The unresolved case of sacral chordoma: from misdiagnosis to challenging surgery and medical therapy resistance.

PURPOSE: A sacral chordoma is a rare, slow-growing, primary bone tumor, arising from embryonic notochordal remnants. Radical surgery is the only hope for cure. The aim of our present study is to analyse our experience with the challenging treatment of this rare tumor, to review current treatment modalities and to assess the outcome based on R status. METHODS: Eight patients were treated in our institution between 2001 and 2011. All patients were discussed by a multidisciplinary tumor board, and an en bloc surgical resection by posterior perineal access only or by combined anterior/posterior accesses was planned based on tumor extension. RESULTS: Seven patients underwent radical surgery, and one was treated by using local cryotherapy alone due to low performance status. Three misdiagnosed patients had primary surgery at another hospital with R1 margins. Reresection margins in our institution were R1 in two and R0 in one, and all three recurred. Four patients were primarily operated on at our institution and had en bloc surgery with R0 resection margins. One had local recurrence after 18 months. The overall morbidity rate was 86% (6/7 patients) and was mostly related to the perineal wound. Overall, 3 out of 7 resected patients were disease-free at a median follow-up of 2.9 years (range, 1.6-8.0 years). CONCLUSION: Our experience confirms the importance of early correct diagnosis and of an R0 resection for a sacral chordoma invading pelvic structures. It is a rare disease that requires a challenging multidisciplinary treatment, which should ideally be performed in a tertiary referral center

Isometric group actions on Banach spaces and representations vanishing at infinity

Our main result is that the simple Lie group $G=Sp(n,1)$ acts properly isometrically on $L^p(G)$ if $p>4n+2$. To prove this, we introduce property ({\BP}_0^V), for $V$ be a Banach space: a locally compact group $G$ has property ({\BP}_0^V) if every affine isometric action of $G$ on $V$, such that the linear part is a $C_0$-representation of $G$, either has a fixed point or is metrically proper. We prove that solvable groups, connected Lie groups, and linear algebraic groups over a local field of characteristic zero, have property ({\BP}_0^V). As a consequence for unitary representations, we characterize those groups in the latter classes for which the first cohomology with respect to the left regular representation on $L^2(G)$ is non-zero; and we characterize uniform lattices in those groups for which the first $L^2$-Betti number is non-zero.Comment: 28 page

Occurrence and prognosis of lymph node metastases in patients selected for isolated limb perfusion with soft tissue sarcoma.

<b> <i>Background and Objectives:</i> </b> Extensive surgery is often required for advanced soft tissue sarcoma (STS) of the limb. In the 1980s, a new approach was developed: isolated limb perfusion (ILP). This study aimed to assess incidence and impact on patient survival based on lymph node metastasis with systematic radical lymphadenectomy during ILP. <b> <i>Methods:</i> </b> Retrospective study of 57 consecutive patients treated by ILP for limb STS with simultaneous radical lymph node dissection in our tertiary referral center between 1992 and 2015. <b> <i>Results:</i> </b> Median age was 62 years (19-87) and 30 patients were male (53%). Lymph node involvement was observed in 13 patients (N1, 23%), regarded as metastatic spreading in 4 angiosarcomas, 3 epithelioid sarcomas, 2 leiomyosarcomas, 2 undifferentiated sarcomas and 2 synovial sarcomas. For the N0 patient group, median survival was 73.9 months (CI 95% 41.9-105.9) compared to 15.1 months (CI 95% 7.4-22.6) in case of metastatic lymph node ( <i>p</i> =0.002). The median disease-free survival was 33,0 months (CI 95% 12,5-53.5) in N0 group and 8.0 months (CI 95% 4.0-11.9) in N1 ( <i>p</i> =0.006). <b> <i>Conclusions:</i> </b> Lymph node metastases of STS patients selected for ILP seemed to have a negative impact on both overall and disease-free survival. Radical lymph node dissection should be included in ILP procedure

Property (T) and rigidity for actions on Banach spaces

We study property (T) and the fixed point property for actions on $L^p$ and other Banach spaces. We show that property (T) holds when $L^2$ is replaced by $L^p$ (and even a subspace/quotient of $L^p$), and that in fact it is independent of $1\leq p<\infty$. We show that the fixed point property for $L^p$ follows from property (T) when 1. For simple Lie groups and their lattices, we prove that the fixed point property for $L^p$ holds for any $1< p<\infty$ if and only if the rank is at least two. Finally, we obtain a superrigidity result for actions of irreducible lattices in products of general groups on superreflexive Banach spaces.Comment: Many minor improvement

