Exploratory Study of Low Resolution Electromagnetic Tomography (LORETA) Real-Time Z-Score Feedback in the Treatment of Pain in Patients with Head and Neck Cancer.

Acute pain from mucositis in patients with head and neck cancer (HNC) undergoing radiation therapy (RT) is common, and may not respond well to narcotics. We used low resolution electromagnetic tomography z-score neurofeedback (LFBz) to investigate whether patients could modify brain wave activity associated with acute pain and whether this would reduce the experience of pain. HNC patients scheduled for RT had baseline pre-pain onset measures (EEG and numeric rating scale) collected before RT and then at pain onset before using analgesics, after each LFBz session and at the end of RT. Up to six sessions of LFBz training were offered over the remaining RT. Up to six 20-min sessions of LFBz were offered over the remaining RT. Data were collected before and after each LFBz session and at the end of RT. Seventeen patients recruited; fourteen were treated and reported decreased pain perception. LFBz allowed patients to modify their brain activity in predesignated areas of the pain matrix toward the direction of their baseline, pre-pain condition (including Brodmann areas (BAs) 3, 4, 5, 13, 24, and 33). LFBz can modify brain regions relevant for pain and these changes were associated with self-reported decreases in pain perception.

Italian version of the M.D. Anderson Symptom Inventory--Head and Neck Module: linguistic validation.

BACKGROUND: Head and neck cancer (HNC) patients can experience symptoms due to the tumor itself or to the treatment, with an impact on health-related quality of life (HRQoL). Patient-reported outcome (PRO) measures pertaining to HRQoL are used in medical research and to support clinical decisions. PRO instrument applicability and cultural adaptation must be tested for each population. The aim of this study is to linguistically validate the Italian translation of the M.D. Anderson Symptom Inventory--Head and Neck Module (MDASI-HN). METHODS: Following forward and backward translation of the items of the English MDASI-HN into Italian, it was administered along with a cognitive debriefing to HNC patients able to read and understand Italian language. Individual and group responses are presented using descriptive statistics. RESULTS: From May 2013 through September 2013, 56 patients with HNC (18 during curative treatment, 20 in palliative chemotherapy, and 18 in follow-up period) completed the MDASI-HN followed by accompanying cognitive debriefing. Ninety-nine percent of the individual MDASI-HN items were completed. Average time to complete the MDASI-HN was 8.5 min (range 3-15). Results suggested overall ease of completion, relevance, and comprehensibleness of this translated self-report instrument in this Italian patient population. CONCLUSIONS: The Italian version of the MDASI-HN is linguistically valid; future research should explore dimensionality, reliability, and convergent, discriminant, and predictive validity of this patient-reported instrument, in order to use this translated version in outcomes research and clinical settings.

Sonographic examination of the neck after definitive radiotherapy for node-positive oropharyngeal cancer.

BACKGROUND AND PURPOSE: Radiographic determination of viable disease in cervical adenopathy following RT for head and neck cancer can be challenging. The purpose of this study was to evaluate the utility of US, with or without FNA, in regard to the postradiotherapy effects on documented metastatic adenopathy in patients with oropharyngeal cancer. MATERIALS AND METHODS: This study included 133 patients with node-positive oropharyngeal cancer who were irradiated from 1998 to 2004. Sonographic evaluation was performed within 6 months of completion of radiation. Posttreatment US results were compared with pretreatment CT images and were recorded as the following: progression, suspicious, indeterminate, posttreatment change, or regression (positive) versus nonsuspicious or benign (negative). FNAC was classified as nondiagnostic, negative, indeterminate, or positive. Results of US and US-guided FNAC were correlated with findings at neck dissection and disease outcome. RESULTS: Of 203 sonographic examinations, 90% were technically feasible and yielded a nonequivocal imaging diagnosis. Of 87 US-guided FNAs, 71% yielded a nonequivocal tissue diagnosis. The PPV and NPV of initial posttreatment US were 11% and 97%. Sensitivity and specificity were 92% and 28%. The PPV and NPV of US-guided FNA were 33% and 95%, and the sensitivity and specificity were 75% and 74%. On serial sonographic surveillance, of 33 patients with nonsuspicious findings, only 1 (3%) had neck recurrence. Of 22 patients with questionable findings on CT and negative findings on US, none had a neck recurrence. CONCLUSIONS: In experienced hands, serial US is an inexpensive noninvasive reassuring follow-up strategy after definitive head and neck RT, even when CT findings are equivocal.

