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Background: The proliferation marker Ki-67 is a major pathological feature for the description of the state of disease in breast cancer. It helps to define the molecular subtype and to stratify between therapy regimens in early breast cancer and helps to assess the therapy response. Circulating tumor cells (CTCs) are a negative prognostic biomarker for progression free (PFS) and overall survival (OS) in patients with metastatic breast cancer. Therefore, the CTC count is often described as surrogate for the tumor burden. Both, decrease of Ki-67 and CTC count are considered as evidence for therapy response. The presented work analyzed the correlation between the Ki-67 indices of metastatic tissue biopsies and CTC counts in biopsy time-adjacent peripheral blood samples., Patients and Methods: Blood samples from 70 metastatic breast cancer patients were obtained before the start of a new line of systemic therapy. CTCs were enumerated using CellSearch® (Menarini Silicon Biosystems, Bologna, Italy) whereas intact CTCs (iCTCs) and non-intact or apoptotic CTCs (aCTCs) were distinguished using morphologic criteria. The proportion of cells expressing Ki-67 was evaluated using immunohistochemistry on biopsies of metastases obtained concurrently with CTC sampling before the start of a new line of systemic therapy., Results: 65.7% of patients had a Ki-67 index of > 25%. 28.6% of patients had ≥ 5, 47.1% ≥ 1 iCTCs. 37.1% had ≥ 5, 51.4% ≥ 1 aCTCs. No correlation was shown between Ki-67 index and iCTC and aCTC count (r = 0.05 resp. r = 0.05, Spearman's correlation index). High CTC-counts did not coincide with high Ki-67 index. High Ki-67, ≥ 5 iCTCs and aCTCs are associated with poor progression free (PFS) and overall survival (OS)., Conclusion: CTCs and Ki-67 are independent prognostic markers in metastatic breast cancer. High Ki-67 in metastatic tumor tissue is not correlated to high iCTC or aCTC counts in peripheral blood., (© 2023. The Author(s).)

Purpose: Today, the decision to treat patients with chemotherapy for early breast cancer (EBC) is made based on the patient's individual risk stratification and tumor biology. In cases with chemotherapy indication, the neoadjuvant application (NACT) is the preferred option in comparison with primary surgery and adjuvant chemotherapy (ACT). Age remains a relevant factor in the decision-making process. The aim of the present study was to illustrate the impact of age on the use of systemic therapy in clinical routine., Methods: The study separately analyzed chemotherapy use among six age cohorts of EBC patients who had been treated at 104 German breast units between January 2008 and December 2017., Results: In total, 124,084 patients were included, 46,279 (37.3%) of whom had received chemotherapy. For 44,765 of these cases, detailed information on treatment was available. Within this cohort, chemotherapy was administered as NACT to 14,783 patients (33.0%) and as ACT to 29,982 (67.0%) patients. Due to the higher prevalence of unfavorable tumor subtypes, younger patients had a higher rate of chemotherapy (≤ 29y: 74.2%; 30-39y: 71.3%) and a higher proportion of NACT administration ( ≤ 29y: 66.9%; 30-39y: 56.0%) in comparison with elderly patients, who had lower rates for overall chemotherapy (60-69y: 37.5%; ≥ 70y: 17.6%) and NACT (60-69y: 25.5%; ≥ 70y: 22.8%). Pathologic complete response was higher in younger than in older patients (≤ 29y: 30.4% vs. ≥ 70y: 16.7%), especially for HER2- subtypes., Conclusion: The data from the nationwide German cohort reveal relevant age-dependent discrepancies concerning the use of chemotherapy for EBC., (© 2023. The Author(s).)

Purpose: Breast cancer (BC) is the most common malignancy among women and prognosis is strongly influenced by tumor subtype. Neoadjuvant chemotherapy (NAC) is the standard treatment for both locally advanced- and early-stage triple-negative and Her2-positive BC. Pathologic complete response (pCR) to NAC is an important predictor of patient outcomes. Neutrophil-to-lymphocyte-ratio (NLR) in peripheral blood is associated with prognosis in various malignancies. Here, we investigated the value of the pretreatment NLR as a response predictor in neoadjuvant-treated patients with BC., Methods: A retrospective chart analysis of 862 patients with invasive BC treated with NAC at the Heidelberg University Hospital during 2003-2015 was conducted. NLR was calculated as the ratio of the absolute neutrophil and lymphocyte counts in peripheral blood, and pCR was defined as absence of invasive or in situ carcinoma in breast and axillary lymph nodes., Results: A total of 151 patients with invasive BC who underwent NAC were included in this study. NLR tended to be higher in the pCR group than the non-pCR group (p < 0.1). Analyses of BC subtypes demonstrated that NLR was significantly higher in the pCR- compared with the non-pCR group (3.304 vs. 2.379, respectively; p = 0.048) in patients with luminal B/Her2-negative tumors. Further, we found a significant difference in NLR according to remission status in postmenopausal patients (2.861 vs. 2.313, respectively; p = 0.043)., Conclusion: NLR was significantly higher only for patients achieving pCR in the Luminal B/Her2-negative and postmenopausal subgroups. Hence, NLR is a candidate additional predictive factor in patients with Luminal B/Her2-negative BC., (© 2022. The Author(s).)