Nonlinear spectral calculus and super-expanders

Nonlinear spectral gaps with respect to uniformly convex normed spaces are shown to satisfy a spectral calculus inequality that establishes their decay along Cesaro averages. Nonlinear spectral gaps of graphs are also shown to behave sub-multiplicatively under zigzag products. These results yield a combinatorial construction of super-expanders, i.e., a sequence of 3-regular graphs that does not admit a coarse embedding into any uniformly convex normed space.Comment: Typos fixed based on referee comments. Some of the results of this paper were announced in arXiv:0910.2041. The corresponding parts of arXiv:0910.2041 are subsumed by the current pape

On twisted Fourier analysis and convergence of Fourier series on discrete groups

We study norm convergence and summability of Fourier series in the setting of reduced twisted group $C^*$-algebras of discrete groups. For amenable groups, F{\o}lner nets give the key to Fej\'er summation. We show that Abel-Poisson summation holds for a large class of groups, including e.g. all Coxeter groups and all Gromov hyperbolic groups. As a tool in our presentation, we introduce notions of polynomial and subexponential H-growth for countable groups w.r.t. proper scale functions, usually chosen as length functions. These coincide with the classical notions of growth in the case of amenable groups.Comment: 35 pages; abridged, revised and update

The chromatin landscape of primary synovial sarcoma organoids is linked to specific epigenetic mechanisms and dependencies.

Synovial sarcoma (SyS) is an aggressive mesenchymal malignancy invariably associated with the chromosomal translocation t(X:18; p11:q11), which results in the in-frame fusion of the BAF complex gene SS18 to one of three SSX genes. Fusion of SS18 to SSX generates an aberrant transcriptional regulator, which, in permissive cells, drives tumor development by initiating major chromatin remodeling events that disrupt the balance between BAF-mediated gene activation and polycomb-dependent repression. Here, we developed SyS organoids and performed genome-wide epigenomic profiling of these models and mesenchymal precursors to define SyS-specific chromatin remodeling mechanisms and dependencies. We show that SS18-SSX induces broad BAF domains at its binding sites, which oppose polycomb repressor complex (PRC) 2 activity, while facilitating recruitment of a non-canonical (nc)PRC1 variant. Along with the uncoupling of polycomb complexes, we observed H3K27me3 eviction, H2AK119ub deposition and the establishment of de novo active regulatory elements that drive SyS identity. These alterations are completely reversible upon SS18-SSX depletion and are associated with vulnerability to USP7 loss, a core member of ncPRC1.1. Using the power of primary tumor organoids, our work helps define the mechanisms of epigenetic dysregulation on which SyS cells are dependent

LIN28B Underlies the Pathogenesis of a Subclass of Ewing Sarcoma

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Radiotherapy for Soft Tissue Sarcomas after Isolated Limb Perfusion and Surgical Resection: Essential for Local Control in All Patients?

Background: Standard treatment for localized soft tissue sarcoma (STS) is resection plus adjuvant radiotherapy (RTx). In approximately 10% of cases, resection would cause severe loss of function or even require amputation because of the extent of disease. Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-α) and melphalan can achieve regression of the tumor, facilitating limb-saving resection. RTx improves local control but may lead to increased morbidity. Methods: In our database of over 500 ILPs, 122 patients with unifocal STS were treated by ILP followed by limb-sparing surgery. All included patients were candidates for amputation. Results: Surgery resulted in 69 R0 resections (57%), and in 53 specimens (43%) resection margins contained microscopic evidence of tumor (R1). Histopathological examination revealed >50% ILP-induced tumor necrosis in 59 cases (48%). RTx was administered in 73 patients (60%). Local recurrence rate was 21% after median follow-up of 31 months (2-182 months). Recurrence was significantly less in patients with >50% ILP-induced necrosis versus ≤50% necrosis (7% vs. 33%, P = 0.001). A similar significant correlation was observed for R0 versus R1 resections (15% vs. 28%, P = 0.04). In 36 patients with R0 resection and >50% necrosis, of whom 21 were spared RTx, no recurrences were observed during follow-up. Conclusions: In patients with locally advanced primary STS, treated with ILP followed by R0 resection, and with >50% ILP-induced necrosis in the resected specimen, RTx is of no further benefit