Nodal Volume Research Articles

Antitumor efficiency of combination of bortezomib and themosolomide on subcutaneous PDX-model of human glioblastoma.

e15011 Background: Poor clinical effects of standard treatment for glioblastoma determine the need for the development of new therapeutic strategies. Aberrant functioning of the proteasome system, as well as activation of the HIF-1α signaling pathway, are characteristic of glial tumor cells; they can be considered as potential therapeutic targets in the treatment of malignant brain tumors. One of the possible options for improving the results of glioblastoma treatment may involve strategies for inhibiting the HIF-1α pathway. Bortezomib, a proteasome inhibitor, can block the biological effects of HIF-1α. Bortezomib showed a pronounced antitumor effect in in vitro testing on various models of solid malignant tumors, giving grounds for further studies of its effectiveness in vivo. Patient-derived xenograft (PDX) models are characterized by a variety of cell subclones and are therefore considered the most reliable tool for predicting therapeutic responses. Methods: A PDX model of glioblastoma was created in 20 Balb/c Nude mice implanted with a subcutaneously inoculated human glioblastoma. Temozolomide (0.5 mg/kg), bortezomib (0.25 mg/kg), or a combination of temozolomide and bortezomib were administered intraperitoneally daily for 21 days. The tumor histotype was confirmed by histological analysis (staining with hematoxylin and eosin). The antitumor effect was determined by the inhibition of tumor growth (ITG%), the volume of tumor nodes, and the index of tumor growth. Results: The highest value of the inhibition of tumor growth (ITG%) was registered in the group of animals receiving a combination of temozolomide and bortezomib – 85.38%. The values in the groups receiving temozolomide or bortezomib monotherapy were 57.32% and 63.11%, respectively. Conclusions: An analysis of the antitumor efficacy of bortezomib combined with temozolomide in human subcutaneous PDX-glioblastomas demonstrated their synergistic effect.

MRI in head and neck cancer following chemoradiotherapy: what is the optimal delay to demonstrate maximal response?

ObjectivesTo investigate the optimal timing for post-chemoradiotherapy (CRT) reference magnetic resonance imaging (MRI) in head and neck cancer, so as to demonstrate a maximal treatment response. To assess whether this differs in human papillomavirus–related oropharyngeal cancer (HPV-OPC) and whether the MRI timing impacts on the ability to predict treatment success.MethodsFollowing ethical approval and informed consent, 45 patients (40 male, mean age 59.7 ± 7.9 years, 33 HPV-OPC) with stage 3 and 4 HNSCC underwent pre-treatment, 6- and 12-week post-CRT MRIs in this prospective cohort study. Primary tumour (n = 39) size, T2w morphology and diffusion weight imaging (DWI) scores, together with nodal (n = 42) size and necrotic/cystic change, were recorded. Interval imaging changes were analysed for all patients and according to HPV-OPC status. MRI descriptors and their interval changes were also compared with 2-year progression-free survival (PFS).ResultsAll MRI descriptors significantly changed between pre-treatment and 6-week post-treatment MRI studies (p < .001). Primary tumour and nodal volume decreased between 6- and 12-week studies; however, interval changes in linear dimensions were only evident for HPV-OPC lymph nodes. Nodal necrosis scores also evolved after 6 weeks but other descriptors were stable. The 6-week nodal necrosis score and the 6- and 12-week nodal volume were predictive of 2-year PFS.ConclusionApart from HPV-OPC patients with nodal disease, the 6-week post-CRT MRI demonstrates maximal reduction in the linear dimensions of head and neck cancer; however, a later reference study should be considered if volumetric analysis is applied.Key Points• This study provides guidance on when early post-treatment imaging should be performed in head and neck cancer following chemoradiotherapy, in order to aid subsequent detection of recurrent tumour.• Lymph nodes in HPV-related oropharyngeal cancer patients clearly reduced in size from 6 to 12 weeks post-treatment. However, other lymph node disease and all primary tumours showed only a minor reduction in size beyond 6 weeks, and this required a detailed volumetric analysis for demonstration.• Timing of the reference MRI following chemoradiotherapy for head and neck cancer depends on whether the patient has HPV-related oropharyngeal cancer and whether there is nodal disease. MRI as early as 6 weeks post-treatment may be performed unless volumetric analysis is routinely performed.

