Head Lymph Nodes Research Articles

Clinicoradiological and Histopathological Comparative Study of Nodal Metastasis in Head and Neck Cancers

Background: Detection of regional lymph nodes in head and neck cancers greatly modifies the staging, treatment and prognosis of the patient and helps in planning the management of these patients. Methods: A prospective study was conducted in the Department of E.N.T., S.M.G.S. Hospital, G.M.C. Jammu, in collaboration with the Department of Radio diagnosis and Imaging, G.M.C. Jammu & Department of Radiation Oncology GMC, Srinagar from 2008 to 2012 in which patients attending / admitted in the Department of E.N.T., with cancer of head and neck, were assessed for lymph node metastasis (at different levels). 16 patients, all cases of squamous cell carcinoma head and neck, underwent appropriate neck dissections. The patients were examined clinically as well as with ultrasonography for detection of various enlarged lymph nodes at different levels. Computed tomography and magnetic resonance imaging were done, wherever indicated. Patients were subjected to fine needle aspiration cytology in cases of palpable lymph nodes. The removed lymph nodes were examined histopathologically. Results: The findings of clinical, radiological and histopathological studies were compared. We concluded that clinical palpation should be supplemented by ultrasonography in every case of head and neck cancer. However, since computed tomography picks up lymph nodes missed by ultrasonography in a significant number, is important in imaging primary tumour and picks up necrosis and extracapsular spread at the most, it should be included in each case of head and neck cancer. Conclusion: Magnetic resonance imaging being equivalent to computed tomography in picking up the nodes, but lagging behind the criteria such as picking up of nodal necrosis and extra capsular spread of lymph nodes, and is too costly, so may be included as an imaging modality wherever computed tomography is contraindicated.

Potential Role of PET/MRI for Imaging Metastatic Lymph Nodes in Head and Neck Cancer.

This article explores recent developments in PET and MRI, separately or combined, for assessing metastatic lymph nodes in patients with head and neck cancer. The synergistic role of PET and MRI for imaging metastatic lymph nodes has not been fully explored. To facilitate the understanding of the areas that need further investigation, we discuss potential mechanisms and evidence reported so far, as well as future directions and challenges for continued development and clinical research.

Origin of cystic squamous cell carcinoma metastases in head and neck lymph nodes: Addition of EBV testing improves diagnostic accuracy

Most cases of cystic squamous cell carcinoma (SCC) metastases in the upper neck are associated with an oropharyngeal primary, namely human papillomavirus (HPV)-associated SCC arising in the palatine or lingual tonsil. A retrospective study was performed on 22 patients who presented with cystic head and neck SCC metastases. The purpose of the study was to find out whether histological characteristics, p16 protein expression, HPV and Epstein-Barr virus (EBV) status could be useful in predicting the localization of the primary tumor. The primary site was identified in 20 of 22 patients and included the oropharynx in 14 patients (63.6%), the nasopharynx in 3 patients (13.6%), the lungs in 2 cases (9%), and the skin of the auricle in one case (4.5%). No primary was found in two patients (9%). Sixteen of 17 cases (94.1%) originating in Waldayer’s ring (oropharynx and nasopharynx), and both cases with an unknown primary showed morphology of non-keratinizing SCC or non-keratinizing SCC with maturation. All tumors with oropharyngeal primary and both cases with unknown primary showed diffuse p16 staining and presence of HPV DNA. All three cystic metastases of nasopharyngeal carcinoma were EBV-positive and p16/HPV-negative. In contrast, cutaneous and pulmonary metastases showed morphology of a well differentiated keratinizing SCC and poorly differentiated keratinizing SCC, respectively, and were HPV/EBV-negative. We confirmed that cystic SCC lymph node metastases of the head and neck region are strongly associated with the occult primary localized in the oropharynx. The oropharyngeal origin should always be corroborated by p16 immunohistochemistry and HPV-specific testing because SCC arising in other sites, such as nasopharynx, skin or lungs may manifest with cystic neck metastases as well. Addition of EBV testing in p16/HPV-negative cases can disclose the nasopharyngeal origin of the cystic neck metastases in a subset of cases.

Distribution of CD4+CD8+ double positive T cells in a mouse model of allergic asthma.

