Primary hepatic metastatic epitheloid trophoblastic tumor of the uterus treated with multimodal therapy including pembrolizumab and thermoablation. Case report of an extremely rare disease and review of the literature.

Epithelioid trophoblastic tumor (ETT) is a rare gestational trophoblastic tumor, first described by Shih and Kurman in 1998. ETT often present as abnormal vaginal bleeding in women of reproductive age, but unlike more common forms of GTN tend to produce much less human chorionic gonadotropin (hCG) for the volume of disease present. ETT can occur after any gestational event and can occur in both intrauterine and extrauterine sites. We present a case of a 46-year-old female patient incidentally diagnosed with ETT and hepatic metastasis. Therapy was multimodal and involved chemotherapy, operation, thermoablation of liver metastases and immunocheckpoint inhibitor. The patient remains disease free for almost four years now. ETT presents a diagnostic challenge due to their rarity and histologic resemblance to other pathologies. ETT can be relatively chemo resistant and are therefore often treated surgically. Misdiagnosis might delay effective treatment and affects survival.

Skeletal injuries after cesarean section - a rare differential diagnosis of child abuse.

Birth-related fractures are an important differential diagnosis of child abuse in early infancy. While fractures associated to vaginal deliveries are well known, cesarean section is not necessarily known to cause such injuries. Nevertheless neonatal fractures have been described after cesarean sections. To give an overview over the frequency and typical locations of such fractures, the appearance of symptoms and the timespan until diagnosis, a literature research was conducted via Google scholar and Pubmed, using the key words "cesarean section" and "fractures". Birth-related fractures after cesarean sections are rare but can occur, with the long bones being particularly affected. Therefore, birth injuries should always be considered in the forensic medical assessment of fractures in early infancy, even after cesarean section. To enable a differentiation between birth trauma and physical abuse, birth and operation records should be checked for surgical manoeuvres, possible difficulties during the procedure or other risk factors. Birth-related fractures are usually detected early; in rare cases, the diagnosis is made only weeks after birth.

[Endonasal dacryocystorhinostomies with transillumination and intubation in patients with combined pathologies of the nose and after revision]. / Endonasale mikroskopische Dakryozystorhinostomie mit Endoillumination und Intubation bei Patienten mit kombinierten Tränenwegspathologien oder Revisionen.

BACKGROUND: The results of endonasal dacryocystorhinostomies (DCR) with transillumination and intubation are presented. MATERIALS AND METHODS: In the period from 1999 to 2009 follow-up examinations of 50 endonasal DCRs were carried out. All patients over 18 were included. The files were systematically evaluated. The follow-up examinations were performed after a minimum of 6 months with anamnesis of epiphora. RESULTS: 50 endonasal DCRs were performed on 40 patients. Initial surgery was performed on 27 lacrimal ducts, 16 patients had already had operations. Corrective surgery was required in 8 cases (7 endonasal DCRs, 1 external DCRs). 78 % women and 22 % men were included. The median age at the time of operation was 48 years; the median duration of preoperative symptoms was 24 months. In 42 % of the cases a chronic dacryocystitis was found. Pre-existing conditions were sarcoidosis in three cases and one case of Wegener's granulomatosis. As well as lacrimal duct obstruction, additional pathologies were treated in the same session [septoplasty (n = 12), sinus operations (n = 10), and cauterisation of the nasal concha (n = 7), removal of a dacryocele (n = 1), conchectomy (n = 1)]. 20 operations were performed on the right side, 26 on the left side and two bilateral. The median duration of the operation was 51 minutes. No operative complications were encountered. The length of stay in hospital was on average four days. The median of follow-up was 23 months. The success rate was 78 %. DISCUSSION: The success rate of endonasal DCRs is about 70 to 95 %. Thus, the achieved rate in this study is acceptable, especially as 16 of 40 patients underwent revision surgery. Probably this is attributed to the technique of transillumination. The safe intraoperative localisation of the lacrimal sac with a light probe seems to have a positive effect on the removal of obstructions.

[Intraductal application of Levovist® in salivary glands of animals]. / Intraduktale Applikation von Levovist® in Speicheldrüsenausführungsgänge am Tiermodell.

