Intrapapillary capillary loop classification in magnification endoscopy: open dataset and baseline methodology.

PURPOSE: Early squamous cell neoplasia (ESCN) in the oesophagus is a highly treatable condition. Lesions confined to the mucosal layer can be curatively treated endoscopically. We build a computer-assisted detection system that can classify still images or video frames as normal or abnormal with high diagnostic accuracy. METHODS: We present a new benchmark dataset containing 68K binary labelled frames extracted from 114 patient videos whose imaged areas have been resected and correlated to histopathology. Our novel convolutional network architecture solves the binary classification task and explains what features of the input domain drive the decision-making process of the network. RESULTS: The proposed method achieved an average accuracy of 91.7% compared to the 94.7% achieved by a group of 12 senior clinicians. Our novel network architecture produces deeply supervised activation heatmaps that suggest the network is looking at intrapapillary capillary loop patterns when predicting abnormality. CONCLUSION: We believe that this dataset and baseline method may serve as a reference for future benchmarks on both video frame classification and explainability in the context of ESCN detection. A future work path of high clinical relevance is the extension of the classification to ESCN types.

Utility of Likert scale (Deauville criteria) in assessment of Chemoradiotherapy response of primary oropharyngeal squamous cell Cancer site.

INTRODUCTION: The aim of this study is to determine whether Likert scale (Deauville criteria) can be used to classify oropharyngeal squamous cell cancer (OPSCC) patients as 'responders' and 'nonresponders' by utilizing FDG-PET/CT for primary tumor site. The second aim is to compare the performance of methods used in interpretation of posttreatment PET/CT scans (Likert scale, SUVmax, ratios of SUVmax primary lesion to mediastinum 'SUVmax P/M' and SUVmax primary lesion to liver 'SUVmax P/L') in predicting treatment response. METHODS: Seventy-seven PET/CT scans were assessed by Deauville criteria, five-point Likert scale. SUVmax of primary lesion, SUVmax primary to mediastinum and SUVmax primary to liver ratios on first follow-up PET/CT were measured and calculated. Pathology results, clinical and imaging follow-up were used as standart reference. RESULTS: Sensitivity, specificity, positive predictive and negative predictive value of Likert scale were found to be 80%, 89.5%, 53.3% and 96.8% respectively. When Likert scale and PET parameters were compared, no statistically significant difference was found. Receiver operating characteristic (ROC) was used to determine the optimal cut-off points for SUVmax (found as 4) and for ratios (SUVmax P/M = 1.67and SUVmax P/L = 1.7) with the highest specificity and NPV. CONCLUSION: Likert scale adequately categorize patients as 'responders' and 'non-responders'. Since its NPV is high and interpretation is relatively easy, it can be utilized to evaluate OPSCC response to treatment in first follow up FDG PET/CT.

Diagnostic accuracy of F-18 FDG PET or PET/CT for detection of lymph node metastasis in clinically node negative head and neck cancer patients; A systematic review and meta-analysis.

OBJECTIVE: The purpose of the current study was to investigate the diagnostic performance of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) or positron emission tomography/computed tomography (PET/CT) for the detection of cervical lymph node (LN) metastasis in clinically node negative head and neck squamous cell cancer (cN0 HNSCC) patients through a systematic review and meta-analysis. METHODS: The PubMed and EMBASE database, from the earliest available date of indexing through April 30, 2018, were searched for studies evaluating the diagnostic performance of F-18 FDG PET or PET/CT for the detection of LN metastasis in cN0 HNSCC patients. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic (SROC) curves. RESULTS: Across 18 studies (1044 patients), the pooled sensitivity for F-18 FDG PET or PET/CT for the detection of LN metastasis was 0.58 and a pooled specificity of 0.87 for patient based analysis. Neck side based analysis showed the pooled sensitivity of 0.67 and a pooled specificity of 0.85. Level based study demonstrated the pooled sensitivity of 0.53 and a pooled specificity of 0.97 (95% CI; 0.95-0.98). In meta-regression analysis, no definite variable was the source of the study heterogeneity. CONCLUSION: The current meta-analysis showed the low sensitivity and moderate specificity of F-18 FDG PET/CT for the detection of cervical LN metastasis in cN0 HNSCC patients. Level based analysis of F-18 FDG PET or PET/CT has a high specificity and NPV for the detection of cervical metastatic LN detection.

