Oral Surgery and Osteoradionecrosis in Patients Undergoing Head and Neck Radiation Therapy: An Update of the Current Literature.

Osteoradionecrosis (ORN) is a serious long-term complication of head and neck radiotherapy (RT), which is often triggered by dental extractions. It results from avascular aseptic necrosis due to irradiated bone damage. ORN is challenging to treat and can lead to severe complications. Furthermore, ORN causes pain and distress, significantly reducing the patient's quality of life. There is currently no established preventive strategy. This narrative review aims to provide an update for the clinicians on the risk of ORN associated with oral surgery in head and neck RT patients, with a focus on the timing suitable for the oral surgery and possible ORN preventive treatments. An electronic search of articles was performed by consulting the PubMed database. Intervention and observational studies were included. A multidisciplinary approach to the patient is highly recommended to mitigate the risk of RT complications. A dental visit before commencing RT is highly advised to minimize the need for future dental extractions after irradiation, and thus the risk of ORN. Post-RT preventive strategies, in case of dento-alveolar surgery, have been proposed and include antibiotics, hyperbaric oxygen (HBO), and the combined use of pentoxifylline and tocopherol ("PENTO protocol"), but currently there is a lack of established standards of care. Some limitations in the use of HBO involve the low availability of HBO facilities, its high costs, and specific clinical contraindications; the PENTO protocol, on the other hand, although promising, lacks clinical trials to support its efficacy. Due to the enduring risk of ORN, removable prostheses are preferable to dental implants in these patients, as there is no consensus on the appropriate timing for their safe placement. Overall, established standards of care and high-quality evidence are lacking concerning both preventive strategies for ORN as well as the timing of the dental surgery. There is an urgent need to improve research for more efficacious clinical decision making.

Proliferative verrucous leukoplakia: a case report of multiple metachronous oral verrucous carcinoma.

Proliferative verrucous leukoplakia (PVL) is a distinct progressive and multi-focal form of oral leukoplakia, not associated with the traditional risk factors (ie, tobacco and alcohol consumption). The incidence of oral squamous cell carcinoma in PVL patients is high. Here, we describe the case of a patient affected by PVL, who developed two metachronous oral verrucous carcinomas at different sites of the oral mucosa. Owing to the high risk of multiple oral squamous cell carcinoma, periodical clinical and histopathological follow-up is mandatory and should continue lifelong.

Actinomycosis of the Tongue: A Case Report and Review of Literature.

Background: Actinomycosis of the tongue is an uncommon, suppurative infection of lingual mucosa, caused by actinomyces. The clinical diagnosis may present serious difficulties because of its ability to mimic other lesions, including both benign and malignant neoplasms. Methods: Here, we describe the case of a 52-years-old patient affected by an asymptomatic, tumor-like tongue swelling, then diagnosed as actinomycosis. A review of tongue localization of actinomycosis is also reported, with emphasis on clinical findings and therapy. Results and Conclusion: Early diagnosis and treatment, with pus drainage and systemic antibiotic therapy, are pivotal to avoid severe and life-threatening complications.

Elaboration of a nomogram to predict nonsentinel node status in breast cancer patients with positive sentinel node, intraoperatively assessed with one step nucleic amplification: Retrospective and validation phase.

BACKGROUND: Tumor-positive sentinel lymph node (SLN) biopsy results in a risk of non sentinel node metastases in micro- and macro-metastases ranging from 20 to 50%, respectively. Therefore, most patients underwent unnecessary axillary lymph node dissections. We have previously developed a mathematical model for predicting patient-specific risk of non sentinel node (NSN) metastases based on 2460 patients. The study reports the results of the validation phase where a total of 1945 patients were enrolled, aimed at identifying a tool that gives the possibility to the surgeon to choose intraoperatively whether to perform or not axillary lymph node dissection (ALND). METHODS: The following parameters were recorded: Clinical: hospital, age, medical record number; Bio pathological: Tumor (T) size stratified in quartiles, grading (G), histologic type, lymphatic/vascular invasion (LVI), ER-PR status, Ki 67, molecular classification (Luminal A, Luminal B, HER-2 Like, Triple negative); Sentinel and non-sentinel node related: Number of NSNs removed, number of positive NSNs, cytokeratin 19 (CK19) mRNA copy number of positive sentinel nodes stratified in quartiles. A total of 1945 patients were included in the database. All patient data were provided by the authors of this paper. RESULTS: The discrimination of the model quantified with the area under the receiver operating characteristics (ROC) curve (AUC), was 0.65 and 0.71 in the validation and retrospective phase, respectively. The calibration determines the distance between predicted outcome and actual outcome. The mean difference between predicted/observed was 2.3 and 6.3% in the retrospective and in the validation phase, respectively. The two values are quite similar and as a result we can conclude that the nomogram effectiveness was validated. Moreover, the ROC curve identified in the risk category of 31% of positive NSNs, the best compromise between false negative and positive rates i.e. when ALND is unnecessary (<31%) or recommended (>31%). CONCLUSIONS: The results of the study confirm that OSNA nomogram may help surgeons make an intraoperative decision on whether to perform ALND or not in case of positive sentinel nodes, and the patient to accept this decision based on a reliable estimation on the true percentage of NSN involvement. The use of this nomogram achieves two main gools: 1) the choice of the right treatment during the operation, 2) to avoid for the patient a second surgery procedure.

