the patients with outer cortex removal had a local control rate of 66.7% (4/6 patients). The disease-free survival of the full-thickness group was 50% (1/2 patients ), and the disease-free survival of the outer cortex removal patients was 66.7% (4/6 patients). Conclusion Despite the invasive nature of this disease, a high degree of local control can be achieved in this high-risk group with multiple comorbidities using outer cortex drilldown, and, in properly selected patients, full-thickness calvarial resection. We conclude that for patients without evidence of medullary involvement that outer table drilldown offers a well-tolerated approach with reasonable oncologic control.

Objective To evaluate the reliability of medical history taken before hormonal medication administration to identify women with an increased risk for thromboembolic events detected by laboratory screening. Design Prospective study. Setting Outpatient endocrine clinic of a university-based hospital. Patient(s) Four hundred forty-three consecutive women (median age 49 years) who presented with endocrine disorders. Intervention(s) None. Main Outcome Measure(s) Parallel screening, on first visit, with a complete medical history, and same-day laboratory screening for thromboembolic risk. Laboratory examination in a two-step procedure with a standard assay and confirmation by genotyping on the second visit. Result(s) A total of 13.8% (61/443) patients with an abnormal activated protein C (APC) resistance test were identified. Second blood samples revealed a prevalence of factor V (Leiden) heterozygosity in 10.9% (homozygosity in 0.2%). There was a significantly higher prevalence of thrombotic events in a first degree relative of patients with APC resistance (in 18.3%) compared with women with a normal test outcome (in 7.8%). However, medical history (personal and family history) was negative concerning hints for thromboembolic events in more than 80% of patients with a laboratory risk profile for thromboembolic morbidity. No association of APC and factor V testing with the patients' gynecological/obstetric history (e.g., live birth rate, miscarriages) was observed. Conclusion(s) Medical history alone may be inadequate to identify all patients at risk for thromboembolic complications with hormonal treatment.

Neuroblastoma (NB) is the most common tumor diagnosed in the first year of life. More than 90% of stage M NB patients present with disseminated tumor cells (DTCs) in the bone marrow (BM). Although these cells represent a major obstacle to treatment, their global gene expression has, so far, been only poorly analyzed. GD2POS DTCs of stage M NB patients were separated from the remaining BM-derived nontumor mononuclear cells (MNCs) by applying magnetic associated cell sorting. mRNA of diagnostic DTCs (n=22) and MNCs (n=14), primary tumors (n=16), relapse DTCs (n=20) and MNCs (n=14) was isolated and used for RNA-seq (50bp, single-end) in order to characterize the biology of DTCs. Furthermore, four DTC-derived neuroblastoma cell lines were established and used to generate a robust patient-derived zebrafish xenograft model. Annexin V staining (apoptosis), EdU proliferation assays, and transwell migration assays of the four cell lines were performed in vitro at temperatures between 34°C and 37°C. 322 differently expressed genes (DEG) were identified comparing primary tumors and DTCs (q < 0.001, |log2FC|>2). Especially, genes encoded by mitochondrial DNA (mtDNA) were upregulated in DTCs. Furthermore, we found the gene expression signature of relapse DTCs largely resembling those of diagnostic DTCs, with only 113 DEG under relaxed cut-offs (q < 0.01, |log2FC|>0.5). Notably, relapse DTCs showed a positional enrichment of 31 downregulated genes on chromosome 19, including five tumor-suppressor genes: SIRT6, BBC3/PUMA, STK11, CADM4, and GLTSCR2. Genomic analysis of 34 DTC samples revealed clonal deletions affecting a portion of the 31 downregulated genes encoded by chromosome 19. Although these deletions occurred at a higher frequency in relapse patients (9 out of 17 samples) as compared to the diagnostic samples (4 out of 17 samples), the positional distribution of downregulated genes did not coincide with the deleted ones. While chromosomal deletions in relapse samples were mainly found on 19q (8 out of 20 samples), most of the downregulated genes were encoded by 19p, which rarely contained deletions (3 out of 20 samples). The downregulation of PUMA (p=0.002) and CADM4 (p=0.02) was associated with a worse event-free survival in stage M patients (survival analysis performed in R2 with the Oberthuer dataset). Furthermore, four DTC-derived cell lines were tested for suitability of injecting into zebrafish embryos and subsequent functional testing. In vitro analysis revealed that in two cell lines (STA-NB-8 and STA-NB-12) proliferation and apoptosis were not affected by lower temperatures (34°C), at which zebrafish embryos still can develop properly, while in the remaining two cell lines both were impaired. Fewer STA-NB-15 and STA-NB-19 cells were in the S phase at 34°C (18.6% of STA-NB-15 and 24.2% of STA-NB-19 cells) as compared to 37°C (37.8% of STA-NB-15 and 45.1% of STA-NB-19 cells). Additionally, more of the STA-NB-15 cells were undergoing apoptosis at 34°C (50.3% Annexin V positive cells) as compared to 37°C (33.9% Annexin V positive cells). This first RNA-seq analysis of neuroblastoma DTCs revealed their unique expression profile in contrast to tumors, but showed less pronounced differences between diagnostic and relapse DTCs. The latter preferentially affected the downregulation of genes encoded by chromosome 19, which might be associated with treatment failure and disease progression. The establishment of xenografts in zebrafish embryos with DTC-derived cells will enable in vivo functional studies and optimize the generation of patient-derived xenografts in zebrafish embryos, which will allow drug screening and functional studies for personalized treatment approaches. Citation Format: Fikret Rifatbegovic, Sabine Taschner-Mandl, Martin Distel, M. Reza Abbasi, Christian Frech, Andrea Ziegler, Inge M. Ambros, Peter F. Ambros. RNA-seq of diagnostic and relapse disseminated tumor cells (DTCs) in stage M neuroblastoma patients and first steps towards DTC-derived xenografts in zebrafish embryos [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr A38.