Osteoradionecrosis of the hyoid bone: imaging findings.

BACKGROUND AND PURPOSE: ORN is a postradiation complication that has been well-documented in the medical literature. Most cases in the head and neck have been described in the mandible or larynx. Only a handful of cases in the hyoid bone are documented, all in the clinical literature. Our purpose is to present the clinical and imaging features of ORN involving the hyoid bone. MATERIALS AND METHODS: We present a case series of 13 patients with imaging findings highly suggestive of hyoid ORN after radiation therapy for head and neck cancers, in which we observed progressive features of hyoid disruption along with adjacent soft-tissue ulceration. RESULTS: Pretreatment imaging, when available, showed a normal hyoid. Typical postradiation imaging findings included an initial tongue base ulcerative lesion with air approaching the hyoid bone, and subsequent observation of hyoid fragmentation, often with intraosseous or peri-hyoid air and the absence of associated mass-like enhancement. CONCLUSIONS: Findings of hyoid fragmentation, cortical disruption, and soft tissue or intraosseous air in the postradiation therapy patient should strongly suggest the diagnosis of hyoid ORN. It is important recognize this entity because the diagnosis may preclude potentially harmful diagnostic intervention and allow more appropriate therapy.

Enlargement and transformation of thyroglossal duct cysts in response to radiotherapy: imaging findings.

BACKGROUND AND PURPOSE: Thyroglossal duct cyst remnants (TGDC) are a common midline neck mass that is mostly encountered in childhood. Enlargement after an upper respiratory tract infection or, rarely, cancer within TGDC, is a well-documented phenomenon. In the pediatric population, it rarely presents a diagnostic quandary. However, in an adult population, especially one treated for head and neck cancer with radiation therapy (RT), any enlarging cystic mass would be concerning and would raise the specter of metastatic disease. We propose that inflammation associated with RT results in secretory stimulation and/or obstruction of a persistent thyroglossal duct, resulting in changes within a pre-existing TGDC. MATERIALS AND METHODS: We present a case series of 8 patients with subclinical TGDC treated with RT for various head and neck cancers, in which we radiographically observed enlargement or cystic transformation (more cystlike appearance) of the cyst. RESULTS: In all patients there was in retrospect a small thyroglossal remnant, though not necessarily a discernible cyst, that was observed after radiotherapy to enlarge and become more cyst-like. CONCLUSIONS: In patients with pre-existing TGDC undergoing RT to the neck, enlargement and cystic transformation may be encountered radiographically and should not be misinterpreted as a tumor. Our series bolsters a recently reported description of the same phenomenon.

Oral buspirone causes a shift in the dose-response curve between the elevated-plus maze and Vogel conflict tests in Long-Evans rats: relation of brain levels of buspirone and 1-PP to anxiolytic action.

Most studies concerning the effects of oral buspirone in the rat elevated plus-maze (EPM) test, spontaneous motor activity (SMA) test, and Vogel conflict (VC) test have used Sprague-Dawley or Wistar rats. Although it has been documented that the behavior of Long-Evans rats is more sensitive to detection of anxiolytics when compared to the aforementioned strains, the effects of oral buspirone have not been fully characterized in the Long-Evans strain in the EPM and VC tests. Thus, we studied the effects of orally administered buspirone (0.03-10.0 mg/kg) in the EPM, SMA, and VC (0.3-60.0 mg/kg) tests in Long-Evans rats. In a separate experiment, brain and plasma concentrations of buspirone and 1-(2-pyrimidinyl)-piperazine (1-PP) were determined after oral administration of buspirone (0.3 and 10 mg/kg) to relate the behavioral effects of buspirone with brain and plasma concentrations of buspirone and 1-PP. Our results showed that buspirone exhibited an inverted-U-shaped dose-response curve in both the EPM and the VC tests. In the EPM, buspirone produced anxiolytic activity in a low, narrow dose-range (0.03, 0.1, 0.3 mg/kg, p.o.) with maximum efficacy at 0.3 mg/kg, whereas in the VC test, significant anxiolytic activity was observed in a high, narrow dose-range (10, 30 mg/kg, p.o.) with maximum efficacy occurring at 10 mg/kg. In the SMA test, buspirone (10 mg/kg, p.o.) significantly decreased horizontal activity and vertical movements suggestive of sedation. Also, one hour following oral doses of buspirone (0.3 and 10 mg/kg), both buspirone and 1-PP concentrations were higher in brain when compared with those in plasma. Additionally, the concentrations of 1-PP were always higher in brain and in plasma compared with the concentrations of buspirone. Of particular interest is our finding of the shift in the dose-response curve between the EPM and VC tests. This shift in the dose-response curve is discussed in relation to brain levels of buspirone and 1-PP levels and their anxiolytic action.

