Thoracic impedance pneumography in propofol-sedated patients undergoing percutaneous endoscopic gastrostomy (PEG) placement in gastrointestinal endoscopy: A prospective, randomized trial.

STUDY OBJECTIVE: To assess the efficacy of an ECG-based method called thoracic impedance pneumography to reduce hypoxic events in endoscopy. DESIGN: This was a single center, 1:1 randomized controlled trial. SETTING: The trial was conducted during the placement of percutaneous endoscopic gastrostomy (PEG). PATIENTS: 173 patients who underwent PEG placement were enrolled in the present trial. Indication was oncological in most patients (89%). 58% of patients were ASA class II and 42% of patients ASA class III. INTERVENTIONS: Patients were randomized in the standard monitoring group (SM) with pulse oximetry and automatic blood pressure measurement or in the intervention group with additional thoracic impedance pneumography (TIM). Sedation was performed with propofol by gastroenterologists or trained nurses. MEASUREMENTS: Hypoxic episodes defined as SpO2 < 90% for >15 s were the primary endpoint. Secondary endpoints were minimal SpO2, apnea >10s/>30s and incurred costs. MAIN RESULTS: Additional use of thoracic impedance pneumography reduced hypoxic episodes (TIM: 31% vs SM: 49%; p = 0.016; OR 0.47; NNT 5.6) and elevated minimal SpO2 per procedure (TIM: 90.0% ± 8.9; SM: 84.0% ± 17.6; p = 0.007) significantly. Apnea events >10s and > 30s were significantly more often detected in TIM (43%; 7%) compared to SM (1%; 0%; p < 0.001; p = 0.014) resulting in a time advantage of 17 s before the occurrence of hypoxic events. As a result, adjustments of oxygen flow were significantly more often necessary in SM than in TIM (p = 0.034) and assisted ventilation was less often needed in TIM (2%) compared with SM (9%; p = 0.053). Calculated costs for the additional use of thoracic impedance pneumography were 0.13$ (0.12 €/0.11 £) per procedure. CONCLUSIONS: Additional thoracic impedance pneumography reduced the quantity and extent of hypoxic events with less need of assisted ventilation. Supplemental costs per procedure were negligible. KEY WORDS: thoracic impedance pneumography, capnography, sedation, monitoring, gastrointestinal endoscopy, percutaneous endoscopic gastrostomy.

Fertility preservation and management of pregnancy in melanoma patients requiring systemic therapy.

Melanoma is one of the most common cancers in adolescents and adults at fertile age, especially in women. With novel and more effective systemic therapies that began to profoundly change the dismal outcome of melanoma by prolonging overall survival, the wish for fertility preservation or even parenthood has to be considered for a growing portion of melanoma patients-from the patients' as well as from the physicians' perspective. The dual blockade of the mitogen-activated protein kinase pathway by B-Raf proto-oncogene serine/threonine kinase and mitogen-activated protein kinase inhibitors and the immune checkpoint inhibition by anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte-associated protein-4 monoclonal antibodies constitute the current standard systemic approaches to combat locally advanced or metastatic melanoma. Here, the preclinical data and clinical evidence of these systemic therapies are reviewed in terms of their potential gonadotoxicity, teratogenicity, embryotoxicity and fetotoxicity. Recommendations for routine fertility and contraception counseling of melanoma patients at fertile age are provided in line with interdisciplinary recommendations for the diagnostic work-up of these patients and for fertility-protective measures. Differentiated recommendations for the systemic therapy in both the adjuvant and the advanced, metastatic treatment situation are given. In addition, the challenges of pregnancy during systemic melanoma therapy are discussed.

Impact of controlled attenuation parameter on detecting fibrosis using liver stiffness measurement.

BACKGROUND: Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis. AIM: To determine how to use CAP in interpreting liver stiffness measurements. METHODS: This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP. RESULTS: Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis. CONCLUSIONS: Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis.

Guideline Compliance in Surgery for Thyroid Nodules - A Retrospective Study.

