Screening and surveillance recommendations for central nervous system hemangioblastomas in pediatric patients with Von Hippel-Lindau disease.

PURPOSE: Von Hippel-Lindau (VHL) disease is an autosomal-dominantly inherited tumor predisposition syndrome. One of the most common tumors are central nervous system (CNS) hemangioblastomas. Recommendations on the initiation and continuation of the screening and surveillance program for CNS tumors in pediatric VHL patients are based on small case series and thus low evidence level. To derive more robust screening recommendations, we report on the largest monocentric pediatric cohort of VHL patients. METHODS: We performed a retrospective analysis on a pediatric cohort of 99 VHL patients consulted at our VHL center from 1992 to 2023. Clinical, surgical, genetic, and imaging data were collected and statistically analyzed. RESULTS: 42 patients (50% male) developed CNS hemangioblastomas, of whom 18 patients (56% male) underwent hemangioblastoma surgery (mean age at first surgery: 14.9 ± 1.9 years; range 10.2-17). The first asymptomatic patient was operated on at the age of 13.2 years due to tumor progress. Truncating VHL mutation carriers had a significantly higher manifestation rate (HR = 3.7, 95% CI: 1.9-7.4, p < 0.0001) and surgery rate (HR = 3.3, 95% CI: 1.2-8.9, p = 0.02) compared with missense mutation carriers. CONCLUSION: We recommend starting MRI imaging at the age of 12 years with examination intervals every (1-) 2 years depending on CNS involvement. Special attention should be paid to patients with truncating variants. Affected families should be educated regularly on potential tumor-associated symptoms to enable timely MRI imaging and eventually intervention, as CNS hemangioblastoma may develop before screening begins. GERMAN CLINICAL TRIALS REGISTER REGISTRATION NUMBER: DRKS00029553, date of registration 08/16/2022, retrospectively registered.

Asymptomatic Infant Rib Fractures Are Primarily Non-abuse-Related and Should Not Be Used to Assess Physical Child Abuse.

Finding infant rib fractures was for many years an almost undisputed proof that physical child abuse took place. Yet, these rib fractures are virtually always occult and asymptomatic and are only identified when looked for, usually with X-rays, from physical child abuse accusations related to, e.g., suspicion of the shaken baby syndrome. In a recent systematic literature review (searched in Cochran, Embase, PubMed and Sociological Abstracts), Güvensel questioned the diagnostic accuracy of rib fractures to be caused by abuse, due to lack of sufficient scientific evidence. Further, there is currently a world-wide disagreement between physicians considering themselves child abuse specialized, and physicians that explore non-abuse-related symptoms that may mimic physical abuse, which, it is hoped, will significantly reduce current unjustified child abuse diagnoses. In an attempt to help resolving this disagreement, we hypothesize that the probability of physical child abuse-related infant rib fractures is significantly lower than the probability of all other possible non-abuse-related causes of occult asymptomatic infant rib fractures, e.g., from birth trauma, prematurity, osteogenesis imperfecta, hypermobile Ehlers-Danlos Syndrome, severe chronic placental pathology (e.g., massive perivillous fibrin depositions and severe chronic histiocytic intervillositis), and vitamin-D deficiency. As method, we attempted to assess the incidence of these various causes of infant rib fractures, in the Netherlands and the USA. The results are that the estimated Dutch and USA physical abuse-related infant rib fracture incidences are at least about 250 and 45 times lower than the sum of all the non-abuse-related estimates. Because these latter rib fractures are occult and asymptomatic, it is likely that (many) more could be out there. In conclusion, occult asymptomatic rib fractures develop perinatally, virtually always as birth trauma, in infants with sufficiently weak bones due to vitamin D deficiency, transmitted by their vitamin D deficient pregnant mothers. This group also includes cortical rib cracks due to deformation forces, with an estimated 186/100,000 incidence. And, despite obvious uncertainties in all estimated incidences, we provided strong evidence that our hypothesis has relevance, implying that the abundant occult asymptomatic rib fractures, when found in infants, should not be used to assess potential physical child abuse.

