Precision surgery: the role of intra-operative real-time image guidance - outcomes from a multidisciplinary European consensus conference.

Developments within the field of image-guided surgery are ever expanding, driven by collective involvement of clinicians, researchers, and industry. While the general conception of the potential of image-guided surgery is to improve surgical outcome, the specific motives and goals that drive can differ between the different expert groups. To establish the current and future role of intra-operative image guidance within the field of image-guided surgery a Delphi consensus survey was conducted during the 2 European Congress on Image-guided surgery.

Addition of tumour infiltration depth and extranodal extension improves the prognostic value of the pathological TNM classification for early-stage oral squamous cell carcinoma.

Aims: In the 8th edition of the American Joint Committee on Cancer TNM staging manual, tumour infiltration depth and extranodal extension are added to the pathological classification for oral squamous cell carcinoma. The currently available 8th TNM validation studies lack patients with conservative neck treatment, and changes in the classification especially affect patients with small tumours. The aim of this study was to determine the potential impact of the changes in the 8th edition pTNM classification on the prognosis and treatment strategy for oral squamous cell carcinoma in a well-defined series of pT1-T2 patients with long-term follow-up.

Lymphatic drainage patterns of oral maxillary tumors: Approachable locations of sentinel lymph nodes mainly at the cervical neck level.

Background: There is debate if the lymphatic drainage pattern of oral maxillary cancer is to the retropharyngeal lymph nodes or to the cervical lymph nodes. Insight in drainage patterns is important for the indication for neck treatment. The purpose of this study was to identify the lymphatic drainage pattern of oral maxillary cancer via preoperative lymphoscintigraphy.

Meta-analysis of 701 published cases of sinonasal neuroendocrine carcinoma: The importance of differentiation grade in determining treatment strategy.

The aim of this meta-analysis was to provide treatment guidelines for sinonasal neuroendocrine carcinoma (SNC) by combining all available data in the literature. A literature search for all studies concerning SNC was performed against the MEDLINE and EMBASE databases. Available clinical data was normalized, pooled, and statistically analyzed.

Amplification and protein overexpression of cyclin D1: Predictor of occult nodal metastasis in early oral cancer.

Background: Accurate nodal staging is pivotal for treatment planning in early (stage I-II) oral cancer. Unfortunately, current imaging modalities lack sensitivity to detect occult nodal metastases. Chromosomal region 11q13, including genes CCND1, Fas-associated death domain (FADD), and CTTN, is often amplified in oral cancer with nodal metastases.

Impact of chemotherapy on the outcome of osteosarcoma of the head and neck in adults.

Background: There is an ongoing debate about the value of (neo-)adjuvant chemotherapy in high- and intermediate-grade osteosarcoma of the head and neck.

Methods: All records of patients older than 16 years diagnosed with osteosarcoma of the head and neck in the Netherlands between 1993 and 2013 were reviewed.

Results: We identified a total of 77 patients with an osteosarcoma of the head and neck; the 5-year overall survival (OS) was 55%.

Management of the clinically N0 neck in squamous cell carcinoma of the maxillary alveolus and hard palate.

Background: The purpose of this study was to evaluate active surveillance strategy in the clinically negative neck in maxillary squamous cell carcinoma (SCC).

Methods: One hundred fourteen consecutive patients diagnosed with oral maxillary SCC were analyzed retrospectively from 3 centers in The Netherlands. Analysis parameters included regional disease-free survival of N0 patients stratified for T classification, elective radiotherapy (RT) of the neck; and overall survival of the whole cohort, stratified by N classification; salvage neck surgery rates.

Head and neck intensity modulated radiation therapy leads to an increase of opportunistic oral pathogens.

Objectives: The introduction of intensity modulated radiation therapy (IMRT) has led to new possibilities in the treatment of head and neck cancer (HNC). Limited information is available on how this more advanced radiation technique affects the oral microflora. In a prospective study we assessed the effects of various advanced treatments for HNC on the oral microflora, as well as the effects of elimination of oral foci of infection.