Diagnostic guidelines for thyroid nodules focus on malignancy risk assessment to avoid unnecessary diagnostic operations. These guidelines recommend a combination of tests in form of a diagnostic algorithm. The present study analyzed the recommended algorithm and its implementation by different medical professionals. Preoperative diagnostic procedures, laboratory tests and histopathological findings of patients who underwent thyroid surgery between 2006 and 2013 were analyzed. The results were stratified by the assignation by specialized endocrinologists (ENP), general practitioners (GP) or Goethe-University Hospital Frankfurt (UKF). 677 patients were enrolled, of these 62% were assigned by UKF, 18.5% by an ENP and 19.5% by a GP. Ultrasonography rate was significantly higher in UKF (97.6%) compared to patients assigned by GP (90.9%, p<0.0001). Rates for fine-needle aspiration cytology ranged between 47.6% in UKF and 23.2% in ENP (p<0.0001). In over 93% of the patients an analysis of thyroid-stimulating hormone and triiodothyronine/thyroxin was realized. The overall malignancy rate was 11.82%. The malignancy rate was significantly higher if a FNA biopsy was performed (16.35 vs. 8.94%; p=0.0048). A higher malignancy rate could only be seen if the preoperative diagnostic workup included FNA. Besides this, the grade of algorithm adherence showed no effect on the malignancy rate.

Evaluation of Strain Elastography for Differentiation of Thyroid Nodules: Results of a Prospective DEGUM Multicenter Study.

PURPOSE: Many patients with thyroid nodules are presently referred to surgery for not only therapeutic but also diagnostic purposes. The aim of noninvasive diagnostic methods is to optimize the selection of patients for surgery. Strain elastography (SE) enables the ultrasound-based determination of tissue elasticity. The aim of the present study was to evaluate the value of SE for the differentiation of thyroid nodules in a prospective multicenter study. MATERIALS AND METHODS: The study was registered at clinicaltrials.gov and was approved by the local ethics committees of all participating centers. All patients received an ultrasound (US) of the thyroid gland including color Doppler US. In addition, all nodules were evaluated by SE (Hitachi Medical Systems) using qualitative image interpretation of color distribution (SE-ES), strain value and strain ratio. RESULTS: Overall, 602 patients with 657 thyroid nodules (567 benign, 90 malignant) from 7 centers were included in the final analysis. The sensitivity, specificity, NPV, PPV, +LR were 21 %, 73 %, 86 %, 11 %, 0.8, respectively, for color Doppler US; 69 %, 75 %, 94 %, 30 %, 2.9, respectively, for SE-ES; 56 %, 81 %, 92 %, 32 %, 2.9, respectively, for SE-strain value; and 58 %, 78 %, 92 %, 30 %, 2.6, respectively, for SE-strain ratio. The diagnostic accuracy was 71 % for both strain value and strain ratio of nodules. CONCLUSION: SE as an additional ultrasound tool improves the value of ultrasound for the work-up of thyroid nodules. It might reduce diagnostic surgery of thyroid nodules in the future.

[Ultrasound of the Thyroid]. / Die Bedeutung der Sonografie bei der Abklärung von Schilddrüsenerkrankungen.

Thyroid nodules and thyroid abnormalities are common findings in the general population. Ultrasonography is the most important imaging tool for diagnosing thyroid disease. In the majority of cases a correct diagnosis can already be made in synopsis of the sonographic together with clinical findings and basal thyroid hormone parameters and an appropriate therapy can be initiated thereafter. A differentiation of hormonally active vs. inactive nodes, and in particular benign vs. malignant nodules is sonographically, however, not reliably possible. In this context, radioscanning has its clinical significance predominantly in diagnosing hormonal activity of thyroid nodules. Efforts of the past years aimed to improve sonographic risk stratification to predict malignancy of thyroid nodules through standardized diagnostic assessment of evaluated risk factors in order to select patients, who need further diagnostic work up. According to the "Breast Imaging Reporting and Data System" (BI-RADS), "Thyroid Imaging Reporting and Data Systems" (TI-RADS) giving standardized categories with rates of malignancy were evaluated as a basis for further clinical management. Recent technological developments, such as elastography, also showpromising data and could gain entrance into clinical practice. The ultrasound-guided fineneedle aspiration is the key element in the diagnosis of sonographically suspicious thyroid nodules and significantly contributes to the diagnosis of malignancy versus benignity.

PATIENTS' SAFETY AND FEASIBILITY OF INTRAVENOUS URAPIDIL IN THE PRETREATMENT OF PHEOCHROMOCYTOMA PATIENTS IN A NORMAL WARD SETTING - AN ANALYSIS OF 20 CONSECUTIVE CASES.