Purpose: The aim of this study was to investigate whether students' attitude towards online learning in Gynecology and Obstetrics changed during the COVID-19 pandemic. We further examined which variables impacted students' satisfaction with digital learning., Methods: A specifically developed questionnaire was used from June 2020-July 2021 for N = 234 medical students participating in the course "Gynecology and Obstetrics" at University of Heidelberg. Thirty-five items were repeatedly applied in different cohorts to assess structure- and content-related quality of teaching. In addition, their influence on overall satisfaction with digital teaching was analyzed by applying investigative analyses like multiple regression and extreme group comparisons., Results: Especially items associated with content-related quality of teaching (β = 0.24), organization of teaching (β = 0.25) and subjective learning success (β = 0.27) seemed to be relevant predictors for overall satisfaction with courses. Fears and changes due to the pandemic situation also played a role for a subgroup of students. Aspects linked to technical quality of teaching, interactions with teachers and students or advantages of web-based learning appeared to play a subordinate role for overall satisfaction with digital teaching. Comparisons of ratings over time revealed that teaching evaluations almost remained the same., Conclusion: Our results give several hints regarding how digital teaching should be designed and how it can be improved. Further studies are needed to validate our results and to develop methods to improve digital teaching in medicine., (© 2022. The Author(s).)

Purpose: Circulating miRNAs can provide valid prognostic and predictive information for breast cancer diagnosis and subsequent management. They may comprise quintessential biomarkers that can be obtained minimally invasively from liquid biopsy in metastatic breast cancer patients. Therefore, they would be clinically crucial for monitoring therapy response, with the goal of detecting early relapse. This study investigated miRNA expression in patients with early and/or late relapse, and the predictive value for assessing overall (OS) and progression-free survival (PFS)., Methods: Forty-seven patients with metastatic breast cancer from the University Women's Hospital Heidelberg were enrolled in this study. Expression of miR-200a, miR-200b, miR-200c, miR-141, and miR-429 was analyzed by RT-qPCR before a new line of systemic therapy and after the first cycle of a respective therapy. Tumor response was assessed every 3 months using the RECIST criteria. Statistical analysis focused on the relation of miR-200s expression and early vs. late cancer relapse in relation to systemic treatment. The association of miRNAs with PFS and OS was investigated., Results: Before starting a new line of systemic therapy, miR-429 (p = 0.024) expression was significantly higher in patients with early relapse (PFS ≤ 4 months) than in patients with late relapse (PFS > 4 months). After one cycle of systemic therapy, miR-200a (p = 0.039), miR-200b (p = 0.003), miR-141 (p = 0.017), and miR-429 (p = 0.010) expression was higher in early than in late progressive cancer. In addition, 4 out of 5 miR-200 family members (miR-200a, miR-200b, miR-141, and miR-429) predicted PFS (p = 0.048, p = 0.008, p = 0.026, and p = 0.016, respectively). Patients with heightened miRNA levels showed a significant reduction in OS and PFS., Conclusion: Circulating miR-200s were differentially expressed among patients with late and/or early relapse. 4 of 5 members of the miR-200 family predicted significantly early relapse after systemic treatment. Our results encourage the use of circulating miR-200s as valuable prognostic biomarkers during metastatic breast cancer therapy., (© 2022. The Author(s).)

Purpose: The onset of the COVID-19 pandemic posed an eminent challenge for medical teachers worldwide. Face-to-face lectures and seminars were no longer possible, and alternatives had to be found. E-learning concepts quickly emerged as the only practicable solutions and also offered the opportunity to evaluate whether traditional face-to-face lectures could be translated into an online format, independent of the COVID-19 pandemic., Methods: We offered an e-learning program consisting of lecture notes, screencasts with audio narration, and online webinars that covered topics normally taught in traditional lectures and seminars. To evaluate the learning behavior and quality of our e-learning program, we drafted a questionnaire that students completed at the end of the 2020 summer semester that had been designed to enable a comparative analysis of the different e-learning modules., Results: Voluntary participation in the online courses was high. Survey analysis revealed high satisfaction with and a distinctive preference for the format, even under regular, COVID-19-independent conditions. In general, a positive appraisal of e-learning-especially as a substitute for regular lectures-was found. Students also reported higher studying efficiency. Exam results were equal to those of previous semesters., Conclusion: Both acceptance of and satisfaction with our e-learning modules were high, and students displayed increased demand for this kind of e-learning format. We, therefore, conclude that e-learning offerings could serve as reasonable, efficient, student-orientated substitutes for certain medical courses, especially lectures. These curricular adaptations would correlate with the high digitalization seen in students' everyday lives. This correlation may also hold true independent of the ongoing COVID-19 pandemic., (© 2021. The Author(s).)

Purpose: The field of obstetrics and gynecology (OB/GYN) is facing growing competition for young professionals in Germany, with high interest rates among female graduates and a declining proportion of male students who choose residency training in the field. The aim of this study is to analyze general and gender-dependent factors that influence the decision for or against specialty training in OB/GYN among medical students in Germany., Methods: Between February and November 2019, n = 346 medical students in their 5th and 6th year of undergraduate training at Heidelberg University received a questionnaire with 44 items., Results: n = 286 students (61.3 female; 38.7% male) participated in the study. 28% of the female students and 9% of the male students had considered OB/GYN for their specialty training. The students reported different general and gender-specific influencing factors in their choice of a specialty. Both genders desired a good work-life-balance, however, in comparison with their female colleagues, male students had heavily weighted factors related to their later careers and professional success, including competition among colleagues. Male students had gained little practical experience during compulsory internships (26.9% for females vs. 8.8% for males) or had chosen their final-year elective in OB/GYN (15.9% for females vs. 5.5% for males). Female students had worried about the negative effects of their sex on their career (35.4% for females vs. 5.9% for males)., Conclusion: OB/GYN must become more appealing and attractive to young female and male professionals alike. A better compatibility of career and family should go hand in hand with the implementation of differentiated, (extra) curricular teaching approaches that take the different preferences of female and male students into account., (© 2021. The Author(s).)