Child Abuse, Misdiagnosed by an Expertise Center: Part I-Medico-Social Aspects.

Child abuse is a dangerous situation for an infant. Professionals need to weigh the risk of failing to act when children are seriously harmed against the serious harm done by carrying out safeguarding interventions. In severe cases, foster care might be advisable. The negative effects for the child's psychosocial development requires that such placement must be based on very solid evidence. Our aim is to identify why Dutch parents whose child may have a medical condition that could mimic symptoms of child abuse have a significant chance of being erroneously convicted and losing custody of their child. As a method, we describe and analyze the following case. An Armenian-Dutch newborn (uncomplicated term vaginal delivery), starting at two weeks after birth, developed small bruises on varying body locations. At two months, a Well-Baby Clinic physician referred the girl to a university hospital, mentioning that there were no reasons to suspect child abuse and that her Armenian grandmother easily bruised as well. However, before consultation by a pediatrician of the hospital-located Expertise Center for Child Abuse, the parents were suspected of child abuse. Based on the expertise center's protocols, skeletal X-rays were made, which showed three healed, asymptomatic rib fractures, while invalid statistics suggested, incorrectly, a 10-100 times more likely non-accidental than accidental cause of the symptoms (discussed in Part II of this series). The expertise enter physician ignored any argument that could show parental innocence, including the positive parent-child relationship reported by the Well-Baby Clinic and the general practitioner. The girl and her older brother were placed in a family foster home and then in a secret home. The case radically resolved when a large bruise also developed there, and an independent tissue disease specialist diagnosed a hereditary connective tissue disorder in the mother, implying that the girl's bruises and rib fractures could well be disease-related. In conclusion, if child abuse is suspected, and foster care placement considered, the patient and the parents should be thoroughly investigated by an independent experienced pediatrician together with an experienced pediatric clinical psychologist or psychotherapist to produce an independent opinion. Children deserve this extra safeguard before being separated from their parents.

Child Abuse, Misdiagnosed by an Expertise Center-Part II-Misuse of Bayes' Theorem.

A newborn girl had, from two weeks on, small bruises on varying body locations, but not on her chest. Her Armenian grandmother easily bruised, too. Her mother was diagnosed with hypermobility-type Ehlers-Danlos-Syndrome (hEDS), an autosomal dominant connective tissue disorder, with a 50% inheritance probability. Referral to a University Medical Center located "Dutch Expertise Center for Child Abuse" resulted (prior to consultation) in physical abuse suspicion. Protocol-based skeletal X-rays showed three healed, asymptomatic rib fractures. A protocol-based Bayesian likelihood ratio guesstimation gave 10-100, erroneously used to suggest a 10-100 times likelier non-accidental-than-accidental cause. Foster care placement followed, even in a secret home, where she also bruised, suggesting hEDS inheritance. Correct non-accidental/accidental Bayes' probability of symptoms is (likelihood ratio) × (physical abuse incidence). From the literature, we derived an infant abuse incidence between about ≈0.0009 and ≈0.0026 and a likelihood ratio of <5 for bruises. For rib fractures, we used a zero likelihood ratio, arguing their cause was birth trauma from the extra delivery pressure on the chest, combined with fragile bones as the daughter of an hEDS-mother. We thus derived a negligible abuse/accidental probability between <5 × 0.0009 <0.005 and <5 × 0.0026 <0.013. The small abuse incidence implies that correctly using Bayes' theorem will also miss true infant physical abuse cases. Curiously, because likelihood ratios assess how more often symptoms develop if abuse did occur versus non-abuse, Bayes' theorem then implies a 100% infant abuse incidence (unwittingly) used by LECK. In conclusion, probabilities should never replace differential diagnostic procedures, the accepted medical method of care. Well-known from literature, supported by the present case, is that (child abuse pediatrics) physicians, child protection workers, and judges were unlikely to understand Bayesian statistics. Its use without statistics consultation should therefore not have occurred. Thus, Bayesian statistics, and certainly (misused) likelihood ratios, should never be applied in cases of physical child abuse suspicion. Finally, parental innocence follows from clarifying what could have caused the girl's bruises (inherited hEDS), and rib fractures (birth trauma from fragile bones).

