Intensity-modulated radiotherapy with planned Gamma Knife radiosurgery boost for head and neck cancer with extensive disease in proximity to critical structures.

BACKGROUND: To describe intensity-modulated radiotherapy (IMRT) with Gamma Knife Radiosurgery (GKRS) boost for locally advanced head and neck cancer (HNC) with disease near dose-limiting structures. METHODS: Patients with HNC treated with IMRT/GKRS as part of a combined modality approach between 2011 and 2021 were reviewed. Local control, overall survival and disease-specific survival were estimated using the Kaplan Meier method. RESULTS: Twenty patients were included. Nineteen patients had T3-4 tumors. Median follow-up was 26.3 months. GKRS site control was 95%. Two patients progressed at the treated primary site, one patient failed at the edge of the GKRS treatment volume, with no perineural or intracranial failure. 2-year OS was 94.7% (95% CI: 85.2%-100%). Concurrent chemotherapy was given in nine patients (45%). One patient (5%) received induction/concurrent chemotherapy. Brain radionecrosis occurred in three patients, one of which was biopsy-proven. CONCLUSIONS: IMRT plus GKRS boost results in excellent disease control near critical structures with minimal toxicity.

A comparison of digestate management options at a large anaerobic digestion plant.

Increased biogas production from increasing numbers of anaerobic digestion (AD) facilities has increased the mass of digestate applied to agricultural land close to AD plants and has led to an oversupply in some regions. This necessitates long distance digestate transportation accompanied by economic, environmental, and social drawbacks. This work assesses the performance of three different digestate management options (MOs); land application of whole digestate (MO1), digestate separation (MO2), and digestate separation and evaporation (MO3), combined with centralised or decentralised digestate storage. All MOs required the same landbank area, whilst MO2 and MO3 reduced digestate management costs by 9% and 37% (if recovered heat is used) respectively. GHG emissions from MO2 were 41% lower than MO1 if renewable electricity was used. MO3 reduced GHG emissions by 63% compared to MO1, if renewable electricity and recovered heat were used. MO2 required the same centralised digestate storage volume as MO1 while MO3 required 44% of the centralised storage volume. Centralised digestate storage required a maximum of 79 days for digestate transportation (33 trucks/day, 20 m3 capacity) to land for MO1 and MO2, and 35 days for MO3. Decentralised digestate storage required 63 storage tanks and 15 trucks/day for MO1, 69 tanks and 15 trucks/day for MO2, and 68 tanks and 7 trucks/day for MO3. Tank size ranged from 500 m3 to 20,000 m3. MO3 combined with decentralised storage could reduce the cost and GHG emissions (if recovered energy is used), vehicle movements, and the number of storage tanks required for digestate management.

Comprehensive gene cluster analysis of head and neck squamous cell carcinoma TCGA RNA-seq data defines B cell immunity-related genes as a robust survival predictor.

BACKGROUND: The authors aimed to define novel gene expression signatures that are associated with patients' survival with head and neck squamous cell carcinoma (HNSCC). METHODS: TCGA RNA-seq data were used for gene expression clusters extraction from 499 tumor samples by the "EPIG" method. Tumor samples were then partitioned into lower and higher than median level groups for survival relevant analysis by Kaplan-Meier estimator. RESULTS: We found that two gene clusters (_1, _2) are favorably, while two (_3, _4) are unfavorably, associated with patients' survival with HNSCC. Notably, most genes on the top lists of cluster_2 are associated with B cells. A gene expression signature with combined genes from cluster_2 and _4 was further determined to be associated with HNSCC survival rate. CONCLUSION: Our work strongly supported a favorable role of B cells in patients' survival with HNSCC and identified a novel coexpressed gene signature as prognostic biomarker for patients' survival with HNSCC estimation.

Detection and localization of surgically resectable cancers with a multi-analyte blood test.

Earlier detection is key to reducing cancer deaths. Here, we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1005 patients with nonmetastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69 to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was greater than 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.

MicroRNA Profiling and Target Genes Related to Metastasis of Salivary Adenoid Cystic Carcinoma.