Background: Nasal dorsum deprojection is a very important tool in functional and aesthetic rhinoplasty. In classic techniques, resection of dorsal bone and cartilage renders dorsal reconstruction necessary. The concept of dorsal preservation rhinoplasty has been known for more than a century but has experienced a renaissance in recent years, with many critical technical modifications., Materials and Methods: We present the latest technique of piezo-assisted dorsal preservation rhinoplasty with subdorsal triangular resection and subdorsal Cottle modification based on clinical experience of 205 cases. Furthermore, the advantages and disadvantages of this technique are discussed and several other current variations are presented., Results and Discussion: Piezo-assisted osteotomy enables a very precise fracture line and sparing of periosteum, with bone sculpting possible even after mobilization. Subdorsal septal height reduction always precedes completion of the osteotomy and nasal bone mobilization, to ensure patient safety with regard to skull base injury. Using the presented technical modifications, the risk of step deformities in the radix is minimized. In selected patients, dorsal preservation septorhinoplasty enables the surgeon to perform very conservative and precise deprojection of the nose with excellent outcomes, although the spectrum of possible complications is shifted in comparison to classic techniques., Conclusion: The preliminary experience of 205 cases with a revision rate of less than 10% is promising. A final evaluation of the technique will only be possible after further studies and evaluation of long-term results., (© 2020. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: The FUSION-X-US-II prototype was developed to combine 3D-automated breast ultrasound (ABUS) and digital breast tomosynthesis in a single device without decompressing the breast. We evaluated the technical function, feasibility of the examination workflow, image quality, breast tissue coverage and patient comfort of the ABUS device of the new prototype., Methods: In this prospective feasibility study, the FUSION-X-US-II prototype was used to perform ABUS in 30 healthy volunteers without history of breast cancer. The ABUS images of the prototype were interpreted by a physician with specialization in breast diagnostics. Any detected lesions were measured and classified using BI-RADS ® scores. Image quality was rated subjectively by the physician and coverage of the breast was measured. Patient comfort was evaluated by a questionnaire after the examination., Results: One hundred and six scans were performed (61 × CC, 23 × ML, 22 × MLO) in 60 breasts. Image acquisition and processing by the prototype was fast and accurate. Breast coverage by ABUS was approximately 90.8%. Sixteen breast lesions (all benign, classified as BIRADS ® 2) were identified. The examination was tolerated by all patients., Conclusion: The FUSION-X-US-II prototype allows a rapid ABUS scan with mostly high patient comfort. Technical developments resulted in an improvement of quality and coverage compared to previous prototype versions. The results are encouraging for a test of the prototype in a clinical setting in combination with tomosynthesis., (© 2021. The Author(s).)

Purpose: Oncoplastic breast-conserving surgery has been part of clinical routine for several years without an internationally accepted nomenclature, standardization or a systematic evaluation of single surgical procedures., Methods: We carried out a structured survey of breast surgeons (n = 50) during the annual meeting of the German Society for Senology in Berlin 2017. In the run-up to the event, 10 questions were determined and released for an anonymous survey during the consensus meeting., Results: Most surgeons participating in the consensus meeting had an expertise of more than 200 oncologic breast surgeries in the last 3 years and approved the need of a higher rate of standardization in oncoplastic techniques. From the oncological standpoint, oncoplastic surgery is considered safe with a comparable rate of compilations as seen in conventional breast-conserving procedures. Most surgeons approve that using oncoplastic surgery, higher rates of breast conservation and improved aesthetic results can be accomplished. The majority of the participants would endorse a more systematic review of subjective aesthetic results in clinical routine., Conclusions: A higher degree in standardization of oncoplastic breast surgery is required for surgical-technical, educational, and scientific reasons as well as for a more differentiated monetary compensation of the surgical procedures. This process has already been started.

Purpose: Breast-conserving therapy (BCT) is the standard procedure for most patients with primary breast cancer (BC). By contrast, axillary management is still under transition to find the right balance between avoiding of morbidity, maintaining oncological safety, and performing a staging procedure. The rising rate of primary systemic therapy creates further challenges for surgical management., Methods: Patients with primary, non-metastatic BC treated between 01.01.2003 and 31.12.2016 under guideline-adherent conditions were included in this study. For this prospectively followed cohort, breast and axillary surgery patterns are presented in a time-trend analysis as annual rate data (%) for several subgroups., Results: Overall, 6700 patients were included in the analysis. While BCT rates remained high (mean 2003-2016: 70.4%), the proportion of axillary lymph node dissection has declined considerably from 80.1% in 2003 to 16.0% in 2016, while the proportion for sentinel lymph node biopsy (SLND) has increased correspondingly from 10.3 to 76.4%. Among patients with cT1-2, cN0 breast cancer receiving BCT with positive SLND, the rate of axillary completion has decreased from 100% in 2008 to 24.4% in 2016., Conclusions: In the past decade, SLNB has been established as the standard procedure for axillary staging of clinically node-negative patients. Surgical morbidity has been further reduced by the rapid implementation of new evidence from the ACOSOG Z0011 trial into clinical routine. The results reflect the transition towards more individually tailored, less invasive treatment for selected patient subgroups, especially in regards to axillary lymph node management.