Interventions for treating oral leukoplakia to prevent oral cancer.

BACKGROUND: Oral leukoplakia is a relatively common oral lesion that, in a small proportion of people, precedes the development of oral cancer. Most leukoplakias are asymptomatic; therefore, the primary objective of treatment should be to prevent onset of cancer. This review updates our previous review, published in 2006. OBJECTIVES: To assess the effectiveness, safety and acceptability of treatments for leukoplakia in preventing oral cancer. SEARCH METHODS: We searched the following electronic databases: Cochrane Oral Health's Trials Register (to 16 May 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2016, Issue 4), MEDLINE Ovid (1946 to 16 May 2016), Embase Ovid (1980 to 16 May 2016) and CancerLit via PubMed (1950 to 16 May 2016). We searched the metaRegister of Controlled Trials (to 10 February 2015), ClinicalTrials.gov (to 16 May 2016) and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials (to 16 May 2016). We placed no restrictions on the language or date of publication when searching electronic databases. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled people with a diagnosis of oral leukoplakia and compared any treatment versus placebo or no treatment. DATA COLLECTION AND ANALYSIS: We collected data using a data extraction form. Oral cancer development, demonstrated by histopathological examination, was our primary outcome. Secondary outcomes were clinical resolution of the lesion, improvement of histological features and adverse events. We contacted trial authors for further details when information was unclear. When valid and relevant data were available, we conducted a meta-analysis of the data using a fixed-effect model when we identified fewer than four studies with no heterogeneity. For dichotomous outcomes, we calculated risk ratios (RRs) and 95% confidence intervals (CIs). We assessed risk of bias in studies by using the Cochrane tool. We assessed the overall quality of the evidence by using standardised criteria (Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE)). MAIN RESULTS: We included 14 studies (909 participants) in this review. Surgical interventions, including laser therapy and cryotherapy, have never been studied by means of an RCT that included a no treatment or placebo arm. The included trials tested a range of medical and complementary treatments, in particular, vitamin A and retinoids (four studies); beta carotene or carotenoids (three studies); non-steroidal anti-inflammatory drugs (NSAIDs), specifically ketorolac and celecoxib (two studies); herbal extracts (four studies), including tea components, a Chinese herbal mixture and freeze-dried black raspberry gel; bleomycin (one study); and Bowman-Birk inhibitor (one study).We judged one study to be at low risk of bias, seven at unclear risk and six at high risk. In general, we judged the overall quality of the evidence to be low or very low, so findings are uncertain and further research is needed.Five studies recorded cancer incidence, only three of which provided useable data. None of the studies provided evidence that active treatment reduced the risk of oral cancer more than placebo: systemic vitamin A (RR 0.11, 95% CI 0.01 to 2.05; 85 participants, one study); systemic beta carotene (RR 0.71, 95% CI 0.24 to 2.09; 132 participants, two studies); and topical bleomycin (RR 3.00, 95% CI 0.32 to 27.83; 20 participants, one study). Follow-up ranged between two and seven years.Some individual studies suggested effectiveness of some proposed treatments, namely, systemic vitamin A, beta carotene and lycopene, for achieving clinical resolution of lesions more often than placebo. Similarly, single studies found that systemic retinoic acid and lycopene may provide some benefit in terms of improvement in histological features. Some studies also reported a high rate of relapse.Side effects of varying severity were often described; however, it seems likely that interventions were well accepted by participants because drop-out rates were similar between treatment and control groups. AUTHORS' CONCLUSIONS: Surgical treatment for oral leukoplakia has not been assessed in an RCT that included a no treatment or placebo comparison. Nor has cessation of risk factors such as smoking been assessed. The available evidence on medical and complementary interventions for treating people with leukoplakia is very limited. We do not currently have evidence of a treatment that is effective for preventing the development of oral cancer. Treatments such as vitamin A and beta carotene may be effective in healing oral lesions, but relapses and adverse effects are common. Larger trials of longer duration are required to properly evaluate the effects of leukoplakia treatments on the risk of developing oral cancer. High-quality research is particularly needed to assess surgical treatment and to assess the effects of risk factor cessation in people with leukoplakia.

