Driving developments in UK oesophageal radiotherapy through the SCOPE trials.

BACKGROUND: The SCOPE trials (SCOPE 1, NeoSCOPE and SCOPE 2) have been the backbone of oesophageal RT trials in the UK. Many changes in oesophageal RT techniques have taken place in this time. The SCOPE trials have, in addition to adopting these new techniques, been influential in aiding centres with their implementation. We discuss the progress made through the SCOPE trials and include details of a questionnaire sent to participating centres. to establish the role that trial participation played in RT changes in their centre. METHODS: Questionnaires were sent to 47 centres, 27 were returned. RESULTS: 100% of centres stated their departmental protocol for TVD was based on the relevant SCOPE trial protocol. 4DCT use has increased from 42 to 71%. Type B planning algorithms, mandated in the NeoSCOPE trial, were used in 79.9% pre NeoSCOPE and now in 83.3%. 12.5% of centres were using a stomach filling protocol pre NeoSCOPE, now risen to 50%. CBCT was mandated for IGRT in the NeoSCOPE trial. 66.7% used this routinely pre NeoSCOPE/SCOPE 2 which has risen to 87.5% in the survey. CONCLUSION: The results of the questionnaires show how participation in national oesophageal RT trials has led to the adoption of newer RT techniques in UK centres, leading to better patient care.

Oesophageal Chemoradiotherapy in the UK--current practice and future directions.

The SCOPE 1 trial closed to recruitment in early 2012 and has demonstrably improved the quality of UK radiotherapy. It has also shown that there is an enthusiastic upper gastrointestinal clinical oncology community that can successfully complete trials and deliver high-quality radiotherapy. Following on from SCOPE 1, this paper, authored by a consensus of leading UK upper gastrointestinal radiotherapy specialists, attempts to define current best practice and the questions to be answered by future clinical studies. The two main roles for chemoradiotherapy (CRT) in the management of potentially curable oesophageal cancer are definitive (dCRT) and neoadjuvant (naCRT). The rates of local failure after dCRT are consistently high, showing the need to evaluate more effective treatments, both in terms of optimal local and systemic therapeutic components. This will be the primary objective of the next planned UK dCRT trial and here we discuss the role of dose escalation and systemic therapeutic options that will form the basis of that trial. The publication of the Dutch 'CROSS' trial of naCRT has shown that this pre-operative approach can both be given safely and offer a significant survival benefit over surgery alone. This has led to the development of the UK NeoSCOPE trial, due to open in 2013. There will be a translational substudy to this trial and currently available data on the role of biomarkers in predicting response to therapy are discussed. Postoperative reporting of the pathology specimen is discussed, with recommendations for the NeoSCOPE trial. Both of these CRT approaches may benefit from recent developments, such as positron emission tomography/computed tomography and four-dimensional computed tomography for target volume delineation, planning techniques such as intensity-modulated radiotherapy and 'type b' algorithms and new treatment verification methods, such as cone-beam computed tomography. These are discussed here and recommendations made for their use.

Respiratory movement of upper abdominal organs and its effect on radiotherapy planning in pancreatic cancer.

AIMS: Radiotherapy for pancreatic cancer is complicated by the frequent overlapping of the planning target volume (PTV) and the organ at risk (OAR), limiting the dose that can be safely delivered to the tumour. Individualising the margins applied to the clinical target volume (CTV) may reduce OAR irradiation without increasing the risk of geographical miss. We quantified the movement of the pancreas with respiration and evaluated whether individualised margins based on this motion reduced the dose to OARs. MATERIALS AND METHODS: Planning computed tomography scans were acquired in quiet breathing, held expiration and held inspiration. Organ motion was evaluated from displacement of a reproducible point within the pancreas in all directions. Two sets of plans (standard plan: P(stan); individualised plan incorporating movement data: P(ind)) were generated for each patient. The PTV and doses to OARs were evaluated for both sets of plans. RESULTS: The mean (standard deviation) movement of the pancreas in the superior-inferior, lateral and anterior-posterior directions were 15.3 mm (4.3), 5.2 mm (3.5) and 9.7 mm (6.1), respectively. The use of individualised margins reduced the mean PTV volume by 33.5% (9.8) (P=0.0051). The proportional reductions in the percentage of kidney receiving >10 Gy, small bowel >45 Gy and liver >30 Gy were 63.7% (P=0.0051), 29.3% (P=0.0125) and 29.2% (P=0.0107), respectively. For the same level of OAR constraints, individualised margins allowed dose escalation in six of the 10 patients to a mean dose of 63.2 Gy. CONCLUSIONS: The present study shows a simple way of incorporating organ motion into the planning process and can be adopted by any centre without major strain on healthcare resources. The use of individualised margins reduced PTV volume and the dose to OARs. This may offer an opportunity for dose escalation to try and further improve local control.

