Changes in Health-Related Quality of Life following Surgery in Patients with High-Grade Extremity Soft-Tissue Sarcoma:A Prospective Longitudinal Study

Introduction: Changes in health-related quality of life (HRQoL) during the diagnostic and treatment trajectory of high-grade extremity soft-tissue sarcoma (eSTS) has rarely been investigated for adults (18–65 y) and the elderly (aged ≥65 y), despite a potential variation in challenges from diverse levels of physical, social, or work-related activities. This study assesses HRQoL from time of diagnosis to one year thereafter among adults and the elderly with eSTS. Methods: HRQoL of participants from the VALUE-PERSARC trial (n = 97) was assessed at diagnosis and 3, 6 and 12 months thereafter, utilizing the PROMIS Global Health (GH), PROMIS Physical Function (PF) and EQ-5D-5L. Results: Over time, similar patterns were observed in all HRQoL measures, i.e., lower HRQoL scores than the Dutch population at baseline (PROMIS-PF:46.8, PROMIS GH-Mental:47.3, GH-Physical:46.2, EQ-5D-5L:0.76, EQ-VAS:72.6), a decrease at 3 months, followed by an upward trend to reach similar scores as the general population at 12 months (PROMIS-PF:49.9, PROMIS GH-Physical:50.1, EQ-5D-5L:0.84, EQ-VAS:81.5), except for the PROMIS GH-Mental (47.5), where scores remained lower than the general population mean (T = 50). Except for the PROMIS-PF, no age-related differences were observed. Conclusions: On average, eSTS patients recover well physically from surgery, yet the mental component demonstrates no progression, irrespective of age. These results underscore the importance of comprehensive care addressing both physical and mental health.</p

Paroxysmal autonomic instability with dystonia in a patient with tuberculous meningitis: a case report

<p>Abstract</p> <p>Introduction</p> <p>This case report describes an extremely rare combination of paroxysmal autonomic instability with dystonia and tuberculous meningitis. Paroxysmal autonomic instability with dystonia is normally associated with severe traumatic brain injury.</p> <p>Case presentation</p> <p>A 69-year-old man of Indonesian descent was initially suspected of having a community-acquired pneumonia, which was seen on chest X-ray and computed tomography of the chest. However, a bronchoscopy showed no abnormalities. He was treated with amoxicillin-clavulanic acid in combination with ciprofloxacin. However, nine days after admission he was disorientated and complained of headache. Neurological examination revealed no further abnormalities. A lumbar puncture revealed no evidence of meningitis. He was then transferred to our hospital. At that time, initial cultures of bronchial fluid for <it>Mycobacterium tuberculosis </it>turned positive, as well as polymerase chain reaction for <it>Mycobacterium tuberculosis</it>. Later, during his stay in our intensive care unit, he developed periods with hypertension, sinus tachycardia, excessive transpiration, decreased oxygen saturation with tachypnea, pink foamy sputum, and high fever. This constellation of symptoms was accompanied by dystonia in the first days. These episodes lasted approximately 30 minutes and improved after administration of morphine, benzodiazepines or clonidine. Magnetic resonance imaging showed an abnormal signal in the region of the hippocampus, thalamus and the anterior parts of the lentiform nucleus and caudate nucleus.</p> <p>Conclusions</p> <p>In patients with (tuberculous) meningitis and episodes of extreme hypertension and fever, paroxysmal autonomic instability with dystonia should be considered.</p

Longitudinal Serum Protein Analysis of Women with a High Risk of Developing Breast Cancer Reveals Large Interpatient Versus Small Intrapatient Variations:First Results from the TESTBREAST Study

The prospective, multicenter TESTBREAST study was initiated with the aim of identifying a novel panel of blood-based protein biomarkers to enable early breast cancer detection for moderate-to-high-risk women. Serum samples were collected every (half) year up until diagnosis. Protein levels were longitudinally measured to determine intrapatient and interpatient variabilities. To this end, protein cluster patterns were evaluated to form a conceptual basis for further clinical analyses. Using a mass spectrometry-based bottom-up proteomics strategy, the protein abundance of 30 samples was analyzed: five sequential serum samples from six high-risk women; three who developed a breast malignancy (cases) and three who did not (controls). Serum samples were chromatographically fractionated and an in-depth serum proteome was acquired. Cluster analyses were applied to indicate differences between and within protein levels in serum samples of individuals. Statistical analyses were performed using ANOVA to select proteins with a high level of clustering. Cluster analyses on 30 serum samples revealed unique patterns of protein clustering for each patient, indicating a greater interpatient than intrapatient variability in protein levels of the longitudinally acquired samples. Moreover, the most distinctive proteins in the cluster analysis were identified. Strong clustering patterns within longitudinal intrapatient samples have demonstrated the importance of identifying small changes in protein levels for individuals over time. This underlines the significance of longitudinal serum measurements, that patients can serve as their own controls, and the relevance of the current study set-up for early detection. The TESTBREAST study will continue its pursuit toward establishing a protein panel for early breast cancer detection