Berufliche Autonomie ist Voraussetzung fur Zufriedenheit mit der eigenen Tatigkeit. Dem Arztberuf wird ein hohes Mas an Autonomie zugeschrieben, verbunden mit fachlicher und ethisch-moralischer Kompetenz fur lebenswichtige Bereiche. Das sind wesentliche Elemente fur das positive Image dieses Berufes. Zu Beginn der arztlichen Tatigkeit ist die ethischmoralische Kompetenz weitgehend ausgebildet, wahrend die fachliche Kompetenz erst erworben werden muss. Kliniken, in denen die Weiterbildung meist erfolgt, sind oft auch heute noch traditionell hierarchisch organisiert. Die z.T. feudalistischen oder militarischen Strukturen behindern autonome moralische Entscheidungen und bewirken eine strukturelle Verantwortungslosigkeit. Behinderungen und Druck durch Vorgesetzte, finanzielle Sanktionen, Standesdunkel und Profilierungsbestreben werden an typischen Konfliktsituationen aufgezeigt. Es kommt dadurch zu Spannungen, Unzufriedenheit, Gewissenskonflikten und Erkrankungen bis zum Burn out. Engagement von Mitarbeitern wird verhindert, Kreativitat nicht genutzt und Fehler werden nicht konstruktiv bearbeitet. Dadurch konnen Patienten unangemessen belastet oder geschadigt werden. Nicht nur Vorgesetzte, sondern auch Nachgeordnete konnen so in Gefahr geraten, ihre moralischen Werte anderen Interessen unterzuordnen. Es werden Wege zu einer autonomiefordernden Kultur zwischen Arzten und mit anderen Berufsgruppen aufgezeigt. Dazu gehort eine institutionalisierte Kommunikation auf der Basis gegenseitiger Wertschatzung in einem partnerschaftlichen Team, das auch ethische Fragen im Diskurs bearbeiten kann.

Chronic peripheral arterial occlusive disease of the lower limbs may cause tissue damage. Type and extent of peripheral nerve involvement is controversial. We examined 25 patients with peripheral arterial occlusive disease in various grades of severity and 37 age-matched healthy controls using conventional angiography and motor and sensory nerve conduction tests. Subjects with confounding factors for peripheral neuropathies were excluded. We found prolongation of distal motor latencies, decrease of motor and sensory nerve conduction velocities, and reduction in amplitude of the compound muscle action potential. Amplitudes of the compound muscle action potentials were lower in patients with pain at rest than in patients with intermittent claudication and decreased with increasing neurological disability score. Sural nerve conduction velocity, peroneal nerve F-wave chronodispersion, and tibial nerve F-wave persistence were the most frequent abnormal findings. Therefore we concluded that chronic peripheral arterial occlusive disease causes axonal degeneration, resulting in axonal polyneuropathy.