Basal Cell Carcinoma of the Nipple in a Male Patient: A Particular Case Report.

Basal cell carcinoma (BCC) is a common skin cancer worldwide. However, BCC of the nipple and areola complex is rare. Men are more affected than women. Most of the cases were treated with simple excision. We report a case of BCC of the right nipple-areola complex in a 75-year-old man, treated with Mohs surgery and simple mastectomy.

A new clinical cut-off of cytokeratin 19 mRNA copy number in sentinel lymph node better identifies patients eligible for axillary lymph node dissection in breast cancer.

AIMS: Cytokeratin 19 (CK19) mRNA copy number predicts the probability of tumour load in axillary lymph nodes (ALN) and can help in decision-making regarding the axillary dissection. The purpose of this study was to define a new cut-off of CK19 mRNA copy number using the one-step nucleic acid amplification (OSNA) assay on metastatic sentinel lymph nodes (SLN) in order to identify cases at risk of having one or more positive ALN. METHODS: 1296 SLN from 1080 patients were analysed with the OSNA assay. 194 patients with positive SLN underwent ALN dissection and the mean value of CK19 copy number (320 000) of their SLN was set as initial cut-off. Receiver operative characteristics curve identify a best cut-off of 7700 (sensitivity 78%, specificity 57%). A comparison between our and the traditional cut-off (5000) was performed. RESULTS: The cut-off of 7700 successfully identifies patients with positive ALN (p=0.001, false- negative cases: 17%). In the range between 5000 and 7700, one patient with positive ALN would not undergo axillary dissection, whereas eight patients with negative ALN would be correctly identified. CONCLUSIONS: We suggest that the level of CK19 mRNA copy number could be the only parameter to consider in the intraoperative management of the axilla.

Advanced spectral analyses for real-time automatic echographic tissue-typing of simulated tumor masses at different compression stages.

Prototypal software algorithms for advanced spectral analysis of echographic images were developed to perform automatic detection of simulated tumor masses at two different pathological stages. Previously published works documented the possibility of characterizing macroscopic variation of mechanical properties of tissues through elastographic techniques, using different imaging modalities, including ultrasound (US); however, the accuracy of US-based elastography remains affected by the variable manual modality of the applied compression and several attempts are under investigation to overcome this limitation. Quantitative US (QUS), such as Fourier- and wavelet-based analyses of the RF signal associated with the US images, has been developed to perform a microscopic-scale tissue-type imaging offering new solutions for operator-independent examinations. Because materials able to reproduce the harmonic behavior of human liver can be realized, in this study, tissue-mimicking structures were US imaged and the related RF signals were analyzed using wavelet transform through an in-house-developed algorithm for tissue characterization. The classification performance and reliability of the procedure were evaluated on two different tumor stiffnesses (40 and 130 kPa) and with two different applied compression levels (0 and 3.5 N). Our results demonstrated that spectral components associated with different levels of tissue stiffness within the medium exist and can be mapped onto the original US images independently of the applied compressive forces. This wavelet-based analysis was able to identify different tissue stiffness with satisfactory average sensitivity and specificity: respectively, 72.01% ± 1.70% and 81.28% ± 2.02%.

A quantitative and automatic echographic method for real-time localization of endovascular devices.

Current imaging methods for catheter position monitoring during minimally invasive surgery do not provide an effective support to surgeons, often resulting in the choice of more invasive procedures. This study was conducted to demonstrate the feasibility of non-ionizing monitoring of endovascular devices through embedded quantitative ultrasound (QUS) methods, providing catheter self-localization with respect to selected anatomical structures. QUS-based algorithms for real-time automatic tracking of device position were developed and validated on in vitro and ex vivo phantoms. A trans-esophageal ultrasound probe was adapted to simulate an endovascular device equipped with an intravascular ultrasound probe. B-mode images were acquired and processed in real time by means of a new algorithm for accurate measurement of device position. After off-line verification, automatic position calculation was found to be correct in 96% and 94% of computed frames in the in vitro and ex vivo phantoms, respectively. The average errors of distance measurements (bias ± 2SD) in a 41-step 10-cm-long parabolic pathway were 0.76 ± 3.75 mm or 0.52 ± 3.20 mm, depending on algorithm implementations. Our results showed the effectiveness of QUS-based tracking algorithms for real-time automatic calculation and display of endovascular system position. The method, validated for the case of an endoclamp balloon catheter, can be easily extended to most endovascular surgical systems.

