Long-Term Progression-Free Survival of a Pre-Treated Patient with Metastatic Colorectal Cancer Receiving Trifluridine/Tipiracil.

Trifluridine/tipiracil is approved for the use in later or last-line setting in previously treated metastatic colorectal cancer (mCRC) patients who progressed on standard anti-tumor drugs including 5-fluorouracil (5-FU), irinotecan, oxaliplatin, anti-VEGF and anti-EGFR antibodies, or who are not considered candidates for those standard therapies. In this report, we describe a 67-year-old male patient with KRAS-mutated mCRC and metachronous liver and lung metastasis who failed prior 5-FU- and irinotecan-containing regimens, but then showed long-term disease control for 31 months on single-agent trifluridine/tipiracil given as second-line treatment. According to our experience, trifluridine/tipiracil is a feasible and effective treatment option in earlier but not necessarily last-line therapy in mCRC patients who are not considered candidates for doublet or triplet chemotherapy. Besides its efficacy, it is associated with maintained quality of life and a manageable toxicity profile. Considering increasing age of mCRC patients and their wish for maintaining an independent lifestyle, further research on the use of trifluridine/tipiracil in earlier lines of systemic mCRC therapy is warranted.

[Osteoporosis: diagnostics and treatment]. / Osteoporose: Diagnostik und Behandlung.

Osteoporosis is the most common systemic skeletal disease worldwide. Its consequences have a substantial impact on the quality of life of patients and increases the overall morbidity and mortality. Standardized diagnostic procedures and treatment recommendations have been available for years as German and international (S3) guidelines. Nevertheless, there is a considerable gap in the diagnosis and adequate treatment of osteoporosis, especially in Germany. The aim is to detect the disease at an early stage and to establish a specific and consistent treatment of osteoporosis. In this way the quality of life and independence of those affected can be maintained over a long period. In the acute and permanent treatment of manifest osteoporosis, surgeons, orthopedic and trauma surgeons play a key role.

Influence of insufflated carbon dioxide on abdominal temperature compared to oesophageal temperature during laparoscopic surgery.

BACKGROUND: Body core temperature is an important vital parameter during surgery and anaesthesia. It is influenced by several patient-related and surgery-related factors. Laparoscopy is considered beneficial in terms of a variety of parameters, for example, postoperative pain and length of hospital stay. Non-humidified, non-warmed insufflated CO2 applied during laparoscopy is standard of care. This prospective observational trial therefore evaluates the impact of non-humidified CO2 at room temperature on abdominal temperature and its correlation to body core temperature. METHODS: Seventy patients undergoing laparoscopic surgery were included in this prospective observational study. Temperature was measured oesophageal and abdominal before induction of anaesthesia (T1), right before skin incision (T2), 15 min, 30 min and 60 min after skin incision. All patients were treated according to actual guidelines for perioperative temperature measurement. RESULTS: Body core temperature and abdominal temperature correlated moderately (r = 0.6123; p < 0.0001). Bland-Altman plot for comparison of methods showed an average difference of 0.4 °C (bias - 0.3955; 95% agreement of bias from - 2.365 to 1.574). Abdominal temperature further decreased after establishing pneumoperitoneum (T2: 36.2 °C (35.9/36.4) to T5: 36.1 °C (35.6/36.4); p < 0.0001), whereas oesophageal temperature increased (T2: 36.2 °C (35.9/36.4) to 36.4 °C (36.0/36.7); p = 0.0296). Values of oesophageal and abdominal measurement points differed at T4 (36.3 °C (36.0/36.6) vs. 36.1 °C (35.4/36.6); p < 0.0001) and T5 (36.4 °C (36.0/36.7) vs. 36.1 °C (35.6/36.4) p = 0.0003). CONCLUSION: This prospective observational trial shows the influence of insufflated, non-humidified carbon dioxide at room temperature on abdominal temperature during laparoscopic surgery. We show that carbon dioxide applied at these conditions decreases abdominal temperature and therefore might be a risk factor for perioperative hypothermia.

