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Background Ambulatory surgery presents unique challenges regarding adequate pain management and education. Studies have documented issues with transfer of information and patient comfort. Our objective was to explore perioperative nurses’ perspectives of current practices and challenges with pain management and education. Materials and methods We used a qualitative descriptive design and conducted four focus group interviews, with 24 total participants from two perioperative areas of an academic medical center, using a standardized script. Using qualitative analysis software, two investigators reviewed the data and coded major themes and subthemes. The consolidated criteria for reporting qualitative studies guidelines were followed for reporting the data. Results We identified four major themes impacting current perioperative pain management and education practices: communication among the perioperative care team, sources of nurses’ frustrations in the perioperative setting, patient expectations for pain, and nurse-driven pain management and education. Nurses highlighted their work became easier with adequate information transfer and trust from physicians. Frustrations stemmed from surgeon, system, and patient factors. Nurses often use their clinical experience and judgment in managing patients throughout the perioperative period. Furthermore, nurses felt patients have limited pain education and stressed education throughout the surgical care pathway could improve overall care. Conclusions Perioperative pain management, assessment, and education practices are inconsistent, incomplete, and sources of frustrations according to participants. Participant experiences highlight the need for improved and standardized models. Patient pain education should use a multidisciplinary approach, beginning at the point of surgery scheduling and continuing through postoperative follow-up.

Refereed/Peer-reviewed Deregulation of cyclin-dependent kinase 2 (CDK2) and its activating partners, cyclins A and E, is associated with the pathogenesis of a myriad of human cancers and with resistance to anticancer drugs including CDK4/6 inhibitors. Thus, CDK2 has become an attractive target for the development of new anticancer therapies and for the amelioration of the resistance to CDK4/6 inhibitors. Bioisosteric replacement of the thiazole moiety of CDKI-73, a clinically trialled CDK inhibitor, by a pyrazole group afforded 9 and 19 that displayed potent CDK2-cyclin E inhibition (Ki = 0.023 and 0.001 μM, respectively) with submicromolar antiproliferative activity against a panel of cancer cell lines (GI50 = 0.025–0.780 μM). Mechanistic studies on 19 with HCT-116 colorectal cancer cells revealed that the compound reduced the phosphorylation of retinoblastoma at Ser807/811, arrested the cells at the G2/M phase, and induced apoptosis. These results highlight the potential of the 2-anilino-4-(1-methyl-1H-pyrazol-4-yl)pyrimidine series in developing potent and selective CDK2 inhibitors to combat cancer.

Although surgery and radiotherapy remain the most commonly used treatments for non-melanoma skin cancer, there are a variety of alternatives. Here we discuss the use of electrochemotherapy and ablative treatments and examine the evidence for their effectiveness against a number of non-melanoma skin cancers.

Small-for-size-liver grafts (SFSG) in adult transplant recipients have elevated risk of graft failure, limiting its application in clinical liver transplantation. Relevant preclinical model of SFSG is lacking. Relevant to deceased-donor split liver transplant and living-donor liver transplant in adult recipients, in this study, we present our initial characterization of SFSG model using monosegments of a discarded human donor liver.

PURPOSE/OBJECTIVE(S): Trismus is caused by injury to the masticatory muscles resulting from cancer or its treatment. Contouring these muscles to reduce dose and radiation related trismus can be problematic due to interobserver variability. This study aimed to evaluate the reduction in interobserver variability achievable with a new contouring atlas.MATERIALS/METHODS: The atlas included: medial and lateral pterygoids (MP, LP), masseter (M) and temporalis (T) muscles, and the temporo-mandibular joint (TMJ). Seven clinicians delineated five paired structures on CT scans from 5 patients without the atlas. After ≥5 weeks, contouring was repeated using the atlas. Using contours generated by the clinicians on the same 5 CT scans as reference, dice similarity coefficient (DSC), mean distance-to-agreement (DTA) and centre of mass (COM) difference were compared with and without the atlas. Comparison was also performed split by training grade. Mean and standard deviation (SD) values were measured.RESULTS: The atlas reduced interobserver variability for all structures. Mean DTA significantly improved for MP (p = 0.01), M (p CONCLUSION: A new atlas for contouring masticatory muscles during radiotherapy planning for head and neck cancer reduces interobserver variability and could be used as an educational tool.