BACKGROUND/AIM: Perineural invasion and distant metastasis lead to a poor prognosis of adenoid cystic carcinoma and there is no effective therapy available. MicroRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression, which can be biomarkers or therapeutic targets for certain cancer types. We aimed to identify miRNAs and their target genes possibly involved in metastasis of salivary gland adenoid cystic carcinoma (SACC). MATERIALS AND METHODS: Using Nanostring nCounter analysis, we examined miRNA expression in two SACC cell lines: SACC-83 and SACC-LM, with low and high lung metastasis rates, respectively. We then verified the differentially expressed miRNAs with real-time polymerase chain reaction in the cell lines and in tumor samples from patients with SACC. miRNA target-gene expression was also analyzed. RESULTS: SACC-83 showed higher gene expression of miR-130a, miR-342, and miR-205; SACC-LM showed higher gene expression of miR-99a and miR-155. In human tissue, miR-205 was highly expressed in the primary SACC, while miR-155 and miR-342 were highly expressed in recurrent SACC. Six predicted target genes of miRNA-155 and miR-99a linked to tumorigenesis were further analyzed and RNA expression of ubiquitin-like modifier activating enzyme 2 (UBA2) was higher in SACC than normal salivary gland tissue, and higher in primary compared to recurrent SACC (p<0.05). RNA expression of retinoic acid receptors (RARS) was higher in tissue from primary than recurrent SACC and normal salivary gland (p<0.05), but that in recurrent SACC was not significantly higher than normal salivary gland tissue. RNA expression of minichromosome maintenance 8 homologous recombination repair factor (MCM8) and 24-dehydrocholesterol reductase (DHCR24) was higher in primary SACC than normal salivary gland tissue (p<0.05). CONCLUSION: miR-99a, miR-155, miR-130a, miR-342, and miR-205 may play a role in metastasis of SACC. MiR-155 may be involved in SACC metastasis through UBA2 pathways, and UBA2 may function as a biomarker/mediator of SACC metastasis.

Stereotactic Radiosurgical Treatment of Glomus Jugulare Tumors.

OBJECTIVE: Determine treatment outcomes of stereotactic radiosurgery (SRS) for glomus jugulare tumors (GJT), focusing on three-dimensional volume change and symptoms before and after SRS, as well as complications related to SRS. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Thirty-eight patients treated with SRS between 2000 and 2015. INTERVENTION: SRS treatment of GJT. MAIN OUTCOME MEASURES: The tumor volumes on pre- and posttreatment imaging were compared utilizing the Leskell GammaPlan treatment plan software to assess tumor progression. Pre- and posttreatment symptoms, Fisch classification, and complications were recorded. RESULTS: The mean radiographic follow-up was 39.1 months. The mean dose-to-tumor margin was 13.2 Gy. The mean tumor size at treatment was 5.8 and 5.2 cm at last follow-up. Thirty-three patients had follow-up imaging suitable for analysis. When defining both 10 and 15% tumor size increases as significant, 27 (82%) and 29 (88%) tumors decreased in size or remained stable, respectively. For the seven tumors with documented pre-SRS growth, treatment success was 86%. The mean marginal dose for treatment success and failure were 13.2 and 13.7 Gy, respectively. Patients receiving a higher margin dose had a greater risk of tumor progression (p = 0.0277). Fisch classification did not impact tumor progression rate. Initial tumor volume had no significance on tumor response to SRS. CONCLUSIONS: SRS is an effective treatment option for GJT. Both initial tumor volume and Fisch classification did not impact tumor progression. There were no significant patient or lesion characteristics that distinguished treatment success and/or failure.

Chemokine and Chemokine Receptor Profiles in Metastatic Salivary Adenoid Cystic Carcinoma.

AIM: To characterize the chemokine pattern in metastatic salivary adenoid cystic carcinoma (SACC). MATERIALS AND METHODS: Real-time polymerase chain reaction (RT-PCR) was used to compare chemokine and chemokine receptor gene expression in two SACC cell lines: SACC-83 and SACC-LM (lung metastasis). Chemokines and receptor genes were then screened and their expression pattern characterized in human tissue samples of non-recurrent SACC and recurrent SACC with perineural invasion. RESULTS: Expression of chemokine receptors C5AR1, CCR1, CCR3, CCR6, CCR7, CCR9, CCR10, CXCR4, CXCR6, CXCR7, CCRL1 and CCRL2 were higher in SACC-83 compared to SACC-LM. CCRL1, CCBP2, CMKLR1, XCR1 and CXCR2 and 6 chemokine genes (CCL13, CCL27, CXCL14, CMTM1, CMTM2, CKLF) were more highly expressed in tissues of patients without tumor recurrence/perineural invasion compared to those with tumor recurrence. CCRL1 (receptor), CCL27, CMTM1, CMTM2, and CKLF (chemokine) genes were more highly expressed in SACC-83 and human tissues of patients without tumor recurrence/perineural invasion. CONCLUSION: CCRL1, CCL27, CMTM1, CMTM2 and CKLF may play important roles in the development of tumor metastases in SACC.