BACKGROUND: Several methods are well established for the imaging of salivary glands. Excluding the invasive method sialendoscopy all other methods show the salivary duct system inadequately. The aim of this study is to demonstrate a method to visualize the salivary duct system by B-mode ultrasound. MATERIAL AND METHODS: In 10 parotid glands of common pig cadavers the ultrasound contrast agent Levovist (®), which is galactose stabilized by palmitic acid was applied into the main salivary ducts while simultaneously performing a transcutaneous B-mode ultrasound. RESULTS: In all cadavers a visualization of the salivary duct system could be achieved by the application of Levovist (®) because of contrast enhancement. This effect arises as a result of an increased reflection of ultrasound waves on the surface of the microbubbles contained in the contrast agent. CONCLUSION: A reproducible visualization of the salivary duct system with B-mode ultrasound is possible by an intraductal application of an ultrasound contrast agent. In future this could be established as a reliable and fast method for imaging of the salivary ducts without ionizing radiation for the patient.

Error analysis for determination of accuracy of an ultrasound navigation system for head and neck surgery.

OBJECTIVE: The use of conventional CT- or MRI-based navigation systems for head and neck surgery is unsatisfactory due to tissue shift. Moreover, changes occurring during surgical procedures cannot be visualized. To overcome these drawbacks, we developed a novel ultrasound-guided navigation system for head and neck surgery. A comprehensive error analysis was undertaken to determine the accuracy of this new system. MATERIALS AND METHODS: The evaluation of the system accuracy was essentially based on the method of error definition for well-established fiducial marker registration methods (point-pair matching) as used in, for example, CT- or MRI-based navigation. This method was modified in accordance with the specific requirements of ultrasound-guided navigation. The Fiducial Localization Error (FLE), Fiducial Registration Error (FRE) and Target Registration Error (TRE) were determined. RESULTS: In our navigation system, the real error (the TRE actually measured) did not exceed a volume of 1.58 mm(3) with a probability of 0.9. A mean value of 0.8 mm (standard deviation: 0.25 mm) was found for the FRE. The quality of the coordinate tracking system (Polaris localizer) could be defined with an FLE of 0.4 +/- 0.11 mm (mean +/- standard deviation). The quality of the coordinates of the crosshairs of the phantom was determined with a deviation of 0.5 mm (standard deviation: 0.07 mm). CONCLUSION: The results demonstrate that our newly developed ultrasound-guided navigation system shows only very small system deviations and therefore provides very accurate data for practical applications.

[Navigation-assisted sonography for soft tissues in the head and neck region]. / Navigationsunterstützte Weichteilsonographie für den Kopf-Hals-Bereich.

BACKGROUND: In soft tissue surgery of the head and neck region tissue shifts limit the usefulness of conventional CT/MRI-based navigation procedures. Furthermore, changes caused by invasive measures cannot be visualized. METHODS: A novel navigation device for sonography of soft tissues was developed. This consists of a navigated ultrasound scanner, a navigated surgical instrument, and a personal computer with custom-made software. Its use makes an additional visualization by means of CT or MRI dispensable. RESULTS: The system deviation (three-dimensional error) of this newly developed prototype was less than 1 mm. The practical application in a model setup showed good handling properties of the system. Orientation and approach of the surgical instrument to the sonographically visualized target structure were rapid and accurate. CONCLUSION: This new navigation system does not require additional CT or MRI images. The navigated ultrasound probe shows tissue changes in real time. This navigation system is especially suitable for invasive procedures in soft tissues.

Navigation-supported and sonographically-controlled fine-needle puncture in soft tissues of the neck.

In surgery, sonography has been a well-accepted means of orientation for years. The immediate vicinity of many vital structures in the head and neck region calls for a very exact visualization of the surgical instrument in the 2-D ultrasonic picture. We report on the development of a new method for navigation-supported and sonographically-controlled fine-needle puncture in soft tissues of the neck. Our system comprises a navigated ultrasound probe, a navigated fine-puncture needle and a coordinate sensor. A personal computer with specially-developed software assists calibration and surgical application. The applicability test for the system is described. In vitro, a model lymph node of 9 mm in diameter had been hit. It is shown that the target structure can be aimed at very precisely by the navigated puncture needle. An accuracy of 97% and a specificity of 99% could be demonstrated. The development of a very precise and easy-to-handle method for navigation-supported fine-needle puncture in the neck region is presented. The outstanding advantage of this method is that no rigid reference gadget fixed to the patient's body is necessary. That makes this method very suitable for surgery in the neck region. Contrary to other sonographically-supported navigation methods in the head and neck region, preoperative imaging (CT or MRT) is dispensable.

[Quality management: reduced waiting time and enhanced efficiency in a university ear, nose, and throat outpatient department]. / Qualitätsmanagement: Verkürzung von Wartezeiten und Effizienzsteigerung bei der Versorgung ambulanter Patienten an einer HNO-Universitätsklinik.