The present study describes the distribution of CD4+CD8+ double-positive (DP) T cells in various immune compartments of mice with ovalbumin (OVA)-induced allergic asthma. It was found that the absolute number of DP T cells was considerably increased in the mediastinal lymph nodes and lungs of asthmatic mice as compared with that determined in the healthy subjects. On the contrary, the absolute counts of DP T cells was significantly decreased in the head and neck lymph nodes, and in peripheral blood of OVA-immunized mice. These results suggest that DP T cells may be involved in the pathogenesis of allergic asthma.

Relationship between the location of primary head & neck malignancy and lymph node ratio (LNR) in a contemporary series of patients with suspected nodal metastasis

Relationship between the location of primary head & neck malignancy and lymph node ratio (LNR) in a contemporary series of patients with suspected nodal metastasis

Shear Wave Elastography in Head and Neck Lymph Node Assessment: Image Quality and Diagnostic Impact Compared with B-Mode and Doppler Ultrasonography

The aim of this study was to assess the diagnostic performance of shear wave elastography (SWE) in comparison to B-mode and Doppler ultrasonography in differentiating benign from malignant head and neck lymph nodes (HNLNs). Sixty-two HNLNs from 56 patients were prospectively examined using B-mode, Doppler and SWE. The standard of reference was histopathology or cytology and follow-up. Qualitative malignant criteria (hilum infiltration, cortical hypo-echogenicity, irregular margins, abnormal vessels) were assessed on a five-point scale. Four quantitative parameters were obtained: long axis length, short axis length, short axis/long axis ratio, resistive index and maximum shear elasticity modulus (μmax). Diagnostic performance was analyzed with special emphasis on the sub-centimeter HNLN subgroup. Thirty HNLNs were malignant (48%). μmax intra-observer reproducibility was 0.899 (0.728 in sub-centimeter subgroup). Malignant HNLNs were stiffer (μmax = 72.4 ± 59.0 kPa) compared with benign nodes (μmax = 23.3 ± 25.3 kPa) (p < 0.001). Among the quantitative criteria, μmax had the highest diagnostic accuracy (area under the curve = 0.903 ± 0.042), especially in the sub-centimeter subgroup (area under the curve = 0.929 ± 0.045; p < 0.001) in which the area under the curve was significantly higher compared with the other quantitative criteria (p < 0.05). The additional use of SWE combined with B-mode tended to improve diagnostic accuracy (p > 0.05). SWE is a promising reproducible quantitative tool with which to predict malignant HNLNs, especially sub-centimeter nodes.

Individualized Super Selective Nodal Radiation Therapy for Clinically Negative Lymph Nodes (cN0) in Head and Neck Squamous Cell Carcinoma Patients Based on Sentinel Node(s) Identification: A Prospective Phase 2 Study of SPECT/CT-guided Volume De-escalation

Due to a risk of 18% to 45% of occult metastases among the clinically free of nodes head and neck squamous cell carcinoma (HNSCC) patients, prophylactic neck irradiation is often mandatory. Based on international guidelines for the selection of the neck node levels, this prophylactic treatment still leads to unnecessary large irradiation of normal tissues because bilateral drainage is the rule in only 30% to 50% of individuals, and 15% to 30% of the tumors drain in unpredicted nodal basins. Sentinel lymph node (SLN) single-photon emission computerized tomography (SPECT/CT) lymphoscintigraphy makes it possible to individually predict cervical subregions requiring prophylactic irradiation in cN0 patients. This ongoing prospective phase 2 study analyzes its oncological safety. Twenty-one patients with newly diagnosed cN0 SCC of the oral cavity, oropharynx, larynx, or hypopharynx were included. All patients were imaged with SPECT/CT after 99mTc nanocolloid injection around the tumor. The neck levels containing up to 4 hottest nodes were identified and selected for prophylactic irradiation (CTVn-LS) by volumetric modulated arc therapy. A comparative virtual planning was performed with volumes selected according to international guidelines (CTVn-IG). Migration was observed in all of the 21 patients (1 with gamma probe only) with an average of 2.7 sentinel nodes detected per patient. CTVn-LS was totally encompassed by CTVn-IG in all patients but 2 with an unpredicted drainage in retropharyngeal levels. On average, CTVn-LS and related planning target volume (PTV) were 2 times smaller than IG ones. This led to significant dose decrease in identified organs at risk as well as remaining volume at risk. With a median follow-up of 14 months, no regional relapse was observed, while 2 patients had a local one (9%). Currently, 3 patients have died (1 patient from geriatric degradation and 2 experienced fatal local relapse). SPECT/CT lymphoscintigraphy of SLN allows individualization of prophylactic node CTV in cN0 HNSCC patients eligible for definitive radiation therapy. Both CTV and PTV are significantly reduced, which results in a significant dose decrease in all identified organs at risk. At a median follow-up of 14 months, no regional relapse was observed, but further follow-up and recruitment are necessary to ensure the oncological safety.