Hepatic vessel segmentation for 3D planning of liver surgery experimental evaluation of a new fully automatic algorithm.

RATIONALE AND OBJECTIVES: The aim of this study was to identify the optimal parameter configuration of a new algorithm for fully automatic segmentation of hepatic vessels, evaluating its accuracy in view of its use in a computer system for three-dimensional (3D) planning of liver surgery. MATERIALS AND METHODS: A phantom reproduction of a human liver with vessels up to the fourth subsegment order, corresponding to a minimum diameter of 0.2 mm, was realized through stereolithography, exploiting a 3D model derived from a real human computed tomographic data set. Algorithm parameter configuration was experimentally optimized, and the maximum achievable segmentation accuracy was quantified for both single two-dimensional slices and 3D reconstruction of the vessel network, through an analytic comparison of the automatic segmentation performed on contrast-enhanced computed tomographic phantom images with actual model features. RESULTS: The optimal algorithm configuration resulted in a vessel detection sensitivity of 100% for vessels > 1 mm in diameter, 50% in the range 0.5 to 1 mm, and 14% in the range 0.2 to 0.5 mm. An average area overlap of 94.9% was obtained between automatically and manually segmented vessel sections, with an average difference of 0.06 mm(2). The average values of corresponding false-positive and false-negative ratios were 7.7% and 2.3%, respectively. CONCLUSIONS: A robust and accurate algorithm for automatic extraction of the hepatic vessel tree from contrast-enhanced computed tomographic volume images was proposed and experimentally assessed on a liver model, showing unprecedented sensitivity in vessel delineation. This automatic segmentation algorithm is promising for supporting liver surgery planning and for guiding intraoperative resections.

Optimal enhancement configuration of silica nanoparticles for ultrasound imaging and automatic detection at conventional diagnostic frequencies.

OBJECTIVES: To experimentally investigate the acoustical behavior of silica nanoparticles within conventional diagnostic ultrasound fields and to determine a suitable configuration, in terms of particle size and concentration, for their employment as targetable contrast agents. We also assessed the effectiveness of a novel method for automatic detection of targeted silica nanoparticles for future tissue typing applications. MATERIALS AND METHODS: Silica nanospheres of variable size (160, 330, and 660 nm in diameter) and concentration (10¹°-10¹³ part/mL) were dispersed in different custom-designed agarose-based gel samples and imaged at 7.5 MHz with a conventional echograph linked to a research platform for radiofrequency signal acquisition. Off-line analysis included evaluation of backscattered ultrasound amplitude, image brightness, and nanoparticle automatic detection through radiofrequency signal processing. RESULTS: Amplitude of nanoparticle-backscattered signals linearly increased with particle number concentration, but image brightness did not show the same trend, because the logarithmic compression caused the reaching of a "plateau" where brightness remained almost constant for further increments in particle concentration. On the other hand, both backscatter amplitude and image brightness showed significant increments when particle diameter was increased. Taking into account particle size constraints for tumor targeting (pore size of tumor endothelium and trapping effects because of reticulo-endothelial system limit the dimension of effectively employable particles to less than 380 nm), a suitable compromise is represented by the employment of 330-nm silica nanospheres at a concentration of about 1 to 2 x 10¹¹ part/mL. These particles, in fact, showed the best combination of number concentration and diameter value to obtain an effective enhancement on conventional echographic images. Furthermore, also the sensitivity of the developed method for automatic nanoparticle detection had a maximum (72.8%) with 330-nm particles, whereas it was lower with both bigger and smaller particles (being equal to 64.1% and 17.5%, respectively). CONCLUSIONS: Silica nanoparticles at a diameter of about 330 nm are very promising contrast agents for ultrasound imaging and specific tumor targeting at conventional diagnostic frequencies, being in particular automatically detectable with high sensitivity already at low doses. Future studies will be carried out to assess the acoustic behavior of nanoparticles with different geometries/sizes and to improve sensitivity of the automatic detection algorithm.