Head and neck cancer patients require close clinical follow up to monitor and address sequelae of treatment and for adequate cancer surveillance. The goal of this study is to determine barriers and risk factors for head and neck cancer patients who are lost-to-follow-up.A chart review of the Head and Neck Cancer Registry was performed to identify patients who were lost-to-follow-up (LTF). LTF was defined as missing two consecutive appointments as recommended by their oncologic surgeon. Those identified as LTF were contacted via email and phone to complete a 16-question survey addressing possible barriers to follow up.Of the 353 patients reviewed, 53 met the criteria for LTF (15%). Forty-eight participants were contacted, and 23 surveys were completed (48%). Of the 23 patients that responded, 22% reported difficulty scheduling an appointment, 30% had transportation barriers, 22% had personal or work obligations that prevented follow up, 17% did not follow up because they "felt better," and 39% were following up with an otolaryngologist or oncologist closer to home. Only three participants (13%) were aware of the recommended 5-year surveillance period.Head and neck cancer patients have a variety of reasons they are lost to follow-up. Understanding these barriers is critical to creating a patient-centered model that balances both clinical surveillance needs and reasonable expectations for patients. Improvements can be made to educate patients on the recommended length of follow-up and its importance.

Micronutrients and their supplementation have been investigated in the development, severity, and treatment of tinnitus. This study aimed to evaluate associations between tinnitus parameters and levels of zinc, manganese, and vitamin B12.This retrospective study analyzed National Health and Nutrition Examination Survey 2011-2012 and 2015-2016 participants aged 20-69 who answered whether they had symptoms of tinnitus in the past year. Persons with tinnitus symptoms further reported how regularly they had symptoms and how disruptive symptoms were. Multivariable regressions accounting for age, gender, and race/ethnicity were used to evaluate the influence of low serum/blood levels of zinc, manganese, and vitamin B12 on tinnitus presence, regularity, and disruptiveness.This study included 9439 participants, with 16.2% of the sample reporting tinnitus symptoms. In multivariable regression models, low blood manganese was associated with tinnitus regularity (proportional OR: 1.47 [95% CI: 1.06, 2.05], p = 0.0213) and tinnitus disruptiveness (proportional OR: 1.78 [95% CI: 1.08, 2.96], p = 0.0250), but not tinnitus presence (p = 0.4813). Low serum zinc and low serum vitamin B12 did not have statistically significant associations with analyzed tinnitus parameters.A nationally representative analysis found that low blood manganese was significantly associated with tinnitus regularity and disruptiveness, but found that serum zinc and vitamin B12 had no association with tinnitus parameters. These findings suggest that low micronutrient levels are unlikely to be contributors to tinnitus; however, the results suggest further research on manganese supplementation in patients with tinnitus may be merited.

Introduction Published studies have reported a rise in MRSA isolates in head and neck infections, but the microbiology of complicated pediatric rhinosinusitis is unclear. One study of such patients showed that MRSA isolates were seen only in the last three years of data collection, suggesting a possible recent increased prevalence. Given the public health concerns of increasing rates of antimicrobial resistance, the goal of this study was to investigate the microbiologic patterns and outcomes of complicated pediatric rhinosinusitis. Methods Retrospective cohort of pediatric patients admitted to our children's hospital with complicated acute rhinosinusitis from 2004 to 2014. Results The mean age of 250 hospitalized children with complicated rhinosinusitis was 7.6 ± 4.9 years; 109 of these (43%) underwent surgical procedures. Although MRSA prevalence was highest in 2014, no significant trend in overall MRSA prevalence occurred when considering the entire study period. No significant relationship was identified between MRSA and intra-orbital versus intra-cranial complications. Interestingly, 22.7% of patients with anaerobes detected by culture had persistent abnormal physical examination (PE) findings versus 6.1% of patients without anaerobes (p = 0.025). Furthermore, multivariate analysis also revealed that detection of anaerobes or MRSA was associated with persistent PE findings being 21.8 and 14.8 times more likely, respectively, when compared to other detected pathogens. Discussion Our data indicate modest variability in the annual rates of MRSA associated pediatric rhinosinusitis, however there was no statistically significant pattern of change in MRSA prevalence during 2004–2014. Although detection of MRSA was not significantly associated with either intraorbital or intracranial complications of sinusitis, a significant association with a poorer outcome was observed by multivariate analysis for patients from whom MRSA or anaerobes were detected. These data raise the question as to whether clindamycin is adequate for MRSA and anaerobic coverage.