Background: Subjective assessments of quality of life (QOL) as an important aspect of outcome research have gained in importance over the past few decades. The number of prospective studies on postoperative QOL in septorhinoplasty using disease-specific instruments is sparse. The aim was to assess and compare patient QOL after primary and revision septorhinoplasty performed by a single surgeon in an ENT center., Material and Methods: All patients completed two disease-specific QOL instruments preoperatively and at least 1 year postoperatively: the Rhinoplasty Outcome Evaluation (ROE) and the Nasal Obstruction Symptoms Evaluation (NOSE) scores. General demographic and clinical information (age, gender, medical and surgical history) were collected from all patients. All operations were performed by a single surgeon (F. R.)., Results: A total of 237 patients were included in the study, 208 (87.8%) female and 29 (12.2%) male. The average age was 30.3 ± 8.9 years. The average observation period was 19.3 ± 7.4 months. Using the measurement tool NOSE there was a significant improvement in obstruction in the overall collective (preoperative 49.8 ± 26.2, postoperative 19.1 ± 21.3; p < 0.001) with no significant difference in primary versus revision surgery. The ROE score showed a significant improvement and both collectives (primary and secondary surgery) showed a significant improvement after the intervention. The patients with a primary intervention had a significantly higher postoperative QOL (p < 0.001)., Conclusion: The disease-specific QOL showed a significant increase after primary septorhinoplasty as well as after revision surgery. The NOSE score increased significantly in both intervention groups postoperatively.

Background: Postoperative periorbital edema and ecchymosis after rhinoplasty are mainly caused by the osteotomy with hammer and chisel. The introduction of piezoelectric surgery could lead to a better early postoperative outcome due to improved preservation of soft tissues. The aim of this systematic review was to evaluate the methods and results of studies comparing conventional osteotomy to piezoelectric osteotomy., Methods: A systematic literature search was conducted in the PubMed/MEDLINE and Google Scholar databases. In the primary selection, all studies on the comparison of conventional and piezoelectric osteotomies with regard to postoperative periorbital edema and/or ecchymosis were identified. Secondary selection included only study designs with a control group., Results: Primary selection resulted in 15 thematically relevant publications with a notable increase in annual publications between 2007 and 2017. Six studies with control groups were selected secondarily. Qualitatively and methodologically, the studies were very heterogeneous. The results of five of the six studies indicated a significant advantage of piezo technology compared to conventional osteotomy. Only in one study was no significant difference found in the investigated postoperative outcome., Conclusion: Piezoelectric osteotomy resulted in a reduced propensity for postoperative edema and ecchymosis compared to the conventional osteotomy technique with a chisel. At this time, the results should be regarded as a trend. A definite recommendation favoring piezoelectric osteotomy cannot be made until more studies with higher patient numbers become available.

Purpose: Breast ultrasound could be a valuable tool complementary to mammography in breast cancer screening. Automated 3D breast ultrasound (ABUS) addresses challenges of hand-held ultrasound and could allow double reading analysis of ultrasound images. This trial assesses the inter-rater reliability and double reading analysis of an ABUS system., Methods: To assess the reproducibility and diagnostic validity of the ABUS system, SomoV™, a blinded double reading analysis, was performed in 1019 patients (2038 breasts) by two examiners (examiner A/B) and compared to single reading results, as well as to the reference standard regarding its diagnostic validity. Cohen's kappa coefficients were calculated to measure the inter-rater reliability and agreement of the different diagnostic modalities. Patient comfort and time consumption for image acquisition and reading were analyzed descriptively as secondary objectives., Results: Analysis of inter-rater reliability yielded agreement in 81.6% (κ = 0.37; p < 0.0001) showing fair agreement. Single reading analysis of SomoV™ exams (examiner A/examiner B) compared to reference standard showed good specificity (examiner A: 88.3%/examiner B: 84.5%), fair inter-rater agreement (examiner A: κ = 0.31/examiner B: κ = 0.31), and adequate sensitivity (examiner A: 53.1%/examiner B: 64.2%). Double reading analysis yielded good sensitivity and specificity (73.7 and 77.7%). Mammography (n = 1911) alone detected 160 of 176 carcinomas (sensitivity 90.1%). Adding SomoV™ to mammography would have detected 12 additional carcinomas, resulting in a higher sensitivity of 97.7%., Conclusion: SomoV™ is a promising technique with good sensitivity, high patient comfort, and fair inter-examiner reliability. It allows double reading analysis that, in combination with mammography, could increase detection rates in breast cancer screening.

Objectives: Today´s written part of the medical state examination requires students to retrieve a comprehensive amount of knowledge in a limited period of time. Therefore, the main study objectives were to implement and to evaluate a two-day exam preparation course for the German Medical State Examination in obstetrics and gynecology. The project evaluation focused on acceptability, satisfaction and the gain of knowledge for the participants of such a face-to-face course., Study Design: The two-day intensive training for senior medical students offered a review of the entire exam-relevant content in the field of obstetrics and gynecology in combination with interactive discussions along selected exam questions. Skill gains were assessed using pre- and post-course multiple choice tests. In addition, a qualitative questionnaire assessed attitudes and satisfaction of course participants., Results: A total of 101 fifth year senior medical students from Heidelberg University Medical School participated in the two pilot courses (summer 2014 and winter 2015). Pre- and post-course tests showed a significant skill-gain from 14.9 to 18.0 points [of a maximum of 20; pre-post difference 95 % CI (2.21; 3.98), t test: p < 0.001]. Furthermore, the qualitative results showed high satisfaction with the course, with an average Likert scale grading of 5.63 (2014) and 5.44 (2015) on a scale from 1 ("extraordinary bad") to 6 ("extraordinary good")., Conclusions: This study shows that a two-day intensive course in obstetrics and gynecology is feasible, effective and highly appreciated by senior medical students preparing for the Second German Medical State Examination. It further suggests surplus value for academic clinical departments to recruit future residents. Methods and tools presented in this paper are intended to inspire and guide clinical colleagues in implementing the format at their respective universities.