The Impact of Glucocorticoid Co-Secretion in Primary Aldosteronism on Thyroid Autoantibody Titers During the Course of Disease.

Excess aldosterone is associated with the increased risk of cardio-/cerebrovascular events as well as metabolic comorbidities not only due to its hypertensive effect but also due to its proinflammatory action. Autonomous cortisol secretion (ACS) in the setting of primary aldosteronism (PA) is known to worsen cardiovascular outcome and potentially exhibit immunosuppressive effects. The aim of this study was to determine the impact of ACS status in patients with PA on kinetics of thyroid autoantibodies (anti-TPO, anti-TG) pre and post therapy initiation. Ninety-seven PA patients (43 unilateral, 54 with bilateral PA) from the database of the German Conn's Registry were included. Anti-TPO and anti-TG levels were measured pre and 6-12 months post therapeutic intervention. Patients were assessed for ACS according to their 24- hour urinary cortisol excretion, late night salivary cortisol and low-dose dexamethasone suppression test. Abnormal test results in line with ACS were identified in 74.2% of patients with PA. Following adrenalectomy, significant increases in anti-TPO levels were observed in patients with at least one abnormal test (p = 0.049), adrenalectomized patients with at least two pathological ACS tests (p = 0.015) and adrenalectomized patients with pathologic dexamethasone suppression tests (p = 0.018). No antibody increases were observed in unilateral PA patients without ACS and in patients with bilateral PA receiving mineralocorticoid antagonist therapy (MRA). Our data are in line with an immunosuppressive effect of mild glucocorticoid excess in PA on thyroid autoantibody titers. This effect is uncovered by adrenalectomy, but not by MRA treatment.

Indocyanine green fluorescence imaging during partial adrenalectomy.

BACKGROUND: Indocyanine green (ICG) fluorescence imaging represents an emerging technology that facilitates the assessment of tissue vascularity, tissue distinction, and tumor localization during surgery. The aim of this study was to investigate the potential role of ICG imaging during laparoscopic partial adrenalectomy. METHODS: Indocyanine fluorescence imaging was carried out during laparoscopic partial adrenalectomy for bilateral pheochromocytoma and bilateral Cushing's syndrome. A first bolus of 5 mg ICG was applied intravenously upon exposure of the retroperitoneal plane to identify the adrenal borders. The fluorescence was visualized using a Storz® NIR/ICG endoscopic system. As the camera of this system detects NIR light as a blue signal, the well-vascularized adrenal tissue was expected to show a strong fluorescence in the blue color channel in contrast to the surrounding adipose tissue. Following partial adrenalectomy, a second bolus of 5 mg ICG was applied intravenously to evaluate the vascularity of the remaining adrenal tissue. RESULTS: We investigated six adrenal glands from three patients undergoing bilateral partial adrenalectomy. The indication for surgery was pheochromocytoma in two patients and Cushing's syndrome with bilateral adenomas in one patient. Regarding left adrenalectomies, ICG imaging was helpful in visualizing the adrenal borders and the adrenal vein. Further, it facilitated the identification of the hypofluorescent pheochromocytoma and to resect the entire tumor. On the right side, due to the more apparent anatomy, ICG imaging did not contribute to the conduct of the operation. Four adrenal remnants showed a strong vascularization and two remnants were only reasonably vascularized. CONCLUSION: ICG fluorescence may be helpful in guiding partial adrenalectomy and assessing the vascularity of remaining adrenal tissue.

Parathyroid Autofluorescence-How Does It Affect Parathyroid and Thyroid Surgery? A 5 Year Experience.

