A self-assembled multimodal complex for combined pre- and intraoperative imaging of the sentinel lymph node.

Specific removal of the sentinel lymph node (SLN) during breast cancer surgery presents physicians with the opportunity to detect early metastatic disease. To increase the accuracy of intraoperative SLN detection, new methods with higher sensitivity and specificity are required. We have quantitatively compared conventional preoperative lymphoscintigraphy with albumin radiocolloids ((99m)Tc-NanoColl) with optical intraoperative guidance using the near infrared dye indocyanine green (ICG) in an orthotopic mouse model for metastatic breast cancer. Furthermore, we have applied a self-assembled multimodal complex, in which ICG is non-covalently bound to the albumin radiocolloid, to attain identical dynamics of the radioactive and optical components. The SLN specificity of the multimodal complex is similar to conventional lymphoscintigraphy, while the fluorescent signal-to-noise ratio is improved by 86% compared to ICG alone. In addition, the multimodal complex permits scintigraphic validation of the fluorescent findings. The multimodal ICG-(99m)Tc-NanoColl complex can be used both for lymphoscintigraphy by preoperative single photon emission computed tomography/computed tomography and for surgical navigation by intraoperative fluorescence imaging.

Heterochrony in limb evolution: developmental mechanisms and natural selection.

The tetrapod limb provides several examples of heterochrony-changes in the timing of developmental events. These include species differences in the sequence of skeletal chondrogenesis, in gene transcription in the developing limbs, and in the relative time at which forelimb and hind limb buds develop. Here, we examine (i) phylogenetic trends in limb heterochrony; (ii) changes in developmental mechanisms that may lead to heterochrony; and (iii) the possible role that heterochrony plays in generating adaptive traits. We analyze the published literature and present preliminary data on turtle (Emys orbicularis) and bat (Rousettus amplexicaudatus) limb development. Teleosts, marsupials, and some urodeles show extreme timing differences between forelimb (or pectoral fin) and hind limb (or pelvic fin) development; this heterochrony may, in some cases, be adaptive. Published data on limb chondrogenesis reveal sequence elements that are strongly conserved (possibly owing to constraints); and others that vary between higher taxa (for unknown reasons). We find little evidence that chondrogenic sequences are modified by selection for limb functional traits. There are a few examples of developmental mechanisms that may be modified under heterochrony to produce adaptive changes in the limb (e.g. some cases of hyperphalangy or limb reduction). In conclusion, numerous examples of limb heterochrony have been recorded. However, few cases are obviously adaptive. Indeed, current data and methodologies make it difficult to identify the developmental changes, or selective pressures, that may underlie limb heterochrony. More integrative studies, including studies of heterochrony within populations, are needed to assess the role of timing shifts in limb evolution.

Poly(trimethylene carbonate)-based composite materials for reconstruction of critical-sized cranial bone defects in sheep.

PURPOSE: The use of ceramic materials in repair of bone defects is limited to non-load-bearing sites. We tested poly(trimethylene carbonate) (PTMC) combined with ß-tricalcium phosphate or biphasic calcium phosphate particles for reconstruction of cranial defects. MATERIALS AND METHODS: PTMC-calcium phosphate composite matrices were implanted in cranial defects in sheep for 3 and 9 months. Micro-computed tomography quantification and histological observation were performed for analysis. RESULTS: No differences were found in new bone formation among the defects left unfilled, filled with PTMC scaffolds, or filled with either kind of PTMC-calcium phosphate composite scaffolds. Porous ß-TCP scaffolds as control led to a larger amount of newly formed bone in the defects than all other materials. Histology revealed abundant new bone formation in the defects filled with porous ß-TCP scaffolds. New bone formation was limited in defects filled with PTMC scaffolds or different PTMC-calcium phosphate matrices. PTMC matrices were degraded uneventfully. New bone formation within the defects followed an orderly pattern. CONCLUSIONS: PTMC did not interfere with bone regeneration in sheep cranial defects and is suitable as a polymer matrix for incorporating calcium phosphate particles. Increasing the content of calcium phosphate particles in the composite matrices may enhance the beneficial effects of the particles on new bone formation.

A Retrospective Review of Reconstructive Options and Outcomes of 202 Cases Large Facial Mohs Micrographic Surgical Defects, Based on the Aesthetic Unit Involved.