Role of near-infrared fluorescence imaging in the resection of metastatic lymph nodes in an optimized orthotopic animal model of HNSCC

ObjectivesTo study the role of near-infrared fluorescence imaging in the detection and resection of metastatic cervical lymph nodes in head and neck cancer. Materials and methodsCAL33 head and neck cancer cells of human origin were implanted in the oral cavity of nude mice. The mice were followed up after tumor resection to detect the development of lymph node metastases. A specific fluorescent tracer for αvβ3 integrin expressed by CAL33 cells was injected intravenously in the surviving mice between the second and the fourth month following tumor resection. A near-infrared fluorescence-imaging camera was used to detect tracer uptake in metastatic cervical lymph nodes, to guide of lymph-node resection for histological analysis. ResultsLymph node metastases were observed in 42.8% of surviving mice between the second and the fourth month following orthotopic tumor resection. Near-infrared fluorescence imaging provided real-time intraoperative detection of clinical and subclinical lymph node metastases. These results were confirmed histologically. ConclusionNear infrared fluorescence imaging provides real-time contrast between normal and malignant tissue, allowing intraoperative detection of metastatic lymph nodes. This preclinical stage is essential before testing the technique in humans.

Accuracy of microRNAs as markers for the detection of neck lymph node metastases in patients with head and neck squamous cell carcinoma.

BackgroundThe presence of metastatic disease in cervical lymph nodes of head and neck squamous cell carcinoma (HNSCC) patients is a very important determinant in therapy choice and prognosis, with great impact in overall survival. Frequently, routine lymph node staging cannot detect occult metastases and the post-surgical histologic evaluation of resected lymph nodes is not sensitive in detecting small metastatic deposits. Molecular markers based on tissue-specific microRNA expression are alternative accurate diagnostic markers. Herein, we evaluated the feasibility of using the expression of microRNAs to detect metastatic cells in formalin-fixed paraffin-embedded (FFPE) lymph nodes and in fine-needle aspiration (FNA) biopsies of HNSCC patients.MethodsAn initial screening compared the expression of 667 microRNAs in a discovery set comprised by metastatic and non-metastatic lymph nodes from HNSCC patients. The most differentially expressed microRNAs were validated by qRT-PCR in two independent cohorts: i) 48 FFPE lymph node samples, and ii) 113 FNA lymph node biopsies. The accuracy of the markers in identifying metastatic samples was assessed through the analysis of sensitivity, specificity, accuracy, negative predictive value, positive predictive value, and area under the curve values.ResultsSeven microRNAs highly expressed in metastatic lymph nodes from the discovery set were validated in FFPE lymph node samples. MiR-203 and miR-205 identified all metastatic samples, regardless of the size of the metastatic deposit. Additionally, these markers also showed high accuracy when FNA samples were examined.ConclusionsThe high accuracy of miR-203 and miR-205 warrant these microRNAs as diagnostic markers of neck metastases in HNSCC. These can be evaluated in entire lymph nodes and in FNA biopsies collected at different time-points such as pre-treatment samples, intraoperative sentinel node biopsy, and during patient follow-up. These markers can be useful in a clinical setting in the management of HNSCC patients from initial disease staging and therapy planning to patient surveillance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0350-3) contains supplementary material, which is available to authorized users.

Probiotic preparation modulate immune system response to food proteins (IRC10P.418)