A systematic review of functional outcome and quality of life following reconstruction of maxillofacial defects using vascularized free fibula flaps and dental rehabilitation reveals poor data quality.

Background: Reconstruction and oral rehabilitation of segmental maxillofacial defects resulting from ablative surgery is commonly achieved by osteocutaneous vascularized free fibula (VFFF) transplantation combined with implant-supported dental prostheses. We systematically reviewed the literature regarding impact of oral rehabilitation with or without dental implants on functional outcome and quality of life (Qol) following reconstruction of such segmental maxillofacial defects with VFFF.

Methods: This systematic review was performed according to the PRISMA guidelines.

Human Salivary Gland Stem Cells Functionally Restore Radiation Damaged Salivary Glands.

Adult stem cells are often touted as therapeutic agents in the regenerative medicine field, however data detailing both the engraftment and functional capabilities of solid tissue derived human adult epithelial stem cells is scarce. Here we show the isolation of adult human salivary gland (SG) stem/progenitor cells and demonstrate at the single cell level in vitro self-renewal and differentiation into multilineage organoids. We also show in vivo functionality, long-term engraftment, and functional restoration in a xenotransplantation model.

Accuracy of secondary maxillofacial reconstruction with prefabricated fibula grafts using 3D planning and guided reconstruction.

Background: We compared the pre-operative 3D-surgical plan with the surgical outcome of complex two-stage secondary reconstruction of maxillofacial defects using inserted implants in the prefabricated fibula graft.

Methods: Eleven reconstructions of maxillofacial defects with prefabricated fibulas were performed using a 3D virtual planning. Accuracy of placement of the fibula grafts and dental implants was compared to pre-operative 3D virtual plans by superimposing pre-operative and post-operative CT-scans: we first superimposed the CT-scans on the antagonist jaw, to represent the outcome of occlusion, and then superimposed on the planned fibula segments.

mTHPC mediated, systemic photodynamic therapy (PDT) for nonmelanoma skin cancers: Case and literature review.

Background And Objective: Patients with multiple nonmelanoma skin cancers (NMSCs), like immunosuppressed or nevoid basal cell carcinomas, offer a therapeutic challenge. Photodynamic therapy (PDT) using the systemic photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) has the ability to treat multiple NMSCs up to a depth of 10 mm in a single session. These unique properties offer an attractive alternative to regular therapies (e.

Sparing the region of the salivary gland containing stem cells preserves saliva production after radiotherapy for head and neck cancer.

Each year, 500,000 patients are treated with radiotherapy for head and neck cancer, resulting in relatively high survival rates. However, in 40% of patients, quality of life is severely compromised because of radiation-induced impairment of salivary gland function and consequent xerostomia (dry mouth). New radiation treatment technologies enable sparing of parts of the salivary glands.

Integration of oncologic margins in three-dimensional virtual planning for head and neck surgery, including a validation of the software pathway.

Purpose: Three-dimensional (3D) virtual planning of reconstructive surgery, after resection, is a frequently used method for improving accuracy and predictability. However, when applied to malignant cases, the planning of the oncologic resection margins is difficult due to visualisation of tumours in the current 3D planning. Embedding tumour delineation on a magnetic resonance image, similar to the routinely performed radiotherapeutic contouring of tumours, is expected to provide better margin planning.

Accuracy of fibula reconstruction using patient-specific CAD/CAM reconstruction plates and dental implants: A new modality for functional reconstruction of mandibular defects.

Background: The purpose of this study was to analyze the accuracy of mandibular reconstruction using patient-specific computer-aided designed and computer-aided manufactured (CAD/CAM) reconstruction plates as a guide to place fibula grafts and dental implants in a one-stage procedure using pre-operative 3D virtual planning.

Methods: Seven consecutive patients were analyzed retrospectively, the 3D accuracy of placement of the fibula grafts and dental implants was compared to the virtual plan.

Results: Six out of seven flaps survived for an average follow-up time of 9.

Evidence supporting pre-radiation elimination of oral foci of infection in head and neck cancer patients to prevent oral sequelae. A systematic review.

