Project description:BackgroundWe report a unique case of synchronous sacrococcygeal chordoma in association with rectal invasive adenocarcinoma. Retrorectal tumors are a rare disease caused by a variety of pathologies. To our knowledge, no prior cases of such a coincidental finding of both cancers have been reported in the literature.Case presentationThis is the case of a 74-year-old white middle eastern man, with known hypertension under treatment, who presented with complaints of progressive lower back pain associated with urinary incontinence over the past 12 months. Magnetic resonance imaging (MRI) of the pelvis showed a large midline, well-defined, oval-shaped lesion replacing the sacrococcygeal portion of the spine, with extension to the presacral region. Computed tomography (CT)-guided Tru-Cut biopsy revealed features suggestive of chordoma. At surgery, we performed excision of the entire mass en bloc, sacrectomy with rectus abdominis myocutaneous flap reconstruction and end sigmoid colostomy. Surgical histopathology proved it to be sacral dedifferentiated chordoma and rectal invasive adenocarcinoma. Overall, the patient recovered well postoperatively, was discharged home with functional stoma and on permanent Foley catheter use.ConclusionTo the best of our knowledge, this is the only reported case of such a presentation, and sheds light on the approach and management. We hope that reporting such a case will add value to the medical literature.
Project description:2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET)/computed tomography (CT) is known to be a helpful imaging modality for sacral chordoma, but its detailed characteristics have not been fully described. The purpose of our study was to identify the [18F]FDG PET/CT imaging characteristics of sacral chordoma and compare them with other sacral malignancy. This retrospective study included patients who underwent [18F]FDG PET/CT because of a mass involving the sacrum. Investigated visual findings included visual score and distribution, and semiquantitative parameters measured included standardized uptake values (SUVmax, SUVpeak, SUVmean), tumor-to-liver ratio (TLR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor size. Comparison studies and receiver operating characteristics (ROC) curve analysis were performed to differentiate between sacral chordoma and other sacral malignancy. Ten patients with sacral chordoma were finally included (M:F = 6:4, median age = 67 yr). On [18F]FDG PET/CT, sacral chordomas presented as a mass with minimal-moderate uptake with a usually heterogenous distribution. Compared with 12 patients with other sacral malignancies (M:F = 4:8, median age 42 yr), sacral chordoma showed a significantly lower TLR (median value 2.1 vs 6.3, P = .021). In ROC curve analysis, TLR showed the largest area under the curve (AUC) of 0.79 (cutoff ≤ 4.0; sensitivity 100.0%, specificity 58.3%; P = .004), and SUVmax showed the second largest AUC of 0.73 (cutoff ≤ 6.9; sensitivity 80.0%, specificity 66.7%; P = .034). [18F]FDG PET/CT of sacral chordoma showed minimal-moderate uptake. The TLR of [18F]FDG PET/CT was significantly lower than that of other sacral malignancy and was the most useful parameter for differentiating sacral chordoma, with the largest AUC. SUVmax could be another helpful semiquantitative parameter.
Project description:Surgical resection margins are reportedly the most important predictor of survival and local recurrence with sacral chordomas. We examined the relevance of invasion of the surrounding posterior pelvic musculature (piriformis and gluteus maximus) at initial diagnosis to local recurrence after sacrectomy. We retrospectively reviewed 18 patients with histologically verified sacral chordoma seen at our institution between 1998 and 2005. There were 14 men and four women with a mean age of 65.1 years (range, 31-78 years). The average overall followup was 4.4 years (range, 0.5-10 years), 5.4 years for the living patients (range, 3-10 years), and 2.8 years for the deceased (range, 0.5-5.4 years). Local recurrence occurred in 12 patients (66%) 29 months postoperatively (range, 2-84 months). Six of these patients had wide excisions at initial surgery, five had marginal excisions, and one had an intralesional excision. Ten patients had wide surgical margins, six of whom (60%) had local recurrences. Tumor invasion of adjacent muscles at presentation was present in 14 patients, 12 of whom (85%) had local recurrences. Sacroiliac joint involvement was seen in 10 patients, nine of whom (90%) had local recurrences. The findings suggest obtaining wide surgical margins posteriorly, by excising parts of the piriformis, gluteus maximus, and sacroiliac joints, may result in better local disease control in patients with sacral chordoma.Level IV, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
Project description:Sacral chordomas are rare, slow-growing tumours that are amenable to surgery, but unfortunately often diagnosed late. The aim of the study was to identify presenting symptoms, which may aid diagnosis and reduce the treatment time. Forty-four patients were identified with sacral chordoma between 1989 and 2006. Clinical and pathological records were reviewed retrospectively to elicit the symptoms recorded prior to diagnosis, duration of symptoms, surgical treatment, size of tumour and survival. Eleven patients were excluded, leaving 33 patients in the study group. Thirty-one patients had chordomas arising from the sacrum and two patients from the coccyx. The mean duration of symptoms prior to diagnosis was 120 weeks (2.3 years), with a median of length of 104 weeks (two years) and range of 26 to 416 weeks (0.5 to eight years). The mean maximum tumour size at resection was 8.3 cm, with a mean volume of 614 cm(3) (range 9-2,113 cm(3)). Pain, typically dull and worse with sitting, was the most common presenting symptom in 85% of patients. The classic symptoms of cauda equina (saddle anaesthesia, bladder or bowel dysfunction) occurred in 70% patients (23 patients). Sacral chordoma should be considered in cases of back pain with coccydynia, especially with neurological symptoms.
