Validity of the 3D VECTRA photogrammetric surface imaging system for cranio-maxillofacial anthropometric measurements

Purpose

The use of three-dimensional (3D) photography for anthropometric measurements is of increasing interest, especially in the cranio-maxillofacial field. Before standard implementation, accurate determination of the precision and accuracy of each system is mandatory.

Methods

A mannequin head was labelled with 52 landmarks, and 28 three-dimensional images were taken using a commercially available five-pod 3D photosystem (3D VECTRA; Canfield, Fairfield, NJ) in different head positions. Distances between the landmarks were measured manually using a conventional calliper and compared with the digitally calculated distances acquired from labelling by two independent observers. The experimental set-up accounted for clinical circumstances by varying the positioning (vertical, horizontal, sagittal) of the phantom.

Results

In the entire calliper measurement data set (n?=?410), a significant difference (p?=?0.02) between the directly measured and corresponding virtually calculated distances was found. The mean aberration between both modalities covering all data was 7.96 mm. No differences (p?=?0.94) between the two groups were found using a cut-off of 10 % (leaving n?=?369 distances) due to considerable errors in direct measurements and the necessary manual data translation. The mean diversity of both measurement modalities after cut-off was 1.33 mm (maximum, 6.70 mm). Inter-observer analysis of all 1,326 distances showed no difference (p?=?0.99; maximal difference, 0.58 mm) in the digital measurements.

Conclusion

The precision and accuracy of this five-pod 3D photosystem suggests its suitability for clinical applications, particularly anthropometric studies. Three-hundred-and-sixty degree surface-contour mapping of the craniofacial region within milliseconds is particularly useful in paediatric patients. Proper patient positioning is essential for high-quality imaging.     

Cortical control of adaptation and sensory relay mode in the thalamus

A major synaptic input to the thalamus originates from neurons in cortical layer 6 (L6); however, the function of this cortico–thalamic pathway during sensory processing is not well understood. In the mouse whisker system, we found that optogenetic stimulation of L6 in vivo results in a mixture of hyperpolarization and depolarization in the thalamic target neurons. The hyperpolarization was transient, and for longer L6 activation (>200 ms), thalamic neurons reached a depolarized resting membrane potential which affected key features of thalamic sensory processing. Most importantly, L6 stimulation reduced the adaptation of thalamic responses to repetitive whisker stimulation, thereby allowing thalamic neurons to relay higher frequencies of sensory input. Furthermore, L6 controlled the thalamic response mode by shifting thalamo–cortical transmission from bursting to single spiking. Analysis of intracellular sensory responses suggests that L6 impacts these thalamic properties by controlling the resting membrane potential and the availability of the transient calcium current I_T, a hallmark of thalamic excitability. In summary, L6 input to the thalamus can shape both the overall gain and the temporal dynamics of sensory responses that reach the cortex.Sensory signals en route to the cortex undergo profound signal transformations in the thalamus. One important thalamic transformation is sensory adaptation. Adaptation is a common characteristic of sensory systems in which neural output adjusts to the statistics and dynamics of past stimuli, thereby better encoding small stimulus changes across a wide range of scales despite the limited range of possible neural outputs (1–3). Thalamic sensory adaptation is characterized by a steep decrease in action potential (AP) activity during sustained sensory stimulation (4–7), decreasing the efficacy at which subsequent sensory stimuli are transmitted to the cortex.The widely reported duality of thalamic response mode is another key property of thalamic information processing which further affects how sensory input reaches the cortex. In burst mode, sensory inputs are relayed as short, rapid clusters of APs; in contrast, in tonic mode the same inputs are translated into single APs. Both tonic and burst modes have been described during anesthesia/sleep and wakefulness/behavior, with a pronounced shift toward the tonic mode during alertness (8–12).Although the exact information content of thalamic bursts is not yet clear, it has been suggested that bursting may signal novel stimuli to the cortex, whereas the tonic mode enables linear encoding of fine stimulus details, e.g., when an object is examined (13, 14). One issue hampering the interpretation of burst/tonic responses is that currently it is unknown if the cortex itself is involved in the rapid changes in firing modes seen in the awake and anesthetized animal (15, 16) and which mechanisms initiate these shifts in vivo.On the biophysical level, the response mode depends on the resting membrane potential (RMP), which controls the availability of the transient low-threshold calcium current (I_T) (17). Depolarization decreases the size of the I_T-mediated low-threshold calcium spike (LTS), and fewer burst spikes are fired (18). Similarly, RMP influences adaptation in that depolarization reduces the voltage distance to the AP threshold, thereby increasing the probability that smaller, depressed inputs will trigger APs (6). Thus, the dynamics of the RMP may govern several key properties of signal transformation in the thalamus, thereby providing a common mechanism for controlling thalamic adaptation and response mode.Although subcortical inputs have been shown to influence thalamic firing modes (7, 9), we investigated the impact of cortical activity on thalamic sensory processing. Cortico–thalamic projections from cortical layer 6 (L6) are a likely candidate for regulating thalamic sensory processing with high spatial and temporal precision, because these projections provide a major input to the thalamus and, as shown by McCormick et al. (19), depolarize and modulate firing of thalamic cells in vitro.However, because of the inability to study sensory signals in brain slices, the role of L6 on thalamic input/output properties during sensory processing is not clear. Here, in the ventro posteromedial nucleus (VPM) of the mouse whisker thalamus, we investigate how L6 impacts the transmission of whisker inputs to the cortex. Recent advances in cell-type–specific approaches to dissect specific circuits in vivo (20–22) allowed us to activate the L6–thalamic pathway specifically and determine its impact on thalamic sensory processing.We found that cortical L6 can change key properties of thalamic sensory processing by controlling the interaction of intrinsic membrane properties and sensory inputs. This mechanism enables the cortex to control the frequency-dependent adaptation and the gain of its own input.     