Injury to parathyroid glands during thyroid and parathyroid surgery is common and postoperative hypoparathyroidism represents a serious complication. Parathyroid glands possess a unique autofluorescence in the near-infrared spectrum which could be used for their identification and protection at an early stage of the operation. In the present study parathyroid autofluorescence was visualized intraoperatively using a standard Storz laparoscopic near-infrared/indocyanine green (NIR/ICG) imaging system with minor modifications to the xenon light source (filtered to emit 690 nm to 790 nm light, less than 1% in the red and green above 470 nm and no blue light). During exposure to NIR light parathyroid tissue was expected to show autofluorescence at 820 nm, captured in the blue channel of the camera. Over a period of 5 years, we investigated 205 parathyroid glands from 117 patients. 179 (87.3%) glands were correctly identified by their autofluorescence. Surrounding structures such as thyroid, lymph nodes, muscle, or adipose tissue did not reveal substantial autofluorescence. We conclude that parathyroid glands can be identified by their unique autofluorescence at an early stage of the operation. This may help to preserve these fragile structures and their vascularization and lower the rate of postoperative hypocalcemia.

Accuracy of adrenal imaging and adrenal venous sampling in diagnosing unilateral primary aldosteronism.

INTRODUCTION: The correct differentiation between unilateral and bilateral adrenal involvement in patients with primary aldosteronism (PA) is of utmost importance to justify surgical treatment. The aim of this study was to determine the accuracy of adrenal imaging compared to adrenal venous sampling (AVS), histopathology and postoperative outcome. METHODS: The data of all patients with unequivocal AVS who underwent unilateral laparoscopic adrenalectomy for primary aldosteronism between May 2004 and April 2015 were entered in this retrospective study. We compared computed tomography (CT) and magnetic resonance imaging (MRI) results with corresponding AVS data, histopathology findings and postoperative outcome. RESULTS: A total of 175 patients underwent unilateral laparoscopic adrenalectomy for primary aldosteronism. AVS was successful in 152 patients and postoperative outcome available in 148 patients. Despite unilateral disease according to AVS results, bilateral normal glands were seen in 15 MRI (17·2%) and 7 CT scans (8·5%), respectively. Unilateral enlargement of the nonhypersecreting adrenal gland was found in three MRI (3·5%) and 10 CT scans (12·2%) of patients who showed aldosterone hypersecretion deriving from the contralateral gland. Fifteen MRI (17·2%) and 18 CT scans (22·0%) revealed bilateral adrenal pathology despite unilateral aldosterone hypersecretion. CONCLUSION: The accuracy of CT and magnetic resonance imaging in predicting unilateral disease is poor. AVS appears to be an essential diagnostic step to identify those patients who may benefit from unilateral adrenalectomy.

Changes in Body Mass Index in Pheochromocytoma Patients Following Adrenalectomy.

Catecholamine excess from pheochromocytoma results in cardiovascular symptoms such as arterial hypertension and tachycardia and induces metabolic alterations including glucose intolerance and increase in resting metabolic rate. The objective of our study was to investigate the effect of surgical cure of pheochromocytoma on body-mass-index and the correlation of body-mass-index changes to preoperative endocrine parameters. Pheochromocytoma patients from the Munich ENSAT Registry were matched (1:2) for age and gender to patients from the German Conn's Registry, who had undergone surgery for aldosterone-producing-adenomas. Thereby, 43 pheochromocytoma patients (17 males/26 females) and 86 aldosterone-producing-adenoma patients were analyzed for body-mass-index, blood pressure, and catecholamine levels before and one year after adrenalectomy. Seventy-four percent of pheochromocytoma patients were hypertensive preoperatively and 48% one year postoperatively. Systolic blood pressure did not differ significantly in pre- and postoperative measurements whereas diastolic blood pressure was significantly reduced over time. Moreover, pheochromocytoma patients gained body weight (p<0.001) one year following adrenalectomy accompanied by significant increases in body-mass-index, whereas aldosterone-producing adenoma patients displayed a slight weight loss. Despite weight gain, diagnosis of diabetes mellitus dropped from 9 of 43 investigated pheochromocytoma patients at baseline to 4 at follow-up. A significant correlation between body-mass-index changes to the preoperative catecholamine levels was found only for urinary normetanephrines. These data suggest that normalization of chronic catecholamine excess by adrenalectomy is associated with an increase in body-mass-index, which is more pronounced in patients with high preoperative levels of urinary normetanephrines.

Intraoperative near-infrared autofluorescence imaging of parathyroid glands.