Pre-radiation dental screening of head-neck cancer patients aims to identify and eliminate oral foci of infection to prevent post-radiation oral problems. The evidence for the efficacy of dental screening is unclear. In this systematic review, we analyzed available evidence on the efficacy of pre-radiation elimination of oral foci of infection in preventing oral sequelae.

Photochemical internalization (PCI)-mediated enhancement of bleomycin cytotoxicity by liposomal mTHPC formulations in human head and neck cancer cells.

Background And Objective: Photodynamic therapy (PDT) with photosensitizers that locate in endocytic vesicles of cancer cells can be exploited to promote the intracellular release of anticancer drugs entrapped in endolysosomal vesicles. This new approach is commonly referred to as Photochemical Internalization (PCI). Here we report on the PCI effects of three different formulations (Foscan, Foslip, and Fospeg) of the clinically approved photosensitizer, meta-tetrahydroxyphenyl chlorin (mTHPC) on the anticancer drug bleomycin (BLM) in the head and neck cancer cell lines.

Overdentures on primary mandibular implants in patients with oral cancer: a follow-up study over 14 years.

We aimed to assess oral functioning, patients' satisfaction, condition of peri-implant tissues, and survival of implants up to 14 years after their insertion in patients with oral cancer who had had mandibular overdentures placed over primary implants. Endosseous dental implants were inserted prospectively in the interforaminal region of the mandible during resection of the tumour in 164/180 patients with oral cancer. All 58 patients were evaluated by questionnaires and clinical assessments during a final assessment in 2012.

Localization of liposomal mTHPC formulations within normal epithelium, dysplastic tissue, and carcinoma of oral epithelium in the 4NQO-carcinogenesis rat model.

Background And Objective: Foslip and Fospeg are liposomal formulations of the photosensitizer mTHPC (Foscan), which is used for photodynamic therapy (PDT) of malignancies. Literature suggests that liposomal mTHPC formulations have better properties and increased tumor uptake compared to Foscan. To investigate this, we used the 4NQO-induced carcinogen model to compare the localization of the different mTHPC formulations within normal, precancerous, and cancerous tissue.

mTHPC-mediated photodynamic therapy of early stage oral squamous cell carcinoma: a comparison to surgical treatment.

Background: mTHPC-mediated photodynamic therapy (PDT) is used for treatment of early head and neck squamous cell carcinoma. This study is a retrospective comparison of PDT with transoral surgery in the treatment of early primary squamous cell carcinoma of the oral cavity/oropharynx.

Methods: PDT data were retrieved from four study databases; surgical results were retrieved from our institutional database.

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® in rat liver. As a next step towards clinical translation, the effect of two liposomal formulations of mTHPC, Fospeg® and Foslip®, on FDPS response was investigated.

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

Background: 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.

Methods: 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.

Fully 3-dimensional digitally planned reconstruction of a mandible with a free vascularized fibula and immediate placement of an implant-supported prosthetic construction.

Background: Reconstruction of craniofacial defects becomes complex when dental implants are included for functional rehabilitation. We describe a fully 3-dimensional (3D) digitally planned reconstruction of a mandible and immediate prosthetic loading with a fibula graft in a 2-step surgical approach.

Methods: A 54-year-old man had development of osteoradionecrosis of the mandible.

The future of medical diagnostics: review paper.

While histopathology of excised tissue remains the gold standard for diagnosis, several new, non-invasive diagnostic techniques are being developed. They rely on physical and biochemical changes that precede and mirror malignant change within tissue. The basic principle involves simple optical techniques of tissue interrogation.

Fluorescence localization and kinetics of mTHPC and liposomal formulations of mTHPC in the window-chamber tumor model.

Background And Objective: Foslip® and Fospeg® are liposomal formulations of the photosensitizer mTHPC, intended for use in Photodynamic Therapy (PDT) of malignancies. Foslip consists of mTHPC encapsulated in conventional liposomes, Fospeg consists of mTHPC encapsulated in pegylated liposomes. Possible differences in tumor fluorescence and vasculature kinetics between Foslip, Fospeg, and Foscan® were studied using the rat window-chamber model.