Rhinophyma is a benign dermatological disease of the nose which affects primarily Caucasian men in their fifth decade of life. Its main characteristic is a slowly progressive hyperplasia of the sebaceous glands and the adjacent tissue with irregular thickening of the nasal skin and nodular deformation. It is defined as the end stage of acne rosacea. The main reasons for patients to seek medical help are cosmetic problems and functional impairments such as nasal airway obstruction or even difficulty in eating. Surgery is indisputably the treatment of choice for rhinophyma. This article gives an overview on the clinical and histopathologic findings of rhinophyma as well as the different treatment options with their pros and cons as described in literature.

Background: The treatment of keloids remains challenging due to sparse knowledge about the pathogenesis of this disease. Transforming growth factor (TGF)-beta1 plays a central role in keloid formation. Cell-matrix communication is controlled by integrins, the expression of which can be regulated by TGF-beta1., Methods: Using immunohistochemistry we compared expression patterns of alpha1beta1, alpha2beta1 und alpha3beta1 in normal skin and keloid tissue. Secondly, the effect of TGF-beta1-antisense after 48 h and 72 h incubation in a keloid-derived fibroblast monolayer was analyzed by means of reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry., Results: alpha1beta1 and alpha2beta1 were highly expressed in keloid fibroblasts. Incubation with TGF-beta1-antisense lead to a reduction on protein level. RT-PCR demonstrated an increase of all alpha subunits, while on an mRNA level a decrease of the subunit beta1 could be observed., Conclusion: Integrin expression is directly modulated by TGF-beta1. An abnormal response in the keloid as a result of an altered TGF-beta1 pathway could be a key element to understanding the development of keloids.

A 76-year-old woman presented with fever, redness, swelling, and pain under the chin. Some submental lymph nodes were detected by ultrasound and computed tomography. The diagnosis was a submental phlegmon, for which surgery was performed. The lymph nodes were removed, and antibiotic therapy with daily lavage was done. The histology of the lymph nodes suggested giant cell arteritis.

Autologous transplantation is regarded as the gold standard in the treatment of congenital or acquired deformities. However, the availability of autologous tissue for transplantation is often limited. Regenerative medicine aims to activate individuals' own intrinsic regenerative mechanisms and embraces tissue engineering, cell/system biology, gene therapy and stem-cell biology. Most approaches in tissue engineering are based on the expansion of small autologous cell aggregates. Tissue engineering supplemented by isolated and amplified stem cells is another very promising option for producing autologous transplants and getting over the limited availability. The association of stem cell-based tissue engineering and gene therapy allows the creation of regenerative tissue in the optimal ambience of regulatory proteins. This leads to great opportunities in the transplantation of skin, bones or cartilage. This paper presents the current status and the possible benefits, but also the limitations, of regenerative medicine in reconstructive surgery of the head and neck.

Complications after rhinoplasty could often be prevented if less of the support structures of the nose were resected and cartilage transplants were used to give stability. Long-term complications depend heavily on the nasal anatomy, Which is why the surgeon must be able to identify anatomical variants and adapt the surgical technique as necessary. Thus, rhinoplasty techniques have moved away from excisional methods and shifted toward repositioning and restructuring existing tissues. Conservative reduction and preservation of support structures will maximize the aesthetic and functional results. Checking the shape of the tip of the nose is the critical step, and stabilization of the nasal base in particular leads to a good long-term outcome with preservation of the nasal tip projection. The surgeon needs to stabilize the structure of the nose by building up the structure and must also anticipate the effects of scar contracture. This entails structural grafting with autologous cartilage. In this paper, the authors present the grafting techniques most commonly used to sculpt the nasal framework; in primary and secondary rhinoplasty. Tried and tested grafts are presented, with the appropriate nomenclature relating to each and also the anatomical locations of and clinical indications for each.

Chronic wounds are characterized by slow or nonexistent wound healing. Usually their treatment is expensive. Therefore new concepts in management are of interest in order to reduce treatment time and costs. One option is vacuum sealing. The concept of topical negative pressure is not new, and many chronic nonhealing wounds could be closed successfully with the help of vacuum sealing. Until now, there has been no documented case of vacuum sealing in head and neck reconstructive surgery. Our case shows the effectiveness of a vacuum-assisted device in successful closure of a chronic nonhealing wound in this region.

Aberrant wound healing results in unsightly scarring, hypertrophic scarring, and keloid formation, causing functional and cosmetic deformities, discomfort, psychological stress, and patient dissatisfaction. Scar management, both surgical and non-surgical, continue to be important issues for the facial plastic surgeon. Many techniques for the management of hypertrophic scars and keloids have been proven through extensive use, but few are supported by prospective studies with adequate control groups. Several new therapies showed good results in small-scale trials, but these have not been repeated in larger trials with long-term follow-up. This article presents an overview of the available therapies and provides recommendations for the treatment of abnormal scarring. The recommendations focus on the management of hypertrophic scars and keloids. Strategies for the management of keloids and hypertrophic scars are of continuing interest and studies are necessary to understand the basic mechanisms causing aberrant wound healing. In addition, an overview of new developments in molecular wound management and gene therapy, as they relate to facial plastic surgery, is provided.