The association between frailty and MRI features of cerebral small vessel disease

Abstract: Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype

Tumor-specific uptake of fluorescent bevacizumab-IRDye800CW microdosing in patients with primary breast cancer:a phase I feasibility study

PURPOSE: to provide proof of principle of safety, breast tumor-specific uptake and positive tumor margin assessment of the systemically administered near-infrared fluorescent (NIRF) tracer bevacizumab-IRDye800CW targeting vascular endothelial growth factor (VEGF)-A in breast cancer patients. EXPERIMENTAL DESIGN: Twenty patients with primary invasive breast cancer eligible for primary surgery received 4.5 mg bevacizumab-IRDye800CW as intravenous bolus injection. Safety aspects were assessed as well as tracer uptake and tumor delineation during surgery and ex vivo in surgical specimens using an optical imaging system. Ex vivo multiplexed histopathology analyses were performed for evaluation of biodistribution of tracer uptake and co-registration of tumor tissue and healthy tissue. RESULTS: None of the patients experienced adverse events. Tracer levels in primary tumor tissue were higher compared to those in the tumor margin (P < 0.05) and healthy tissue (P < 0.0001). VEGF-A tumor levels also correlated with tracer levels (r = 0.63, P < 0.0002). All but one tumor showed specific tracer uptake. Two out of 20 surgically excised lumps contained microscopic positive margins detected ex vivo by fluorescent macro- and microscopy and confirmed at the cellular level. CONCLUSIONS: Our study shows that systemic administration of the bevacizumab-IRDye800CW tracer is safe for breast cancer guidance and confirms tumor and tumor-margin uptake as evaluated by a systematic validation methodology. The findings are a step towards a phase II dose-finding study aimed at in vivo margin assessment and point to a novel drug assessment tool that provides a detailed picture of drug distribution in tumor tissue

Ex vivo feasibility study of endoscopic intraductal laser ablation of the breast

Objective: To determine the feasibility and safety of breast endoscopic thulium laser ablation for treatment of intraductal neoplasia. Study Design: Ductoscopy is a minimally invasive endoscopic approach of the milk ducts of the breast via the nipple. Besides diagnosis in women with pathologic nipple discharge (PND), it allows non-invasive removal of intraductal lesions with a stalk like papillomas. Removal, however, is often incomplete and flat lesions cannot be targeted. We therefore developed laser ductoscopy. Methods: Dosimetry of laser ductoscopy was assessed in thirteen mastectomy specimens, applying power settings of 1–5 W with 100–1000 ms pulsed exposure to a 375-μm outer diameter thulium fiber laser. Subsequently histology was obtained from the breast tissue that was treated with the Thulium laser. Results: Endoscopic view was maintained during ductoscopic laser ablation at 1–3 W. Increasing power to 4–5 W caused impaired vision due to shrinkage of the main duct around the ductoscope tip. Histology revealed localized ablation of the duct wall. Conclusion: We show for the first time that laser ductoscopy is technically feasible. The Thulium laser enables a superficial intraductal ablation and is a useful tool for intraductal interventions. An in vivo prospective study is needed to further demonstrate its potential. Lasers Surg. Med. 50:137–142, 2018

Design of a novel miniature breast biopsy needle for ductoscopy

Background. The majority of the benign and malignant lesions in the breast arise from the ductal epithelium and terminal ductlobular unit. A minimally invasive procedure called ductoscopy is able to visualize these lesions as it inspects the ductal epithelium using a small micro-endoscope. Unfortunately, it is currently challenging to obtain a tissue sample during ductoscopy and reach the most distal duct. Methods. In this study we have, therefore, developed a novel miniature (∅1.2 mm) biopsy needle that can be used during ductoscopy. This biopsy needle consists of two coaxial counter-rotating hollow blades with a distal cutout to resect lesions from the ductal wall. Three cutouts were manufactured resulting in a beveled, straight, and reverse-beveled blade. The blades were actuated using a novel mechanism containing two helical paths that allows for the counter-rotating motion of the blades at different velocities. In a proof-of-principle experiment, the performance of the biopsy needle was evaluated using a polymeric duct model and gelatin tissue phantom. Results. During the experiment, the straight and reverse-beveled blades were able to obtain a sufficiently large tissue sample for histopathological examination. Based on these promising results, a second experiment was performed in which the micro-endoscope was integrated in the needle and we were able to take a biopsy from a chicken breast. Conclusions. In a future clinical instrument, the biopsy needle will be miniaturized and optimized to allow for an efficient, safe, and effective intraductal biopsy procedure without the need for an invasive excisional biopsy procedure.</p