BACKGROUND: The introduction of Diagnosis-Related Groups, which standardize payment for each clinical service, entails keeping the inpatient treatment as short as possible. Thus outpatient treatment is gaining in importance. To cope with this change, organizational and structural modifications of clinic routine are necessary. METHODS: In the ear, nose, and throat outpatient clinic of Johann Wolfgang Goethe University in Frankfurt, Germany, a hotline was established that allows patients to make appointments and get advice based on quality management guidelines according to DIN EN ISO 9001:2000. The development of this project is described here step by step, from planning to inclusion in the daily clinic routine. RESULTS: Patient visits became more effective despite increasing demand. This resulted in high satisfaction of patients and clinic personnel alike. CONCLUSION: This model may contribute considerably to coping with the increasing demand for clinic appointments and to optimal use of a clinic's human resources.

Time-variant parametric estimation of transient quadratic phase couplings between heart rate components in healthy neonates.

The heart rate variability (HRV) can be taken as an indicator of the coordination of the cardio-respiratory rhythms. Bispectral analysis using a direct (fast Fourier transform based) and time-invariant approach has shown the occurrence of a quadratic phase coupling (QPC) between a low-frequency (LF: 0.1 Hz) and a high-frequency (HF: 0.4-0.6 Hz) component of the HRV during quiet sleep in healthy neonates. The low-frequency component corresponds to the Mayer-Traube-Hering waves in blood pressure and the high-frequency component to the respiratory sinus arrhythmia (RSA). Time-variant, parametric estimation of the bispectrum provides the possibility of quantifying QPC in the time course. Therefore, the aim of this work was a parametric, time-variant bispectral analysis of the neonatal HRV in the same neonates used in the direct, time-invariant approach. For the first time rhythms in the time course of QPC between the HF component and the LF component could be shown in the neonatal HRV.

[Quality assessment according to DIN EN ISO 9001:2000: certification in a university ENT department]. / Qualitätsmanagement nach DIN EN ISO 9001:2000: Zertifizierung einer HNO-Universitätsklinik.

BACKGROUND: In 2003, our department inaugurated a quality management system. The certification according to DIN EN ISO 9001:2000 as required by the hospital management was achieved in August 2005. The aims were optimization of internal operating schedules and standardization of procedures according to logistic interfaces with external structures. METHODS: Since 2000, the implementation of an internal quality management system is required by German law and threatened by penalty in case of non-implementation. Beside a basic audit and optimization of all organizational procedures, all core processes were determined and the approvals checked. These aims involve both the quality of operational procedures, in and outpatient treatment, research, study and teaching and aspects of service such as quickness of scheduling and forwarding of reports as well as economic aspects and efficiency. The department of "quality management", whose main tasks are the professional guidance and the training of the quality management representatives, plays an important role. RESULTS: Realization of the new regulations and restructuring resulted in an increase in effectiveness and an improvement in operational procedures. In particular, patients and staff have benefited from the reorganized and modified sequence of operations. CONCLUSION: Implementation of a quality management system in different hospital departments is recommended.

[Intraoperative endosonographic guided resection of tongue carcinoma]. / Intraoperative endosonographisch gesteuerte Resektion von Zungenkarzinomen.

BACKGROUND: Exact estimation of a tumor's size and the definition of adequate resection margins in carcinomas of the tongue are often difficult because of the tumor's extension and deep infiltration. METHODS: We have developed a method that allows intraoperative visualisation and marking of tumor margins. Intra-operative endosonography was performed on nine patients with carcinomas of the tongue using a 8-12 MHz linear array transducer. The oral cavity was flooded with normal saline solution and the transducer was immersed therein. This allowed scanning in a non-contact mode. The tumor margins were marked with a surgical suture under endosonographic monitoring. RESULTS: In the nine patients studied, the histological margins corresponded to the sonographic margins. The sonographic marking proved to be useful during the resection of the tumor and histological safety margins were respected in each case. CONCLUSIONS: This non-invasive procedure provides a quick and reliable orientation during the resection of tongue carcinoma, and a more precise and individual definition of resection margins is possible. Intraoperative non-contact use of endosonography is a promising method.

Prognostic impact of EBV-related LMP-1, histologic type, and environmental factors in nasopharyngeal carcinoma in a German population.