Farm-level greenhouse gas (GHG) footprinting tools produce markedly different results from common input datasets. These tools are typically empirical, broad scope models which are valuable for their ability to account for a range of on-farm GHG sources using non-specialist data. Many of these tools are publicly available, and are employed by users from a range of backgrounds to provide enterprise-level carbon footprints. They may be used to inform mitigation strategies and policy developments, though are often developed outside the peer-review system, and as such the methodology employed may be sparsely documented. The study reported here rigorously tests these tools and discusses differential findings. Five farm-level tools were tested using data from a variety of beef production enterprises. Beef production was chosen as an emissions intensive form of livestock production, and the focus of considerable mitigation effort globally. Considerable inconsistencies between tools were found in the resulting estimates. Estimates of emissions stemming directly from livestock were variable, and the largest contributor to the overall farm footprint (43–92% of total). As such, consistent calculation of these emissions is of considerable importance. Similar variability was found in other emissions categories. The emissions intensity of beef production was calculated for each estimate and compared to published values from LCA literature. Some tools produced estimates concurrent with these values, whilst others markedly underestimated in comparison. This study highlights the differences between estimates produced by these tools, and explores the reasons behind them. Of relevance to users is the finding that even where farm-level estimates appear similar between tools, the composition of these estimates can vary. As such, different tools respond differently to system changes. In highlighting and exploring the impacts this can have, the conclusions of this study provide a key reference point for tool users and developers.

Purpose The purpose of this study was to determine the effect of deformable image registration (DIR) on cumulative organ at risk dose–volume histogram (DVH) parameter summation for more than three brachytherapy fractions. The reproducibility of different methods of DIR was tested. DIR was then used to assess the stability of the anatomic position of the DVH parameters within the bladder and rectum. Methods and Materials DIR was completed for 39 consecutive cervical cancer brachytherapy patients' planning CTs. Accumulated DVH parameters ( D 2cc and D 0.1cc ) for bladder and rectum were compared with dose summation without DIR. Reproducibility of DIR results was assessed for different methods of implementation based on adding contour biases added to the DIR algorithm. Vol D2cc and Vol D0.1cc structures were created from the overlap of the D 2cc and D 0.1cc isodose and the bladder or rectum, respectively. The overlap of Vol D2cc and Vol D0.1cc structures was calculated using the Dice similarity coefficient. Results DIR accumulated D 2cc and D 0.1cc decreased by an average of 2.9% and 4.2% for bladder and 5.08% and 2.8% for rectum compared with no DIR. DIR was most reproducible when the bladder or rectum contour was masked. The average Dice similarity coefficient was 0.78 and 0.61 for the bladder D 2cc and D 0.1cc as well as 0.83 and 0.62 for rectal D 2cc and D 0.1cc , respectively. Conclusions Dose decreases were observed for accumulated DVH parameters using DIR. Adding contour-based biases to the algorithm increases the reproducibility of D 2cc and D 0.1cc accumulation. The anatomic position of Vol D2cc was more stable than Vol D0.1cc .

Vineyards are usually cultivated in soils characterised by low soil organic carbon (SOC) content and have high risks of soil erosion and degradation. Increasing SOC stocks in these cropping systems has the potential to contribute to climate change mitigation through SOC sequestration and to enhance soil quality. We conducted a meta-analysis and compared the SOC stock response ratio, the SOC stock rate of change, and the SOC sequestration rate in vineyards under different SOC sequestration (SCS) practices relative to conventional management. SCS practices included organic amendments (OA), biochar amendments (BC), returning pruning residues to the soil (PR), no-tillage (NT), cover cropping (CC), and several combinations of these practices. The average SOC sequestration rate of SCS management was 7.53 Mg CO2-eq. ha−1 yr−1 to a 30-cm soil depth. The highest SOC sequestration rate (11.06 Mg CO2-eq. ha−1 yr−1) was achieved under a combination of OA+NT and the lowest (2.82 Mg CO2-eq. ha−1 yr−1) was observed under PR treatments. Field experiments performed in particularly hot and dry bioclimatic zones were associated with lower SOC sequestration rates relative to those performed in more temperate areas. The high SOC sequestration rates obtained for many SCS practices, and the large land area dedicated to viticulture worldwide (7.45 Mha), imply that the adoption of SCS practices in vineyards can contribute to the global efforts to offset atmospheric greenhouse gas concentrations via SOC sequestration to mitigate climate change.