Radiofrequency Ablation for Cervical Metastatic Lymph Nodes in Children and Adolescents With Papillary Thyroid Carcinoma: A Preliminary Study

ObjectiveTo evaluate the safety and efficacy of radiofrequency ablation (RFA) for metastatic lymph nodes (LNs) in children and adolescents with papillary Thyroid Carcinoma (PTC).Materials and MethodsFrom December 2014 to March 2018, 10 metastatic LNs(mean volume 0.30 ± 0.38 ml, range 0.06-1.23ml) in 5 children and adolescents (3 females, 2 males; mean age 15.60 ± 2.97 years, range 12-19 years) with PTC treated by RFA were evaluated in this study. The mean number of surgical procedures performed before RFA was 1.2 (range 1-2) and the mean number of treated metastatic LNs per patient was 2 (rang 1-3). RFA was performed with an 18–gauge bipolar RF applicator under local anesthesia. Follow-up consisted of US and serum thyroglobulin (Tg) level at 1, 3, 6, 12 months and every 12 months thereafter.ResultsAll the patients were well tolerant to RFA procedure and no procedure-related complications occurred. During a mean follow-up time of 52.00 ± 21.44 months, the initial volume of LNs was 0.30 ± 0.38 ml, which significantly decreased to 0.01 ± 0.03 ml (P = 0.005) with a mean VRR of 99.28 ± 2.27%. A total of 9 metastatic LNs (90.00%) completely disappeared. After RFA, 2 patients developed newly metastases. One patient had additional RFA. The other one with multiple LN metastases underwent total thyroidectomy with central neck dissection.ConclusionAs a less invasive and effective technique, RFA may provide another alternative to the existing therapeutic modalities for cervical metastatic LNs in children and adolescents with PTC.

High dose simultaneous integrated boost for node positive cervical cancer

IntroductionLymph node metastases presenting with locally advanced cervical cancer are poor prognostic features. Modern radiotherapy approaches enable dose escalation to radiologically abnormal nodes. This study reports the results of a policy of a simultaneous integrated boost (SIB) in terms of treatment outcomes.Materials and methodsPatients treated with radical chemoradiation with weekly cisplatin for locally advanced cervical cancer including an SIB to radiologically abnormal lymph nodes were analysed. All patients received a dose of 45 Gy in 25 fractions and a SIB dose of 60 Gy in 25 fractions using intensity modulated radiotherapy/volumetric modulated arc therapy, followed by high dose rate brachytherapy of 28 Gy in 4 fractions. A control cohort with radiologically negative lymph nodes was used to compare impact of the SIB in node positive patients. Treatment outcomes were measured by overall survival (OS), post treatment tumour response and toxicities. The tumour response was based on cross sectional imaging at 3 and 12 months and recorded as local recurrence free survival (LRFS), regional recurrence free survival (RRFS) and distant recurrence free survival (DRFS).ResultsIn between January 2015 and June 2017, a total of 69 patients with a median follow up of 30.9 months (23 SIB patients and 46 control patients) were identified. The complete response rate at 3 months was 100% in the primary tumour and 83% in the nodal volume receiving SIB. The OS, LRFS, RRFS and DRFS at 3 years of the SIB cohort were 69%, 91%, 79% and 77% respectively. High doses can be delivered to regional pelvic lymph nodes using SIB without excessive toxicity.ConclusionUsing a SIB, a total dose of 60 Gy in 25 fractions chemoradiation can be delivered to radiologically abnormal pelvic nodes with no increase in toxicity compared to node negative patients. The adverse impact of positive nodal status may be negated by high dose deposition using SIB, but larger prospective studies are required to confirm this observation.