INTRODUCTION: This retrospective study addressed the possible involvement of latent Epstein-Barr virus (EBV) infection, in particular LMP-1 expression, and further exogenous factors, i.e. tobacco, alcohol and occupational hazardous substances, in nasopharyngeal carcinoma (NPC) in a German population. PATIENTS AND METHODS: From 1980 to 2000, 44 patients suffering from histologically confirmed NPC were entered into the study. 33 specimens were available for immunostaining (IHC) to analyze LMP-1 expression. Information about environmental exposures were obtained employing a detailed standardized questionnaire. RESULTS: Outcome of patients with squamous cell NPC (SC-NPC) was significant worse than that of those with non-keratinizing NPC (NK-NPC). Age and tumor size correlated with response to therapy. The group with negative conventional LMP-1 staining showed better overall survival after 5 years compared to the group with positive or marginally positive LMP-1 detection (not significant). Nevertheless, after staining by tyramid-augmented IHC (TSA-IHC), nearly all specimens with negative LMP-1-staining in conventional IHC were found to be clearly positive. All patients with SC-NPC were smokers. The distribution of smokers and non-smokers in the group of NK-NPC was balanced. Comparable to the tobacco observation, there was also a correlation between high alcohol consumption and SC-NPC. CONCLUSION: Prognosis of NPC is mainly dependent on histologic type. Prognostic impact of LMP-1 is still unclear since LMP-1 was detected in all specimens using TSA-IHC. Therefore, TSA-IHC-LMP-1 detection might be interesting for diagnostic specification and development of new therapeutic strategies in NPC.

On the spatio-temporal organisation of quadratic phase-couplings in 'tracé alternant' EEG pattern in full-term newborns.

OBJECTIVE: The time courses of quadratic phase-coupling (QPC) of electroencephalographic burst and interburst patterns of the 'trace alternant' (TA) in full-term newborns have been quantified. METHODS: Using the Gabor expansion, a fast Fourier transformation based method, biamplitude, bicoherence and phase-bicoherence time courses of both burst and interburst patterns have been determined (common average reference EEG recordings). With a frequency resolution of 0.25 Hz and a frequency grid of 1-1.5 <==> 3.5-4.5 Hz (region-of-interest), a number of 15 frequency pairs result. These pairs have been investigated. RESULTS: The burst and the interburst patterns are characterized by temporally and topographically different QPC profiles. All differences are dominant at the electrode Fp1 followed by Fp2. There is a significant difference (combined multiple and global test strategy) in the QPC characteristics between both patterns within the time period from 0.75 to 1.5 s after the pattern onset at electrode Fp1. The maximal QPC in burst patterns (especially at Fp1) can be observed during this time period. In contrast to this finding, maximal QPC in interburst patterns (at Fp1) are reached immediately after the onset and at 3 s. Summarising all findings, a QPC-rhythm of 0.1 Hz during TA can be assumed. CONCLUSIONS: It can be assumed that the QPC rhythm of the TA is generated by a pattern-spanning time-variant phase-locking process and there are indications for a possible correspondence between the QPC rhythm and vegetative rhythms. SIGNIFICANCE: This study showed that advanced, time-variant analysis methods quantifying QPC rhythms are able to add new scientific information to the understanding of nature, characteristics and significance of TA in the neonatal EEG.

[Dynamic magnetic resonance tomography (dMRT). It's value in advanced head-neck tumors treated with radiochemotherapy]. / Dynamische Magnetresonanztomographie (dMRT). Wertigkeit bei fortgeschrittenen Kopf-Hals-Tumoren unter Radiochemotherapie.

PURPOSE: With the help of dynamic magnetic resonance tomography (dMRT) the status of tissue microcirculation can be visualized. METHODS: Dynamic MRI was performed in 13 patients with advanced, nonresectable oro- or hypopharynx carcinoma at the beginning and the end of therapy. Maximal signal intensity and exchange rate constant in the tissue of the tumor and the lymph node metastases were analyzed using a pharmacokinetic two-compartment model. RESULTS: In all six patients with clinical complete response (CR), the maximal signal intensity increased after therapy in the tissue of the primary tumor and the lymph node metastases. Furthermore, a high decrease in the parameter k(21) was associated with a better prognosis and could be observed especially after combined radiochemotherapy. CONCLUSION: Our first results indicate that contrast-enhanced dynamic MRI studies before and after radio- or combined radiochemotherapy offer important information about the changes of microcirculation in the tissue of the tumor and lymph node metastases. Furthermore, this information seems to be a promising predictor for clinical outcome of therapy.

[Time variant bispectral analysis based on adaptive recursive Fourier transformation]. / Zeitvariante Bispektralanalyse auf der Basis einer adaptiv rekursiven Fouriertransformation.