OBJECTIVE: To identify parathyroid glands intraoperatively by exposing their autofluorescence using near-infrared light. METHODS: Fluorescence imaging was carried out during minimally invasive and open parathyroid and thyroid surgery. After identification, the parathyroid glands as well as the surrounding tissue were exposed to near-infrared (NIR) light with a wavelength of 690-770 nm using a modified Karl Storz near-infrared/indocyanine green (NIR/ICG) endoscopic system. Parathyroid tissue was expected to show near-infrared autofluorescence, captured in the blue channel of the camera. Whenever possible the visual identification of parathyroid tissue was confirmed histologically. RESULTS: In preliminary investigations, using the original NIR/ICG endoscopic system we noticed considerable interference of light in the blue channel overlying the autofluorescence. Therefore, we modified the light source by interposing additional filters. In a second series, we investigated 35 parathyroid glands from 25 patients. Twenty-seven glands were identified correctly based on NIR autofluorescence. Regarding the extent of autofluorescence, there were no noticeable differences between parathyroid adenomas, hyperplasia and normal parathyroid glands. In contrast, thyroid tissue, lymph nodes and adipose tissue revealed no substantial autofluorescence. CONCLUSION: Parathyroid tissue is characterized by showing autofluorescence in the near-infrared spectrum. This effect can be used to distinguish parathyroid glands from other cervical tissue entities.

Intraoperative optical coherence tomography imaging to identify parathyroid glands.

OBJECTIVE: Optical coherence tomography (OCT) is a non-invasive high-resolution imaging technique that permits characterization of microarchitectural features in real time. Previous ex vivo studies have shown that the technique is capable of distinguishing between parathyroid tissue, thyroid tissue, lymph nodes, and adipose tissue. The purpose of this study was to evaluate the practicality of OCT during open and minimally invasive parathyroid and thyroid surgery. METHODS: During parathyroid and thyroid surgery, OCT images were generated from parathyroid glands, thyroid tissue, lymph nodes, and adipose tissue. The images were immediately assessed by the operating team using the previously defined criteria. Second, the OCT images were blinded with respect to their origin and analyzed by two investigators. Whenever possible the OCT findings were matched to the corresponding histology. RESULTS: A total of 227 OCT images from 27 patients undergoing open or minimally invasive thyroid or parathyroid surgery were analyzed. Parathyroid glands were correctly identified in 69.2%, thyroid tissue in 74.5%, lymph nodes in 37.5%, and adipose tissue in 69.2%. 43 OCT images (18.9%) could not be allocated to one of the tissue types (Table 2). Sensitivity and specificity in distinguishing parathyroid tissue from the other entities were 69% (63 true positive, 13 false negative findings, 15 images where an allocation was not possible) and 66%, respectively (71 true negative, 9 false positive, 28 images where an assessment was not possible). CONCLUSION: OCT is capable of distinguishing between parathyroid, thyroid, and adipose tissue. An accurate differentiation between parathyroid tissue and lymph nodes was not possible. The disappointing results compared to the previous ex vivo study are related to problems handling the endoscopic probe intraoperatively. However, further refinement of this new technology may lead to OCT systems with higher resolution and intraoperative probes that are easier to handle.

Laparoscopic adrenalectomy--10-year experience at a teaching hospital.

BACKGROUND: Minimally invasive adrenalectomy has been adopted as the treatment of choice for benign adrenal tumors. This study aimed to investigate the outcome of laparoscopic adrenalectomies performed over a 10-year period at a teaching hospital. METHODS: All laparoscopic adrenalectomies carried out between 1 April 2000 and 31 March 2010 were evaluated with respect to perioperative management, complications, conversion rate, learning curve, tumor size, and surgically relevant characteristics of different adrenal pathologies. RESULTS: Over a period of 10 years, 215 laparoscopic lateral transabdominal adrenalectomies were carried out for Conn's syndrome (n = 90), Cushing's syndrome (n = 72), pheochromocytoma (n = 30), metastatic disease (n = 8), incidentalomas (n = 10), and other rare adrenal pathologies (n = 5). Morbidity, mortality, and conversion rate were 7.0, 0.9, and 4.2 %, respectively. Patients with Cushing's disease and bilateral adrenalectomy showed a higher complication rate. In retrospect, the indication for a laparoscopic approach was at least questionable in five cases. During these 10 years, four surgeons unfamiliar with the technique received intensive training to a defined plan. CONCLUSIONS: Laparoscopic adrenalectomy represents a safe operating technique associated with few complications and a low conversion rate. Patients with severe Cushing's disease are prone to complications and require intensive monitoring postoperatively. Laparoscopic adrenalectomy is associated with a learning curve, and particular emphasis should be given to surgical training.

