Three-Dimensional Guided Zygomatic Implant Placement after Maxillectomy

Zygomatic implants are used in patients with maxillary defects to improve the retention and stability of obturator prostheses, thereby securing good oral function. Prosthetic-driven placement of zygomatic implants is even difficult for experienced surgeons, and with a free-hand approach, deviation from the preplanned implant positions is inevitable, thereby impeding immediate implant-retained obturation. A novel, digitalized workflow of surgical planning was used in 10 patients. Maxillectomy was performed with 3D-printed cutting, and drill guides were used for subsequent placement of zygomatic implants with immediate placement of implant-retained obturator prosthesis. The outcome parameters were the accuracy of implant positioning and the prosthetic fit of the obturator prosthesis in this one-stage procedure. Zygomatic implants (n = 28) were placed with good accuracy (mean deviation 1.73 ± 0.57 mm and 2.97 ± 1.38° 3D angle deviation), and in all cases, the obturator prosthesis fitted as pre-operatively planned. The 3D accuracy of the abutment positions was 1.58 ± 1.66 mm. The accuracy of the abutment position in the occlusal plane was 2.21 ± 1.33 mm, with a height accuracy of 1.32 ± 1.57 mm. This feasibility study shows that the application of these novel designed 3D-printed surgical guides results in predictable zygomatic implant placement and provides the possibility of immediate prosthetic rehabilitation in head and neck oncology patients after maxillectomy

Novel finite element-based plate design for bridging mandibular defects:Reducing mechanical failure

Introduction: When the application of a free vascularised flap is not possible, a segmental mandibular defect is often reconstructed using a conventional reconstruction plate. Mechanical failure of such reconstructions is mostly caused by plate fracture and screw pull-out. This study aims to develop a reliable, mechanically superior, yet slender patient-specific reconstruction plate that reduces failure due to these causes. Patients and Methods: Eight patients were included in the study. Indications were as follows: fractured reconstruction plate (2), loosened screws (1) and primary reconstruction of a mandibular continuity defect (5). Failed conventional reconstructions were studied using finite element analysis (FEA). A 3D virtual surgical plan (3D-VSP) with a novel patient-specific (PS) titanium plate was developed for each patient. Postoperative CBCT scanning was performed to validate reconstruction accuracy. Results: All PS plates were placed accurately according to the 3D-VSP. Mean 3D screw entry point deviation was 1.54 mm (SD: 0.85, R: 0.10–3.19), and mean screw angular deviation was 5.76° (SD: 3.27, R: 1.26–16.62). FEA indicated decreased stress and screw pull-out inducing forces. No mechanical failures appeared (mean follow-up: 16 months, R: 7–29). Conclusion: Reconstructing mandibular continuity defects with bookshelf-reconstruction plates with FEA underpinning the design seems to reduce the risk of screw pull-out and plate fractures

In vivo quantification of photosensitizer concentration using fluorescence differential path-length spectroscopy:influence of photosensitizer formulation and tissue location

In vivo measurement of photosensitizer concentrations may optimize clinical photodynamic therapy (PDT). Fluorescence differential path-length spectroscopy (FDPS) is a non-invasive optical technique that has been shown to accurately quantify the concentration of Foscan (R) in rat liver. As a next step towards clinical translation, the effect of two liposomal formulations of mTHPC, Fospeg (R) and Foslip (R), on FDPS response was investigated. Furthermore, FDPS was evaluated in target organs for head-and-neck PDT. Fifty-four healthy rats were intravenously injected with one of the three formulations of mTHPC at 0.15 mgkg(-1). FDPS was performed on liver, tongue, and lip. The mTHPC concentrations estimated using FDPS were correlated with the results of the subsequent harvested and chemically extracted organs. An excellent goodness of fit (R-2) between FDPS and extraction was found for all formulations in the liver (R-2 = 0.79). A much lower R-2 between FDPS and extraction was found in lip (R-2 = 0.46) and tongue (R-2 = 0.10). The lower performance in lip and in particular tongue was mainly attributed to the more layered anatomical structure, which influences scattering properties and photosensitizer distribution. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO. 17.6.067001