ICAM-5 (telencephalin) gene expression in head and neck squamous carcinoma tumorigenesis and perineural invasion!

ICAM-5 (telencephalin) is an intercellular adhesion molecule reported to be expressed only in the somatodendritic membrane of telencephalic neurons. We recently identified high ICAM-5 expression in a cDNA array study of head and neck neoplasms with a propensity for perineural invasion. To determine the association of this gene in tumorigenesis and perineural invasion, we analyzed the expression and functional status of ICAM-5 mRNA transcripts in 30 different human cancer cell lines and 25 head and neck squamous carcinoma specimens by reverse-transcriptase polymerase chain reaction (cell lines and specimens) and in vitro functional assays (cell lines). ICAM-5 transcripts were detected in 28 (93%) of 30 cell lines derived from primary head and neck, colon, thyroid, cervical, pancreatic, skin, and adenoid cystic carcinomas. In cell lines, small interfering RNA blocked ICAM-5 expression and inhibited cell proliferation. Treatment with the phosphatidylinositol 3'-kinase (PBK) inhibitor LY294002 resulted in ICAM-5 down-regulation. In tissue specimens, none of the 25 histologically normal oral mucosal specimens had detectable ICAM-5 level, whereas 16 (64%) of the 25 matched primary squamous carcinomas showed expression. Carcinoma specimens high ICAM-5 expression had a high incidence of perineural invasion. Our study indicates that ICAM-5 may play a role in tumorigenesis and perineural invasion, most likely through the P13K/Akt-signaling pathway.

Paraffinoma of the knee.

We present the case of a 90-year-old man with a swollen, painful knee and a history of paraffin injections. Radiography showed soft tissue streaky and nodular calcifications without erosions. MR imaging showed globular areas of low signal intensity on T1- and T2-weighted images which became even more hypointense on STIR sequences, and an infiltrative hypointense region containing areas of high signal on T1-weighted, T2-weighted and STIR images. Biopsy confirmed soft tissue foreign body granulomata, fibrous reaction and areas of inflammation. We believe this to be the first report of MR imaging of paraffinoma outside the breast.

Primary treatment of chondroblastoma with percutaneous radio-frequency heat ablation: report of three cases.

Chondroblastomas are benign cartilaginous lesions; however, intervention is necessary to stop progression and alleviate pain. The authors evaluated three patients in whom minimally invasive percutaneous radio-frequency heat ablation was used to treat pathologically proven chondroblastoma to determine whether this treatment demonstrated long-term success. The authors found that this approach may be an effective alternative to surgical intervention in some cases.

The dose distribution of medium energy electron boosts to the laryngectomy stoma.

An en face, medium energy electron boost of approximately 10 Gy is often given to stomal and peristomal tissues. Because the boost is considered a simple treatment, CT-based treatment planning is rarely used. Further, the results of such a plan might be inaccurate, as the complex dose distribution surrounding the stoma air cavity is poorly modeled by many treatment planning systems. We constructed three phantoms-two with a central vertical cavity to mimic the size and shape of the stoma and proximal trachea and one with a cavity inclined at 45 degrees to the horizontal to better simulate anatomy. These were used to investigate the dose distribution surrounding the stoma. In all cases, the entrance to the stoma opening was centered in a field defined by a 7-cm circular cutout and the phantom was irradiated at a source-surface distance (SSD) of 100 cm with either vertically incident 9- or 12-MeV electrons. Film measurements were made at a range of depths below and lateral to the cavity. For the vertical cavity phantoms, diode measurements were performed and isodose plans using CT scans of the phantoms were generated on a modern treatment planning system. For these two phantoms, the combined effects of lateral scatter from surrounding material and reduced equivalent thickness for electrons which pass directly through the cavity increases the dose within a centimeter of the bottom of cavity by as much as 50% for 9 MeV and 70% for 12 MeV. In material at the shallower ("superior") end of the inclined cavity, a 40-50% overdose was noted. The dose increase is geometry dependent and is not predicted by the available treatment planning system. The potential of such a dose increase to affect normal tissues such as the neopharynx should be considered.

A phase I study of cranial radiation therapy with concomitant continuous infusion paclitaxel in children with brain tumors.