BACKGROUND: For optimal treatment of facial defects following Mohs micrographic surgery (MMS), the aesthetic unit principles should be applied. Often multiple staged procedures and revisions are necessary. OBJECTIVE: To analyze the reconstructive options and outcomes for complex facial defects per aesthetic unit. METHODS: Data of 202 patients, who underwent a facial reconstruction at the department of plastic and reconstructive surgery following MMS, were collected. RESULTS: The central facial units were affected in more than 70%, with over 20% of the defects involving more than 1 unit. Nasal defects required the longest reconstruction time (3-staged forehead flap) and periocular defects the most revisional procedures. In more than 50%, additional operations (range, 1-5) were needed. In 12%, postoperative complications occurred. CONCLUSION: An overview for the reconstructive options of extensive facial skin cancer is presented. Proper treatment requires a structured multidisciplinary approach in order to achieve excellent tumour control and a satisfactory aesthetic and functional end result.

Composite materials based on poly(trimethylene carbonate) and ß-tricalcium phosphate for orbital floor and wall reconstruction.

Poly(trimethylene carbonate) and ß-tricalcium phosphate (PTMC/ß-TCP) composite materials were prepared by coprecipitation and compression molding. The effect of different amounts of the ceramic component (15 and 30 vol %) on the properties was investigated. The effect of lamination with minimal amounts of poly(D,L-lactide) (PDLLA) was assessed as well. It was hypothesized that these composites would be suitable for orbital floor reconstruction, as the polymer component resorbs enzymatically without the formation of acidic compounds, while the ceramic component could induce bone formation. To asses their suitability as load bearing devices, the flexural properties of the prepared (laminated) composites were determined in three point bending experiments and compared with those of currently used reconstruction devices. The flexural modulus of PTMC composites increased from 6-17 MPa when introducing 30 vol % ß-TCP. A laminate of this composite with PDLLA (with respective layer thicknesses of 0.8 and 0.2 mm) had a flexural modulus of 64 MPa. When evaluated in a mechanical engineering model of the orbital floor the (laminated) composites materials showed similar behavior compared to the currently used materials. The results suggest that from a mechanical point of view these (laminated) composite sheets should be well suited for use in orbital floor reconstruction.

Tracer-cocktail injections for combined pre- and intraoperative multimodal imaging of lymph nodes in a spontaneous mouse prostate tumor model.

To improve surgical guidance toward prostate draining lymph nodes, we investigate the potential of intraoperative fluorescence imaging and combined pre- and intraoperative multimodality imaging approaches. Transgenic adenocarcinoma mouse prostate mice with spontaneous prostate tumors are injected intratumorally with: 1. a cocktail of patent blue (Pb) and indocyanine green (ICG); 2. a cocktail of albumin radiocolloids (99mTc-NanoColl), Pb, and ICG; or 3. a cocktail of radiolabeled albumin (99mTc-Vasculosis), Pb, and ICG. The distribution of these imaging agents over the lymph nodes (LNs) are studied at different time points after injection. We find that at 60-min postinjection, ICG significantly improves the detection of the LNs compared to Pb, 53 versus 7%, respectively. Moreover, a cocktail of ICG and 99mTc-NanoColl improves the fluorescent detection rate to 86%, equalling that of the clinically applied 99mTc-NanoColl. A similar overlap is observed in our initial clinical pilot data. Fluorescent detection of the LNs using a ICG with 99mTc-Vasculosis gives similar results as "free" ICG (58%; 60 min). A 99mTc-NanoColl, Pb, and cocktail ICG enriches the standard 99mTc-NanoColl approach by adding optical detection of the sentinel lymph nodes. Furthermore, this approach improves fluorescent-based guidance and enables both accurate surgical planning and intraoperative detection, based on a single injection.

Questioning the value of (99m)Tc-HYNIC-annexin V based response monitoring after docetaxel treatment in a mouse model for hereditary breast cancer.

Annexin V imaging is suggested to provide a good indication of cancer treatment efficacy. To study the accuracy of (99m)Tc-AnxV imaging, we monitored chemo-sensitive and chemo-resistant tumors in a mouse breast cancer model after treatment with docetaxel. Sensitive tumors showed a slight peak in (99m)Tc-AnxV uptake one day post-treatment, while uptake in resistant tumors remained constant. In contrast to immunohistochemical analysis, (99m)Tc-AnxV imaging could not be used to predict tumor response, due to large variation between animals.