In vivo quantification of photosensitizer fluorescence in the skin-fold observation chamber using dual-wavelength excitation and NIR imaging

A major challenge in biomedical optics is the accurate quantification of in vivo fluorescence images. Fluorescence imaging is often used to determine the pharmacokinetics of photosensitizers used for photodynamic therapy. Often, however, this type of imaging does not take into account differences in and changes to tissue volume and optical properties of the tissue under interrogation. To address this problem, a ratiometric quantification method was developed and applied to monitor photosensitizer meso-tetra (hydroxyphenyl) chlorin (mTHPC) pharmacokinetics in the rat skin-fold observation chamber. The method employs a combination of dual-wavelength excitation and dualwavelength detection. Excitation and detection wavelengths were selected in the NIR region. One excitation wavelength was chosen to be at the Q band of mTHPC, whereas the second excitation wavelength was close to its absorption minimum. Two fluorescence emission bands were used; one at the secondary fluorescence maximum of mTHPC centered on 720 nm, and one in a region of tissue autofluorescence. The first excitation wavelength was used to excite the mTHPC and autofluorescence and the second to excite only autofluorescence, so that this could be subtracted. Subsequently, the autofluorescence-corrected mTHPC image was divided by the autofluorescence signal to correct for variations in tissue optical properties. This correction algorithm in principle results in a linear relation between the corrected fluorescence and photosensitizer concentration. The limitations of the presented method and comparison with previously published and validated techniques are discussed

The use of 3D virtual surgical planning and computer aided design in reconstruction of maxillary surgical defects

PURPOSE OF REVIEW: The present review describes the latest development of 3D virtual surgical planning (VSP) and computer aided design (CAD) for reconstruction of maxillary defects with an aim of fully prosthetic rehabilitation. The purpose is to give an overview of different methods that use CAD in maxillary reconstruction in patients with head and neck cancer. RECENT FINDINGS: 3D VSP enables preoperative planning of resection margins and osteotomies. The current 3D VSP workflow is expanded with multimodal imaging, merging decision supportive information. Development of more personalized implants is possible using CAD, individualized virtual muscle modelling and topology optimization. Meanwhile the translation of the 3D VSP towards surgery is improved by techniques like intraoperative imaging and augmented reality. Recent improvements of preoperative 3D VSP enables surgical reconstruction and/or prosthetic rehabilitation of the surgical defect in one combined procedure. SUMMARY: With the use of 3D VSP and CAD, ablation surgery, reconstructive surgery, and prosthetic rehabilitation can be planned preoperatively. Many reconstruction possibilities exist and a choice depends on patient characteristics, tumour location and experience of the surgeon. The overall objective in patients with maxillary defects is to follow a prosthetic-driven reconstruction with the aim to restore facial form, oral function, and do so in accordance with the individual needs of the patient

A novel PPP2R2A::PRKD1 fusion in a cribriform adenocarcinoma of salivary gland

Cribriform adenocarcinoma of salivary gland (CASG) is a rare, salivary gland tumor. In this report, we describe a case of CASG harboring a novel PPP2R2A::PRKD1 fusion. A 58-year-old female presented with an intraoral mass adjacent to the lower left third molar region. Morphological features at histological examination, immunohistochemical staining (p63+, p40-), and tumor location were indicative of CASG. However, due to the potential focal presence of a biphasic component within the tumor, RNA sequencing was performed to confirm the diagnosis. The subsequently found novel PPP2R2A::PRKD1 fusion adds to the rapidly evolving molecular landscape of salivary gland tumors. Additionally, we report that CASG may show some entrapment of pre-existent salivary gland ducts, which may be misinterpreted as tumor cells with myoepithelial differentiation

mTHPC mediated interstitial photodynamic therapy of recurrent nonmetastatic base of tongue cancers:Development of a new method