Usability of Transthoracic Shear Wave Elastography in Differentiation of Subpleural Solid Masses.

In this study, the effectiveness of transthoracic ultrasound elastography in the benign and malign distinction of subpleural/pleural solid lesions was investigated.Between July 2015 and December 2016, 33 consecutive patients with subpleural solid lesions detected via computed tomography (CT) of the thorax were identified and prospectively included in this study. The average for each lesion's shear wave velocity (SWV) value was detected, and benign and malignant lesions' SWV values are statistically compared. The CT and pathology results were used as a reference to compare these values. A receiver operating characteristic analysis was used to determine the cutoff value for benign/malignant neoplasms.The 33 patients (10 female, 23 male) included in the study had a mean age of 56.2 ± 15.40 years (range, 17-84 years), and the mean SWV value of the lesions in 13 (39%) cases evaluated benign after a CT scan, histopathological examination, or both 2.18 ± 0.49 m/s. The mean SWV value of the lesions which were histopathologically diagnosed as malign in 23 (61%) cases was 3.50 ± 0.69 m/s. (P < 0.001). When the cutoff value was set as 2.47 m/s for the SVW value, sensitivity and specificity were determined to be 97.7%.The present study has shown that transthoracic ultrasound shear wave elastography can be an effective radiological examination method in the benign and malign differentiation of subpleural lesions and has the potential for use in the routine clinical application of transthoracic ultrasound elastography, a noninvasive method for evaluating the malignancy potentials of such lesions.

NIR photo-driven upconversion in NaYF4:Yb,Er/PLGA particles for in vitro bioimaging of cancer cells.

Lanthanide-doped fluoride up-converting nanoparticles (UCNPs) represent the new class of imaging contrast agents which hold great potential for overcoming existing problems associated with traditionally used dyes, proteins and quantum dots. In this study, a new kind of hybrid NaYF4:Yb,Er/PLGA nanoparticles for efficient biolabeling were prepared through one-pot solvothermal synthesis route. Morphological and structural characteristics of the as-designed particles were obtained using X-ray powder diffraction (XRPD), scanning and transmission electron microscopy (SEM/TEM), energy dispersive spectroscopy (EDS), Fourier transform infrared (FTIR) and photoluminescence (PL) spectroscopy, while their cytotoxicity as well as up-conversion (UC) labeling capability were tested in vitro toward human gingival cells (HGC) and oral squamous cell carcinoma (OSCC). The results revealed coexistence of the cubic (Fm-3m) and hexagonal (P63/m) phase in spherical and irregularly shaped nanoparticles, respectively. PLGA [Poly(lactic-co-glycolic acid)] ligands attached at the surface of UCNPs particles provide their enhanced cellular uptake and enable high-quality cells imaging through a near-infrared (NIR) laser scanning microscopy (λex = 980 nm). Moreover, the fact that NaYF4:Yb,Er/PLGA UCNPs show low cytotoxicity against HGC over the whole concentration range (10-50 µg/mL) while a dose dependent viability of OSCC is obtained indicates that these might be a promising candidates for targeted cancer cell therapy.

Lymphoepithelial carcinoma of the maxillary sinus: A case report and review of the literature.

RATIONALE: Most cases of lymphoepithelial carcinoma (LEC) occur in the nasopharynx, and LEC in the sinonasal tract is extremely rare; thus, the clinical characteristics of sinonasal LEC are not well known. PATIENT CONCERNS: A 63-year-old Japanese man presented with a three-week history of left cheek pain, nasal obstruction and cheek swelling. DIAGNOSES: Enhanced CT and MRI revealed a tumor of the left maxillary sinus that invaded the left orbit and hard palate, with multiple swollen left cervical lymph nodes. Open biopsy was performed, and the specimen was diagnosed as LEC. INTERVENTIONS: Alternating chemoradiotherapy (ALCRT) followed by salvage surgery was performed. OUTCOMES: Our patient has been disease free for 5 years. LESSONS: A literature review of the epidemiology, etiology, clinical course and management of sinonasal LEC is highlighted. We believe ALCRT followed by salvage surgery to be a highly optimal treatment for sinonasal LEC from the viewpoint of a balance between quality of life and a high curative effect.