CONTEXT: The intravenously administered selective α1 antagonist urapidil represents an alternative to phenoxybenzamine in the preoperative treatment of pheochromocytoma patients. OBJECTIVE: The aim of the study was to investigate the blood pressure changes in pheochromocytoma patients with urapidil pretreatment with special regards to the need for interventions in order to estimate the safety of this treatment in a normal ward setting. DESIGN: The medical records of all patients who underwent adrenalectomy for PCC were reviewed retrospectively. Systolic blood pressure values >180mmHg were defined as hypertensive episodes and systolic blood pressure values < 50mmHg as hypotensive episodes. Episodes of blood pressure instabilities were considered significant and recorded as intervention if they led to a direct action. RESULTS: Twenty consecutive patients who received urapidil pretreatment were enrolled in this retrospective study. Preoperatively, a median of 9 blood pressure measurements per day have been performed on the ward. A total of 2 episodes of hypertension occurred, and 1 episode of hypotension has been recorded. In the period from 25-72 hours postoperatively the median number of blood pressure measurements was 5 per 24 hours. The blood pressure deviations led to a total of 3 interventions for hypertension in 1 (5%) patients and 5 interventions for hypotension in 3 (15%) patients. All interventions could be managed on the normal ward, without the need to transfer the patient to an ICU. CONCLUSIONS: Intravenous urapidil can safely be administered on a normal ward without putting patients at risk. Intensive monitoring beyond 24 hours postoperatively was not necessary, the blood pressure measurements during the shift on a normal ward were sufficient for maintaining patients' safety.

[Ultrasound of the thyroid]. / Die Bedeutung der Sonografie bei der Abklärung von Schilddrüsenerkrankungen.

Thyroid nodules and thyroid abnormalities are common findings in the general population. Ultrasonography is the most important imaging tool for diagnosing thyroid disease. In the majority of cases a correct diagnosis can already be made in synopsis of the sonographic together with clinical findings and basal thyroid hormone parameters and an appropriate therapy can be initiated thereafter. A differentiation of hormonally active versus inactive nodes, and in particular benign versus malignant nodules is sonographically, however, not reliably possible. In this context, radioscanning has its clinical significance predominantly in diagnosing hormonal activity of thyroid nodules. Efforts of the past years aimed to improve sonographic risk stratification to predict malignancy of thyroid nodules through standardized diagnostic assessment of evaluated risk factors in order to select patients, who need further diagnostic work up. According to the "Breast Imaging Reporting and Data System" (BI-RADS), "Thyroid Imaging Reporting and Data Systems" (TI-RADS) giving standardized categories with rates of malignancy were evaluated as a basis for further clinical management. Recent technological developments, such as elastography, also show promising data and could gain entrance into clinical practice. The ultrasound-guided fine-needle aspiration is the key element in the diagnosis of sonographically suspicious thyroid nodules and significantly contributes to the diagnosis of malignancy versus benignity.

Severe 25-hydroxyvitamin D deficiency identifies a poor prognosis in patients with hepatocellular carcinoma - a prospective cohort study.

BACKGROUND: Vitamin D is involved in many biological processes. The role of vitamin D in patients with hepatocellular carcinoma (HCC) remains inconclusive, although there is evolving evidence that vitamin D may modulate cancer development and progression. AIM: To evaluate serum vitamin D as prognostic parameter in HCC, we performed a prospective cohort study. METHODS: HCC patients were prospectively recruited and 25-hydroxyvitamin D3 (25(OH)D3 ) levels were determined. 25(OH)D3 levels were compared to stages of cirrhosis and HCC stages with nonparametric Kruskal-Wallis tests and Spearman correlations in 200 HCC patients. The association of the 25(OH)D3 levels and overall survival (OS) was assessed in uni- and multivariate Cox regression models. RESULTS: Two-hundred patients with HCC were included. The mean follow-up time was 322 ± 342 days with a range of 1-1508 days. Nineteen patients underwent liver transplantation and 60 patients died within the observation time. The mean serum 25(OH)D3 concentration was 17 ± 13 ng/mL with a range of 1-72 ng/mL. 25(OH)D3 serum levels negatively correlated with the stage of cirrhosis as well as with stages of HCC. Patients with severe 25(OH)D3 deficiency had the highest mortality risk (hazard ratio 2.225, 95% confidence interval 1.331-3.719, P = 0.002). Furthermore, very low 25(OH)D3 levels were associated with mortality independently from the MELD score and high alpha-Fetoprotein levels (>400 ng/mL) in a multivariate Cox regression model. CONCLUSIONS: We conclude that 25(OH)D3 deficiency is associated with advanced stages of hepatocellular carcinoma and it is a prognostic indicator for a poor outcome.

EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography. Part 2: Clinical applications.

The clinical part of these Guidelines and Recommendations produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology EFSUMB assesses the clinically used applications of all forms of elastography, stressing the evidence from meta-analyses and giving practical advice for their uses and interpretation. Diffuse liver disease forms the largest section, reflecting the wide experience with transient and shear wave elastography . Then follow the breast, thyroid, gastro-intestinal tract, endoscopic elastography, the prostate and the musculo-skeletal system using strain and shear wave elastography as appropriate. The document is intended to form a reference and to guide clinical users in a practical way.

EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography. Part 1: Basic principles and technology.

The technical part of these Guidelines and Recommendations, produced under the auspices of EFSUMB, provides an introduction to the physical principles and technology on which all forms of current commercially available ultrasound elastography are based. A difference in shear modulus is the common underlying physical mechanism that provides tissue contrast in all elastograms. The relationship between the alternative technologies is considered in terms of the method used to take advantage of this. The practical advantages and disadvantages associated with each of the techniques are described, and guidance is provided on optimisation of scanning technique, image display, image interpretation and some of the known image artefacts.

[Palpation and elastography of thyroid nodules in comparison]. / Vergleich von Palpation und Elastographie an Schilddrüsenknoten.

UNLABELLED: In addition to ultrasound, elastography is available for evaluation of thyroid nodules for several years. AIM: of this study was to verify a statistically significant correlation between palpation and elastography as well as between scintigraphy and elastography, respectively. PATIENTS, METHODES: 97 solitary thyroid nodules in 67 women (mean age 63.0 ± 14.8 years) and 30 men (mean age 63.4 ± 18.5 years) were colour-coded by a colour spectrum from blue (soft) via yellow to red (hard) (Sonix touch ultrasound system, Ultrasonix, Canada) with a 6-14 MHz probe. These colour codes were classified into an elastography score of ES 1 to ES 4. RESULTS: 50 nodules were not palpable, 47 were addressed as "soft" (n = 16), "indifferent" (n = 24) or "hard" (n = 7). Elastography values were higher with increasing stiffness of the palpable nodules. Medians of elastography score were for the soft nodules ES 2, for the indifferent nodules ES 2.5 and for the hard nodules ES 4. A statistically significant correlation could be confirmed by the Jonckheere-Terpstra test (p = 0.01) and Spearman's rank correlation (p = 0.03). No correlation between elastography and scintigraphic uptake could be observed (p = 0.41). CONCLUSION: In detectable nodules, palpation is correlated with elastography. Since non-palpable nodules may have differences in elasticity too, elastography can provide additional data, which may influence the further diagnostic procedures and treatment essentially. Based on these results, scintigraphy cannot be replaced by elastography.

[Gangliocytic paraganglioma--a rare differential diagnosis of a submucosal duodenal tumor]. / Gangliozytisches Paragangliom--eine seltene Differenzialdiagnose eines submukösen duodenalen Tumors.

We report on the case of a 36-year-old male patient who was found to have a submucosal duodenal tumour during the diagnostic work-up of gastrointestinal bleeding. After exclusion of other tumour manifestations complete endoscopic resection was performed. Histologically a gangliocytic paraganglioma was diagnosed, a very rare type of a duodenal neuroendocrine tumour. This case report discusses the epidemiology, diagnostic work-up and therapeutic options for this rare tumour type.

Differentiation between benign and malignant adrenal mass using contrast-enhanced ultrasound.

PURPOSE: Adrenal masses can be detected by ultrasound with high sensitivity and specificity. The aim of the present study was to evaluate CEUS in a large patient population using CEUS patterns identified in a previous pilot study. MATERIALS AND METHODS: 116 adrenal masses were evaluated by ultrasound, including CEUS with the contrast agent Sonovue®. The dynamic of contrast enhancement (CE) was analyzed using time-intensity curves. The time of the first CE in the adrenal mass was used to define four CEUS patterns: pattern I = early arterial CE, pattern II = arterial CE, pattern III = late CE, pattern IV = no CE. In addition, all patients received CT/MRI and hormonal testing. In suspicious cases biopsy or adrenalectomy was performed. RESULTS: CEUS patterns I&II were seen in all patients with primary or secondary malignant lesions of the adrenal gland (n = 16). The sensitivity and specificity of CEUS for the diagnosis of malignant adrenal mass were 100 % (CI [75;100]) and 67 % (CI [56;75]), respectively. Overall histology was available as a reference method for 40 adrenal masses. In 68 % of histologically diagnosed adrenal masses, MRI/CT and CEUS were congruent concerning the characterization of malignant versus benign adrenal mass. CONCLUSION: Contrast-enhanced ultrasound may be a useful method in the diagnostic work-up of adrenal mass with excellent sensitivity for the diagnosis of malignancy.

Real-time elastography and contrast-enhanced ultrasound for the assessment of thyroid nodules.