Backscattering intensity measurements in optical coherence tomography as a method to identify parathyroid glands.

BACKGROUND AND OBJECTIVE: Previous studies have shown that the use of optical coherence tomography (OCT) permits the differentiation between parathyroid tissue, thyroid tissue, lymph nodes and adipose tissue. We investigated the backscattering intensity profiles of OCT images in order to determine whether significant differences between these tissue types exist. METHODS: Mean backscattering intensity profiles were obtained from OCT images of parathyroid glands, thyroid tissue, lymph nodes and adipose tissue. The profiles were analyzed employing Fisher's Linear Discriminant Analysis (LDA). The results were cross validated employing improved parameter estimation techniques. RESULTS: Mean backscattering intensity profiles from 300 OCT images of 34 patients undergoing thyroid or parathyroid surgery were analyzed. The overall rate of correct classifications was 96.15%. The cross validation employing improved parameter estimation techniques yielded results identical to those derived from Fisher's LDA. CONCLUSION: Besides the individual assessment of OCT images by interpreting morphological criteria, backscattering intensity measurements can reliably distinguish between different tissue entities.

Polypropylene meshes coated with a polysaccharide based bioadhesive for intra-abdominal mesh fixation in a rabbit model.

BACKGROUND: In this study, we evaluate a new bioadhesive for intra-abdominal onlay mesh fixation of a polypropylene-polyvinylchloride graft. METHODS: Three pieces of a commercially available polypropylene/polyvinylfluoride mesh, each 3 × 3 cm in size, and three pieces of the same mesh coated with a polysaccharide bioadhesive were fixated to the surface of the anterior abdominal wall of 30 New Zealand white rabbits. The fixation was performed either by using four transabdominal Prolene(®) 4/0 sutures, four spiral tacks (Protack 5 mm Tyco), or cyanoacrylate glue (Glubran(®) GEM, Viareggio, Italy). Each mesh position and the according kind of fixation were randomized before implantation. The animals were sacrificed 12 weeks postoperatively. After determining the extent of intra-abdominal adhesions, the meshes were excised en bloc with the anterior abdominal wall for tensile strength measurements and histological analysis. RESULTS: All meshes coated with the bioadhesive adhered to the intact peritoneum without extra fixation. Irrespective of the fixation technique coated meshes led to more and stronger adhesions. Mesh shrinkage by scarring was increased in coated meshes fixed with glue and low in uncoated meshes fixed with tacks. Testing the tensile strength, coated meshes fixed with transfascial sutures achieved the best results (16.14 ± 6.1 N), whereas coated meshes fixed with glue showed the lowest strength (10.39 ± 4.81 N). The foreign body reaction was considerably more distinctive using coated mesh. The mesh ingrowth was not influenced by this reaction. CONCLUSIONS: All meshes coated with the new bioadhesive were self-adhesive in that way; they stayed in position when attached to the peritoneum. Although this may facilitate intra-operative mesh fixation, the bioadhesive displayed several disadvantages, such as stronger adhesions and an increased shrinkage of the implant. The tensile strength was not influenced by the use of the bioadhesive. At present, we see no major advantage for polysaccharide bioadhesive applied in this study.

Optical coherence tomography as a method to identify parathyroid glands.