Structure of signaling-competent neurotensin receptor 1 obtained by directed evolution in Escherichia coli

Crystallography has advanced our understanding of G protein–coupled receptors, but low expression levels and instability in solution have limited structural insights to very few selected members of this large protein family. Using neurotensin receptor 1 (NTR1) as a proof of principle, we show that two directed evolution technologies that we recently developed have the potential to overcome these problems. We purified three neurotensin-bound NTR1 variants from Escherichia coli and determined their X-ray structures at up to 2.75 Å resolution using vapor diffusion crystallization experiments. A crystallized construct was pharmacologically characterized and exhibited ligand-dependent signaling, internalization, and wild-type–like agonist and antagonist affinities. Our structures are fully consistent with all biochemically defined ligand-contacting residues, and they represent an inactive NTR1 state at the cytosolic side. They exhibit significant differences to a previously determined NTR1 structure (Protein Data Bank ID code 4GRV) in the ligand-binding pocket and by the presence of the amphipathic helix 8. A comparison of helix 8 stability determinants between NTR1 and other crystallized G protein–coupled receptors suggests that the occupancy of the canonical position of the amphipathic helix is reduced to various extents in many receptors, and we have elucidated the sequence determinants for a stable helix 8. Our analysis also provides a structural rationale for the long-known effects of C-terminal palmitoylation reactions on G protein–coupled receptor signaling, receptor maturation, and desensitization.Neurotensin is a 13-amino-acid peptide, which plays important roles in the pathogenesis of Parkinson’s disease, schizophrenia, antinociception, and hypothermia and in lung cancer progression (1–4). It is expressed throughout the central nervous system and in the gut, where it binds to at least three different neurotensin receptors (NTRs). NTR1 and NTR2 are class A G protein–coupled receptors (GPCRs) (5, 6), whereas NTR3 belongs to the sortilin family. Most of the effects of neurotensin are mediated through NTR1, where the peptide acts as an agonist, leading to GDP/GTP exchange within heterotrimeric G proteins and subsequently to the activation of phospholipase C and adenylyl cyclase, which produce second messengers in the cytosol (5, 7). Activated NTR1 is rapidly phosphorylated and internalizes by a β-arrestin– and clathrin-mediated process (8), which is crucial for desensitizing the receptor (9). Several lines of evidence suggest that internalization is also linked to G protein–independent NTR1 signaling (10, 11). To improve our mechanistic understanding of NTR1 and to gain additional insight into GPCR features such as helix 8 (H8), we were interested in obtaining a structure of this receptor in a physiologically relevant state.To date, by far the most successful strategy for GPCR structure determination requires the replacement of the intracellular loop 3 by a fusion protein, as the intracellular domain is otherwise too small to provide crystal contacts. The fusion protein approach has provided a wealth of valuable structural data on GPCRs, but as it renders the crystallized constructs signaling-inactive, the most important functionality—the activation of G proteins—cannot be confirmed for these structures. This leads inevitably to a degree of uncertainty regarding the physiological relevance of intracellular structural aspects, and it also impedes the elucidation of signaling mechanisms, as functional assays and structure determination cannot be performed with the same GPCR constructs.Crystallization in the absence of fusion proteins was so far mainly possible for rhodopsin (12), the A_2A adenosine receptor (A2AR) (13), and the β₁-adrenergic receptor (14). Together, they share a high stability, which is either given naturally (rhodopsin) or it is due to stabilizing mutations. High stability appeared to be crucial for crystallographic success, as it allowed the application of harsh short-chain detergents. These tend to form small micelles, which may explain why crystal contact formation can occur under these conditions despite the small extra- and intracellular domains of class A GPCRs.Besides the stability requirement and/or the necessity of fusion proteins, structural studies of GPCRs have also been complicated by the need of eukaryotic expression systems [e.g., Spodoptera frugiperda (Sf9) insect cells], as prokaryotes exhibit generally low functional expression levels of wild-type GPCRs. However, prokaryotes such as Escherichia coli offer several advantages compared with insect cells, including quick genetic modification strategies, growth to high cell densities, fast doubling times, inexpensive media, absence of glycosylation, and robust handling. Furthermore, E. coli is well suited for producing fully isotope-labeled proteins—a crucial requirement for many NMR studies, which are limited to date.To exploit these advantages, we recently developed a directed evolution method for high functional GPCR expression levels in E. coli (15). In contrast to screening a few hundred mutants one by one, this strategy allows the simultaneous, competitive testing of >10⁸ different protein variants for highest prokaryotic expression and functionality. Briefly, diverse libraries of NTR1 variants were either obtained synthetically (16, 17) or by error-prone PCR on the wild-type sequence (15). The libraries were ligated to a plasmid encoding an inducible promoter, which was subsequently used to transform E. coli. Selection pressure for high functional expression levels was applied by incubating the induced cells with fluorescently labeled neurotensin, which allowed enrichment of the best expressing cells by fluorescence-activated cell sorting (FACS). The outlined procedure was performed in cycles, leading to a gradual adaptation of the NTR1 population toward high functional expression levels, and additionally, it gave rise to an increase in thermostability for certain variants.In a second technology, termed CHESS (cellular high-throughput encapsulation, solubilization and screening), we adapted this concept to directly evolve NTR1 variants for high thermostability in short-chain detergent micelles—a property that is not only beneficial for structural studies but also for in vitro drug screening (18). The crucial development of CHESS was to surround, simultaneously, every E. coli cell by a semipermeable polysaccharide capsule. This allows us to solubilize the receptor mutants with harsh short-chain detergents, each mutant inside its own encapsulated cell, all at once and in the same test tube. Both the solubilized receptors and their encoding plasmids are maintained within the same capsules. Long-term incubation under these conditions followed by labeling of the encapsulated solubilized receptors with fluorescent neurotensin and rounds of FACS enrichment ensured a strong selection pressure and a gradual adaption of the NTR1 population toward high stability in harsh short-chain detergents (18).In this work, we present the crystal structures of three evolved NTR1 variants, which were either obtained by evolving high functional expression levels in E. coli or by directed evolution for stability in detergent micelles. In contrast to the majority of crystallized GPCRs, our NTR1 variants are devoid of bulky modifications at the cytoplasmic face and can thus remain signaling-active, which allows us to gain unique insights into the structure–function relationship of NTR1.     