A qualitative study on the patient's narrative in the progression of chronic venous disease into a first venous leg ulcer: a series of events.

BACKGROUND: A venous leg ulcer (VLU) has a significant negative impact on quality of life. Prevention of a VLU is not yet imbedded in clinical practice because risk factors for developing a first VLU are not well known. OBJECTIVES: To explore further the progression of chronic venous disease (CVD) into a first VLU from the patient's perspective. METHODS: A qualitative study using semistructured interviews was conducted among male and female patients with a VLU. Patients from primary and secondary care, under and over 50 years of age, and with first and recurrent VLUs were included. The interviews were transcribed and analysed using a narrative approach to a thematic analysis. Transcripts were organized in chronological order and an iterative process was used to code the transcripts. RESULTS: Four key themes and the connections made between them emerged from the 11 narratives on the progression of CVD towards a first VLU: 'comorbidity', 'mobility', 'work and lifestyle' and 'acknowledgment of CVD'. Comorbidity was linked to reduced mobility and late acknowledgment of CVD. Comorbidity also affected work and lifestyle and vice versa. Work and lifestyle affected mobility and was linked to the acknowledgment of CVD. CONCLUSIONS: A reduction in mobility as a result of comorbidity and work and lifestyle occurred before the VLU developed. Patients did not recognize symptoms of CVD and did not acknowledge the chronicity of CVD. Healthcare professionals should be aware of reductions in mobility and the knowledge deficit in patients with CVD. What's already known about this topic? Not all patients with chronic venous disease (CVD) develop a venous leg ulcer (VLU). A patient's quality of life decreases significantly when a VLU develops. Risk factors for the development of a first VLU in patients with CVD are not well known, unlike risk factors for other chronic wounds like diabetic foot ulcer and pressure ulcers. What does this study add? The patient's narrative towards the development of a first VLU, a series of events. Insight into the events (comorbidity, mobility, work and lifestyle) that patients themselves link to the development of a VLU. Insight into the patients' acknowledgment of CVD in the progression of CVD towards a first VLU. What are the clinical implications of this work? More awareness is needed of CVD symptoms among patients and healthcare providers, as well as more awareness for prevention of a VLU in clinical practice. New insights (for further studies) are needed into the concept of mobility and the development of a VLU. Improved patient education and follow-up are needed for patients with CVD.

A scoping review on Chronic Venous Disease and the development of a Venous Leg Ulcer: The role of obesity and mobility.

OBJECTIVE: The risk factors obesity and reduced mobility are not well known in the development of a Venous Leg Ulcer (VLU). The aim of this scoping review is to explore the mechanisms by which obesity and reduced mobility contribute the development of a VLU in patients with Chronic Venous Disease (CVD). METHODS: For this scoping review a search was performed in May 2019 in the Cochrane Library and Pubmed to identify studies on the working mechanisms of obesity and mobility in developing a VLU. Hand searches were performed to find additional studies explaining the working mechanisms (indirectly related to the VLU). Two reviewers independently reviewed the abstracts and full-text articles. RESULTS: Twenty-eight studies met our eligibility criteria. Disturbed range of ankle motion and gait can lead to a reduced Calf Muscle Pump (CMP) function which leading to a venous outflow disorder. Increased abdominal pressure due to obesity can lead to a venous outflow obstruction and increased adipose tissue mass results in an increase in adipokine secretion. The venous outflow disorder, outflow obstruction and increased adipokine secretion can all lead to chronic systemic inflammation, increased endothelial permeability and hence microcirculatory dysfunction. This alone can result in a VLU. CONCLUSION: Obesity and reduced mobility can lead to a reduction of the CMP function, an increase in abdominal pressure and an increase in adipose tissue mass. This can simultaneously lead to haemodynamic changes in the macro- and microcirculation of the lower extremities and eventually in a VLU. In patients with obesity and reduced mobility the microcirculation alone can lead to skin changes and eventually a VLU. Therefore, early recognition of CVD symptoms in patients with obesity and reduced mobility is crucial to diagnose and treat CVD to prevent a VLU.