SERBEST DİSPLEYSIRLI BİR STİRLİNG MOTORUNUN NODAL TERMODİNAMİK VE DİNAMİK ANALİZİ

In this study, the dynamic and thermodynamic features of free displacer Stirling engines were investigated by preparing a simulation program. The dynamic component of the simulation program involves the movement equations of power piston, crankshaft and displacer. The thermodynamic component is a nodal analysis based on 24 nodal volumes. The study indicates that starting these engines requires an initial speed is required as the displacer system natural frequency. While the engine is running, the displacer exhibits some secondary vibrations (named as beatings) and causes irregularities in its work and power generation however, it can be minimized by changing some working parameters such as displacer mass, working fluid mass, external loading, spring constant etc. For each value of the working fluid charging pressure, a different spring is needed. While the spring constant is the same, the displacer mass can vary in a limited range. The thermal performance of the engine increases as the displacer mass is decreasing. For an engine working between 1000 K heater temperature, 356 K cooler temperature and 18 bar charging pressure, the effective thermal efficiency ranges between 21 and 26 %. An engine with a 3.5 liter total inner volume is capable of generating about 3.9 kW effective power and 4.7 kW indicated power. A strong relation is observed between engine performance and phase angle.

Mapping of Cervical and Upper Mediastinal Lymph Node Recurrence for Guiding Clinical Target Delineation of Postoperative Radiotherapy in Thoracic Esophageal Squamous Cell Carcinoma.

BackgroundThe lower neck and upper mediastinum are the major regions for postoperative radiotherapy (PORT) in thoracic esophageal squamous cell carcinoma (TESCC). However, there is no uniform standard regarding the delineation of nodal clinical target volume (CTVnd). This study aimed to map the recurrent lymph nodes in the cervical and upper mediastinal regions and explore a reasonable CTVnd for PORT in TESCC.MethodsWe retrospectively reviewed patients in our hospital with first cervical and/or upper mediastinal lymph node recurrence (LNR) after upfront esophagectomy. All of these recurrent lymph nodes were plotted on template computed tomography (CT) images with reference to surrounding structures. The recurrence frequency at different stations was investigated and the anatomic distribution of recurrent lymph nodes was analyzed.ResultsA total of 119 patients with 215 recurrent lymph nodes were identified. There were 47 (39.5%) patients with cervical LNR and 102 (85.7%) patients with upper mediastinal LNR. The high-risk regions were station 101L/R, station 104L/R, station 106recL/R, station 105 and station 106pre for upper TESCC and station 104L/R, station 106recL/R, station 105, station 106pre and station 106tbL for middle and lower TESCCs. LNR in the external group of station 104L/R was not common, and LNR was not found in the narrow spaces where the trachea was in close contact with the innominate artery, aortic arch and mediastinal pleura. LNR below the level of the cephalic margin of the superior vena cava was also not common for upper TESCC.ConclusionsThe CTVnd of PORT in the cervical and upper mediastinal regions should cover station 101L/R, station 104L/R, station 106recL/R, station 105 and station 106pre for upper TESCC and station 104L/R, station 106recL/R, station 105, station 106pre and station 106tbL for middle and lower TESCCs. Based on our results, we proposed a useful atlas for guiding the delineation of CTVnd in TESCC.

Unilateral versus bilateral nodal irradiation: Current evidence in the treatment of squamous cell carcinoma of the head and neck.

Cancers of the head and neck region often present with nodal involvement. There is a long-standing convention within the community of head and neck radiation oncology to irradiate both sides of the neck electively in almost all cases to include both macroscopic and microscopic disease extension (so called elective nodal volume). International guidelines for the selection and delineation of the elective lymph nodes were published in the early 2000s and were updated recently. However, diagnostic imaging techniques have improved the accuracy and reliability of nodal staging and as a result, small metastases that used to remain undetected and were thus in the past included in the elective nodal volume, will now be included in high-dose volumes. Furthermore, the elective nodal areas are situated close to the parotid glands, the submandibular glands and the swallowing muscles. Therefore, irradiation of a smaller, more selected volume of the elective nodes could reduce treatment-related toxicity. Several researchers consider the current bilateral elective neck irradiation strategies an overtreatment and show growing interest in a unilateral nodal irradiation in selected patients. The aim of this article is to give an overview of the current evidence about the indications and benefits of unilateral nodal irradiation and the use of SPECT/CT-guided nodal irradiation in squamous cell carcinomas of the head and neck.