Gene Variability Between Perineural-positive and Perineural-negative Squamous Cell Skin Cancers.

AIM: To identify differentially expressed genes (DEGs) between perineural invasion-positive (PP) and -negative (PN) cutaneous squamous cell cancers (CSCC). MATERIALS/METHODS: Forty CSCC samples with and without perineural invasion were processed for RNA isolation and hybridization to Affymetrix-U219 DNA microarrays. Raw gene expression data were normalized by Robust Multi-array Averaging (RMA) and log2 transformed. Gene expression-based classification models were created and accuracies evaluated using leave-one-out cross-validation. RESULTS: At a stringent limma p-value (p<0.001), 24 genes were differentially expressed between PP and PN samples. The cross-validated performance of the eight classification models exhibited a mean accuracy of 85-95%. Diagonal linear discriminant was most accurate at 95%, followed by Bayesian compound covariate at 94%. The poorest accuracy (85%) was observed for 1-Nearest neighbor and Support vector machines. CONCLUSION: Gene expression may distinguish between PP and PN CSCC. Understanding these gene patterns may potentiate more timely diagnosis of perineural invasion and guide comprehensive therapies.

Age-related changes of hyoid bone position in healthy older adults with aspiration.

OBJECTIVES/HYPOTHESIS: Aspiration, the passage of a bolus below the vocal folds, increases morbidity and mortality in the elderly by increasing the risk of aspiration pneumonia and other conditions. We hypothesized that altered position of the hyoid bone associated with aging may negatively affect airway protection during swallowing (i.e., aspiration) in older adults. STUDY DESIGN: Retrospective study. METHODS: We re-reviewed computed tomography (CT) scans of the head from 40 older adults (65-80 years old), comprised of 20 aspirators and 20 nonaspirators, obtained from a previous cohort study. In addition, CT scans of the head from 40 young adults (20-40 years old) were retrieved from a medical records database. Three-dimensional reconstruction and 2-dimensional sagittal views were used to measure the distance between the mandible and hyoid bone. Comparisons between age groups, genders, and aspiration status were made. RESULTS: Older adults had a larger distance between the hyoid and mandible in both latitude and longitudinal positions compared to the young adults. Among older males, there was evidence that the hyoid bone in the aspirators tended to be positioned more posterior compared to the nonaspirators. CONCLUSIONS: The distance between the hyoid and mandible is increased with aging, and a more posterior position of the hyoid bone is correlated with aspiration in older males. These findings suggest that age-related changes in hyoid bone position may be a component of decreased swallowing safety and aspiration in older adults and warrant further investigation. LEVEL OF EVIDENCE: N/A.

Evaluation of the biomethane potential from multiple waste streams for a proposed community scale anaerobic digester.

This paper examines the biomethane potential from organic waste for a proposed community scale anaerobic digester in a rural town. The biomethane potential test is used to assess the suitability of waste streams for biomethane production and to examine the variation in biomethane potential between waste sub-streams. A methodology for accurately estimating the biomethane potential from multiple heterogeneous organic waste substrates is sought. Five main waste streams were identified as possible substrates for biogas production, namely Abattoir waste (consisting of paunch and de-watered activated sludge); cheese factory effluent; commercial and domestic food waste; pig slurry and waste water treatment sludge. The biomethane potential of these waste streams ranged from as low as 99 L CH4 kg VS(-1) for pig slurry to as high as 787 L CH4 kg VS(-1) for dissolved air floatation (DAF) sludge from a cheese effluent treatment plant. The kinetic behaviour of the biomethane production in the batch test is also examined. The objective of the paper is to suggest an optimum substrate mix in terms of biomethane yield per unit substrate for the proposed anaerobic digester. This should maximize the yield of biomethane per capital investment. Food waste displayed the highest biomethane yield (128 m(n)(3) t(-1)) followed by cheese waste (38 m(n)(3) t(-1)) and abattoir waste (36 m(n)(3) t(-1)). It was suggested that waste water sludge (16 m(n)(3) t(-1)) and pig slurry (4 m(n)(3) t(-1)) should not be digested. However, the biomethane potential test does not give information on the continuous operation of an anaerobic digester.