Prospective evaluation of relationships between radiotherapy dose to masticatory apparatus and trismus.

AIMS: This feasibility study aimed to identify relationships between radiation doses to the masticatory apparatus as a combined block or as individual subunits with changes in trismus following radiotherapy. MATERIAL AND METHODS: Twenty patients from a single center were recruited prospectively as part of a randomized trial comparing proactive exercises in the management of trismus. Patients with stage III/IV oral cavity or oropharyngeal squamous cell cancers received intensity-modulated radiotherapy with concurrent systemic therapy. All patients had trismus prior to radiotherapy. Maximal inter-incisor distance (MID) was measured pre- and 6 months from the start of radiotherapy. Bilateral muscles of mastication: medial and lateral pterygoids (MP and LP), masseters (M), temporalis (T), temporomandibular joint (TMJ) were contoured on CT images. The block comprised all muscles excluding the TMJ below the orbital floor. Mean dose, equivalent uniform dose (EUD) and V35-V60 Gy were compared with change in MID. RESULTS: In six patients, the MID deteriorated at 6 months from the start of radiotherapy compared with 14 whose MID improved. No significant association was observed between age, gender, smoking, alcohol status, exercise compliance, cisplatin, tumor site, stage, V35-V60 Gy or EUD with change in MID. A clinical outlier was excluded. Without the outlier (n = 19), a significant association was seen between mean dose and change in MID at 6 months for the ipsilateral block (p = .01), LP (p = .04) and M (p < .01). All patients where trismus deteriorated at 6 months received mean doses >40 Gy to the block. CONCLUSION: Higher mean radiation doses to the ipsilateral block, LP and M were significantly associated with deterioration in trismus. Limiting dose to these structures to ≤40 Gy for tumors not invading the masticatory muscles may improve treatment-related sequelae. The ipsilateral block, LP and M should be studied further as possible alternative avoidance structures in radiotherapy treatment planning.

Positron Emission Tomographic Imaging Elucidates the Complex Relationship Between Glucose Uptake and Tissue Blood Flow Mechanism in Squamous Cell Oral Cancer Patients.

BACKGROUND Through the clinical use of positron emission tomography, we aimed to elucidate the complex relationship between glucose uptake and squamous cell oral cancer (ScOC) growth, along with its mechanism with respect to tissue blood flow (tBF). MATERIAL AND METHODS We retrospectively reviewed a total of 69 newly diagnosed ScOC patients by Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). Maximum and mean standard uptake values (SUV↑ and SUV) were recorded to assess glucose uptake. Multi-shot spin-echo echo-planar imaging-based pseudo-continuous arterial spin labeling (pcASL) technique at 3.0 T MRI was used to obtain tBF values in ScOC (tBF-ScOC). Patients were divided according to T-stage and location. Pearson's correlation coefficients were calculated between both SUV and tBF-ScOC for significant correlations. RESULTS Forty-one (59.4%) patients had oropharynx and the other 28 (40.6%) patients had laryngopharynx. Significant positive correlations were detected between SUV↑, SUV, tBF-ScOC and non-advanced T-stage (T1a, T1b, T2 and T3), while a negative correlation was observed in the advanced T-stage (T4a and T4b). CONCLUSIONS Using PET imaging, we established the relationship between glucose uptake and ScOC growth on the basis of the division of T-stage and tumor location of ScOC, thereby elucidating the underlying mechanism. Our findings provide insights important to the diagnosis, treatment, and care of ScOC patients.

Matching the reaction-diffusion simulation to dynamic [18F]FMISO PET measurements in tumors: extension to a flow-limited oxygen-dependent model.