BACKGROUND AND OBJECTIVE: The identification of parathyroid glands can be a major problem in parathyroid surgery. The purpose of this study was to evaluate the feasibility of optical coherence tomography (OCT) in distinguishing between parathyroid tissue, thyroid tissue, lymph nodes, and adipose tissue. METHODS: Ex vivo OCT images as well as histological sections were generated from parathyroid glands, thyroid tissue, lymph nodes and fat in order to define significant morphologic differences between these entities. As a second step all OCT images were separately evaluated by two blinded investigators and later compared to the corresponding histology. Sensitivity and specificity of OCT in distinguishing between the different tissues were determined. To assess the interobserver agreement, κ coefficients were calculated from the ratings of each investigator for each OCT image seen. RESULTS: A total of 320 OCT images from 32 patients undergoing thyroid surgery, parathyroidectomy or lymphadenectomy were compared with the corresponding histology. The sensitivity and specificity in distinguishing parathyroid tissue from the other entities was 84% (second investigator: 82%) and 94% (93%) respectively. Unweighted κ using four diagnostic categories was 0.97 (95% CI, 0.94-0.99) showing substantial agreement between both investigators. CONCLUSION: OCT is highly sensitive in distinguishing between parathyroid tissue, thyroid tissue, lymph nodes and adipose tissue. These ex vivo results should be confirmed by using OCT imaging intraoperatively.

[Osteoporosis: diagnostics and treatment]. / Osteoporose: Diagnostik und Behandlung.

Osteoporosis is the most common systemic skeletal disease worldwide. Its consequences have a substantial impact on the quality of life of patients and increases the overall morbidity and mortality. Standardized diagnostic procedures and treatment recommendations have been available for years as German and international (S3) guidelines. Nevertheless, there is a considerable gap in the diagnosis and adequate treatment of osteoporosis, especially in Germany. The aim is to detect the disease at an early stage and to establish a specific and consistent treatment of osteoporosis. In this way the quality of life and independence of those affected can be maintained over a long period. In the acute and permanent treatment of manifest osteoporosis, surgeons, orthopedic and trauma surgeons play a key role.

Thyroidal Angiotensin-Converting Enzyme 2 Protein Expression and Thyroid Function Tests in Patients with COVID-19: Results from a Retrospective Case Series and a Prospective Cohort Study.

Background: Infection with SARS-CoV-2 has initially been known as a respiratory disease but in the course of the pandemic the understanding has emerged that severity is owing to fatal inflammatory responses apart from lung injury. In this context, endocrine disorders such as thyroiditis as well as pituitary dysfunction in addition to nonthyroidal illness syndrome have been described. Furthermore, angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 cell receptor, has been detected in most endocrine tissues, including the thyroid gland. Objective: To evaluate histopathologic changes and compare thyroidal ACE2 protein expression in thyroid tissue from patients who died from severe COVID-19 with thyroid tissue from patients without SARS-CoV-2 infection in a retrospective case series. Furthermore, to assess and compare alterations in thyroid function tests (TFTs) between patients with or without SARS-CoV-2 infection as well as association of TFTs with the severity of the disease in a prospective cohort study. Methods: Thyroid tissue of deceased COVID-19 patients (n = 23) was analyzed for histopathology and ACE2 expression by immunohistochemical staining. A total of 153 patients with confirmed SARS-CoV-2 were evaluated regarding TFTs and divided into a severe (intubation, intensive care treatment) and an intermediate group. Results: Thyroidal ACE2 expression was detected in 87% of the deceased COVID-19 patients. Normal thyroid tissue from patients without SARS-CoV-2 infection showed no ACE2 protein expression. Half of the severely ill COVID-19 patients had low free triiodothyronine (fT3) levels. Combination of low fT3 and thyrotropin (TSH) was associated significantly with deadly disease. Conclusion: The high percentage of positive ACE2 immunostaining in deceased patients compared with normal thyroid tissue of patients without SARS-CoV-2 infection suggests involvement of the thyroid in COVID-19, although further research will have to show the pathogenic role of thyroidal ACE2 in COVID-19. Abnormal fT3 and a TSH of ≤0.5 mU/L were associated with a fatal outcome in our severely ill SARS-CoV-2 patient cohort. Therefore, assessment of TFTs is crucial in the treatment of severely ill COVID-19 patients. Trial Registration: COVID-19 Registry of the LMU University Hospital Munich (CORKUM), WHO trial ID DRKS00021225.