Umgang mit Patientenverfugungen im klinischen Alltag – Immer haufiger bringen Patienten Patientenverfugungen mit. Zudem ist seit zwei Jahren die Verbindlichkeit von Patientenverfugungen gesetzlich geregelt. Doch nach wie vor treten im Umgang mit den Willenserklarungen Fragen und Unsicherheiten auf – eine Herausforderung an die ethische Reflexion.

Purpose: Precise and comprehensive analysis of neuroblastoma genetics is essential for accurate risk evaluation and only pangenomic/multilocus approaches fulfill the present-day requirements. We present the establishment and validation of the PCR-based multiplex ligation-dependent probe amplification (MLPA) technique for neuroblastoma. Experimental Design: A neuroblastoma-specific MLPA kit was designed by the SIOP Europe Neuroblastoma Biology Committee in cooperation with MRC-Holland. The contained target sequences cover 19 chromosomal arms and reference loci. Validation was performed by single locus and pangenomic techniques (n = 174). Dilution experiments for determination of minimal tumor cell percentage were performed and testing of reproducibility was checked by interlaboratory testing (n = 15). Further 156 neuroblastomas were used for establishing the amplification cutoff level. Results: The MLPA technique was tested in 310 neuroblastomas and 8 neuroblastoma cell lines (including validation and amplification cutoff level testing). Intertechnique validation showed a high concordance rate (99.5%). Interlaboratory MLPA testing (κ = 0.95, P < 0.01) revealed 7 discrepant of 1,490 results (0.5%). Validation by pangenomic techniques showed a single discordance of 190 consensus results (0.5%). The test results led to formulation of interpretation standards and to a kit revision. The minimal tumor cell percentage was fixed at 60%. Conclusions: The recently designed neuroblastoma-specific MLPA kit covers all chromosomal regions demanded by the International Neuroblastoma Risk Group for therapy stratification and includes all hitherto described genetic loci of prognostic interest for future studies and can be modified or extended at any time. Moreover, the technique is cost effective, reliable, and robust with a high interlaboratory and intertechnique concordance. Clin Cancer Res; 17(4); 792–804. ©2011 AACR.

Since the late 1990s financial strategies for opening Eastern European markets and entry strategies of foreign banks in most CESEE countries included triggers for strong credit growth, especially in the private sector. What are the transition results on the macro level? Does this credit growth contribute to financial and economic development or is there a risk of a transition-driven overshooting? We review the literature and empirical studies on financial development, credit growth and economic growth. In Updating Cottarelli et al (2005), we compare the credit boom of the private sector in CESEE during the process of economic transformation to the so called “equilibrium level” and discuss whether or not this credit boom was healthy. We find that results and impact differ across the countries due to country specifics and the different developments of the financial sector. We conclude by discussing policy challenges with regard to financial stability and transition perspectives.

Over the past 20 years, many companies have benefited from the globalization of markets, and international marketing activities have risen constantly (Ronkainen/Czinkota 2002, p. xiii). As better measurement is supposed to entail better marketing (Ambler/Kokkinaki 2002, p. 225), academics and practitioners attribute increasing importance to assessing marketing performance and identifying the causal linkage of marketing activities and financial returns (Reinecke/Reibstein 2002, p. 18, Seggie/Cavusgil/Phelan 2007, pp. 834-835). This is also due to the corporate trend for greater accountability of marketing, the discontent with traditional metrics as well as the availability of modern information and communication technologies (Seggie/Cavusgil/Phelan 2007, pp. 835-836). The ability to evaluate performance accurately not only enables assessing current operations, but also quantifying marketing’s added value for the firm and its impact on long-term profitability (Farley/Kopalle 2006, p. 312, O’Sullivan/Abela 2007, p. 88). Furthermore, performance indicators can be major drivers for marketing or sales employees and managers (Huizingh/Zengerink 2001, p. 3). The importance of evaluating marketing activities is also shown by the scientific interest of the “Marketing Science Institute” which puts it on top of its research priorities, and the “Journal of Marketing” which dedicated an entire issue on this topic (Marketing Science Institute 2006, p. 5, Journal of Marketing 2004, No. 4).