Pseudoexfoliation (PEX) syndrome is a systemic disease involving the extracellular matrix. It increases the risk of glaucoma, an irreversible cause of blindness, and susceptibility to heart disease, stroke and hearing loss. Single nucleotide polymorphisms (SNPs) in the LOXL1 (Lysyl oxidase-like 1) gene are the major known genetic risk factor for PEX syndrome. Two coding SNPs, rs1048861 (G > T; Arg141Leu) and rs3825942 (G > A; Gly153Asp), in the LOXL1 gene are strongly associated with the disease risk in multiple populations worldwide. In the present study, we investigated functional effects of these SNPs on the LOXL1 protein. We show through molecular modelling that positions 141 and 153 are likely surface residues and hence possible recognition sites for protein-protein interactions; the Arg141Leu and Gly153Asp substitutions cause charge changes that would lead to local differences in protein electrostatic potential and in turn the potential to modify protein-protein interactions. In RFL-6 rat fetal lung fibroblast cells ectopically expressing the LOXL1 protein variants related to PEX (Arg141_Gly153, Arg141_Asp153 or Leu141_Gly153), immunoprecipitation of the secreted variants showed differences in their processing by endogenous proteins, possibly Bone morphogenetic protein-1 (BMP-1) that cleaves and leads to enzymatic activation of LOXL1. Immunofluorescence labelling of the ectopically expressed protein variants in RFL-6 cells showed no significant difference in their extracellular accumulation tendency. In conclusion, this is the first report of a biological effect of the coding SNPs in the LOXL1 gene associated with PEX syndrome, on the LOXL1 protein. The findings indicate that the disease associated coding variants themselves may be involved in the manifestation of PEX syndrome. Refereed/Peer-reviewed

Introduction Interfractional anatomical alterations may have a differential effect on the dose delivered by step-and-shoot intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT). The increased degrees of freedom afforded by rotational delivery may increase plan robustness (measured by change in target volume coverage and doses to organs at risk [OARs]). However, this has not been evaluated for head and neck cancer. Materials and methods A total of 10 patients who required repeat computed tomography (CT) simulation and replanning during head and neck IMRT were included. Step-and-shoot IMRT and VMAT plans were generated from the original planning scan. The initial and second CT simulation scans were fused and targets/OAR contours transferred, reviewed, and modified. The plans were applied to the second CT scan and doses recalculated without repeat optimization. Differences between step-and-shoot IMRT and VMAT for change in target volume coverage and doses to OARs between first and second CT scans were compared by Wilcoxon signed rank test. Results There were clinically relevant dosimetric changes between the first and the second CT scans for both the techniques (reduction in mean D 95% for PTV2 and PTV3, D min for CTV2 and CTV3, and increased mean doses to the parotid glands). However, there were no significant differences between step-and-shoot IMRT and VMAT for change in any target coverage parameter (including D 95% for PTV2 and PTV3 and D min for CTV2 and CTV3) or dose to any OARs (including parotid glands) between the first and the second CT scans. Conclusions For patients with head and neck cancer who required replanning mainly due to weight loss, there were no significant differences in plan robustness between step-and-shoot IMRT and VMAT. This information is useful with increased clinical adoption of VMAT.

Background Acute cervical lymphadenitis is a common condition often times requiring antibiotic therapy and possible surgical drainage. The objective of this study was to describe the clinical characteristics, diagnostic and therapeutic management of children requiring surgical drainage for acute cervical lymphadenitis. Methods A retrospective, descriptive study was performed at a Midwestern US tertiary-care children's hospital on all immunocompetent children who underwent an incision and drainage procedure of cervical lymphadenitis from January 1999 to July 2009. Results A total of 277 patients were identified. Males represented 51% and the median age was 28 months (IQR: 13–59). Lymphadenitis was unilateral in 243 (87.7%) cases and bilateral in 19 (6.9%). Median length of hospital stay was 4 days (IQR: 3–5). Aerobic, anaerobic, acid fast bacillus (AFB), and fungal cultures were obtained intraoperatively in 99%, 98%, 82%, and 78% of cases, respectively. However no fungal cultures were positive and only 1% of anaerobic and 2% of AFB cultures were positive. The most common bacterial etiology was Staphylococcus aureus (35.7%) and Streptococcus pyogenes (18.8%). Of all cultures, 32% were negative. Overall, 22% were positive for methicillin susceptible S. aureus (MSSA) and 13.7% for methicillin resistant S. aureus (MRSA), with 96% MSSA and 100% MRSA susceptible to clindamycin. Median duration of discharge antibiotics prescribed was 10 days (IQR: 7–11). Only 12 (4.5%) patients required a repeat incision and drainage within 3 months. Conclusions A single antibiotic that treats S. pyogenes and S. aureus should be the empiric antibiotic for cervical lymphadenitis requiring incision and drain. We recommend sending only aerobic cultures intraoperatively as a routine practice as other pathogens are rare.