Weight velocity equations with 14-448 days time separated weights should not be used for infants under 3 years of age.

Abnormal growth of infants may indicate disease of the children, thus methods to identify growth disorders are wanted in medicine. We previously showed that two-time-points weight growth velocities at age t, calculated by a commercial software product as [Weight(t) - Weight(t - X)]/X, with X = 448 days, were erroneous due to the long separation of 448 days. We were convinced that shorter X-values would solve this accuracy problem. However, our hypothesis is that: "shorter time separations than 448 days cause a decreased accuracy of numerical weight velocity equations in realistic infant weights until an age of about three years". Supporting evidence comes from analyzing how shorter X-values will affect the accuracy of two-time-points weight velocity calculations. We systematically varied X between 1 and 448 days of various P50/0SD-related standard weight curves: (a) P50/0SD with the weights separated by 1 day and X = 1,28,224,448 days; (b) P50/0SD with the weights at variable ages and X = 14-448 days; and (c) case (b) and incorporating weight fluctuations typically occurring in infants. Cases (b) and (c) include details observed in a clinical case. Our results show that the combination of weight fluctuations and varying time intervals between consecutive weights make weight velocity predictions worse for shorter X values in children younger than three years. Because these two causes of failure occur naturally in infants whose weight is regularly measured, other weight velocity equations face the same causes for inaccuracy. In conclusion, our hypothesis suggests that any software that predicts weight velocities should be abandoned in infants < 3 years. Practically, it should require that when (commercial) software weight velocity prediction suggests a medical problem, careful clinical checking should be mandatory, e.g. by linking predicted and exact weight velocities at age t (the latter from the mathematical first derivative at age t of standard weight curves).

Preoperative endoscopic pyloric balloon dilatation decreases the rate of delayed gastric emptying after Ivor-Lewis esophagectomy.

Delayed gastric emptying (DGE) after Ivor-Lewis esophagectomy occurs postoperatively in up to 50% of the patients. This pyloric dysfunction can lead to severe secondary complications postoperatively such as early aspiration, pneumonia or may even have an impact on anastomotic healing and therefore leakage. Early detection of DGE is essential to prevent further complications. The common treatment postoperatively is endoscopic pyloric balloon dilatation (EPBD) after symptoms already occurred. In our work, we analyzed patients who received a preoperative EPBD during the routine restaging endoscopy and compared those patients to a control group to analyze if preoperative EPBD may prevent postoperative DGE and secondary additional complications. We performed a single-center retrospective analysis of 115 patients who received an Ivor-Lewis esophagectomy by the same surgeon between June 2015 and October 2017. Out of these 115 patients, 91 (79.1%) patients received EPBD preoperatively during the staging/restaging endoscopy (PDG, pyloric dilatation group). In 24 (20.9%) patients, preoperative EPBD was not performed due to stenotic esophageal tumors or logistic reasons (NDG, non-pyloric dilatation group). Data of the PDG and NDG group were compared regarding the rate of postoperative DGE as well as DGE and EPBD related complications. In total, 21 (18.3%) patients developed pyloric dysfunction requiring a total of 27 EPBD during follow-up. There were 12 (13.2%) patients in the PDG and 9 (37.5%) patients in the NDG (p = 0.014), respectively. DGE-related complications such as anastomotic leaks (p = 0.466), pulmonary complications (p = 0.466) and longer median hospital stay (p = 0.685) were more frequent in the NDG group; however this difference did not reach statistical significance. The success rate for postoperative EPBD with 20-mm balloons was lower (58.5%) compared to the usage of 30-mm balloons (93.3%). All pre- and postoperative EPBD were performed without any complications. Preoperative EPBD is feasible, safe and can be combined with restating endoscopy. It seems that preoperative EPBD reduces the incidence of DGE and can prevent the need for early postoperative endoscopic interventions. Our recommendation is therefore to perform an EPBD preoperatively when possible to reduce postoperative complications to a minimum. For postoperative EPBD, we recommend the use of the 30-mm balloon due to lower redilatation rates.