Aberrant wound healing results in unsightly scarring, hypertrophic scarring, and keloid formation, causing functional and cosmetic deformities, discomfort, psychological stress, and patient dissatisfaction. Scar prevention and management continue to be important issues for the facial plastic surgeon. This article presents an overview on the pathogenesis of a scar and of the different types of scars. Differences between keloids, hypertrophic scars and normal scars include distinct scar appearance, histologic morphology and cellular function in response to growth factors. Recent advances in our understanding of the wound healing process reveal possible causes for hypertrophic scars and keloids. This information might assist in the development of efficacious prevention and treatment for hypertrophic scar and keloid formation. This article also describes the strategies available for scar prevention. Recommendations focus on the management of hypertrophic scars and keloids.

Background: Tissue engineering is a promising method for the generation of chondrogenic grafts for reconstructive surgery. In cultured chondrocytes, the dedifferentiation of cells seems unavoidable for multiplication., Methods: In this study, we investigated the expression of distinct markers during the dedifferentiation of human chondrocytes (HC) harvested during septoplasty and human mesenchymal stem cells (hMSC) from cartilage biopsies in cell culture using the microarray technique., Results: The genes for collagen 1alpha1, 2alpha1, 3alpha1, 4alpha1, 11alpha1, biglycan, fibromodulin and lumican were activated during the dedifferentiation of the HCs, collagen 9alpha2, 9alpha3, 10alpha1 and chondroadherin were inactivated. During chondrogenic differentiation of hMSCs, the genes for collagen 3alpha1, 9alpha2, 9alpha3, 10alpha1, 11alpha1 were activated, collagen 4alpha1 and fibromodulin inactivated and the genes for Col 1alpha1, biglycan und chondroadherin constantly expressed., Conclusion: The genetic profile for the investigated markers in human chondrocytes generated from hMSCs resembles the profile in differentiated chondrocytes. Collagen 2alpha1, 9alpha2, 9alpha3, 10alpha1 could represent markers for the differentiation of chondrocytes, Col 1alpha1, 3alpha1 und 4alpha1, biglycan, fibromodulin and lumican markers for the dedifferentiation into a more fibroblastoid cell type.

The difficulties in facial reconstruction derive from the unique character of the face and the availability of local matching tissues. Facial reconstructive surgery must aim at a functionally and aesthetically rehabilitated patient. The performance of facial plastic surgery requires an understanding and the application of many important principles. The aim of this paper is to review the critical factors to be considered in the management of surgical wounds by second-intention healing, primary closure, skin grafting, and repair with local or distant free flaps. The key concepts useful in flap choice and implementation are discussed. In addition, an overview of new developments in tissue engineering and gene therapy as they relate to facial plastic surgery is provided.

Background: External auditory canal cholesteatoma (EACC) is a rare entity in otolaryngology, which is histomorphologically identical with middle ear cholesteatoma. The cause of EACCt is, however, still not clear. The aim of this study was to describe the expression of beta-catenin, MMP-2, and MMP-9 in EACC matrix compared to the normal auditory meatal skin (AMS)., Methods: Thirteen specimens were obtained during surgical procedure. EACC and AMS specimens were immunostained with antibodies for beta-catenin, MMP-2, and MMP-9., Results: Only the basal layers of the EACC specimens were positive for beta-catenin. The suprabasal layers showed diminished or negative immunostaining for beta-catenin. In all layers, AMS was homogeneously positive for beta-catenin. In contrast, the immunostaining for the gelatinases was equally increased in all layers of EACC, whereas AMS was weekly positive., Conclusion: The reduced immunoreactivity for beta-catenin may have been present because of the lessened cell-cell adhesion in the suprabasal layers of EACC. The increased expression of the metalloproteinases might point at an increased lack of integrity of EACC matrix. Recent studies revealed a balance between disintegrating and stabilising factors in normal tissue, which is disturbed in inflamed and neoplastic tissue. In EACC matrix, an imbalance of these factors, represented by reduced beta-catenin and increased gelatinase expression, is possible. Increased desquamation, the accumulation of keratin debris, and loss of tissue-stability support our findings.

Background: Recent technical developments in metered pump systems allow the production and use of preservative-free nasal products. The aim of the current study is to compare the tolerability of a preservative-free dexpanthenol (5%) nasal spray with that of the established dexpanthenol (5%) nasal ointment, also without preservatives. The main outcome measure was in vivo mucociliary clearance., Method: Mucociliary clearance was assessed by saccharin migration time in 20 volunteers. Wash-out phases were 7 days and the spray or ointment was always applied 20 min before the saccharin test. The study was designed to test for non-inferiority., Results: Saccharin migration time was slightly longer after ointment administration, however, these were not significantly different to nasal spray. The saccharin migration time showed a significant correlation with the age of the volunteers. The upper confidence limit of dexpanthenol nasal spray was markedly less than that of the ointment. Therefore, dexpanthenol nasal spray is at least equal to if not better than dexpanthenol nasal ointment., Conclusions: Due to its ease of administration, preservative-free dexpanthenol nasal spray offers a valuable therapeutic alternative.