Aims Nasopharyngeal cancer (NPC) is relatively uncommon, especially in the Western world. We report our single institution experience of 20 years of data in 128 patients with NPC, including responses to different treatment modalities and outcomes by histological subtype. Materials and methods NPC patients presenting from 1992 to 2005 were located on the cancer registry database. Demographic data included age, gender, length of presenting symptoms and stage. World Health Organization classification (2005) was used for histological subtyping. The date of recurrence and survival outcomes were analysed using Kaplan–Meier curves. Results Presentation data were analysed from 128 patients; the survival analysis included 123 patients. The median age at presentation was 57.7 years. Stage III and IV presentation rates were 34 and 38%, respectively. The most common presenting symptom was a palpable neck lump (55%) and the median duration of symptoms was 16 weeks. Forty-eight patients received radiotherapy alone and 75 received chemoradiotherapy. The median overall survival in chemoradiotherapy patients was 80.3 months versus 28.5 months with radiotherapy alone ( P = 0.003). A significant difference was also seen with recurrence-free survival (RFS) ( P = 0.017). Type 1 keratinising carcinoma had a significantly worse overall survival ( P = 0.04) and a similar but non-statistically significant trend was seen for RFS ( P = 0.051). The multivariate analysis for overall survival showed that histological subtype (hazard ratio 2.7, 95% confidence interval 1.3–5.5, P = 0.034), age (hazard ratio 2.3, 95% confidence interval 1.1–4.9, P = 0.018) and N stage (hazard ratio 3.7, 95% confidence interval 1.4–9.4, P = 0.024) were prognostic factors. Conclusions We present the first large-scale, single-centre retrospective review of NPC in a UK-based population. Demographic data were similar to that in other Western populations, with a significantly worse survival outcome in the keratinising group. Further prospective study of outcome in Western populations accounting for newer radiotherapy techniques such as intensity-modulated radiotherapy and dose escalation, particularly in the keratinising population who were more likely to present with an isolated local recurrence, is recommended.

Our aim was to investigate the effect of active manuka honey on radiation-induced mucositis. A total of 131 patients diagnosed with head and neck cancer who were having radiotherapy to the oral cavity or oropharyngeal area were recruited into the study, and were randomly allocated to take either manuka honey or placebo (golden syrup) 20 ml 4 times daily for 6 weeks. Mucositis was assessed according to the Radiation Therapy Oncology Group (RTOG) scale at baseline, weekly during radiotherapy, and twice weekly thereafter until the mucositis resolved. The patient's weight was recorded at the same time as the mucositis was assessed. Throat swabs to identify bacterial or fungal infections were taken at baseline, and during and after radiotherapy. There was no significant difference between honey and golden syrup in their effects on mucositis. Active manuka honey did not improve mucositis, but both the honey and the syrup seemed to be associated with a reduction in bacterial infections. Compliance was a problem after the onset of mucositis, which may have affected the findings.

We present the scientific case for inclusion of penetrators into the Europan surface, and the candidate instruments which could significantly enhance the scientific return of the joint ESA/NASA Europa-Jupiter System Mission (EJSM). Moreover, a surface element would provide an exciting and inspirational mission highlight which would encourage public and political support for the mission. Whilst many of the EJSM science goals can be achieved from the proposed orbital platform, only surface elements can provide key exploration capabilities including direct chemical sampling and associated astrobiological material detection, and sensitive habitability determination. A targeted landing site of upwelled material could provide access to potential biological material originating from deep beneath the ice. Penetrators can also enable more capable geophysical investigations of Europa (and Ganymede) interior body structures, mineralogy, mechanical, magnetic, electrical and thermal properties. They would provide ground truth, not just for the orbital observations of Europa, but could also improve confidence of interpretation of observations of the other Jovian moons. Additionally, penetrators on both Europa and Ganymede, would allow valuable comparison of these worlds, and gather significant information relevant to future landed missions. The advocated low mass penetrators also offer a comparatively low cost method of achieving these important science goals. A payload of two penetrators is proposed to provide redundancy, and improve scientific return, including enhanced networked seismometer performance and diversity of sampled regions. We also describe the associated candidate instruments, penetrator system architecture, and technical challenges for such penetrators, and include their current status and future development plans.