Abstract Probiotics are microorganisms which have been reported to have beneficial effect on human health to the different extent. Presented study uses probiotic preparation (one commercial were used) to modulate mucosal immune system response to food allergens beta-lactoglobulin and ovalbumin. Mice were orally fed with 5x107 CFU DICOFLOR® by 24 days. Then mice were orally immunized with antigen on 10, 17 and 24 day of experiment. At 35 days post-immunization, significant decreases in serum Ag-specific IgG and IgA titers were observed: 2^6 and 2^4 for β-LG immunized mice and 2^7 and 2^2 for OVA-immunized mice, respectively . Specific IgA titer in fecal extracts was slightly higher than that in groups not supplemented with DICOFLOR®. On 48th day of the experiment, DTH test was performed. No response was observed 24 and 48 hours after DTH challenge by groups supplemented with probiotics preparation. Lymphocytes from spleen, head and neck lymph nodes, Peyer’s patches and mesenteric lymph nodes were phenotyped for CD8+, CD4+and CD4+CD8+ T cells. In Peyer’s patches, mice immunized β-LG and supplemented with probiotics showed elevated numbers of CD4+CD8+ and CD8+ T cell subsets compared to β-LG group not supplemented with probiotic. Similar results were found for OVA group. Results show that probiotics has potential to modulate immune response to food allergens. Those potential could be used to prevent symptoms of allergy to food allergens.

Correlation of fine-needle aspiration with fluorodeoxyglucose positron emission tomography and ultrasonography imaging in head and neck lymph nodes

Fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established tracer technique, particularly useful for oncologic conditions. However, in the head and neck region, this modality may have limitations due to the complex anatomy and high frequency of normal variants in FDG-PET uptake resulting in diagnostic errors. Hence, FDG-PET results often require additional diagnostic investigations including ultrasonography (US), and guided fine-needle aspirations (FNAs) in order to improve diagnosis and patient care. A total of 87 cases of head and neck lymph node FNA were accessioned in the cytopathology laboratory between 2010 and 2013, 75 cases with corresponding standard uptake values (SUVs) were selected to form the current study cohort. Patient demographics, primary tumor site, size of the biopsied lymph node, PET SUV, and US findings, as well as FNA diagnoses and surgical follow-ups were reviewed. SUVs were grouped into 5 ranges: A (2.2-2.9), B (3.0-4.9), C (5.0-6.9), D (7.0-9.9), and E (10.0 +). The SUV cutoff of 5.0 was seen in the groups C, D, and E, which increased the probability of malignancy in the FNA specimens from 67% to 100%. The average size of the lymph nodes was 18.57 mm (range 6-41 mm); it was 13.4, 14.2, 19.7, 18.4, and 20.2 for groups A, B, C, D, and E, respectively. The lymph node measurements represented similarities in groups A and B (13.4, 14.2), and groups C, D, and E (19.7, 18.4, 20.2). Albeit a few exceptions, an increase in the lymph node size 14.2 to 19.7 (ie, from groups A and B to groups C, D, and E) correlated with SUV and US abnormalities. Abnormal US findings were pronounced (100%) in group E, and ranged between 67% and 73% of the cases in other groups. This study documents the usefulness of SUV range in FDG-PET results and not an absolute "cutoff" number for diagnosing suspicious head and neck lymph nodes due to an overlap in the SUVs between malignant and benign lesions. False positive and negative results may occur in hyperplastic and necrotic lymph nodes. An increase in the lymph node size generally compares well with SUVs and US abnormalities; use of US-guided FNAs in these cases can be helpful to achieve definite diagnosis.

Accuracy of palpation, ultrasonography, and computed tomography in the evaluation of metastatic cervical lymph nodes in head and neck cancer.

Introduction:India accounts for the majority of oral cancer cases occurring worldwide. The metastasis of oral cancer to the regional lymph nodes and distant sites determines the prognosis and the survival rate of this disease.Objectives:The aim and objectives of this study were to evaluate the accuracy of preoperative clinical methods such as palpation, ultrasonography (USG), and computed tomography (CT) in comparison with postoperative histopathological findings in determination of metastatic cervical lymph nodes and also to assess whether combining these techniques increases the specificity and sensitivity of lymph node metastasis in oral squamous cell carcinoma (SCC).Methodology:Totally, 26 consecutive biopsy proven cases of oral SCC were included, and the nodal status was evaluated by palpation, CT and ultrasound (US) and confirmed by histopathological examination. The results were presented in terms of sensitivity, specificity, predictive values, accuracy, and P value.Results:Palpation, USG, and CT findings were compared with histopathologic findings by Fisher's exact test and the “P” value for palpation, US and CT were 0.003, 0.000, 0.000, respectively, which are statistically significant.Conclusion:US examination combined with CT gives a better assessment of the neck for nodal metastasis.

The predictive value of single-photon emission computed tomography/computed tomography for sentinel lymph node localization in head and neck cutaneous malignancy.