The initiation of coronary angioplasty and stenting in a single outpatient centre in Barbados / La iniciación de la angioplastia y el estent de la arteria coronaria en un centro ambulatorio en Barbados

Percutaneous transluminal coronary angioplasty (PTCA) is a novel procedure to Barbadian healthcare. Only one centre in Barbados provides PTCA and stenting. This is a retrospective study aimed at describing the initial results of coronary angioplasty and stenting in the first 48 patients at the Carib-American Heart Centre and exploring the feasibility and safety of coronary angioplasty and stenting in Barbados. Forty-eight patients underwent PTCA during the period March 2002 to June 2004 inclusive, with or without intracoronary stenting. Most (64.6%) of the patients were male and 43.7% were diabetic. The most common vessels involved were the left anterior descending coronary artery (LAD) and the right coronary artery (RCA). In one patient, attempted stenting was unsuccessful but PTCA reduced stenosis. One patient had previous PTCA and stenting of the LAD and two patients had coronary artery bypass grafting (CABG) prior to the procedure. Twenty-one per cent of the patients treated had severe triple vessel disease. There were no cases of restenosis or acute vessel closure, during or immediately following the procedure that required emergency PTCA or CABG. All patients were discharged within 24 hours of the procedure. Procedural success was 100%. In conclusion, outpatient PTCA and stenting is safe and feasible in the Barbadian population. Coronary artery bypass grafting is still the procedure of choice for treating coronary artery disease (CAD) involving the left main coronary artery but PTCA is indicated in some cases of severe triple vessel disease.

La angioplastia coronaria transluminal percútanla (ACTP) es un procedimiento nuevo en la atención a la salud en Barbados. Sólo un centro en Barbados ofrece ACTP y estent (o cánula intraluminal de arteria coronaria). El presente trabajo es un estudio retrospectivo destinado a describir los resultados iniciales de la angioplastia y el estent coronarios en los primeros 48 pacientes en el Centro Caribe-americano de Cardiología, y explorar la factibilidad y seguridad de la angioplastia y el estent en Barbados. Cuarenta y ocho pacientes fueron sometidos a ACTP durante el periodo de marzo 2002 a junio 2004 inclusive, con o sin estent intracoronario. La mayor parte (64.6%) de los pacientes eran varones y un 43.7% eran diabéticos. Los vasos más comúnmente involucrados fueron la arteria coronaria descendente anterior izquierda (DAI) y la arteria coronaria derecha (ACD). En un paciente, el intento de estent no tuvo éxito, pero la ACTP redujo la estenosis. A un paciente le fue practicada previamente la ACTP y el estent de la DAI, y a dos pacientes se les realizó injerto de bypass de la arteria coronaria (IBAC) antes del procedimiento. El veintiún por ciento de los pacientes tratados tuvo enfermedad vascular triple. No hubo ningún caso de reestenosis o cierre vascular agudo, durante o inmediatamente después del procedimiento, que requiriera ACTP o IBAC de emergencia. Todos los pacientes fueron dados de alta dentro de las 24 horas tras el procedimiento. El éxito de los procedimientos fue del 100%. En conclusión, el estent y el ACTP ambulatorios son seguros y factibles para la población barbadense. El injerto de bypass de la arteria coronaria sigue siendo el procedimiento de elección para tratar casos de la enfermedad de la arteria coronaria (EAC) que involucren la arteria coronaria izquierda principal, pero la ACTP se indica en algunos casos de enfermedad vascular triple.

The initiation of coronary angioplasty and stenting in a single outpatient centre in Barbados.