Positron-emission tomography (PET) with hypoxia specific tracers provides a noninvasive method to assess the tumor oxygenation status. Reaction-diffusion models have advantages in revealing the quantitative relation between in vivo imaging and the tumor microenvironment. However, there is no quantitative comparison of the simulation results with the real PET measurements yet. The lack of experimental support hampers further applications of computational simulation models. This study aims to compare the simulation results with a preclinical [18F]FMISO PET study and to optimize the reaction-diffusion model accordingly. Nude mice with xenografted human squamous cell carcinomas (CAL33) were investigated with a 2 h dynamic [18F]FMISO PET followed by immunofluorescence staining using the hypoxia marker pimonidazole and the endothelium marker CD 31. A large data pool of tumor time-activity curves (TAC) was simulated for each mouse by feeding the arterial input function (AIF) extracted from experiments into the model with different configurations of the tumor microenvironment. A measured TAC was considered to match a simulated TAC when the difference metric was below a certain, noise-dependent threshold. As an extension to the well-established Kelly model, a flow-limited oxygen-dependent (FLOD) model was developed to improve the matching between measurements and simulations. The matching rate between the simulated TACs of the Kelly model and the mouse PET data ranged from 0 to 28.1% (on average 9.8%). By modifying the Kelly model to an FLOD model, the matching rate between the simulation and the PET measurements could be improved to 41.2-84.8% (on average 64.4%). Using a simulation data pool and a matching strategy, we were able to compare the simulated temporal course of dynamic PET with in vivo measurements. By modifying the Kelly model to a FLOD model, the computational simulation was able to approach the dynamic [18F]FMISO measurements in the investigated tumors.

Profile of apoptotic proteins in oral squamous cell carcinoma: A cluster analysis of 171 cases

Oral squamous cell carcinoma (OSCC) is the eighth most prevalent cancer worldwide. In recent large-scale studies, by immunohistochemistry and cluster analysis, several markers were associated with patient survival in various tumors. The aim of this study was to analyze the expression profiles of 23 proteins that have been linked to the inhibition (Bcl-2, Bcl-x, Bcl-xL, Bcl-2-related protein A1, BAG-1, and survivin) and promotion (Bak, Bax, Bim/Bod, Bim-Long, Bad, Bid, PUMA, Apaf-1, caspase-2, caspase-3, caspase-6, caspase-7, caspase-8, caspase-9, caspase-10, Smac/DIABLO, and cytochrome c) of apoptosis in OSCC. METHODS: Two-hundred and twenty nine cases of OSCC, arranged in a tissue microarray, were immunohistochemically analyzed, and the results were quantified on an automated imaging system. The data were analyzed using a random forest clustering method. RESULTS: Overall protein expression patterns defined two chief clusters: an anti-apoptotic cluster (142 cases) and a pro-apoptotic cluster (29 cases). These groups could not be explained by any clinical or pathological characteristic, and overall and disease-free survival did not differ between them. CONCLUSIONS: Although there was no association with survival, the cluster analysis demonstrated specific protein profiles that could be of interest for using targeted therapies: in one of the clusters, the expression of pro-apoptotic proteins was more prominent, demonstrating a pro-apoptotic profile and highlighting the importance of apoptosis during OSCC development.

Long Term Outcome of Routine Image-enhanced Endoscopy in Newly Diagnosed Head and Neck Cancer: a Prospective Study of 145 Patients.

Synchronous second primary tumors (SPTs), especially esophageal squamous cell neoplasia (ESCN), in patients with head and neck squamous cell carcinoma (HNSCC) are not uncommon. Image-enhanced endoscopy (IEE) screening may identify SPTs while there is no evidence to support its benefit. We prospectively recruited an adult cohort with newly-diagnosed HNSCC for IEE screening of upper gastrointestinal (UGI) tract neoplasia. 145 HNSCC patients were recruited. 22 (15.2%) patients had synchronous UGI tract neoplasia, including 20 ESCNs and 2 gastric adenocarcinoma. At a median follow-up of 2.72 (±1.73) years, the 3-year overall survival (OS) rate was 0.71. HNSCC patients with synchronous ESCN/UGI tract neoplasia had poorer prognosis than those without (multivariate analysis, hazard ratio [HR] 2.75/2.79, 95% confidence interval [CI] 1.11~6.82/1.15~6.80, p = 0.03/0.02). HNSCC patients with advanced (stage III&IV) ESCN had worst survivals (p < 0.001). Among those with synchronous ESCNs, hypopharyngeal cancers were associated with poorer prognosis when compared with oral cancers (HR 2.36, 95% CI 1.08~5.15, p = 0.03). IEE screening for UGI SPTs in HNSCC patients could be used for risk stratification and prognosis prediction. HNSCC patients with advanced ESCN had the worst prognosis. Further studies are needed to demonstrate the survival benefits from IEE screening.