Preoperative localization of sentinel lymph nodes in head and neck cutaneous malignancies can be aided by single-photon emission computed tomography/computed tomography (SPECT/CT); however, its true predictive value for identifying lymph nodes intraoperatively remains unquantified. This study aims to understand the sensitivity, specificity, and positive and negative predictive values of SPECT/CT in sentinel lymph node biopsy for cutaneous malignancies of the head and neck. Blinded retrospective imaging review with comparison to intraoperative gamma probe confirmed sentinel lymph nodes. A consecutive series of patients with a head and neck cutaneous malignancy underwent preoperative SPECT/CT followed by sentinel lymph node biopsy with a gamma probe. Two nuclear medicine physicians, blinded to clinical data, independently reviewed each SPECT/CT. Activity within radiographically defined nodal basins was recorded and compared to intraoperative gamma probe findings. Sensitivity, specificity, and negative and positive predictive values were calculated with subgroup stratification by primary tumor site. Ninety-two imaging reads were performed on 47 patients with cutaneous malignancy who underwent SPECT/CT followed by sentinel lymph node biopsy. Overall sensitivity was 73%, specificity 92%, positive predictive value 54%, and negative predictive value 96%. The predictive ability of SPECT/CT to identify the basin or an adjacent basin containing the single hottest node was 92%. SPECT/CT overestimated uptake by an average of one nodal basin. In the head and neck, SPECT/CT has higher reliability for primary lesions of the eyelid, scalp, and cheek. SPECT/CT has high sensitivity, specificity, and negative predictive value, but may overestimate relevant nodal basins in sentinel lymph node biopsy.

Analysis of selected risk factors for nodal metastases in head and neck cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) accounts for 20 % of all skin malignancies and 20 % of deaths. In contrast to mucosal SCC, treatment results are very good. However, regional metastases are present in 5–20 % of cases, and the prognosis for patients with metastases is 50 % lower. It has been reported that several risk factors are responsible for the head and neck lymph node regional metastasis, such as: poor cell differentiation, local recurrence, immunosuppression, and tumour dimension. Multivariate analysis of metastatic neck lesions in head and neck cSCC. Retrospective analysis of patients treated at our department for head and neck cSCC. The study includes 100 patients: 66 males (66 %) and 34 females (34 %), aged 26–98 years (mean age 74.6). The tumour was evaluated for: sex predilection, local recurrence, stage (according to 7th edition of American Joint Committee on Cancer TNM staging), differentiation, and site. Most patients (79 cases; 79 %) were treated for primary cSCC, while the other 21 patients presented local recurrence of cSCC. Neck metastases were diagnosed in five patients with primary cSCC and in three with recurrent cSCC. No distant metastasis was observed. The most common tumour location was the auricle (29 cases; 29 %). Neck dissection was performed most frequently in patients with lip tumours (17/22 cases; 77 %). Neck metastasis was diagnosed most often in patients with cSCC on the lip (2 patients) and buccal region (2 patients). The most common tumour location in males was the auricle (25/66 cases; 38 %) whereas in females the nasal and buccal regions were the most common locations, with 8 patients each (8/34 cases; 23 %). Neck dissection was performed in 20 of the 66 males (30 %) and in 12 of the 34 females (35 %). Neck metastasis was confirmed in 5 females (15 %) and 3 males (5 %). The most common histopathological tumour stage was G2 (57 cases; 57 %). Of the eight patients with confirmed neck metastasis, four had poorly-differentiated (histopathological stage G3). Thus, 4 of the 24 patients (17 %) with stage G3 tumours experienced metastasis. Our findings suggest that factors such as local recurrence, degree of cell differentiation, tumour dimension and/or location, can increase the risk of neck metastases. For this reason, in patients with such risk factors, neck dissection should be considered to evaluate for metastatic lesions.