An appropriate investigation of quadratic phase couplings (QPC) in non-stationary signals requires time-variant methods of bispectral analysis. A new approach for time-variant estimation of power spectrum and bispectrum based on an adaptively, recursively estimated Fourier transform (ADFT) is presented in this paper. A reduced calculation effort and the possibility of the calculation of the bispectrum for selected frequency triples are important advantages of this method. Because of the recursive calculation, the ADFT is convenient for analysing ongoing signals. This will be demonstrated for simulated and real biomedical signals.

Time-variant non-linear phase-coupling analysis of EEG burst patterns in sedated patients during electroencephalic burst suppression period.

OBJECTIVES: The quadratic phase-coupling (QPC) within burst patterns during electroencephalic burst suppression has been quantified. METHODS: It can be shown that a QPC exists between the frequency ranges 0-2.5 and 3-7.5 Hz and between the frequency ranges 0-2.5 and 8-12 Hz. By means of time-variant bicoherence analysis, a strong phase-locking between the modulating and the modulated component can be identified. The phase-locking is demonstrable within the first 250 ms after the burst onset and comes up to the maximum between 750 and 1250 ms. RESULTS: The effect is maintained over the whole first part of the burst (2 s) with a decreasing tendency after 1250 ms. All these effects cannot be found in the EEG before entering the burst suppression period (BSP). The transient coupling phenomena in the EEG bursts during BSP can be regarded as indicators for short-term interrelations between the underlying electrophysiologic processes. CONCLUSIONS: It can be suggested that the method introduced for the quantification of the sedation depth should be used.

Intraoperative B-mode endosonography of tongue carcinoma.

BACKGROUND: Exact estimation of a tumor's size and definition of adequate resection margins in carcinomas of the tongue are often difficult because of the tumor's extension and deep infiltration. METHODS: We developed a method that allows intraoperative visualization and marking of tumor margins: intraoperative endosonography was performed in five patients with carcinomas of the tongue with an 8- to 12-MHz linear array transducer. The oral cavity was flooded with normal saline solution, and the transducer was immersed therein. This allowed scanning in a noncontact mode. The tumor margins were marked with a surgical suture under endosonographic monitoring. RESULTS: In the five patients studied, histologic margins corresponded to sonographic margins. The sonographic marking proved to be useful during the resection of the tumor, and histologic safety margins were respected in each case. CONCLUSIONS: This noninvasive procedure provides a quick and reliable orientation during resection of tongue carcinoma, and a more precise and individual definition of resection margins is possible. Intraoperative noncontact use of endosonography is a promising method, and further studies may confirm this.

Sonography of nasal tip anatomy and surgical tip refinement.

The amorphous or wide nasal tip is the most commonly encountered nasal tip deformity, but little has been done to measure the effect of standard rhinoplasty techniques on nasal tip width. In the clinical routine, nasal tip width and soft-tissue cover thickness are estimated by inspection and palpation rather than by measurement. In this study, a B-mode sonograph with a 12-MHz transducer was used in a noncontact mode to measure tip width 0.5 cm occipital to the tip defining point, distance between the alar cartilage domes, and thickness of the soft-tissue cover overlying the lower lateral cartilages. These parameters were measured 3 to 8 weeks before and 56 days to 19 months after a transdomal suture tip plasty in 18 patients. The distance between the alar cartilage domes seemed to be an important factor for tip width because interdomal distance, not soft-tissue cover thickness, correlated with tip width before surgery (correlation: 0.53). Conversely, the degree of tip refinement correlated with preoperative soft-tissue cover thickness (correlation: 0.75), but not with interdomal distance. Ultrasonic imaging of nasal soft tissues may help to assess the effect of different tip refining procedures and other soft-tissue changes after rhinoplasty.

Quantification of transient quadratic phase couplings within EEG burst patterns in sedated patients during electroencephalic burst-suppression period.

The time dynamics of the quadratic phase coupling within burst patterns during electroencephalic burst-suppression has been quantified. It can be shown that a transient quadratic phase coupling (QPC) exists between the frequency ranges 0 to 2.5 and 3 to 7.5 Hz and between the frequency ranges 0 to 2.5 and 8 to 12 Hz. The QPC can be explained by an amplitude modulation, where the slow rhythm modulates the rhythmic activities with a higher frequency. By means of time-variant bicoherence analysis, a strong phase-locking between the modulating and the modulated component can be identified. The phase-locking is demonstrable within the first 250 ms after the burst onset and comes up to the maximum between 750 and 1250 ms. The effect is maintained over the whole first part of the burst (2 s) with a decreasing tendency after 1250 ms. All these effects cannot be found in the EEG before entering the burst suppression period (BSP). The transient coupling phenomena in the EEG bursts during BSP can be regarded as indicators for short-term interrelations between the underlying electrophysiologic processes.