Peptidoglycan-binding protein TsaP functions in surface assembly of type IV pili

Type IV pili (T4P) are ubiquitous and versatile bacterial cell surface structures involved in adhesion to host cells, biofilm formation, motility, and DNA uptake. In Gram-negative bacteria, T4P pass the outer membrane (OM) through the large, oligomeric, ring-shaped secretin complex. In the β-proteobacterium Neisseria gonorrhoeae, the native PilQ secretin ring embedded in OM sheets is surrounded by an additional peripheral structure, consisting of a peripheral ring and seven extending spikes. To unravel proteins important for formation of this additional structure, we identified proteins that are present with PilQ in the OM. One such protein, which we name T4P secretin-associated protein (TsaP), was identified as a phylogenetically widely conserved component of the secretin complex that co-occurs with genes for T4P in Gram-negative bacteria. TsaP contains an N-terminal carbohydrate-binding lysin motif (LysM) domain and a C-terminal domain of unknown function. In N. gonorrhoeae, lack of TsaP results in the formation of membrane protrusions containing multiple T4P, concomitant with reduced formation of surface-exposed T4P. Lack of TsaP did not affect the oligomeric state of PilQ, but resulted in loss of the peripheral structure around the PilQ secretin. TsaP binds peptidoglycan and associates strongly with the OM in a PilQ-dependent manner. In the δ-proteobacterium Myxococcus xanthus, TsaP is also important for surface assembly of T4P, and it accumulates and localizes in a PilQ-dependent manner to the cell poles. Our results show that TsaP is a novel protein associated with T4P function and suggest that TsaP functions to anchor the secretin complex to the peptidoglycan.Type IV pili systems (T4PSs) are involved in the assembly of long, thin fibers, which are found on the surfaces of many bacteria and archaea (1). Type IV pili (T4P) function in host cell adhesion, twitching motility, virulence, DNA uptake, and biofilm formation and are evolutionary related to type II secretion systems (T2SSs), bacterial transformation systems, and the archaellum (2–4). T4PSs can be divided into T4aPSs and T4bPSs that are distinguished based on pilin size and assembly systems (5, 6). T4aPSs form the most abundant class, and the T4P formed by these systems can undergo cycles of extension, adhesion, and retraction, which is a feature that distinguishes them from the other bacterial surface structures (7, 8). T4aP retract at rates up to 1 μm/s and can generate forces up to 150 pN (9, 10). Generally, T4bPSs are not associated with retraction. Here, we focus on T4aPSs and refer to these as T4PSs unless specifically indicated. T4PSs have been studied extensively in many bacteria but are especially well characterized in Neisseria and Pseudomonas spp. and in Myxococcus xanthus. Different nomenclature is used for different T4PSs (Table S1). Here, the Neisseria gonorrhoeae nomenclature is used.T4P are composed of major (e.g., PilE) and minor (in N. gonorrhoeae; e.g., PilV, PilX, ComP) pilins that are synthesized as preproteins with a type III signal peptide. After cleavage of the signal peptide by the prepilin peptidase PilD (11, 12), the T4P are assembled by a multiprotein complex (13). In Gram-negative bacteria, the proteins of T4PSs can be divided into three subcomplexes: the inner membrane (IM) motor complex, the alignment complex, and the outer membrane (OM) pore complex (6). The IM motor complex drives both the assembly and the retraction of T4P. Pilin subunits are extruded from the IM by the platform protein PilG (14) and the hexameric ATPase PilF (15). Disassembly of T4P with retraction occurs when PilF is replaced by the hexameric ATPase PilT (7, 16). PilU, a PilT paralog, is involved in retraction to a lesser extent (17). The alignment complex consisting of PilM, PilN, PilO, and