The effect of aсtive hexose correlated compound on (multi) nodular euthyroid goiter: A double-blind placebo-controlled study

Aim: of the study is to evaluate the effectiveness of Аctive Hexose Correlated Compound (АНСС®) use in monotherapy and its impact on the echographic characteristics of the thyroid gland during (multi) nodular goiter. Methods: The study involved 27 people with (multi) nodular euthyroid goiter. The main treatment group consisted of 13 patients who received АНСС®. The placebo control group consisted of 14 participants. The duration of the drug intake lasted for 100 days. Three visiting schedules were arranged including initial, intermediate and final visits. Research methods included clinical examinations, laboratory tests, a thyroid ultrasound (classification by K-TIRADS) and completing a questionnaire. Results: The laboratory tests confirmed the euthyroid status of patients in both groups at baseline and at the end of the study. A decrease in the total volume of the right and left lobes of the thyroid gland was noted among the main treatment group. In addition, a decrease in the volume of all types of nodules was seen in this group. A decrease in the volume of the type 2 colloid node was statistically significant. On the contrary, a statistically significant increase in the average volume of the same type of node among the control group was seen. Overall, the average volume of the node decreased by 37.2% in the main group and increased by 4.9% in the control group by the end of the study. Conclusion: The results of this double-blind, placebo-controlled study make it possible to assess the efficiency of АНСС® in (multi) nodular goiter affecting primarily the volume of nodes (mainly of the 2nd and 3rd types). This is especially important when a potential surgery or radioiodine therapy may carry a high risk of complications among patients.

Estimation of Genetic Parameters and Wood Yield Selection Index in a Clonal Trial of Korean Pine (Pinus koraiensis) in Northeastern China

In order to determine suitable traits for selecting high-wood-yield Korean pine materials, eleven morphological characteristics (tree height, basal diameter, diameter at breast height, diameter at 3 meter height, stem straightness degree, crown breadth, crown height, branch angle, branch number per node, bark thickness, and stem volume) were investigated in a 38-year-old Korean pine clonal trial at Naozhi orchard. A statistical approach combining variance and regression analysis was used to extract appropriate traits for selecting elite clones. Results of variance analysis showed significant difference in variance sources in most of the traits, except for the stem straightness degree, which had a p-value of 0.94. Moderate to high coefficients of variation and clonal repeatability ranged from 10.73% to 35.45% and from 0.06% to 0.78%, respectively. Strong significant correlations on the phenotypic and genotypic levels were observed between the straightness traits and tree volume, but crown breadth was weakly correlated to the volume. Four principal components retaining up to 80% of the total variation were extracted, and stem volume, basal diameter, diameter at breast height, diameter at 3 meter height, tree height, and crown height displayed high correlation to these components (r ranged from 0.76 to 0.98). Based on the Type III sum of squares, tree height, diameter at breast height, and branch number showed significant information to explain the clonal variability based on stem volume. Using the extracted characteristics as the selection index, six clones (PK105, PK59, PK104, PK36, PK28, and K101) displayed the highest Qi values, with a selection rate of 5% corresponding to the genetic gain of 42.96% in stem volume. This study provides beneficial information for the selection of multiple traits for genetically improved genotypes of Korean pine.

The impact of neck lymph node volumetric status on local control of the primary tumour (LTC) in radiotherapy for oral cavity and oropharyngeal cancer

The study analyses the impact of volumetric nodal involvement (total nodal volume – TNV) on local control of the primary tumour (LTC) in radiotherapy for oral cavity and oropharyngeal cancer. The results show a significant decrease of the LTC (within a constant GTV) by about 10–20%, when the TNV increases from 10 to 40 cm3. It suggests delivering an extra boost dose of 3–4 extra fractions of 2.0 Gy fractions to the primary tumour in the case of nodal involvement (initial total nodal volume).