Project description:Chordomas are rare slow growing, malignant bone tumors of the axial skeleton with no approved medical treatment. As the majority of chordomas express cMET and its ligand, HGF, and crosstalks between EGFR and MET-signaling exist, we aimed to explore cMET activity in chordoma cell lines and clinical samples. We investigated nine chordoma patients and four chordoma cell lines for cMET expression. Two clival and two sacral chordoma cell lines were tested for chromosomal abnormalities of the MET gene locus; we studied the influence of HGF on the autocrine secretion and migration behavior, as well as protein expression and phosphorylation. Two MET/ALK inhibitors were investigated for their effects on cell viability, cell cycle, cyclin alterations, apoptosis, and downstream signaling pathways. Moderate and strong expression of membrane and cytoplasmic cMET in chordoma patients and cell lines used, as well as concentration-dependent increase in phospho cMET expression after HGF stimulation in all four chordoma cell lines was shown. U-CH2, MUG-Chor1, and UM-Chor1 are polysomic for MET. Chordoma cell lines secreted EGF, VEGF, IL-6, and MMP9 upon HGF-stimulation. Sacral cell lines showed a distinct HGF-induced migration. Both inhibitors dose-dependently inhibited cell growth, induce apoptosis and cell-cycle arrest, and suppress downstream pathways. Heterogeneous responses obtained in our in vitro setting indicate that cMET inhibitors alone or in combination with other drugs might particularly benefit patients with sacral chordomas.
Project description:Next-generation RNA sequencing (NGS) was used for the combinatorial analysis of mRNA-miRNA gene expression profiles in sacral chordoma and nucleus pulposus samples, and to predict miRNA-mRNA regulatory networks with altered activity in chordoma. We identified a gene set including key regulators of the Hippo pathway, which is targeted by differently expressed miRNAs, and validated their altered expression by RT-qPCR. These newly identified miRNA/RNA interactions are predicted to have a role in the self-renewal process of chordoma stem cells, which might sustain the high rate of recurrence for this tumor.
Project description:Delirium, the clinical expression of acute encephalopathy, is a common neuropsychiatric syndrome that is related to poor outcomes, such as long-term cognitive impairment. Disturbances of functional brain networks are hypothesized to predispose for delirium. The aim of this study in non-delirious elderly individuals was to investigate whether predisposing risk factors for delirium are associated with fMRI network characteristics that have been observed during delirium. As predisposing risk factors, we studied age, alcohol misuse, cognitive impairment, depression, functional impairment, history of transient ischemic attack or stroke, and physical status. In this multicenter study, we included 554 subjects and analyzed resting-state fMRI data from 222 elderly subjects (63% male, age range: 65-85 year) after rigorous motion correction. Functional network characteristics were analyzed and based on the minimum spanning tree (MST). Global functional connectivity strength, network efficiency (MST diameter) and network integration (MST leaf fraction) were analyzed, as these measures were altered during delirium in previous studies. Linear regression analyses were used to investigate the relation between predisposing delirium risk factors and delirium-related fMRI characteristics, adjusted for confounding and multiple testing. Predisposing risk factors for delirium were not associated with delirium-related fMRI network characteristics. Older age within our elderly cohort was related to global functional connectivity strength (β = 0.182, p < 0.05), but in the opposite direction than hypothesized. Delirium-related functional network impairments can therefore not be considered as the common mechanism for predisposition for delirium.
Project description:mRNA microarray profiling was performed on healthy gingival biopsies from nonhuman primates (NHPs) (between 3 and 23 years old, and periodontitis gingival biopsies from NHPs (12-22 years old)
Project description:The article presents a dataset on the characteristics of stablecoins. Stablecoins represent a relatively young but increasingly important branch of the cryptocurrency market. Although they all share the same goal of maintaining a stable value in the digital market, they form a highly heterogeneous group. They differ in terms of collateral and stabilization mechanism, peg, availability of the technical documentation, presence on crypto exchanges or age. The dataset is cross-sectional and was created based on internet research. Individual information was collected from websites of the stablecoin projects and a crypto-data aggregator, and to a lesser extent from other auxiliary sources (websites related to finance and cryptocurrencies). The dataset is unique as there are no publicly available databases encompassing the features of stablecoins. It can be used in all stablecoin-related analyses to characterise the examined coins and to investigate the relationship between cryptocurrency market developments and stablecoin features.