PilP is proposed to connect the IM motor complex and the OM pore complex, and it is also thought to be involved in the stability and/or gating of the OM complex (18–20). In the OM, PilQ forms a homooligomeric ring that serves as a conduit for T4P (21–23).PilQ is a member of the secretin protein family. Proteins belonging to this family are present in many Gram-negative bacteria and are components of T4PSs, T2SSs, type III secretion systems (T3SSs), and extrusion systems of filamentous phages (24). Secretins are multidomain proteins with a signal sequence and a conserved C-terminal OM-spanning domain. Most secretins contain multiple copies of an N-terminal α/β domain (the N domains). PilQ proteins are integral OM proteins and form large gated channels. Oligomeric secretin complexes with different symmetries have been identified. Structural characterization by EM of purified PilQ from Neisseria meningitidis showed a dodecameric structure with a chamber sealed at both ends (25, 26), whereas the T2SS secretins PulD (27) and GspD (28) of the Klebsiella oxytoca pullanase and Vibrio cholerae toxin secretion systems, respectively, showed dodecameric structures with a chamber open at the periplasmic side and closed at the OM side. The structure of the InvG secretin complex of the T3SS of the Salmonella typhimurium needle complex showed 15-fold symmetry and is open at both ends (29), and the phage pIV secretin showed 14-fold symmetry (30). The structure of the C-terminal OM-spanning domain involved in multimer formation is currently not known. Crystal structures of the periplasmic N domains of GspD of the T2SS of enterotoxigenic Escherichia coli (31), of EscC of the T3SS of S. typhimurium (32), and of N. meningitidis PilQ (25) showed that these domains consist of α-helices packed against three-stranded β-sheets. Secretins of T4P systems also contain B domains, which are not present in other secretins and are located N-terminal to the N domains. The structure of the B2 domain of N. meningitidis PilQ consists of several β-strands (25). Remarkably, when the sequence conservation of the B2 domain was mapped to the structure of the B2 domain of N. meningitidis PilQ, a highly conserved patch was identified that was proposed to form the binding site for a currently unidentified T4PS protein (25).Secretins interact with several other proteins. Pilotin proteins are small lipoproteins that interact with the extreme C terminus of secretins and are responsible for OM targeting and oligomerization of secretins (33–38). Secretins of T4PSs also interact with the alignment complex. For N. meningitidis, Pseudomonas aeruginosa, and M. xanthus PilQ, a direct interaction was demonstrated between the respective PilPs and the N0 domains of the PilQs (25, 39, 40). Recently, ExeA of the T2SS of Aeromonas hydrophila (41) and FimV of the T4PS of P. aeruginosa (42) were also implicated in secretin assembly. They contain, respectively, PF01471 and LysM peptidoglycan (PG)-binding domains that might attach them to the PG. However, neither of these two proteins is ubiquitously conserved in bacteria assembling T4P.We have previously shown that the PilQ secretin of N. gonorrhoeae embedded in OM sheets is surrounded by a peripheral structure, which is formed by an additional peripheral ring as well as spikes (43). The proteins that make up these structures are not known. Here, we identify a widely conserved protein, which we name T4P secretin-associated protein (TsaP), that is important for the formation of the peripheral structure. Phylogenomic analysis of 450 genomes of Proteobacteria showed that the presence of the tsaP gene is strongly linked to the presence of genes for T4aPSs. We characterize the TsaP protein and demonstrate the importance of TsaP for T4aP assembly in the two phylogenetically widely separated model organisms N. gonorrhoeae and M. xanthus.     