Percutaneous transluminal coronary angioplasty (PTCA) is a novel procedure to Barbadian healthcare. Only one centre in Barbados provides PTCA and stenting. This is a retrospective study aimed at describing the initial results of coronary angioplasty and stenting in the first 48 patients at the Carib-American Heart Centre and exploring the feasibility and safety of coronary angioplasty and stenting in Barbados. Forty-eight patients underwent PTCA during the period March 2002 to June 2004 inclusive, with or without intracoronary stenting. Most (64.6%) of the patients were male and 43.7% were diabetic. The most common vessels involved were the left anterior descending coronary artery (LAD) and the right coronary artery (RCA). In one patient, attempted stenting was unsuccessful but PTCA reduced stenosis. One patient had previous PTCA and stenting of the LAD and two patients had coronary artery bypass grafting (CABG) prior to the procedure. Twventy-one per cent of the patients treated had severe triple vessel disease. There were no cases of re-stenosis or acute vessel closure, during or immediately following the procedure that required emergency PTCA or CABG All patients were discharged within 24 hours of the procedure. Procedural success was 100%. In conclusion, outpatient PTCA and stenting is safe and feasible in the Barbadian population. Coronary artery bypass grafting is still the procedure of choice for treating coronary artery disease (CAD) involving the left main coronary artery but PTCA is indicated in some cases of severe triple vessel disease.

Phenotype of FAECB (Facility for Automated Experiments in Cell Biology) Chinese hamster ovary mutants with minimal UV-sensitivity.

The Facility for Automated Experiments in Cell Biology (FAECB) collection of over 200 lines of ultraviolet (UV)-sensitive mutant Chinese hamster ovary (CHO) cells has previously been studied for complementation group assignment (CG), with representatives of rodent UV CGs 1-6 (ERCC1-6) and the new rodent XRCC9/FANCG group identified. Ten mutants from the collection, including a further six derived from wildtype AA8, three UV-sensitive double-mutants of CHO ERCC1 cell line UV4, and a UV-sensitive mutant of CHO XRCC1 cell line EM9, had not been assigned or characterized in these previous studies. These 10 mutants include 8 with approximately 1.5-fold the UV-sensitivity of the parental line (AA8, EM9, or UV4), and 2 with about 2-fold the UV-sensitivity of AA8. The present study reports the partial characterization of these 10 mutants in terms of sensitivity to UV (with and without caffeine), ionizing radiation, mitomycin C (MMC) and ethyl methanesulfonate (EMS); proficiency in DNA repair (unscheduled DNA synthesis (UDS)); and UV-mutability. The phenotypes of the 10 cell lines were heterogeneous, a number showed reduced UDS or UV-sensitization by caffeine, whilst others showed marked sensitivity to EMS or MMC, and they may have mutations in different genes involved in nucleotide excision repair, post-replicational repair, base excision repair or recombinational repair. Previous mutants isolated as part of the FAECB collection have proved to be extremely important in characterizing mammalian DNA repair processes and cloning human repair genes and these current mutants, whilst not as hypersensitive to UV, may still have the potential to make further contributions.

Primary non-Hodgkin's lymphoma of the frontal sinus: how we diagnosed it.

Isolated primary non-Hodgkin's lymphoma of the frontal sinus is rare. We describe the case of a middle-aged man who came to us with signs of orbital cellulitis complicating an acute infected frontal mucocele. His condition was initially controlled with medical therapy and subsequent endoscopic sinus surgery, but his symptoms eventually returned. We were able to diagnose the lymphoma only by approaching the sinus externally to obtain a biopsy. This case highlights the importance of making a full visual inspection of the involved sinus in order to avoid missing an unexpected, albeit a rarely encountered, pathology.

Sleep disorders in children and teens. Helping patients and their families get some rest.

Diagnosing sleep disorders in children and adolescents is challenging and rewarding and requires integration of medical, neurodevelopmental, and behavioral histories. Most patients can be successfully treated once a thorough evaluation has been completed and age-appropriate differential diagnosis of common sleep disorders has been considered. With appropriate knowledge and tools, physicians may find that pediatric sleep disorders are some of the most treatable problems in medicine.

Using hypnosis to help deaf children help themselves: report of two cases.

This is a report of deaf children who demonstrated the ability to quickly learn hypnotic skills and apply them effectively to the management of their problems. The children were taught hypnosis through American Sign Language, their preferred mode of communication. As with hypnosis with hearing children, we focused upon induction with fantasy and imaginative involvement, creation in imagination of a metaphor for, or imagery of, the desired outcome, and associated sense of pride (ego-strengthening), positive expectation, and teaching self-hypnosis to emphasize the importance of repeated, daily practice. Case examples presented are an 11-year-old deaf girl who used hypnosis to eliminate multiple warts, and a 9-year-old deaf boy with mild developmental disability whose self-hypnosis skills were applied to the management of myoclonus. In the former, the clinician is also the sign language communicator and in the latter, a professional sign language interpreter and parent are both intimately involved in the communication and hypnosis process.