BACKGROUND: The prognosis of children with high-grade astrocytomas of the central nervous system is grim and has not been substantially improved by conventional chemoradiotherapy. We performed a multi-institutional phase I study to determine the toxicities and tolerance of concurrent external beam radiation of the brain and a unique dose-schedule of paclitaxel as a radiation sensitizer. PROCEDURE: Paclitaxel was delivered intravenously as a continuous 24 h/day, 7 days/week infusion during the entire 6-week course of fixed schedule standard radiation therapy. The dose of paclitaxel was escalated in patient cohorts in standard phase I design. RESULTS: Eleven patients (eight brain stem gliomas, one glioblastoma multiforme, and two gliomatosis cerebri) were treated. Dose-limiting toxicity was encountered in the two patients treated at 6 mg/(m(2)/24 h), both of whom developed severe obstipation requiring prolonged hospitalization. CONCLUSIONS: We have shown in this first study of its kind that paclitaxel can be administered safely to children as a 6-week continuous infusion concurrent with cranial irradiation. The maximally tolerated and recommended phase II dose is 4 mg/(m(2)/day). The benefits of taxanes as clinical radiation sensitizers for children with high-grade gliomas, if any, remain to be determined.

Advanced oropharyngeal carcinoma treated with surgery and radiotherapy: oncologic outcome and functional assessment.

INTRODUCTION/PURPOSE: Surgery and postoperative radiotherapy (XRT) is a standard therapy for locally advanced resectable oropharyngeal carcinoma. This maximizes local-regional control, but does not address the potential for occult distant metastases. Additionally, some patients may suffer poor functional outcome after this intensive local therapy. This report reviews our institutional experience with modern radical surgery and XRT for this disease. METHODS: A retrospective chart review was performed on 51 consecutive patients treated from 1991 to 1997 at the University of Pennsylvania with radical surgery and postoperative XRT. This study included patients with locally advanced, stage III/IV (exclusive of T1-2N1) squamous carcinoma of the oropharynx. All patients had a good performance status (ECOG 0-1). Patients who received adjuvant chemotherapy were excluded. No patient had gross residual disease after surgery; the median XRT dose was 63.7 Gy. Survival, local-regional control (LRC), and freedom from distant metastases (DM) were calculated actuarially. In patients who remained free of disease, functional status was determined using the List Performance Status Scale (PSS). RESULTS: With a median follow-up in surviving patients of 34 months, the 3-year actuarial overall survival was 51%. The 3-year LRC was 73%, and the freedom from DM was 69%. The most significant factor predicting for failure was the number of pathologically positive nodes (P <.001 for survival and DM; P =.003 for LRC). In 29 patients who were evaluable for the List PSS, the mean normalcy-of-diet score was 48; the mean eating-in-public score was 53; and the mean understandability-of-speech score was 75. There was a trend toward better PSS scores in patients with T1-2 tumors versus T3-4 tumors, although this did not reach statistical significance. CONCLUSIONS: Surgery and postoperative XRT offer relatively good LRC and moderate overall survival rates. Results, however, remain suboptimal, particularly with respect to the risk of DM and the functional outcome. These data provide a baseline for comparison with maturing results from multimodality trials in which radical surgery is not used in all patients with locally advanced oropharyngeal carcinoma.

Pyrazolecarboxamide human neuropeptide Y5 receptor ligands with in vivo antifeedant activity.

1-Aryl-3-carboxamido-5-alkylpyrazoles were prepared based on a hit found in high-throughput screening of our corporate compound library in an assay measuring affinity for the human neuropeptide Y5 receptor. 1-(3-Trifluoromethylphenyl)-3-[N-(5-quinolinyl)carboxamido]-5-methylpyrazole (31) bound to the human neuropeptide Y5 receptor with a 80 nM IC(50 )and was shown to inhibit cumulative food consumption 43.2% 2-6 h after ip dosing in a fasting-induced feeding model in rats.

Radiological imaging for the diagnosis of bone metastases.

Primary neoplasms of the skeleton are rare, but metastatic involvement is, unfortunately, a common occurrence. This is particularly true for certain primary tumors. Skeletal metastases are clinically significant because of associated symptoms, complications such as pathological fracture and their profound significance for staging, treatment and prognosis. Detection of bone metastases is, thus, an important part of treatment planning. The frequency with which metastases are detected varies considerably with the type of primary tumor and with the methodology utilized for detection. Four main modalities are utilized clinically: plain film radiography, CT scan, nuclear imaging and magnetic resonance imaging. In this discussion, we will review literature on the radiology of skeletal metastases with respect to lesion detection, assessment of response to treatment and possible therapeutic implications. The bulk of the discussion will focus on MRI and nuclear studies since most of the recent advances have been made in these areas.