Complete fully automatic segmentation and 3-dimensional measurement of mediastinal lymph nodes for a new response evaluation criteria for solid tumors

We aimed to automatically detect and segment mediastinal lymph nodes, and to establish an objective method and reliable new response evaluation criteria to monitor the effectiveness of cancer treatment. The image processing techniques were applied and developed 3D measurement of the mediastinal lymph nodes based on automatic settings when segmenting the lymph node image. A repeatable and consistent lymph node evaluation system was created based on such features as the position of occurrence, grayness, and number of serial sections of lymph nodes. A total of 200 lymph node samples from Tri-Service General Hospital, Taiwan, were examined for statistical analysis. The proposed approach used weighted k-nearest neighbors for classification, achieving superior results with an accuracy and specificity of 97.5% and 99.4%, respectively. The volume of the lymph nodes was used as the reference index for tumor invasiveness evaluation. The error in the lymph node volume was 1.71% according to the verification results. Receiver operating characteristic (ROC) curves for each analysis were constructed and the area under the curve (AUC) was calculated with histopathology diagnosis as outcome for determining the optimal volume threshold of benign and malignant lymph nodes. It was observed that the lymph node volume was highly correlated with tumor invasion (p-value was less than 0.05). The experiment showed that the volume for the area under the ROC curve was 0.90 of tumor invasion evaluation. The lymph node volume was most effective in predicting tumor invasiveness, with the value 798.53 mm3 used as the standard for judging benignity and malignancy.

Severe acute respiratory syndrome coronavirus 2 vaccination for patients with solid cancer: Review and point of view of a French oncology intergroup (GCO, TNCD, UNICANCER)

The impacts of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on cancer care are multiple, entailing a high risk of death from coronavirus disease 2019 (COVID-19) in patients with cancer treated by chemotherapy. SARS-CoV-2 vaccines represent an opportunity to decrease the rate of severe COVID-19 cases in patients with cancer and also to restore normal cancer care. Patients with cancer to be targeted for vaccination are difficult to define owing to the limited contribution of these patients in the phase III trials testing the different vaccines. It seems appropriate to vaccinate not only patients with cancer with ongoing treatment or with a treatment having been completed less than 3 years ago but also household and close contacts. High-risk patients with cancer who are candidates for priority access to vaccination are those treated by chemotherapy. The very high-priority population includes patients with curative treatment and palliative first- or second-line chemotherapy, as well as patients requiring surgery or radiotherapy involving a large volume of lung, lymph node and/or haematopoietic tissue. When possible, vaccination should be carried out before cancer treatment begins. SARS-CoV-2 vaccination can be performed during chemotherapy while avoiding periods of neutropenia and lymphopenia. For organisational reasons, vaccination should be performed in cancer care centres with messenger RNA vaccines (or non-replicating adenoviral vaccines in non-immunocompromised patients). Considering the current state of knowledge, the benefit-risk ratio strongly favours SARS-CoV-2 vaccination of all patients with cancer. To obtain more data concerning the safety and effectiveness of vaccines, it is necessary to implement cohorts of vaccinated patients with cancer.

Modeling zonal exchanges and nodal system representation in multi-zonal spot electricity markets

A novel model for the solution of the flow-based market coupling problem in multi-zonal spot electricity markets with zonal exchanges is presented in this paper. The problem considers a hybrid network configuration, i.e. a zonal market layer with zonal portfolio offers / bids submitted by the participants and zonal market clearing prices, and a nodal physical layer with nodal representation of the transmission system flows and relevant constraints. The model provides the optimal supply / demand cleared quantities and zonal exchanges, endogenously bounded by grid physical constraints, e.g. branch physical limits. The model retains the intuitiveness of the zonal exchanges, namely exchanges are cleared only from low-price zones to high-price zones. The model exhibits a dynamic/optimal allocation of zonal to nodal volumes. This market setup is fully compliant with the current market design in Europe, where portfolio participation in spot market with zonal prices, intuitive exchanges and with nodal flow-based constraints is the preferred scheme of the European Commission based on Regulation 2015/1222. The model is compared in terms of overall social welfare, pricing and cleared exchanges with the currently applied approach in Europe plus a “tuning” model for the simulation of redispatching to avoid congestion in physical branches.