Eczema as the first manifestation of a lung cancer.

Lung cancer combined with eczema is a rare disease. We report a case of 58-year-old man with eczema as the first manifestation of a lung cancer. Skin examination revealed diffuse erythema, dander, itchy rash, and scratch. Chest contrast-enhanced computed tomography showed a heterogeneously enhanced irregular mass in the right lung. Punch biopsy of the tumor confirms squamous cell lung cancer. Eczema vanished nearly completely after one cycle of chemotherapy.

In Vivo Correlation of Glucose Metabolism, Cell Density and Microcirculatory Parameters in Patients with Head and Neck Cancer: Initial Results Using Simultaneous PET/MRI.

OBJECTIVE: To demonstrate the feasibility of simultaneous acquisition of 18F-FDG-PET, diffusion-weighted imaging (DWI) and T1-weighted dynamic contrast-enhanced MRI (T1w-DCE) in an integrated simultaneous PET/MRI in patients with head and neck squamous cell cancer (HNSCC) and to investigate possible correlations between these parameters. METHODS: 17 patients that had given informed consent (15 male, 2 female) with biopsy-proven HNSCC underwent simultaneous 18F-FDG-PET/MRI including DWI and T1w-DCE. SUVmax, SUVmean, ADCmean, ADCmin and Ktrans, kep and ve were measured for each tumour and correlated using Spearman's ρ. RESULTS: Significant correlations were observed between SUVmean and Ktrans (ρ = 0.43; p ≤ 0.05); SUVmean and kep (ρ = 0.44; p ≤ 0.05); Ktrans and kep (ρ = 0.53; p ≤ 0.05); and between kep and ve (ρ = -0.74; p ≤ 0.01). There was a trend towards statistical significance when correlating SUVmax and ADCmin (ρ = -0.35; p = 0.08); SUVmax and Ktrans (ρ = 0.37; p = 0.07); SUVmax and kep (ρ = 0.39; p = 0.06); and ADCmean and ve (ρ = 0.4; p = 0.06). CONCLUSION: Simultaneous 18F-FDG-PET/MRI including DWI and T1w-DCE in patients with HNSCC is feasible and allows depiction of complex interactions between glucose metabolism, microcirculatory parameters and cellular density.

FDG PET/CT for Management and Assessing Outcomes of Squamous Cell Cancer of the Oral Cavity.

OBJECTIVE: FDG PET/CT has excellent diagnostic accuracy for detecting locoregional nodal and distant metastases, can be used to assess therapeutic response, and provides valuable information about prognosis in patients with oral cavity cancer. The aim of this article is to summarize the value of FDG PET/CT in the treatment of patients with squamous cell cancer of the oral cavity. CONCLUSION: FDG PET/CT is a valuable imaging study in the management of oral squamous cell cancer and in predicting patient outcome.

Ketoacidosis in a patient with type 2 diabetes - flatbush diabetes.

There is increasing recognition of a group of patients with type 2 diabetes who can present with ketoacidosis. Most reports have been of patients of African descent; however, the condition has been reported in other groups. This is a case of a Caucasian patient who has had three presentations with ketoacidosis and whose diabetes is not usually insulin-dependent.

Radiation treatment for newly diagnosed esophageal cancer with prior radiation to the thoracic cavity.

The purpose of this report is to communicate the use of single-positron emission computed tomography scan in planning radiation treatments for patients with a history of radiation to the thoracic cavity. A patient presented with obstructive esophageal cancer, having previously received chemotherapy and radiation therapy to the mediastinum for non-Hodgkin lymphoma 11 years earlier. Owing to a number of comorbidities, the patient was not a surgical candidate and was referred to the University of Washington Medical Center for radiation therapy. Prior dose to the spinal cord and lung were taken into account before designing the radiation treatment plan.