Treatment of epithelioid hemangioendothelioma of bone using a novel combined approach.

Radiofrequency (RF) treatment has been used for a variety of malignant and benign conditions. However, treatment of a bone malignancy has yet to be reported. The authors present a 21-year old woman with multifocal epithelioid hemangioendothelioma (EH) treated by a combination of surgical excision, chemotherapy and four RF ablations. Follow-up radiographs of the RF-treated sites reveal no evidence of recurrent disease 71, 58, 49 and 33 months, respectively, after treatment.

Intra-articular lipoma with osteochondroid metaplasia in the knee joint.

We describe a case of lipoma with osteochondroid metaplasia in the knee joint. Although the location of the lesion and radiographic findings were unusual, computed tomography and magnetic resonance imaging were useful in characterizing adipose, cartilaginous and osseous tissue components within the lesion.

Increased abdominal visceral fat is associated with reduced bone density in HIV-infected men with lipodystrophy.

OBJECTIVE: To examine the relationship between bone density and changes in regional and whole body composition in HIV-infected men with and without lipodystrophy. DESIGN: Cross-sectional, observational study of HIV-infected men with and without lipodystrophy and matched HIV-negative controls. SETTING: Tertiary care academic medical institution. PATIENTS: A total of 59 men, belonging to three different groups: HIV-positive men with lipodystrophy (n = 21), HIV-positive men without lipodystrophy (n = 20), and age-matched and body mass index-matched HIV-negative controls (n = 18). METHODS: Bone density, markers of bone turnover and indices of calcium metabolism were measured in all subjects. Quantitative computed tomography was used both to determine volumetric bone density of the spine and to quantify abdominal visceral fat. Dual energy X-ray absorptiometry was used to determine whole body composition and bone density. Statistical comparisons were performed according to lipodystrophy categorization and protease inhibitor exposure. RESULTS: Men with HIV-associated lipodystrophy had reduced lumbar spine bone density compared with both HIV-infected non-lipodystrophic men [mean +/- SD, 132 +/- 29 versus 154 +/- 30 mg/cm(3); P = 0.02] and HIV-negative controls [mean +/- SD 132 +/- 29 versus 148 +/- 18) mg/cm(3); P = 0.04]. Lumbar spine bone density was reduced significantly in HIV lipodystrophy patients independently of protease inhibitor use. In an analysis among all HIV-infected subjects, increased visceral abdominal fat area was associated with decreased lumbar spine bone density (r, -0.47; P = 0.002). The association between visceral fat and bone density remained significant (P = 0.007) after controlling for age, body mass index, lowest body weight, protease inhibitor use, and extremity fat in a multivariate regression model. Markers of bone turnover were not related to bone density or lipodystrophy status. CONCLUSIONS: Lumbar spine bone density is reduced in association with increased visceral fat in HIV-infected men with lipodystrophy. Further studies are needed to determine the mechanisms of osteopenia in HIV lipodystrophy and whether increased marrow fat occurs in such patients and affects bone density.

Effects of testosterone and exercise on muscle leanness in eugonadal men with AIDS wasting.

Loss of lean body and muscle mass characterizes the acquired immunodeficiency syndrome (AIDS) wasting syndrome (AWS). Testosterone and exercise increase muscle mass in men with AWS, with unclear effects on muscle composition. We examined muscle composition in 54 eugonadal men with AWS who were randomized to 1) testosterone (200 mg im weekly) or placebo and simultaneously to 2) resistance training or no training in a 2 x 2 factorial design. At baseline and after 12 wk, we performed assessments of whole body composition by dual-energy X-ray absorptiometry and single-slice computed tomography for midthigh cross-sectional area and muscle composition. Leaner muscle has greater attenuation. Baseline muscle attenuation correlated inversely with whole body fat mass (r = -0.52, P = 0.0001). This relationship persisted in a model including age, body mass index, testosterone level, viral load, lean body mass, and thigh muscle cross-sectional area (P = 0.02). Testosterone (P = 0.03) and training (P = 0.03) increased muscle attenuation. These data demonstrate that thigh muscle attenuation by computed tomography varies inversely with whole body fat and increases with testosterone and training. Anabolic therapy in these patients increases muscle leanness.