Total metabolic lesion volume of lymph nodes measured by 18F-FDG PET/CT: a new predictor of macrophage activation syndrome in adult-onset Still\u2019s disease

BackgroundTo investigate the potential utility of quantitative parameters obtained by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the assessment of disease severity and the occurrence of macrophage activation syndrome (MAS) in adult-onset Still’s disease (AOSD).MethodsFifty-seven patients with AOSD who underwent pre-treatment 18F-FDG PET/CT were recruited in this study and compared with 60 age- and sex-matched healthy controls. Clinical features and laboratory data were recorded. The systemic score was assessed to determine the disease severity. The maximal standardized uptake value (SUVmax), metabolic lesion volume (MLV), and total lesion glycolysis (TLG) were used to evaluate the involved organs and tissues that abnormally accumulated 18F-FDG. Multivariate analysis was performed to identify the PET/CT-derived risk factors contributing to the AOSD-related MAS, and their diagnostic efficiency was evaluated.ResultsHigh 18F-FDG accumulation was observed in the bone marrow (SUVmax median, 5.10), spleen (SUVmax median, 3.70), and lymph nodes (LNs, SUVmax median, 5.55). The SUVmax of the bone marrow (rho = 0.376, p = 0.004), SUVmax of the spleen (rho = 0.450, p < 0.001), TLGtotal of LNs (rho = 0.386, p = 0.017), and MLVtotal of LNs (rho = 0.391, p = 0.015) were correlated with the systemic score. The SUVmax of the spleen (p = 0.017), TLGtotal of LNs (p = 0.045), and MLVtotal of LNs (p = 0.012) were higher in patients with MAS than in those without MAS. A MLVtotal of LNs > 62.2 (OR 27.375, p = 0.042) was an independent predictive factor for MAS with a sensitivity of 80.0% and a specificity of 93.9%.ConclusionsThe glucose metabolic level of the spleen could be an effective and easy-to-use imaging indicator of disease severity, and MLVtotal of LNs > 62.2 was a strong predictor of MAS occurrence in patients with AOSD.

Radiomic Model Predicts Lymph Node Response to Induction Chemotherapy in Locally Advanced Head and Neck Cancer

This study developed a pretreatment CT-based radiomic model of lymph node response to induction chemotherapy in locally advanced head and neck squamous cell carcinoma (HNSCC) patients. This was a single-center retrospective study of patients with locally advanced HPV+ HNSCC. Forty-one enlarged lymph nodes were found from 27 patients on pretreatment CT and were split into 3:1 training and testing cohorts. Ninety-three radiomic features were extracted. A radiomic model and a combined radiomic-clinical model predicting lymph node response to induction chemotherapy were developed using multivariable logistic regression. Median age was 57 years old, and 93% of patients were male. Post-treatment evaluation was 32 days after treatment, with a median reduction in lymph node volume of 66%. A three-feature radiomic model (minimum, skewness, and low gray level run emphasis) and a combined radiomic-clinical model were developed. The combined model performed the best, with AUC = 0.85 on the training cohort and AUC = 0.75 on the testing cohort. A pretreatment CT-based lymph node radiomic signature combined with clinical parameters was able to predict nodal response to induction chemotherapy for patients with locally advanced HNSCC.

Outcomes and Prognostic Factors of Salvage Radiation for Postoperative Lymph Node Recurrence of Esophageal Squamous Cell Carcinoma.