[Genetics of pheochromocytoma and the relevance in surgery]. / Genetik von Phäochromozytomen und ihre Bedeutung in der Chirurgie.

Chromaffin tumors, e.g. pheochromocytomas and paragangliomas are caused by germline mutations of several susceptibility genes in 30-40% of the patients. The corresponding syndromes are multiple endocrine neoplasia type 2 (MEN2, RET gene), von Hippel-Lindau disease (VHL), neurofibromatosis type 1 (NF1), paraganglioma syndrome types 1-5 (PGL1-5, SDHx gene) and familial pheochromocytoma due to mutations in the MAX and TMEM127 genes. Clinically, screening for such diseases should be carried out by clinical symptoms and mutation analyses. Important indications can be found in the history of patients and their families, young age of manifestation (<30 years), extra-adrenal localization and the presence of metastatic pheochromocytomas. Organ-preserving endoscopic adrenal operations are nowadays standard for hereditary pheochromocytomas. Previous studies have shown that the reoccurrence of tumors in residual tissue is rare and can occur many years later and that metastatic tumors arising from such recurrences are very rare. When a mutation is detected in a susceptibility gene, a multidisciplinary follow-up care tailored to each individual syndrome is essential.

A systematic review on risk factors in developing a first-time Venous Leg Ulcer.

Venous Leg Ulcers (VLU) occur in about 1% of the Western population. A VLU takes 3-12 months to heal, it recurs often, and it has a negative impact on the quality of life. The risk factors for the development of a first VLU are not well-understood and prevention of a first VLU therefore remains underappreciated. The aim of this study was to identify risk factors for developing a first VLU in adults (aged > 18 years) by searching the literature. We searched the Cochrane Library, Pubmed, Cinalh and Narcisto identify studies that investigated risk factors in developing a VLU. The last search was performed in January 2018. Two reviewers independently reviewed the abstracts and full-text articles, and assessed the methodological quality of the included studies. Results of studies using duplex scanning, and comparing participants with and without VLUs were included in the qualitative analysis. Where possible a quantitative meta-analysis was conducted. We found five studies that investigated the relation of several risk factors with VLU development. The methodological differences of the studies made it impossible to perform a quantitative analysis. The risk factors higher age (four studies), higher body mass index (four studies), low physical activity (four studies), arterial hypertension (four studies), deep vein reflux (three studies), deep venous thrombosis (three studies) and family history of VLU (three studies) were significantly associated with a VLU in the majority of the studies. To what extent they influence the development of a VLU remains unclear because of the limited number of studies that investigated the association of these risk factors with VLU development, and the heterogeneity of these studies. Further studies are needed to confirm the association of these risk factors with the development of a VLU and to explore overweight and low physical activity in more detail.

Limitations of Weight Velocity Analysis by Commercial Computer Program Growth Analyser Viewer Edition.

Commercial software package "Growth Analyser Viewer Edition" ("GAVE") aims to document, monitor and analyze growth and development in children and adolescents. Although its clinical and scientific use is widespread, there are no published studies that describe the method and its validation. We were informed that GAVE calculates the weight velocity (kg/year) at age t from the weight difference between t and 448 days earlier or at birth, divided by the time difference. We recently discussed a case of false child abuse diagnosis (Pediatric Condition Falsification), resulting in the separation of the child from its parents, in which GAVE played a negative contributing role. To prevent such inappropriate diagnoses, we analyzed GAVE from a schematic representation of the measured clinical weight curve, with precisely defined weight velocities. In conclusion, the 448 days included for weight velocity predictions by GAVE caused the erroneous outcomes. Until the necessary changes to the software are implemented and validated, we advise against the use of GAVE in infants younger than 1.5 years, if multiple weight changes occur within 448 days, and following a long-lasting weight velocity change. Our analysis suggests to discard all medical software packages that lack public description and proof of validation.

Periocular CO2 laser resurfacing: severe ocular complications from multiple unintentional laser impacts on the protective metal eye shields.