Antigen expression level threshold tunes the fate of CD8 T cells during primary hepatic immune responses

CD8 T-cell responses to liver-expressed antigens range from deletional tolerance to full effector differentiation resulting in overt hepatotoxicity. The reasons for these heterogeneous outcomes are not well understood. To identify factors that govern the fate of CD8 T cells activated by hepatocyte-expressed antigen, we exploited recombinant adenoassociated viral vectors that enabled us to vary potential parameters determining these outcomes in vivo. Our findings reveal a threshold of antigen expression within the liver as the dominant factor determining T-cell fate, irrespective of T-cell receptor affinity or antigen cross-presentation. Thus, when a low percentage of hepatocytes expressed cognate antigen, high-affinity T cells developed and maintained effector function, whereas, at a high percentage, they became functionally exhausted and silenced. Exhaustion was not irreversibly determined by initial activation, but was maintained by high intrahepatic antigen load during the early phase of the response; cytolytic function was restored when T cells primed under high antigen load conditions were transferred into an environment of low-level antigen expression. Our study reveals a hierarchy of factors dictating the fate of CD8 T cells during hepatic immune responses, and provides an explanation for the different immune outcomes observed in a variety of immune-mediated liver pathologic conditions.The liver is acknowledged to possess unique tolerogenic properties, which have likely evolved to maintain immunological unresponsiveness toward food-derived and microbial antigens that enter the circulation via the gut (1, 2). This tolerogenic capability of the liver is demonstrated in animal models of liver transplantation, in which liver allografts are accepted across complete MHC mismatch barriers and are able to protect other donor tissues from rejection (reviewed in ref. 3). In humans, the tolerogenic hepatic environment is likely to contribute to impaired immune clearance of the hepatitis B virus (HBV) and hepatitis C virus (HCV), which result in persistent infection in a significant proportion of exposed individuals and are associated with major morbidity and mortality. In contrast, effective immune responses to hepatotropic pathogens leading to resolution of infection are observed in most hepatitis A and E virus infections, the majority of individuals infected with HBV during adulthood, and a minority of those infected by HCV (reviewed in refs. 4, 5). The liver is also susceptible to a variety of autoimmune-mediated conditions (6). Collectively, these observations indicate that effective immune responses can be initiated and/or sustained in the liver despite its apparent predisposition toward the generation of tolerance. Unfortunately, there is no small animal model in which to study the parameters that determine the balance between intrahepatic immunity and tolerance in viral hepatitis. Thus, the factors that shape immune outcome have not yet been identified.By studying the fate of antigen-specific CD8 T cells transferred into mice expressing antigen in the liver, it has been shown that, despite being a nonlymphoid organ, the liver is able to support primary CD8 T-cell activation (7). However, depending on the choice of antigen expressed and mode of delivery, the outcome of intrahepatic CD8 T-cell activation has been varied, ranging from deletion and/or functional silencing (8–10) to cytotoxic T lymphocyte (CTL) development (11, 12). This observed diversity of T-cell fates parallels the heterogeneous outcomes of liver-immune interactions observed during hepatotropic viral infections in humans. Thus, reconciliation of these findings holds the potential to yield critical insights into the immunopathological basis of immune-mediated liver disease as well as liver-associated tolerance.In this study, we developed an integrated system in which we manipulated parameters predicted to influence the generation of effector CD8 T cells encountering their cognate antigen on hepatocytes. By identifying three key determinants of the generation of functional effector cells in response to hepatocyte-expressed antigen, this study provides, for the first time to our knowledge, a unified model that explains and predicts the functional outcome of CD8 T-cell activation by liver-expressed antigen and reconciles findings from a number of previous studies that addressed this question.     