Purpose The patient’s role in toxicity reporting is increasingly acknowledged but requires the adaptation and validation of toxicity reporting instruments for patient use as most toxicity scales are designed for physician use. Recording of radiotherapy related late toxicity is important and needs to be improved. A patient-scored symptom questionnaire of late treatment effects using LENT–SOMA was compared with a recognised quality of life tool (EORTC QLQ-C30/H&N35). Materials/methods LENT–SOMA and EORTC QLQ-C30 patient questionnaires were prospectively completed by 220 head and neck cancer patients over 3 years and 72 completed EORTC QLQ-H&N35 questionnaires at 2 years post-radiotherapy. Results Endpoints common to both questionnaires (pain, swallowing, dental pain, dry mouth, opening mouth, analgesics) were matched. Spearman rank correlation coefficients with ρ > 0.6 (P < 0.001) were obtained for all “matched” scales except for analgesics scale, ρ = 0.267 (P < 0.05). There was good agreement between LENT–SOMA and EORTC QLQ-H&N35 except for analgesic endpoints. Global quality of life scores correlated negatively with average LENT–SOMA scores (P < 0.001). Significant differences in average LENT–SOMA scores between treatment modalities were found. The LENT–SOMA questionnaire has demonstrated a high Cronbach’s α value (0.786) indicating good reliability. Conclusions LENT–SOMA patient questionnaire results agreed well with those from the EORTC QLQ-H&N35 questionnaire for toxicity items where they could be compared explicitly, particularly for subjective endpoints. Patient-reported late toxicity had a negative impact on quality of life. The LENT-SOMA patient questionnaire is both reliable and sensitive to differences between patients treated with different modalities. A patient-based questionnaire is an important contributor to capturing late radiotherapy effects.

The Venetian adventurer Nicolò Manuzzi composed a detailed manuscript about the Moghul Empire late in the 17th century towards the end of his life. It contained an accurate description of the Indian Rhinoplasty. Although it was returned to Europe from India early in the 18th century it was never published. Had it been disseminated amongst the surgeons of the day we can speculate that the 'BL' letter to the Gentleman's Magazine in 1794 would not have been such a surgical 'bombshell' but more a damp squib! This paper records Manuzzi's story which finally came to light when his manuscript was translated into English and published in 1907. We believe that these details are not well known amongst plastic surgeons.

Purpose: Patient-based reporting of symptoms is increasingly important in providing treatment toxicity information. However, observer-based scoring systems such as the CTCAEs which incorporate the LENT-SOMA scales are not adapted for patient-based reporting. We aim to (1) report the late toxicity in patients following head and neck radiotherapy using a LENT-SOMA patient-based questionnaire, (2) describe how the responses help to improve the questionnaire and (3) adapt the questionnaire for patient reporting using CTCAEs. Methods: A 31-item LENT-SOMA patient questionnaire was administered prospectively to 220 patients pre-treatment and at eight time periods post-radical head and neck radiotherapy over 3 years. Exploratory factor analysis was carried out and questionnaire reliability was evaluated using Cronbach’s α coefficient. Results: At 3-years follow-up, grade 3/4 toxicity was recorded for xerostomia (44%), hoarseness (14.3%), altered taste (6.1%) and oropharyngeal pain (1.9%). Factor analysis indicated that questionnaire division according to anatomical sub-site was reasonable. Cronbach’s α was 0.851 (95% CI: 0.820–0.883) indicating high reliability. Good compliance was obtained with all questions except for the ‘weight loss’ item. A satisfaction survey showed that the questionnaire was clear and concise. Teeth and mandible sections have been removed. Dietary change due to xerostomia has been incorporated in line with CTCAEs. LENT-SOMA scoring of analgesic needs and dysphagia not described in CTCAEs were found useful and have been retained. Conclusions: The questionnaire has enabled reporting of late toxicity and the responses have enabled refinement of the questionnaire. It is reliable, feasible and has been validated for patient-based collection of CTCAEs late toxicity data.