Comparison of Survival Between Patients With Single vs Multiple Primary Cutaneous Melanomas

Importance: Melanoma is one of the most rapidly increasing forms of cancer worldwide. Most studies about survival among patients with melanoma consider only the primary tumor and disregard the potential effect of multiple primary tumors. A better understanding of the prognosis of patients with multiple primary melanoma is important for patient counselling and follow-up strategies. Objective: To describe the epidemiologic features of multiple primary melanoma in patients from the Netherlands. Design, Setting, and Participants: This retrospective, population-based cohort study included adults with histologically proven, primary, invasive cutaneous melanoma in the Netherlands between January 1, 2000, and December 31, 2014, with a median follow-up of 75.1 months, using data from PALGA, the Dutch Nationwide Network and Registry of Histopathology and Cytopathology. Follow-up data were retrieved from the Netherlands Cancer Registry. Statistical analysis was performed from August 1, 2018, to September 3, 2018. Main Outcomes and Measures: A multivariable Cox model with a time-varying covariate was performed to assess overall survival between patients with a single primary melanoma vs those with multiple primary melanomas. Secondary outcomes included incidence of multiple primary melanoma, differences in Breslow thickness, and time between first and second multiple primary melanoma. Results: Of the 56929 study patients, 31916 (56.1%) were female, with a mean (SD) age of 56.4 (16.2) years. A total of 54645 single primary melanomas and 4967 multiple primary melanomas in 2284 patients were included. The median Breslow thickness decreased from 0.90 mm (interquartile range, 0.55-1.70 mm) for the first melanoma to 0.65 mm (interquartile range, 0.45-1.10 mm) for the second melanoma (P <.001). For their second melanoma, 370 patients (16.2%) had a higher T stage, 1112 (48.7%) had the same T stage, and 802 (35.1%) had a lower T stage. In addition, 841 of 2284 second melanomas (36.8%) in patients with multiple primary melanomas were found during the first year of follow-up, whereas 624 of 2284 (27.3%) were found after 5 years of follow-up. These proportions did not vary when stratified for melanoma stage. Worse overall survival was seen among patients with multiple primary melanomas compared with patients with a single primary melanoma (hazard ratio, 1.31; 95% CI, 1.20-1.42; P <.001). Conclusions and Relevance: A significant decrease in Breslow thickness between the first and second multiple primary melanoma was found, and overall survival among patients with multiple primary melanomas was significantly worse than that among patients with a single primary melanoma. These findings suggest that more strict follow-up strategies may be warranted for patients with multiple primary melanomas.

Trends in Sentinel Lymph Node Biopsy Enactment for Cutaneous Melanoma

Background: Over recent years, sentinel lymph node biopsy (SLNB) recommendations in guidelines for cutaneous melanoma have changed considerably. We aimed to assess trends in enactment of SLNB to evaluate to what extent guidelines were adhered to, and to identify clinical and pathological determinants of (non-)adherence. Methods: Clinicopathological data from the Dutch nationwide network and registry of histopathology and cytopathology were retrieved from patients diagnosed with primary cutaneous melanoma in The Netherlands between 2003 and 2014. SLNB enactment was analyzed per year. Multivariable regression models were developed to assess the determinants of SLNB enactment. Results: A total of 51,510 primary cutaneous melanomas in 49,514 patients were diagnosed, of which 24,603 melanomas were eligible for SLNB as they were staged T1b or higher. In practice, only 9761 (39.7%) patients underwent SLNB, with an increasing trend from 39.1% in 2003 to 47.8% in 2014 (p < 0.001). A total of 759 (2.9%) of 26,426 patients without SLNB indication underwent SLNB anyway. Variables significantly associated with enactment of SLNB were male sex, younger age, and melanoma on sites other than the head and neck. Conclusions: Although there was an increasing trend in time in SLNB enactment, enactment of SLNB did not comply well with recommendations in (inter)national guidelines. Female sex, higher age, and melanoma located on the head and neck were associated with non-enactment of SLNB