Mutational analysis of the N-linked glycans on Autographa californica nucleopolyhedrovirus gp64.

gp64 is the major envelope glycoprotein in the budded form of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV). gp64 is essential for AcMNPV infection, as it mediates penetration of budded virus into host cells via the endocytic pathway. In this study, we used site-directed mutagenesis to map the positions of the N-linked glycans on AcMNPV gp64, characterize their structures, and evaluate their influence on gp64 function. We found that four of the five consensus N-glycosylation sites in gp64 are used, and we mapped the positions of those sites to amino acids 198, 355, 385, and 426 in the polypeptide chain. Endoglycosidase H sensitivity assays showed that N-linked glycans located at different positions are processed to various degrees. Lectin blotting analyses showed that each N-linked glycan on gp64 contains alpha-linked mannose, all but one contains alpha-linked fucose, and none contains detectable beta-linked galactose or alpha2,6-linked sialic acid. The amounts of infectious progeny produced by AcMNPV mutants lacking one, two, or three N-linked glycans on gp64 were about 10- to 100-fold lower than wild-type levels. This reduction did not correlate with reductions in the expression, transport, or inherent fusogenic activity of the mutant gp64s or in the gp64 content of mutant budded virus particles. However, all of the mutant viruses bound more slowly than the wild type. Therefore, elimination of one or more N-glycosylation sites in AcMNPV gp64 impairs binding of budded virus to the cell, which explains why viruses containing these mutant forms of gp64 produce less infectious progeny.

The absence of Harvey ras mutations during development and progression of squamous cell carcinomas of the head and neck.

We have examined the incidence of Harvey ras mutations in human squamous cell carcinomas (SCC) of the upper aerodigestive tract using the polymerase chain reaction (PCR) followed by direct sequencing. No mutations were detected at codons 12, 13, 59 or 61 of this gene in any of six papillomas, five erythroplakias, 56 squamous cell carcinomas, and 16 SCC cell lines. Some of the SCC were lymph node metastases (three) or tumours which had recurred following radiotherapy (seven). We conclude that Harvey ras mutations are not a common event in the pathogenesis or recurrence of SCCs from Caucasian subjects, in contrast to the situation with Indian populations (Saranath et al., 1991).

Anaerobic degradation of toluene and xylene by aquifer microorganisms under sulfate-reducing conditions.

Toluene and the three isomers of xylene were completely mineralized to CO2 and biomass by aquifer-derived microorganisms under strictly anaerobic conditions. The source of the inoculum was gasoline-contaminated sediment from Seal Beach, Calif. Evidence confirming that sulfate was the terminal electron acceptor is presented. Benzene and ethylbenzene were not degraded under the experimental conditions used. Successive transfers of the mixed cultures that were enriched from aquifer sediments retained the ability to degrade toluene and xylenes. Greater than 90% of 14C-labeled toluene or 14C-labeled o-xylene was mineralized to 14CO2. The doubling time for the culture grown on toluene or m-xylene was about 20 days, and the cell yield was about 0.1 to 0.14 g of cells (dry weight) per g of substrate. The accumulation of sulfide in the cultures as a result of sulfate reduction appeared to inhibit degradation of aromatic hydrocarbons.

Effects of pesticides on filth fly predators (Coleoptera: Histeridae, Staphylinidae; Acarina: Macrochelidae, Uropodidae) in caged layer poultry manure.

A field study on two caged layer poultry operations assessed whether selected pesticides would affect beneficial predators. Sampling was done three times during the 5-wk period before treatment, 3 d after each of two weekly treatments, and 5-6 times during the 10 wk after the second treatment. Cyromazine (0.1%) applied topically had no detrimental effect on any of the predator taxa. Dimethoate (0.5%) applied as a spot treatment to wet areas of the manure also did not reduce predator abundance. Permethrin (0.05%) applied as a direct treatment to the hens resulted in slight reductions in numbers of Histeridae and Staphylinidae in the manure. A resurgence of Fanniinae occurred at one site 3 wk after permethrin application. Treatment of whole houses with dimethoate (0.5%) resulted in short-term reductions (up to 3 wk) of predatory mites and reductions of Histeridae and Staphylinidae for 4-10 wk.