Data was retrospectively analysed on 72 consecutive patients treated primarily with resection and concomitant neck dissection for intraoral carcinomas. Twenty prognostic variables were assessed by univariate analysis to assess their influence on survival. Seven variables were significant at the 5% level. Survival was negatively influenced by six tumour related factors, increasing T stage (P=0.039), increasing N stage (P=0.004), greater than two nodes histologically positive nodal disease (P=0.017), tumour size4 cm (P=0.022), residual disease at the primary site (P=0.012), extracapsular nodal spread (P=0.01) and the one treatment related factor analysed, adjuvant radiotherapy (P=0.039). Subsequent multivariate analysis was performed via the cox stepwise regression method to assess the influence on survival of all factors which achieved significance at the 20% level. There were only two variables which made a significant difference (P0.05) to the multivariate model. The presence of lymphovascular invasion (P=0.015) and histological evidence of mandibular invasion (P=0.047). Lymphovascular invasion appeared in the final model despite not achieving statistical significance at the 5% level on univariate analysis. A final cox survival model was constructed. The relative risk of death for those with cervical metastases (N2 and above) at diagnosis was 3.74 (P=0.005). The addition of lymphovascular invasion to the cox model revealed an increase in the relative risk of death in the presence of lymphovascular invasion of 2.99 (P=0.015). Patients with nodal negative disease and one single node positive provided the baseline risk as there was no significant difference between these two groups. The presence of histological evidence of lymphovascular invasion in oral carcinoma surgical specimens has a significant impact on survival outcome in oral carcinoma patients.

Introduction Post-operative residual disease in differentiated thyroid cancer is an indication for external beam radiotherapy (EBRT) especially if there is poor radioiodine uptake by the residual disease. There are no standardized guidelines or consensus in target delineation for radiotherapy in thyroid cancer. Aims To determine the pattern of recurrence in patients with well differentiated thyroid cancer who received adjuvant or definitive radiotherapy as well as radioiodine ablation following surgery or biopsy with a view to better defining future target volume delineation for radiotherapy. Materials and methods Forty-nine patients with differentiated thyroid cancer received radical external beam radiotherapy and radioiodine ablation (3.5 GBq) following thyroidectomy or biopsy between 1990 and 2000. Nineteen patients had macroscopic residual (11) or inoperable disease (8), whilst 30 patients had clear (5) or microscopic positive resection margin (24), and 1 patient the resection margin status was unknown. All the patients were deemed high risk for local recurrence or progressive disease. The thyroid bed and regional nodes were irradiated using two radiotherapy techniques: (1) non co-planar lateral fields (NCLF) in coronal plane using 6 MV photons to a dose of 45–50 Gy in 16 fractions over 22 days and (2) anterior–posterior parallel pair of 6 MV photons to a dose of 40–42.5 Gy in 16 fractions over 22 days. There was no attempt to irradiate the lymph nodes in that part of the anterior and posterior mediastinum extending from the brachiocephalic veins to the carina. Results The median follow-up was 5.4 years (range 0.9–12.4 years). The actuarial 5-year cause-specific survival and local control for the whole group was 75.7% and 81.4%, respectively. Of the 4 patients with mediastinal recurrence, all had neck recurrences and two had distant metastases. All the medisastinal recurrences occurred in superior mediastinum (level VII) and all were treated with NCLF in coronal plane radiotherapy technique. Furthermore, mediastinal recurrences did not occur in isolation. The 5-years loco-regional control rate was 89.1% for those with clear or microscopic positive margins and 69.2% for those with macroscopic residual or inoperable disease. Five-year cause specific survival was 58.3% for patients with macroscopic residual or inoperable disease and 91.4% for those with clear or microscopic positive margins. Conclusion The status of postoperative margin relating to bulk of disease influences local control and cause specific survival. Surgical resection in locally advanced thyroid cancer should be performed by an experienced surgeon to achieve macroscopic clearance where possible. The majority of recurrences were loco-regional. The few superior mediastinal recurrences did not occur in isolation. All the mediastinal recurrences occurred in the superior mediastinum (level VII). We recommend the target volume should encompass the thyroid bed and regional neck nodes and the superior mediastinum level VII excluding the lymph nodes on both sides of the trachea within the anterior and posterior mediastinum extending from the brachiocephalic veins to the carina (compartment 4). Thus, this should facilitate dose escalation to improve loco-regional control and avoiding radiation induced mediastinal toxicity.

Background and purpose To identify objective pre-treatment clinical parameters that could be used to predict for patients at high risk of requiring enteral tube feeding prior to head and neck radiotherapy. Patients and methods A retrospective study was conducted on 160 consecutive patients attending for radiotherapy assessment. Regression analysis was used to determine various pre-treatment nutritional and tumour specific parameters associated with the use of enteral nutrition either before (prophylactic) or during (reactive) radiotherapy (RT). The significant parameters identified were then selected into categorical variables and compared between those who needed reactive enteral nutrition and the remainder of the group who did not. These results were used to generate predictive factors that could be used to identify those at high risk of malnutrition during RT for whom early or prophylactic enteral nutrition should be considered. Results Fifty patients required enteral feeding of which 60% required this prior to radiotherapy. Multivariate analysis identified the following factors to be significant—body mass index, performance status (PS), advanced stage, pre-treatment weight loss, low serum albumin and protein, age, and smoking. The most significant categorical predictive parameters for reactive enteral feeding were stage 3–4 disease, PS 2-3, and smoking >20/day. The combination of these factors predicted a 75% chance of needing enteral nutrition. Conclusion Nutritional assessment is important prior to radiotherapy and is multifactorial. Using a combination of relatively simple and objective parameters, (performance status, smoking and disease stage) it is possible to identify those at high risk of needing enteral nutrition prior to starting RT.