BACKGROUND AND OBJECTIVES: A 36-year-old woman underwent CO2 laser resurfacing for periocular rhytides using protective stainless steel Cox II ocular shields. Immediately after the treatment, corneal lesions were seen in both eyes. The left eye subsequent developed corneal ulceration and scarring, a deformed iris, cataract, and lower eye lashes showing signs of acute burns. The right cornea had a small inferior mid-peripheral superficial lesion and concomitant lower mid-peripheral burned eye lashes. Our objective was to determine the most likely cause of these ocular complications. STUDY: We estimated temperature-time combinations that could induce corneal injury and cataract. Heat conduction effects from a heated cornea to the lens and from a heated ring of periocular skin to the cornea were computed. The temperature response of a shield following CO2 laser irradiation was determined. RESULTS: We computed that cataract can develop when the corneal temperature reaches, for example, 80 °C for 14 seconds. A periocular ring of heated skin contributes little to the corneal temperature. After 7 pulses of consecutive CO2 laser bursts in 7.5 seconds, the total shield area already reached a homogeneous temperature of 63 °C. CONCLUSION: Despite uncertainties in procedural details and modeling of cataract temperatures, the eye injuries were caused beyond doubt by heating of tear-covered metal eye shields by at least 10 consecutive but unintentional laser impacts. Lasers Surg. Med. 50:980-986, 2018. © 2018 Wiley Periodicals, Inc.

Pediatric Condition Falsification Misdiagnosed by Misjudged Weight Growth from the Curve of Measured Weights.

BACKGROUND Pediatric condition falsification (PCF) is a rare form of child abuse in which a caregiver fabricates or induces illness in the child. The diagnosis is difficult and controversial and can easily include false positives. CASE REPORT A boy, 3.18 kg birthweight (P25 curve), lost weight between age 56 to120 days. Cow milk allergy was suspected, feeding was changed to elementary formula, and he started catch-up weight growth while remaining significantly underweight. His pediatrician continuously interpreted his low weight as insufficient growth, despite prescribing 3 times the normal caloric intake, concluded that the mother purposely malnourished her son, diagnosed PCF, and the boy was separated from his family (days 502-755 of age). PCF was confirmed by 2 other pediatricians and 3 child protection physicians and was supported by 4 child protection agencies and 6 judges. However, proper analysis of the weight growth (kg/year) from the weight curve showed a normal weight gain. Beyond 120 days of age, weight gain at home was significantly above normal (during 347-489 days: 6.2 versus 3 kg/year of the P50). He reached P25 again at around 516 days. CONCLUSIONS The question "How could so many physicians misjudge weight gain?" has scientific and sociologic aspects. Scientifically, low weight was wrongly interpreted as insufficient weight growth, requiring that physicians learn how to assess weight gain from weight curves. Sociologically, physicians seem to follow a diagnosis made by a colleague without proper evaluation. Arguments provided by the parents against this diagnosis seemed to be neglected. Confirmation bias occurs when any information against PCF is disregarded.

Indoor allergen levels in settled airborne dust are higher in day-care centers than at home.

BACKGROUND: Early-life sensitization to indoor allergens predicts asthma development. The aim of this study was to compare allergen concentrations in day-care centers (DCC) with those in private homes. METHODS: Settled airborne dust was collected 4 times a year from 20 German DCC (620 samples) and from the homes of children and day-care workers (602 samples) using electrostatic dust collectors (EDC). The samples were analyzed with fluorescence enzyme immunoassays recognizing domestic mite allergens (DM), Fel d 1, Can f 1, and Mus m 1. Pet allergen thresholds that discriminate samples from homes with cats or dogs from those without were calculated using receiver-operating characteristics. Influences on allergen levels were analyzed using multilevel models. RESULTS: Allergen loads were on average higher in DCC than in homes. In DCC, 96% of the samples were positive for DM, 95% for Can f 1, 90% for Fel d 1, and 83% for Mus m 1. In homes, 84% contained DM, 48.5% Can f 1, 33% Fel d 1, and 43% Mus m 1. The threshold level for homes with dogs was 75 ng/m² Can f 1 (96.8% sensitivity, 96% specificity), and the threshold level for homes with cats was 46 ng/m² Fel d 1 (92% sensitivity, 94.9% specificity). In DCC, Can f 1 and Fel d 1 loads were higher than these thresholds in 37% and 54% of the samples, respectively. Allergen levels were significantly influenced by the season and room type; however, carpets on floors had no influence. CONCLUSIONS: Mite, mouse, cat, and dog allergens were mostly higher in DCC than in homes. Exposure to dog and cat allergens in DCC often reached levels of households with pets.