Chronic consumption of alcohol is an accepted social custom worldwide. In the upper aerodigestive tract, local morphologic, metabolic and functional alterations can be present due such consumption. Gastroesophageal reflux or alterations in sleep structure are typical examples of functional disorders. While alcohol was initially described as a risk enhancer only in smokers, a number of epidemiological studies have now shown that chronic alcohol consumption increases the risk of head and neck cancer independently of exposure to tobacco smoke. In addition, alcohol leads to an accumulation of pathologic microbes within the mucosa, leading to chronic infection. Susceptibility to carcinogens and cell proliferation in the mucosa are increased, resulting in genetic changes with the development of dysplasia, leucoplakia and carcinoma. Chronic alcohol consumption is correlated with an increased risk of cancer and increased mortality in a dose-dependent relationship. A number of biologically plausible mechanisms exist by which alcohol may cause cancer.

Background and Objective: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant fibrovascular dysplasia with the main symptom of recurrent epistaxis. At present, only limited data are available on long-term results in the treatment of epistaxis. A part from the surgical treatment of the bleeding telangiectasia with argon plasma, an additional postoperative long-term treatment with estriol nose-ointment was performed and the results were analysed., Patients and Methods: 69 patients with HHT were treated with APC and estriol nose ointment. 43 patients could be examined over a follow-up period of more than 20 months. The bleeding frequency and intensity as well as the patient's satisfaction with the treatment result were evaluated and the serum estriol level determined., Results: After more than 20 months, the bleeding frequency and intensity were reduced in 95% of the patients compared to their preoperative findings. Under the influence of estriol, former berry-like telangiectasias became flatter and more even. Neither systemic side effects under topically applied estriol nor a relevant increase of serum estriol levels were observed., Conclusion: The combined treatment regimen with APC and topically applied estriol provides a new treatment concept of epistaxis in HHT.

We studied a 6-year-old boy and a 2-year-old girl with bronchitis fibroplastica following Fontan operation. Large endobronchial casts of rubber-like consistency resulted in life-threatening pulmonary failure. In one patient symptoms improved after optimizing heart function with diuretics, and in the other a dramatic improvement with the resolution of the clinical symptoms and normalized serum albumin followed subcutaneous high-molecular-weight heparin treatment. The severe relapse after discontinuation of the heparin medication and the once more successful treatment with heparin suggest that in addition to optimizing heart function, high-molecular-weight heparin might be a therapeutic option for this poorly understood condition.

Background: Adhesion molecules are implicated in various stages of tumor progression and metastasis. Soluble forms of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were recently described. The aim of this study was to determine a differences in concentration of these molecules in patients with head and neck squamous cell carcinoma (HNSCC) compared to healthy controls., Patients and Methods: We investigated the circulating levels of sICAM-1 and sVCAM-1 in sera from patients with various head and neck squamous cell carcinomas (n = 52) as well as from normal, healthy controls (n = 35). Serum concentrations were determined as serum immunoreactivity by using a quantitative sandwich enzyme immunoassay technique. For statistical analysis, the Student's t-test was performed., Results: The majority of the patients with HNSCC were found to have high concentrations of sICAM-1 and sVCAM-1. The mean level of sICAM-1 in patients was 313 ng/ml and in the control group 237 ng/ml (p = 0.0005). The mean level of sVCAM-1 in patients was 624 ng/ml and in the control group 435 ng/ml (p = 0.009). The concentrations of sICAM-1 and sVCAM-1 were significantly higher in HNSCC patients., Conclusions: These results show the difference in expression of these adhesion molecules in patients with HNSCC compared to healthy controls. Endothelial adhesion molecule determination may find clinical applications in the follow-up of cancer therapy. For this reason, studies incorporating the longitudinal follow-up of patients are required.

Follicular dendritic cells (FDC) constitute an essential component of B cell follicles, normally serving as antigen-presenting cells and as cells regulating the germinal center reaction. FDC sarcoma is a very rare tumor. We report the case of a 55-year-old male patient who showed persistent cervical lymph node swelling. On biopsy the tumor consisted of spindle cells with nuclear atypia. Immunophenotypic investigation of the tumor tissue revealed a FDC sarcoma of a cervical lymph node. The tumor cells were characterized immunohistochemically especially by the expression of CD21 and focal expression of CD68. In conclusion, FDC sarcoma has to be considered in cases of tumors of uncertain origin in cervical lymph nodes, tonsils, soft palate, or nasopharynx. For clinical practice, it is important to note that sarcomas in cervical lymph nodes are not necessarily metastases but can be primary tumors.

Background and Objective: External otitis is characterized by otalgia, otorrhea, itching, and hearing loss. Treatment usually consists of local application of corticosteroids and antibiotics. Chronic external otitis is accompanied by thickening of the skin in the external auditory channel. This reduces the effect of the applied substances. Local injection of suitable drugs may support the conservative treatment. The aim of the study was to evaluate the efficacy of local injection of triamcinolone acetonide in the external auditory channel., Patients/methods: Thirteen patients with external otitis resistant to conservative treatment received an injection of triamcinolone acetonide in the external auditory channel. The improvement achieved was assessed by clinical examination and questionnaires., Results: The symptoms improved substantially in all patients; most of the patients were cured completely., Conclusions: Our results demonstrate that local injection of triamcinolone acetonide is effective in the management of chronic external otitis.