We have established a method to estimate the number of clones in peripheral blood, using rearranged T cell receptor γ genes as clonal markers, selecting cells at random, and establishing the sizes of the clones to which they belong. Clone sizes were quantified by a clone-specific PCR test based on the VNJ junctional sequence, which typically detects 1–2 copies of its target gene. All clones chosen for study were subsequently quantified in blood, and sizes ranged from 3 × 10 − 6 (1 cell in 330,000 CD8+CD45RO+ cells) to 3.5 × 10 − 2 permitting numbers of clones to be estimated from the harmonic mean of clone size. Two independent estimates from a healthy young adult (20–30 years old) gave repertoires of 94,000 and 110,000 clones. Two other healthy young adults gave repertoires of 40,000 and 55,000 clones. Repertoires in four healthy active older (> 75 years old) adults were more variable but generally lower, being 3600, 5500, 14,000 and 97,000 clones, despite enlarged clones making up > 1% of the compartment in the last individual. Overall, young adults had smaller clones ( p = 0.026, non-directional Mann–Whitney U -test). If the human body contains 5 l of blood, clones have 2 × 10 3 –1.0 × 10 7 cells in blood. These results confirm a diverse repertoire of rearranged T cell receptor gamma genes. The number of clones thus defined are broadly consistent with other estimates of repertoire, despite differences in marker genes used and subsets of cells studied.

Alginate/antacid anti-reflux preparations are designed to provide symptom relief by forming a physical barrier on top of the stomach contents in the form of a neutral floating gel or raft. This study tested the in vitro effectiveness of a range of liquid products in forming rafts that were cohesive, buoyant, voluminous, resistant to reflux and durable under conditions of movement (resilient). The products tested had a wide range of acid neutralising capacities (ANCs). It was found that products with a high ANC and no calcium ion source formed rafts of low strength, weight and volume, which appeared more as floating precipitates than coherent gels. Products with a high ANC and a calcium ion source formed medium strength, weight and volume rafts. Products with a low ANC formed strong coherent rafts with medium to large weight and volume, and those with low ANC and a calcium ion source formed the strongest rafts. Products with stronger rafts were found to be more resilient and more resistant to reflux in an in vitro reflux model. Significant overall differences in raft buoyancy were found between products forming coherent rafts but these could not be related to the product formulation or amount of available carbon dioxide.

The pKZ1 recombination mutagenesis model has provided a sensitive assay where we study somatic intrachromosomal recombination (SICR) as a mutation end-point. SICR is associated with non-homologous end-joining repair of double-strand breaks and can result in chromosomal inversions and deletions, both of which are common chromosomal aberrations identified in cancers. It has been difficult to study the effect of cancer-associated genes on chromosomal changes prior to tumour formation in vivo because of a lack of appropriate test systems. We hypothesised that cancer-associated genes play a role in formation of chromosomal aberrations and that the pKZ1 model would provide a system in which such a role could be studied in the initial steps of carcinogenesis. Transgenic tumour model mice were bred to pKZ1 mice to produce double transgenic animals. SICR inversion events were scored in mouse tissues at an early time, prior to evident tumour formation, and compared with endogenous pKZ1 SICR levels. Over-expression of the c-myc proto-oncogene resulted in a significant 2.1-fold increase in SICR in spleen. Loss of Msh2 and expression of the SV40 T antigen resulted in a significantly reduced SICR frequency (0.3 of the endogenous frequency in pKZ1 mice) in spleen and prostate respectively. Therefore SICR was affected in the case of all three cancer-associated genes studied. We hypothesise that the increase and decrease in SICR in the presence of cancer-associated genes results from incorrect repairing of double-strand breaks. The data presented here suggest that the pKZ1 model may provide a powerful tool for studying the effect of cancer-associated genes on chromosomal changes in the early stages of carcinogenesis.