Interstitial photodynamic therapy (iPDT) can be an option in the management of locally recurrent base of tongue cancer after (chemo)radiation treatment. The purpose of the current study was to develop a technique to implant light sources into the tumor tissue. Twenty patients with previously irradiated locally recurrent base of tongue cancers who were not candidates for salvage surgery or reirradiation or refused these therapies were included in this study. The treatment planning was done on MRI. The light sources were implanted using modified brachytherapy techniques. The iPDT could be conducted in all patients without short-term complications. At 6 months, 9 patients had complete response with 4 patients still free of disease (46-80 months). Long-term complications included pharyngocutaneous fistula in 6 patients, serious bleeding in 1 patient, and cutaneous metastasis in 2 patients. The initial results are encouraging. There is room for improvement to control the destructive potential of iPDT through planning and monitoring tool

Epidermal Growth Factor Receptor-Targeted Fluorescence Molecular Imaging for Postoperative Lymph Node Assessment in Patients with Oral Cancer

Rationale: In most oral cancer patients, surgical treatment includes resection of the primary tumor combined with the excision of lymph nodes (LN), either for staging or treatment. All LNs harvested during surgery require tissue processing and subsequent microscopic histopathological assessment to determine the nodal stage. In this study, we investigated the use of the fluorescent tracer cetuximab-800CW to discriminate between tumor-positive and tumor-negative LNs before histopathological examination. Methods: Here, we report a retrospective ad hoc analysis of a clinical trial designed for resection margin evaluation of oral squamous cell carcinoma patients (NCT02415881). Two days prior to surgery, patients were intravenously administered with 75 mg cetuximab followed by 15 mg cetuximab-800CW, an Epidermal Growth Factor Receptor (EGFR)-targeting fluorescent tracer. Fluorescence images were obtained of excised, formalin-fixed LNs and correlated with histopathological assessment. Results: Fluorescence molecular imaging of 514 LNs (61 pathologically positive nodes) can detect tumor-positive LNs ex vivo with 100% sensitivity and 86.8% specificity (AUC 0.97). In this cohort, the number of LNs that require microscopic assessment was decreased by 77.4%, without missing any metastasis. Additionally, in 7.5% of the fluorescence false-positive LNs, we identified metastases missed by standard histopathological analysis. Conclusion: Our findings suggest that EGFR-targeted fluorescence molecular imaging can aid in the detection of LN metastases in the ex vivo setting in oral cancer patients. This image-guided concept can improve the efficacy of postoperative LN examination and identify additional metastases, which safeguards appropriate postoperative therapy and may improve patient prognosis

EGFR-targeted fluorescence molecular imaging for intraoperative margin assessment in oral cancer patients: a phase II trial

Abstract Inadequate surgical margins occur frequently in oral squamous cell carcinoma surgery. Fluorescence molecular imaging (FMI) has been explored for intraoperative margin assessment, but data are limited to phase-I studies. In this single-arm phase-II study (NCT03134846), our primary endpoints were to determine the sensitivity, specificity and positive predictive value of cetuximab-800CW for tumor-positive margins detection. Secondary endpoints were safety, close margin detection rate and intrinsic cetuximab-800CW fluorescence. In 65 patients with 66 tumors, cetuximab-800CW was well-tolerated. Fluorescent spots identified in the surgical margin with signal-to-background ratios (SBR) of ≥2 identify tumor-positive margins with 100% sensitivity, 85.9% specificity, 58.3% positive predictive value, and 100% negative predictive value. An SBR of ≥1.5 identifies close margins with 70.3% sensitivity, 76.1% specificity, 60.5% positive predictive value, and 83.1% negative predictive value. Performing frozen section analysis aimed at the fluorescent spots with an SBR of ≥1.5 enables safe, intraoperative adjustment of surgical margins