Oral appliances are used to treat snoring and sleep apnea. Yet, their success cannot be predicted without a therapeutical trial. This uncertainty and the high prices of the appliances are the reasons for their limited use. We tested a cheap, custom fit mandibular advancement device (SnorBan) for the treatment of sleep disordered breathing in order to assess its efficacy. 39 consecutive patients (51.1 +/- 9.2 years, BMI = 27.4 +/- 4.5 kg/m2) with different degrees of sleep disordered breathing (AHI = 16.6/h +/- 15.6/h) received the device after a thorough clinical examination. After getting used to the device a second polysomnography was performed. The AHI improved significantly from 16.6/h to 8.2/h (P < 0.01) in the whole group. The only patient who became worse could not get used to the device. Time with snoring dropped significantly from 16.3% to 6.6%, 59.1% of the sleep apnea patients were successfully treated as their RDI dropped below 10/h. The sleep efficiency remained unchanged. Slow wave sleep and REM-sleep increased significantly from 12% to 16% (P < 0.05). The overall compliance was 75%. The custom fit mandibular advancement device Snorban is a cheap and effective treatment for a number of patients with snoring and sleep apnea. The oral appliance is proven to be a useful and simple, non-surgical treatment option. Polysomnographic follow-up is mandatory as breathing may worsen with the device while asleep.

The erbium: YAG laser (wavelength 2940 nm; pulse duration 0.350 ms; pulse energy 0.1-1.7 J) allows vaporization of very thin skin layers without scarring and minimal lateral thermal injury due to an extremely short pulse duration. It permits exact ablation of relatively large areas of facial skin. We report our results with 216 patients following treatment for different facial lesions (facial wrinkles, acne scars, syringomas, and circumscribed sebaceous gland hyperplasia) using a new erbium: YAG laser system. Good-to-excellent cosmetic results were obtained in these patients. Our findings show that the erbium: YAG laser is an elegant and promising new method for the treatment of facial lesions.

It is now well known that chronic alcohol abuse is an important factor for developing head and neck squamous cell carcinoma (HNSCC). While hospitalized, these patients are at great risk for developing an unexpected alcohol-withdrawal syndrome. Compared to common markers of alcohol abuse, carbohydrate-deficient transferrin (CDT) has been found to be more sensitive and specific. It is therefore very useful for detecting alcoholism and controlling compliance of alcohol withdrawal. We analyzed the serum concentrations of CDT, liver enzymes and mean corpuscular volume in 49 male patients with HNSCC. Elevated CDT levels were found in more than 25% of patients who earlier denied a history of chronic alcohol abuse. Over one-third of these patients developed an alcohol-withdrawal syndrome. These findings demonstrated that analysis of elevated CDT serum levels was a valuable method for detecting chronic alcohol abuse and recognizing patients at risk for developing an alcohol-withdrawal syndrome post-operatively.

Patients with hereditary hemorrhagic telangiectasia (M. Osler-Rendu-Weber disease) often suffer from recurrent epistaxis that poses considerable therapeutic problems. Dermoplasty, electrocoagulation, laser coagulation, iridium brachytherapy and systemic administration of estrogens have been proposed for treatment. Until recently argon plasma coagulation (APC) was not used in ENT surgery, but theoretical considerations render APC a promising therapeutic method for controlling nasal bleeding. Coagulation of tissue is limited to 1-2 mm of penetration and therefore risk of damage to adjacent tissue is low. Effects are best in tissues with high electric conductivity, especially for coagulating bleeding lesions and blood vessels. We have now treated four patients with telangiectasias in the nasal mucosa who had long histories of treatment for epistaxis. The patients were satisfied with the postoperative results and the frequency and intensity of bleeding were significantly reduced. Initial clinical experiences show that APC is a useful alternative for the treatment of bleeding telangiectasias in the nasal mucosa.

Unlabelled: Rotavirus (RV), a common cause of infectious enteritis in young children including neonates, has not been associated with central nervous symptoms in standard textbooks. However, involvement of the CNS has been reported recently in case reports and small series. From 786 neonatal admissions in 1991 we retrospectively analysed the records of 215 inpatient neonates (68 preterm and 147 term infants) who developed diarrhoea during their stay on the neonatal ward and in whom stools were investigated for RV antigen by ELISA. All 215 neonates were continuously monitored for bradycardia-apnoea-episodes (BAE) at least 2 days before and during the entire diarrhoeal period. In neonates with RV antigen in stools (n = 114) we found a higher incidence of BAE compared to neonates with RV negative stools (33% vs 8%, P < 0.001 for bradycardia; 7% vs 0%, P < 0.05 for apnoea). Furthermore, bradycardia episodes of RV positive neonates were more often followed by cyanosis (11 vs 0%, P < 0.05) and intervention was more often necessary (31 vs 14%, P < 0.05) than in the RV negative neonates., Conclusion: RV infection was associated with a high incidence of BAE in neonates with diarrhoea during the acute phase of disease suggesting CNS involvement.

The diagnostic tactics in the clarification of urogenital tuberculosis are referred to the changes for the individual examinations mentioned. Some tables show the results of radiological investigations on 200 patients with proved renal tuberculosis, the extend of the triple staging proposed by us being specified. In addition to expositions on the radiopathology of urogenital tuberculosis, the differential diagnosis is indicated, its focus lying in the comparsion of 118 patients with clinical-bacteriological and/or histologically confirmed non-specific chronic pyelonephritis. The comparison of patients from two 3-year groups 1959-1961 and 1971-1973 as well as between natives and foreigners shows a change in the clinical radiological picture of renal tuberculosis.

The Caudal Dysplasia syndrome and the Femoral Hypoplasia-Unusual Facies syndrome have been reported to be more frequent among infants of diabetic mothers. We report a newborn girl who presented with features compatible with both syndromes. The possibility that both conditions represent different manifestations of the same disorder is discussed.