Is there any role for minimally invasive surgery in NET?

Neuroendocrine tumors (NET) represent the variability of almost benign lesions either secreting hormones occurring as a single lesion up to malignant lesions with metastatic potential. Treatment of NET is usually performed by surgical resection. Due to the rarity of NET, surgical treatment is mainly based on the experience and recommendations of experts and less on the basis of prospective randomized studies. In addition, the development and establishment of new surgical procedures is made more difficult by their rarity. The development of laparoscopic-assisted surgery has significantly improved the treatment of many diseases. Due to the well-known advantages of laparoscopic surgery, this method has also been increasingly used to treat NET. However, due to limited comparative data, the assumed superiority of laparoscopic surgery in the area NET remains often unclear or not yet proven. This review focuses on the present usage of laparoscopic techniques in the area of NET. Relating to the current literature, this review presents the evidence of various laparoscopic procedures for treatment of adrenal, pancreatic and intestine NET as well as extraadrenal pheochromocytoma and neuroendocrine liver metastases. Further, this review focuses on recent new developments of minimally invasive surgery in the area of NET. Here, robotic-assisted surgery and single-port surgery are promising approaches.

Airway and Blood Inflammatory Markers in Waste Collectors.

Waste collectors are exposed to a heterogeneous mixture of bioaerosols able to induce health effects. The study aim was to evaluate inflammatory processes in blood and in the respiratory tract via analysis of atopy and club cell secretory protein 16 (CC16) in serum, exhaled nitric oxide (FeNO), and cellular and soluble mediators in nasal lavage fluid (NALF) and induced sputum (IS). Sixty nine current waste collectors (48% smokers) and 28 former waste collectors (25% smokers) were included in the cross-sectional study. In both groups, 63 and 64% of workers reported complaints of the eyes, nose and/or upper airways. Thirty two percent of the current and 25% of the former workers were classified as atopics. More atopics suffered from rhinitis and conjunctivitis than non-atopics (64% vs. 40% in current workers; 71% vs. 40% in former workers). CC16 values of present non-smokers were significantly higher compared to smokers. In total, FeNO values of 31 participants were lower than 10 ppb, 94% of them were smokers and 85% had respiratory symptoms of lower airways. Most of the IS biomarkers were significantly higher in smokers than in non-smokers. Non-smoking workers with respiratory symptoms of lower airways had slightly elevated mediator IS concentrations compared to asymptomatic non-smokers. We conclude that inflammatory changes in waste collectors are detectable in the content of IS biomarkers, exhaled NO, and serum CC16, which all are influenced by the smoking habit. No significant differences in biomarkers are detectable between current and former waste collectors.

Progressive multifocal leukoencephalopathy associated with fumaric acid esters treatment in psoriasis patients.