Primary presentation and clinical course of pediatric and adolescent patients with differentiated thyroid carcinoma after radioiodine therapy.

Introduction: Differentiated thyroid carcinoma (DTC) in childhood and during adolescence is extremely rare. Pediatric DTC commonly presents with advanced disease at diagnosis including a high prevalence of cervical lymph node metastases and pulmonary metastases. Studies in children with DTC are limited. Therefore, we aimed to evaluate the initial presentation, effectiveness of radioiodine therapy (RIT), and long-term outcome of prepubertal in comparison to pubertal/postpubertal patients. Methods: Eighty-five pediatric and young patients aged 6.4 to 21.9 years with histopathologically confirmed DTC were retrospectively included. They all underwent total thyroidectomy followed by RIT. Initial presentation and outcome of prepubertal and pubertal/postpubertal patients were compared 1 year after RIT, during follow-up, and at the last visit of follow-up. Results: Prepubertal patients presented with significantly higher T and M stages. One year after RIT, 42/81 (52%) patients still presented with evidence of disease (ED). During follow-up of a median of 7.9 years, prepubertal patients were less often in complete remission (58% vs. 82% in pubertal patients). At the last visit of follow-up, 19/80 (24%) patients still had ED without statistical differences between the two groups (42% prepubertal vs. 18% pubertal/postpubertal, p-value 0.06). None of our patients died disease-related over the observed period. Conclusion: Prepubertal children with DTC presented with a more advanced tumor stage at the initial presentation. During follow-up, they present more often with ED. However, at the end of our study, we did not observe statistically relevant differences in patient outcomes between the prepubertal and pubertal/postpubertal groups.

Activation of peroxisome proliferator-activated receptor-gamma by glitazones reduces the expression and release of monocyte chemoattractant protein-1 in human mesothelial cells.

Human peritoneal mesothelial cells (MC) play an important role in inflammatory processes of the peritoneal cavity by producing various cytokines and chemokines, such as monocyte chemoattractant protein-1 (MCP-1). The present study was designed to assess the effect of the peroxisome proliferator-activated receptor-gamma- (PPARγ-) activator rosiglitazone on the mesothelial MCP-1 expression and release. Primary cultures of MC were obtained from omental tissue. MCP-1 antigen concentrations were measured in the cell supernatant by ELISA and MCP-1 mRNA levels by real-time polymerase chain reaction. The presence of PPARγ on MC was assayed in a Western Blot analysis. MC constitutively express PPARγ. Activation of this receptor via rosiglitazone (0,1-10 µmol/L) resulted in significantly reduced amounts of mesothelial MCP-1 release as well as MCP-1 mRNA. The use of the PPARγ inhibitor GW-9662 could completely prevent the rosiglitazone effects. Rosiglitazone was also effective in reducing TNFα-induced enhanced secretion of MCP-1. Our findings indicate that glitazones are effective in reducing constitutive and TNFα-stimulated mesothelial MCP-1 mRNA expression and release.

[Osteoporosis: diagnostics and treatment]. / Osteoporose: Diagnostik und Behandlung.

Osteoporosis is the most common systemic skeletal disease worldwide. Its consequences have a substantial impact on the quality of life of patients and increases the overall morbidity and mortality. Standardized diagnostic procedures and treatment recommendations have been available for years as German and international (S3) guidelines. Nevertheless, there is a considerable gap in the diagnosis and adequate treatment of osteoporosis, especially in Germany. The aim is to detect the disease at an early stage and to establish a specific and consistent treatment of osteoporosis. In this way the quality of life and independence of those affected can be maintained over a long period. In the acute and permanent treatment of manifest osteoporosis, surgeons, orthopedic and trauma surgeons play a key role.