Purpose: Recurrence of esophageal squamous cell carcinoma (ESCC) in regional lymph nodes (LNs) after surgical section can be treated with salvage resection, radiotherapy (RT) or chemoradiotherapy (CRT). RT or CRT is more widely used in clinic. This paper investigates the effects, toxicities and prognostic risk factors of salvage RT or CRT on patients with LN recurrence.Methods: We retrospectively analyzed the clinical outcomes of 103 patients receiving salvage RT or CRT for LN recurrence after ESCC resection. In total, 39 patients received RT alone and 64 received concurrent CRT. All the patients received intensity modulated radiation therapy (IMRT), administered with a median dose of 62 Gy (range, 50–70 Gy).Results: The median follow-up time was 44.5 months, and median survival was 22.5 months (5.5–99.5 months). One-, 3-, and 5-year overall survival (OS) were 80.6, 37.0, and 25.8%, respectively. One- and 2-year progression free survival (PFS) were 57.3 and 34.0%, respectively. Grade 3 or above toxicity was low (16.5%) and no treatment-related deaths occurred. In univariate analysis of OS, pN0 (p = 0.039), smaller LN volume (≤25 cm3, p = 0.019), combined chemotherapy (p = 0.041) and single LN recurrence (p = 0.001) were associated with prolonged OS. And pT1-2 (p = 0.044), pN0 (p = 0.042), irradiation dose (>60 Gy, p = 0.044), combined chemotherapy (p = 0.019) and single LN recurrence (p = 0.002) were associated with prolonged PFS. In multivariate analysis, the patients with only one recurrent node had a significant better OS (HR = 0.556, 95% CI 0.324–0.956, p = 0.034) and PFS (HR = 0.528, 95% CI 0.339–0.847, p = 0.008).Conclusions: Salvage RT or CRT for regional LN recurrence is effective and acceptable. Fewer recurrent nodes may indicate a better long-term survival.

Epstein–Barr Virus (EBV) Viral Load in Tumor Cells Did Not Predict Tumor Extensiveness in Nasopharyngeal Cancer

Background: Nasopharyngeal cancer is commonly associated with Epstein–Barr virus (EBV) infection, especially undifferentiated non-keratinized histology. EBV DNA quantification through nasopharyngeal brushing was previously reported to be not related to disease stage. This study aimed to reinvestigate the relationship of EBV viral load in tumor tissue with tumor extensiveness by more accurate EBV DNA quantification through microscopically confirmed tumor cells from nasopharyngeal biopsy. Method: The specimens for EBV DNA quantification were derived from histopathology slides which were pre-treated following the QIAsymphony® SP protocol for tissue DNA extraction. Then, the extracted DNA underwent real-time polymerase chain reaction (RT-PCR) using the artus® EBV RG PCR Kit for EBV DNA quantification. The tumor volume was determined by delineating the gross tumor based on 3D imaging of the patient’s nasopharynx. Result: Twenty-four subjects were included in this study. All subjects were stage III and above, with more males (75%) than females. EBV viral load in tumor cells was found to have no correlation to tumor volume both in local and nodal regions. The median local tumor volume was 81.3 cm3 ± 80 cm3. The median EBV viral load in tumor cells was 95,644.8 ± 224,758.4 copies/100 ng of DNA. The median nodal or regional tumor volume was 35.7 ± 73.63 cm3. Conclusion: EBV viral load from tumor cells from nasopharyngeal biopsy has no relationship with tumor extensiveness in nasopharyngeal cancer. The presence and amount of EBV in tumor cells did not translate into larger or smaller tumors. The EBV viral proteins and RNAs were perhaps more likely to confer some prognostic information due to the fact that those molecules were related to carcinogenesis.

Effect of Selenium on Quantitative Structural Changes in Dexamethasone-Induced Immunodeficiency Rat Models.

Background: One of the major indices of immunodeficiency is lymphoid organ atrophy. Some trace elements are candidates for the treatment of this defect. These conditions may induce structural changes in the sub-components of lymphoid organs. Therefore, this study evaluated the effect of selenium on volumetric changes in dexamethasone (DEX)-induced lymphoid organ atrophy in an animal model.Methods:This study was conducted at Histomorphometry and Stereology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran, in September 2016 to September 2017. Thirty-two male rats were divided into four groups: Group I; control (normal saline, 0.5 mL/kg, intraperitoneally), Group II; DEX (0.4 mg/kg; intraperitoneally), Group III; selenium plus DEX (similar to Group II and Group IV), and Group IV; selenium (0.1 mg/kg; orally). At the end of the experiment, the rats’ thymus, spleen, and lymph nodes were removed, processed, and stained by hematoxylin and eosin (H&E). The volume and volume density of theses organs were estimated by stereology. The results were analyzed using the Mann–Whitney U-test and the Kruskal–Wallis test.Results: The volume of the thymus as well as its cortex and medulla; the volume of the spleen as well as the volume density of its white pulp, periarterial lymphatic sheath zone, and follicles; and the volume of the lymph nodes as well as their inner (P=0.001) and outer (P=0.007) cortices showed a significant reduction in the DEX-treated animals in comparison with the controls. In the DEX plus selenium-treated animals, maximum effects were observed on the increment in the thymic cortex (P=0.001), the outer cortex of the lymph nodes (P=0.012), and the splenic follicles (P=0.018) in comparison with the DEX group. There was no significant difference between the animals receiving selenium treatment and the controls in terms of lymphoid organs. Conclusion: Selenium may improve lymphoid organ structures in an immunodeficiency rat model but has no effect on normal lymphoid tissues.