FoxP3 and indoleamine 2,3-dioxygenase immunoreactivity in sentinel nodes from melanoma patients

Objective1) Assess FoxP3/indoleamine 2,3-dioxygenase immunoreactivity in head and neck melanoma sentinel lymph nodes and 2) correlate FoxP3/indoleamine 2,3-dioxygenase with sentinel lymph node metastasis and clinical recurrence. Study DesignRetrospective cohort study. MethodsPatients with sentinel lymph node biopsy for head and neck melanoma between 2004 and 2011 were identified. FoxP3/indoleamine 2,3-dioxygenase prevalence and intensity were determined from the nodes. Poor outcome was defined as local, regional or distant recurrence. The overall immunoreactivity score was correlated with clinical recurrence and sentinel lymph node metastasis using the chi-square test for trend. ResultsFifty-six sentinel lymph nodes were reviewed, with 47 negative and 9 positive for melanoma. Patients with poor outcomes had a statistically significant trend for higher immunoreactivity scores (p=0.03). Positive nodes compared to negative nodes also had a statistically significant trend for higher immunoreactivity scores (p=0.03). Among the negative nodes, there was a statistically significant trend for a poor outcome with higher immunoreactivity scores (p=0.02). ConclusionFoxP3/indoleamine 2,3-dioxygenase immunoreactivity correlates with sentinel lymph node positivity and poor outcome. Even in negative nodes, higher immunoreactivity correlated with poor outcome. Therefore higher immunoreactivity may portend a worse prognosis even without metastasis in the sentinel lymph node. This could identify a subset of patients that may benefit from future trials and treatment for melanoma through Treg and IDO suppression.

Eliminating radiotherapy to the contralateral retropharyngeal and high level II lymph nodes in head and neck squamous cell carcinoma is safe and improves quality of life.

Radiation treatment volumes in head and neck squamous cell carcinoma (HNSCC) are controversial. The authors report the outcomes, patterns of failure, and quality of life (QOL) of patients who received treatment for HNSCC using intensity-modulated radiation therapy (IMRT) that eliminated the treatment of contralateral retropharyngeal lymph nodes (RPLNs) in the clinically uninvolved neck. A prospective institutional database was used to identify patients who had primary oral cavity, oropharyngeal, hypopharyngeal, laryngeal, and unknown primary HNSCC for which they received IMRT. There were 3 temporal groups (generations 1-3). Generation 1 received comprehensive neck IMRT with parotid sparing, generation 2 eliminated the contralateral high level II (HLII) lymph nodes, and generation 3 further eliminated the contralateral RPLNs in the clinically uninvolved neck. Patterns of failure and survival analyses were completed, and QOL data measured using the MD Anderson Dysphagia Inventory were compared in a subset of patients from generations 1 and 3. In total, 748 patients were identified. Of the 488 patients who received treatment in generation 2 or 3, 406 had a clinically uninvolved contralateral neck. There were no failures in the spared RPLNs (95% confidence interval, 0%-1.3%) or in the high contralateral neck (95% confidence interval, 0%-0.7%). QOL data were compared between 44 patients in generation 1 and 51 patients in generation 3. QOL improved both globally and in all domains assessed for generation 3, in which reduced radiotherapy volumes were used (P < .007). For patients with locally advanced HNSCC, eliminating coverage to the contralateral HLII lymph nodes and contralateral RPLNs in the clinically uninvolved side of the neck is associated with minimal risk of failure in these regions and significantly improved patient-reported QOL.

Mucosal Vaccination Shapes the Expression of Salivary Antibodies and Establishment of CD8+ T‐Cells

Mucosal vaccination for preventing periodontitis shows promising results. However, various administration routes and adjuvants may have a substantial role in the efficacy of the vaccination. The aim of the study is to compare different modes of mucosal vaccination with whole-cell Porphyromonas gingivalis and to test the role of various adjuvants as potential modifiers of this process. Mucosal vaccine was administered through oral or nasal routes to BALB/C mice. The tested adjuvants included Escherichia coli cholera toxin, E. coli labile toxin (LT), and unmethylated CpG dinucleotide (CpG). Control mice were vaccinated subcutaneously. Saliva and serum were collected; anti-P. gingivalis salivary immunoglobulin A (IgA) and serum IgG were quantified. A quantitative enzyme-linked immunosorbent assay to measure anti-P. gingivalis IgA levels was established. In addition, cells were extracted from head and neck lymph nodes, and the relative CD8(+) cells were quantified using flow cytometry. All mucosal vaccination modes induced anti-P. gingivalis salivary IgA but not anti-P. gingivalis serum IgG. Subcutaneous vaccination induced both salivary IgA and serum IgG against P. gingivalis. Mucosal vaccination also induced greater establishment of CD8(+) cells compared to the subcutaneous vaccination. Oral mucosal vaccinations with LT or CpG were the most efficient for salivary IgA expression and CD8 cell establishment in lymph nodes. Oral and nasal mucosal vaccination induced a local host response with little systemic effect. The use of CpG or LT as adjuvants with the oral mucosal vaccination was the most efficient vaccination mode in the present mouse model.