BACKGROUND: Fumaric acid esters (FAEs) are a systemic treatment for psoriasis considered to have a favourable long-term safety profile without an increased risk for immunosuppression. However, progressive multifocal leukoencephalopathy (PML), a rare, opportunistic viral infection of the central nervous system, has been linked anecdotally to FAE treatment. OBJECTIVE: To assess clinical features and outcomes of FAE-associated PML cases. METHODS: Systematic literature search in multiple databases up to 25th February 2016 for reports of PML in psoriasis patients treated with FAEs. RESULTS: Eight cases (four male, four female) of FAE-associated PML were identified. Median age was 64 years (range 42-74 years); median FAE treatment duration was 3 years (range 1.5-5 years). Six patients were treated with a formulation containing dimethyl fumarate (DMF) and monoethyl fumarates, and two patients with a DMF formulation. Patients exhibited neurological symptoms, such as aphasia, hemiparesis and dysarthria. PML diagnosis was based on MRI findings and presence of JC virus in cerebrospinal fluid and/or brain tissue. All cases were linked to moderate-to-severe reductions in absolute lymphocyte counts, with nadirs ranging from 200 to 792 cells per mm3 . Median exposure to lymphocytopenia was 2 years (range 1-5 years). In all cases, FAE treatment was discontinued; PML was treated with mefloquine plus mirtazapine. Three patients improved, two had stable disease, two had residual symptoms, and one patient died to an immune reconstitution inflammatory syndrome. CONCLUSION: Progressive multifocal leukoencephalopathy is infrequently linked to FAE treatment, but underreporting cannot be excluded. Physicians treating patients with FAEs should be vigilant for the occurrence of PML, and both clinicians and patients should be alert for onset of new neurological symptoms. Periodic monitoring of lymphocyte counts and FAE discontinuation in case of moderate-to-severe lymphocytopenia is recommended to minimize the risk for PML.

Liquid-based versus conventional cytology of oral brush biopsies: a split-sample pilot study.

OBJECTIVE: The aim of this prospective split sample study was to evaluate the applicability of liquid-based cytology (LBC) of oral brush biopsies for detection of oral cancer. METHODS: Two different preparation techniques were investigated: the conventional transfer procedure to glass slides and the LBC preparation method. The obtainments of epithelial cells were performed five times with a nylon brush and transferred onto five glass slides. Additionally, the brushes, which were normally discarded, were stored in a fixative solution. Conventional slides and respective thin layers from a total of 113 cases were reviewed with both techniques. RESULTS: Thin layers showed excellent morphology on a clear background, which allowed an accurate diagnosis. In contrast, the conventional glass slides showed significantly more blood contamination and cell overlapping. The sensitivity of conventional cytological diagnosis was 96.3%, the specificity archived 90.6%, the positive predictive value was 96.3% and the negative predictive value scored 90.6%. The sensitivity of the cytological diagnosis using thin layers archived 97.5%, the specificity was 68.8%, the positive predictive value revealed 88.76% and negative predictive value was 91.7%. CONCLUSION: Our findings indicate that in oral cytology, LBC may replace other types of wet-fixed preparations using the full amount of collected cells, resulting in enhanced specimen quality archiving comparable values of diagnostic accuracy. CLINICAL RELEVANCE: LBC facilitates the cell collection due to simpler handling and less transfer errors by dentists and may improve the overall diagnostic accuracy of oral brush biopsies in future.

Perioperative α-receptor blockade in phaeochromocytoma surgery: an observational case series.

BACKGROUND: Mortality associated with surgery for phaeochromocytoma has dramatically decreased over the last decades. Many factors contributed to the dramatic decline of the mortality rate, and the influence of an α-receptor blockade is unclear and has never been tested in a randomized trial. We evaluated intraoperative haemodynamic conditions and the incidence of complications in patients with and without α-receptor blockade undergoing surgery for catecholamine producing tumours. METHODS: Haemodynamic conditions and perioperative complications were assessed in 110 patients with (B) and 166 without (N) α-receptor blockade. Data were analysed as a consecutive case series of 303 cases and subsequently via propensity score matching, and presented as mean and confidence interval (CI). RESULTS: No difference in maximal intraoperative systolic arterial pressures (B = 178 mm Hg (CI 169-187) vs N = 185 mm Hg (CI 177-193; P = 0.2542) and hypertensive episodes above 250 mm Hg were found (P = 0.7474) for the closed case series. No major complications occurred. Propensity score matching (75 pairs) revealed a significant difference of 17 mm Hg in maximal intraoperative systolic bp for these selected pairs (P = 0.024). CONCLUSIONS: Only a slight difference in mean maximal systolic arterial pressure was detected between patients with or without an α-receptor blockade. There was no difference in the incidence of excessive hypertensive episodes between groups and no major complications occurred. The basis for the general recommendation of perioperative α- receptor blockade for phaeochromocytoma surgery demands further study.