Plain Radiographs Fail to Reflect Femoral Offset in Total Hip Arthroplasty

Successful biomechanical reconstruction is a major goal in total hip arthroplasty (THA). We measured leg length (LL), global (GO) and femoral offset (FO) change on anteroposterior pelvis radiographs and on three-dimensional computed-tomography (3D-CT) with fiducial landmarks after cementless THA on 18 hips of cadaveric specimens. Measurements on radiographs were performed twice by four examiners and showed high interobserver (mean CCC ≥ 0.79) and intraobserver agreements (mean ICC ≥ 0.88). Mean differences between radiographic and 3D-CT measurements were 1.0 (SD 2.0) mm for LL, 0.6 (SD 3.6) mm for GO and 1.4 (SD 5.2) mm for FO. 1% of radiographic LL-, 15% of GO- and 35% of FO measurements were outside a tolerance limit of 5 mm. Radiographs seem acceptable for measuring LL/GO change but fail to reflect FO change in THA.     

Can Total Knee Arthroplasty Be Safely Performed Among Nonagenarians? An Evaluation of Morbidity and Mortality Within a Total Joint Replacement Registry

As the nonagenarian patient population continues to grow, more patients aged 90 and over will become candidates for total knee arthroplasty (TKA). This study evaluated the patient characteristics and incidence of postoperative morbidity and mortality of 216 nonagenarian TKA patients among 81,835 primary TKA patients followed by a total joint replacement registry. Nonagenarians had a greater number of comorbidities preoperatively, experienced a higher rate of deep vein thrombosis and 30 day mortality, and had a longer hospital length of stay. However, nonagenarians did not have an increased risk of infection nor pulmonary embolism and postoperative mortality was within expected rates for individuals 90 years and older. Higher readmission rates, however, highlight the benefits of close follow up during a prolonged postoperative period.     

The Effect of Chronic Kidney Disease on Total Hip Arthroplasty

Patients with chronic kidney disease (CKD) undergoing total hip arthroplasty (THA) were evaluated for risk of revision, surgical site infection (SSI), thromboembolic events, mortality and readmission. 20,720 primary TKA cases were included (smaller sample for readmission evaluation, N = 9322). The prevalence of CKD among THA patients was 6.1% (N = 1269). After adjustment for age, gender, race, general health, and diabetes, CKD patients were at 1.4 (95% confidence interval 1.1–1.8) increased risk of readmission within 90 days. The adjusted risks for revision (overall, aseptic, and septic), SSI (deep and superficial), deep vein thrombosis, pulmonary embolism, and mortality (30-day, 90-day, ever) were not significantly different between patients with CKD and those without CKD. However, increased risk for 90-day readmission underscores that CKD patients are a fundamentally different population of patients.     

Outcomes after curative or palliative surgery for locoregional recurrent breast cancer

Background

Locoregional recurrence (LRR) after breast cancer is an independent predictor for later systemic disease and poor long-term outcome. As the surgical treatment is complex and often leaves the patient with extensive defects, reconstructive procedures involving flaps, and thus plastic surgical assistance, are often required. The aim of the present study was to evaluate our institution’s approach to surgical treatment for locoregional recurrence of a breast cancer.

Methods

In the present retrospective, single-centre study, we evaluate our experience with 12 patients who underwent surgery for locally recurrent breast cancer at Aarhus University Hospital between 2006 and 2010. Nine patients underwent wide local excision. The remaining three patients underwent full thickness chest wall resection.

Results

There was no perioperative mortality and no major complications. Minor complications occurred in four (33 %) of the patients. Median overall survival was 22 months, regardless of the surgery being curative or palliative. A median disease-free survival of 18 months was achieved for patients having achieved radicality.

Conclusions

Both wide local excision and full thickness chest wall resection offer the opportunity of local control and palliation in patients with LRR. The plastic surgical reconstructive procedures are associated with a low complication rate, and thus not postponing further adjuvant therapy. However, a multidisciplinary approach with a highly careful patient selection is critical in order to ensure the best outcome for the patient. Level of Evidence: Level IV, therapeutic study.