Intraoperative Detection of Micrometastases in Whole Excised Lymph Nodes Using Fluorescent Paired-Agent Imaging Principles: Identification of a Suitable Staining and Rinsing Protocol.

Correctly identifying nodal status is recognized as a critical prognostic factor in many cancer types and is essential to guide adjuvant treatment. Currently, surgical removal of lymph nodes followed by pathological examination is commonly performed as a standard-of-care to detect node metastases. However, conventional pathology protocols are time-consuming, yet less than 1 % of lymph node volumes are examined, resulting in a 30-60 % rate of missed micrometastases (0.2-2 mm in size). This study presents a method to fluorescently stain excised lymph nodes using paired-agent molecular imaging principles, which entail co-administration of a molecular-targeted imaging agent with a suitable control (untargeted) agent, whereby any nonspecific retention of the targeted agent is accounted for by the signal from the control agent. Specifically, it was demonstrated that by dual-needle continuous infusion of either an antibody-based imaging agent pair (epidermal growth factor receptor (EGFR) targeted agent: IRDye-800CW labeled Cetuximab; control agent: IRDye-700DX-IgG) or an Affibody-based pair (EGFR targeted Affibody® agent: ABY-029; control agent IRDYe-700DX carboxylate) at 0.3 ml/min. The results demonstrated the possibility to achieve >99 % sensitivity and > 95 % specificity for detection of a single micrometastasis (~0.2 mm diameter) in a whole lymph node within 22 min of tissue processing time. The detection capabilities offer substantial improvements over existing intraoperative lymph node biopsy methods (e.g., frozen pathology has a micrometastasis sensitivity <20 %).

Long-term neck and shoulder function among survivors of oropharyngeal squamous cell carcinoma treated with chemoradiation as assessed with the neck dissection impairment index.

Of interest is the long-term neck and shoulder impairment of patients treated with primary chemoradiotherapy (CRT). This is important for counseling patients regarding treatment decisions when discussing primary CRT. A cross-sectional study to identify factors that contribute to neck and shoulder dysfunction in patients treated with primary CRT. We utilized the neck dissection impairment index (NDII). Eighty-seven patients treated between 2003 and 2010, who were free of disease, responded; 24 of these 87 underwent post-CRT neck dissection. Mean interval since completion of CRT was over 5 years (62.7 months). Mean age, 63.5 years, male:female 75:12. Mean NDII score was 87.4 (SD 22.1, range 5-100). Multiple linear regression revealed worse NDII scores for patients with larger pre-CRT gross tumor nodal volume (GTVnodal), controlled for age, sex, body mass index (BMI), and the presence of neck dissection (p = 0.02). There were significant associations with increasing GTVnodal and "low" scores for components of the NDII that assessed neck pain (p = 0.02), neck stiffness (p = 0.01), lifting heavy objects (p = 0.02), reaching overhead (p = 0.02), and ability to do work (p = 0.02). Physical therapy (PT) was evaluated as an "anchor" but it was prescribed "as needed." Regression revealed participation in PT was associated with higher GTVnodal, lower BMI, presence of neck dissection, and female sex (p = 0.00007). GTVnodal was an independent predictor of neck and shoulder impairment. High GTVnodal was associated with increased pain and stiffness, and increased difficulty lifting heavy objects, reaching overhead, overall ability to perform work-related tasks and was associated with participation in post-treatment PT.