OBJECTIVE: Work-up of thyroid nodules remains challenging. Recent technologies enable determination of tissue elasticity and perfusion using ultrasound devices. The aim of the present study was to evaluate real-time elastography (RTE) and contrast-enhanced ultrasound with Sonovue (CEUS) for the differentiation of benign and malignant thyroid nodules. MATERIALS AND METHODS: Inclusion criteria were: nodules ≥1 cm, non-functioning or hypo-functioning on radionuclide scanning, and cytological/histological assessment. All patients received conventional ultrasound, RTE and CEUS. RTE was classified as: Elasticity-Score (ES)1 = soft, ES2 = predominantly soft, ES3 = predominantly hard, ES4 = hard nodule. CEUS-video clips were digitally recorded and analyzed using time-intensity-curves within selected regions-of-interest. RESULTS: Fifty-three nodules in 50 patients were available for analysis. Forty-six nodules were benign on cytology/histology, 6 nodules were papillary carcinoma and one nodule was a follicular carcinoma. Nodule margin irregularity was the ultrasound pattern most predictive of malignancy with sensitivity 57% (95% confidence interval: 18-90%) and specificity 85% (71-94% p<0.05). When using ES3&4 for the diagnosis of malignant nodules sensitivity and specificity were 86% (42-99.7%) and 87% (75-95%), respectively (p = 0.0003). The only malignant nodule missed with RTE was a follicular carcinoma. Sensitivity for the diagnosis of papillary carcinoma therefore was 100%. No specific CEUS pattern could be identified to differentiate between benign and malignant nodules. CONCLUSIONS: RTE seems to be a useful tool in the work-up of thyroid nodules to exclude papillary thyroid cancer. However, follicular carcinoma remains a challenging problem. CEUS did not improve the characterization of thyroid nodules in this preliminary study.

Contrast-enhanced ultrasound for imaging of adrenal masses.

PURPOSE: The number of incidentally discovered adrenal masses is growing due to the increased use of modern high-resolution imaging techniques. However, the characterization and differentiation of benign and malignant adrenal lesions is challenging. This study aimed to evaluate contrast-enhanced ultrasound for the characterization of adrenal masses. MATERIALS AND METHODS: We studied 58 patients with adrenal masses detected with computed tomography, magnetic resonance imaging, or ultrasound. 7 patients had bilateral adrenal lesions. Contrast-enhanced ultrasound was performed using high-resolution ultrasound (3.5 - 7 MHz) and intravenous injection of 2.4 ml SonoVue. The contrast enhancement pattern of all adrenal lesions was documented. RESULTS: The 18 malignant adrenal tumors were significantly larger at the time of diagnosis compared to the 40 benign lesions (p < 0.03). The majority of benign adrenal lesions (37 / 40) had a nonspecific type of contrast enhancement (24 / 40) or a peripheral to central contrast filling (13 / 40) described as the iris phenomenon. Similar findings were observed in malignant adrenal tumors: most malignant lesions also showed nonspecific (6 / 18) or peripheral to central contrast filling (9 / 18). Peripheral to central contrast filling had 50 % sensitivity (26 - 74 %) and 68 % specificity (51 - 81 %) for indicating malignancy. CONCLUSION: Contrast-enhanced ultrasound facilitates the visualization of vascularization even in small adrenal masses, but it does not help to distinguish malignant and benign lesions.

Real-time tissue elastography versus FibroScan for noninvasive assessment of liver fibrosis in chronic liver disease.

PURPOSE: Transient elastography (FibroScan, [TE]) and serum fibrosis markers such as the FibroTest (FT) are established methods for the noninvasive staging of liver fibrosis. A study using real-time elastography (HI-RTE), which is integrated in a conventional ultrasound system, was recently published with comparable results to transient elastography. The aim of the present study was to validate real-time elastography using the formulas calculated in previous studies and to compare the results to transient elastography and FibroTest for the noninvasive assessment of liver fibrosis. MATERIALS AND METHODS: One hundred and thirty-four patients with chronic liver disease and either histological assessment of liver fibrosis (n = 112) or proven liver cirrhosis (n = 22) were included in the study. All patients received TE, HI-RTE, and biochemical evaluation on the same day as presentation. The calculation of the elasticity score of real-time elastography was performed in accordance with the two previously published studies. RESULTS: The Spearman correlation coefficient between transient elastography, real-time elastography and FibroTest with the histological Chevallier score was statistically significant with 0.78, 0.34, and 0.67, respectively (p < 0.01). The diagnostic accuracy expressed as areas under ROC curves was 0.84, 0.69 and 0.85 for the diagnosis of significant fibrosis (F > or = 2), and 0.97, 0.65, and 0.83 for the diagnosis of cirrhosis, respectively. CONCLUSION: Real-time elastography in its present form cannot replace transient elastography for noninvasive assessment of liver fibrosis.