Evaluation of the biomethane yield from anaerobic co-digestion of nitrogenous substrates.

This paper examines three substrates for anaerobic co-digestion: abattoir waste; cheese waste and food waste. These substrates were assessed in detail for suitability for biomethane production. Biomethane potential (BMP) assays were carried out in mono and co-digestion for the three substrates and two mixes: T1 (40% abattoir waste; 50% cheese waste and 10% food waste on a wet weight basis) and T2 (30% abattoir waste; 40% cheese waste and 30% food waste). The C:N ratio of both mixes was below optimum. Low levels suggest that the production of free ammonia (NH3) in semi-continuous digestion was of primary concern. Both mixes were digested in a semi-continuous process for 25 weeks. The recommended operating condition for T1 was a loading rate of 3 kg VS mn(-3) day(-1) at a retention time of 23 days. The biomethane yield was 305 L CH4 kg(-1) volatile solids (VS) which was 87% of the BMP value and equivalent to 61% biodegradability. For T2 (with the higher C:N ratio) a higher loading rate of 4kg VS mn(-3) day(-1) at a lower retention time of 15 days was recommended. The biomethane yield was 439 L CH4 kg(-1) VS (99% of the BMP value and 84% biodegradibility). At these conditions, levels of total ammonical nitrogen (TAN) were 4109 and 4831 mg L(-1) for T1 and T2, respectively. These values are on the large side according to the literature. The temperature was reduced to 35 degrees C to minimize toxicity associated with TAN. Ratios of volatile acids to bicarbonate were typically in the range of 0.2-0.3 suggesting stable operation.

Improving hydrolysis of food waste in a leach bed reactor.

This paper examines the rate of degradation of food waste in a leach bed reactor (LBR) under four different operating conditions. The effects of leachate recirculation at a low and high flow rate are examined with and without connection to an upflow anaerobic sludge blanket (UASB). Two dilution rates of the effective volume of the leach bed reactors were investigated: 1 and 6 dilutions per LBR per day. The increase in dilution rate from 1 to 6 improved the destruction of volatile solids without connection to the UASB. However connection to the UASB greatly improved the destruction of volatile solids (by almost 60%) at the low recirculation rate of 1 dilution per day. The increase in volatile solids destruction with connection to the UASB was attributed to an increase in leachate pH and buffering capacity provided by recirculated effluent from the UASB to the leach beds. The destruction of volatile solids for both the low and high dilution rates was similar with connection to the UASB, giving 82% and 88% volatile solids destruction respectively. This suggests that the most efficient leaching condition is 1 dilution per day with connection to the UASB.

Aging-related geniohyoid muscle atrophy is related to aspiration status in healthy older adults.

BACKGROUND: Age-related muscle weakness due to atrophy and fatty infiltration in orofacial muscles may be related to swallowing deficits in older adults. An important component of safe swallowing is the geniohyoid (GH) muscle, which helps elevate and stabilize the hyoid bone, thus protecting the airway. This study aimed to explore whether aging and aspiration in older adults were related to GH muscle atrophy and fatty infiltration. METHOD: Eighty computed tomography scans of the head and neck from 40 healthy older (average age 78 years) and 40 younger adults (average age 32 years) were analyzed. Twenty aspirators and 20 nonaspirators from the 40 older adults had been identified previously. Two-dimensional views in the sagittal and coronal planes were used to measure the GH cross-sectional area and fatty infiltration. RESULTS: GH cross-sectional area was larger in men than in women (p < .05). Decreased cross-sectional area was associated with aging (p < .05), and cross-sectional area was significantly smaller in aspirators compared with nonaspirators, but only among the older men (p < .01). Increasing fatty infiltration was associated with aging in the middle (p < .05) and posterior (p < .01) portions of the GH muscle. There was no significant difference in fatty infiltration of the GH muscle among aspirators and nonaspirators. CONCLUSION: GH muscle atrophy was associated with aging and aspiration. Fatty infiltration in the GH muscle was increased with aging but not related to aspiration status. These findings suggest that GH muscle atrophy may be a component of decreased swallowing safety and aspiration in older adults and warrants further investigation.