Effect of time-of-flight technique on the diagnostic performance of 18F-FDG PET/CT for assessment of lymph node metastases in head and neck squamous cell carcinoma.

Precise assessment of lymph node metastases is critical to the treatment outcome and overall survival of patients with head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to investigate the effect of time-of-flight (TOF) technique on the diagnostic performance of (18)F-FDG PET/CT for assessment of lymph node metastases in HNSCC patients. In 39 patients with an initial diagnosis of HNSCC, preoperative staging (18)F-FDG PET/CT was performed to assess lymph node metastases before surgery and histologic verification. Potential lymph node metastases were evaluated and documented separately for the right and left neck in accordance with the head and neck lymph node level classification. Two experienced readers measured lesion volume and uptake for every PET-positive lymph node. Sensitivity, specificity, image quality, and the PET characterization of the lesion (benign or malignant) were compared between different reconstruction methods (TOF PET and standard high-definition PET) and matrices for both readers. TOF PET significantly increased the maximal standardized uptake value (SUVmax) but had no significant effect on lesion volume. However, a higher SUVmax did not result in a significant increase in small-lesion detection. Sensitivity and image quality were slightly improved with TOF PET but not significantly so. Matrix, on the other hand, had a significant effect on detected lesion numbers, sensitivity, and image quality. For preoperative assessment of lymph node metastases in HNSCC, (18)F-FDG PET/CT using TOF technique increases SUVmax in lesions and improves image quality but has no significant impact on small-lesion detectability.

The use of ultrasound in the search for the primary site of unknown primary head and neck squamous cell cancers

Although human papillomavirus detection in cervical lymph nodes of head and neck squamous cell cancers (HNSCC) of unknown primary site (UP) is indicative of a primary tumor of the oropharynx (OP), localization can remain elusive. Therefore, we investigated ultrasonography (US) for the identification of the primary tumor. Eligible cases had HNSCC of UP after evaluation by a head and neck surgical oncologist. Controls were healthy volunteers. Transcervical and intraoral ultrasonography was performed by a standard protocol using convex (3.75-6.0 MHz and 5-7.5 MHz) transducers. US findings were compared with operative examination (exam under anesthesia, direct laryngoscopy) and biopsies. The primary outcome of interest was the presence or absence of a lesion on US. 10 cases and 20 controls were enrolled. PET/CT scans were negative/nonspecific (9), or suspicious (1) for a primary lesion. On US, predominantly hypoechoic (9 of 10) lesions were visualized consistent with base of tongue (n=7) or tonsil (n=3) primary tumors. On operative examination, 5 of 10 were appreciated. Two additional primaries were confirmed with biopsies "directed" by preoperative US. This represents an overall diagnostic rate of 70%, which is 20% higher than our detection rate for 2008-2010. The three cases in which a suspicious lesion was visualized on US, yet remained UP despite further interventions, could represent false positives, misclassification or operator variability. No lesions were suspected among the controls. Ultrasound has promise for detection of UPs of the OP and therefore warrants further investigation.

Organism-level models: When mechanisms and statistics fail us

Purpose: To describe the unique characteristics of models that represent the entire course of radiation therapy at the organism level and to highlight the uses to which such models can be put. Methods: At the level of an organism, traditional model-building runs into severe difficulties. We do not have sufficient knowledge to devise a complete biochemistry-based model. Statistical model-building fails due to the vast number of variables and the inability to control many of them in any meaningful way. Finally, building surrogate models, such as animal-based models, can result in excluding some of the most critical variables. Bayesian probabilistic models (Bayesian networks) provide a useful alternative that have the advantages of being mathematically rigorous, incorporating the knowledge that we do have, and being practical. Results: Bayesian networks representing radiation therapy pathways for prostate cancer and head & neck cancer were used to highlight the important aspects of such models and some techniques of model-building. A more specific model representing the treatment of occult lymph nodes in head & neck cancer were provided as an example of how such a model can inform clinical decisions. A model of the possible role of PET imaging in brain cancer was used to illustrate the means by which clinical trials can be modelled in order to come up with a trial design that will have meaningful outcomes. Conclusions: Probabilistic models are currently the most useful approach to representing the entire therapy outcome process.