Stomach Dose-Volume Predicts Acute Gastrointestinal Toxicity in Chemoradiotherapy for Locally Advanced Pancreatic Cancer.

AIMS: Gastrointestinal toxicity impedes dose escalation in chemoradiotherapy for hepatobiliary malignancies. Toxicity risk depends on clinical and radiotherapy metrics. We aimed to identify predictive factors using data from two prospective phase II clinical trials of locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: Ninety-one patients with available data from the ARCII (59.4 Gy in 33 fractions with gemcitabine, cisplatin and nelfinavir, n = 23) and SCALOP (50.4 Gy in 28 fractions with capecitabine or gemcitabine, n = 74) trials were studied. The independent variables analysed comprised age, sex, performance status, baseline symptoms, tumour size, weight loss, chemotherapy regimen and dose-volume histogram of stomach and duodenum in 5 Gy bins. The outcome measures used were Common Terminology Criteria of Adverse Events (CTCAE) grade and risk of CTCAE grade ≥2 acute upper gastrointestinal toxicity (anorexia, pain, nausea and/or vomiting). The risk of CTCAE grade ≥2 events was modelled using multivariable logistic regression and prediction of severity grade using ordinal regression. RESULTS: CTCAE grade ≥2 symptoms occurred in 38 patients (42%). On univariate analysis, stomach V35-45Gy was predictive of risk (odds ratio 1.035, 95% confidence interval 1.007-1.063) and grade (1.023, 1.003-1.044) of toxicity. The area under the curve was 0.632 (0.516-0.747) with toxicity risk 33/66 (50%) above and 5/25 (20%) below the optimal discriminatory threshold (7.1 cm3). Using a threshold of 30 cm3, risk was 13/20 (65%) versus 25/71 (35%). The optimal multivariable logistic regression model incorporated patient sex, chemotherapy regimen and stomach V35-45Gy. Receiving gemcitabine rather than capecitabine (odds ratio 3.965, 95% confidence interval 1.274-12.342) and weight loss during induction chemotherapy (1.216, 1.043-1.419) were significant predictors for the SCALOP cohort, whereas age predicted toxicity risk in ARCII only (1.344, 1.015-1.780). Duodenum dose-volume did not predict toxicity risk or severity in any cohort. CONCLUSIONS: In chemoradiotherapy for LAPC the volume of stomach irradiated to a moderately high dose (35-45 Gy) predicts the incidence and severity of acute toxicity. Other predictive factors can include age, sex, recent weight loss and concomitant chemotherapy agents.

Molecular Taxonomy and Tumourigenesis of Colorectal Cancer.

Over the last 5 years there has been a surge in interest in the molecular classification of colorectal cancer. The effect of molecular subtyping on current treatment decisions is limited to avoidance of adjuvant 5-fluorouracil chemotherapy in stage II microsatellite unstable-high disease and avoidance of epidermal growth factor receptor-targeted antibodies in extended RAS mutant tumours. The emergence of specific novel combination therapy for the BRAF-mutant cohort and of the microsatellite unstable-high cohort as a responsive group to immune checkpoint inhibition shows the growing importance of a clinically relevant molecular taxonomy. Clinical trials such as the Medical Research Council FOCUS4 trial using biomarkers to select patients for specific therapies are currently open and testing such approaches. The integration of mutation, gene expression and pathological analyses is refining our understanding of the biological subtypes within colorectal cancer. Sharing of data sets of parallel sequencing and gene expression of thousands of cancers among independent groups has allowed the description of disease subsets and the need for a validated consensus classification has become apparent. This biological understanding of the disease is a key step forward in developing a stratified approach to patient management. The discovery of stratifiers that predict a response to existing and emerging therapies will enable better use of these treatments. Improved scientific understanding of the biological characteristics of poorly responsive subgroups will facilitate the design of novel biologically rational combinations. Novel treatment regimens, including the combination of new drugs with radiation, and the discovery and validation of their associated predictive biomarkers will gradually lead to improved outcomes from therapy.

Care, compassion and courage: the museum of mental health nursing - an ethnographic archaeology.

Like a museum with carefully positioned exhibits mental health nursing would look different if the display of fashionable dead things in its cultural lineage were viewed through a different lens. This paper has the aim of using transcribed interview data from mental health nurses to explore how their perception of nursing culture represents a particular historical identity (pseudo names given to ensure confidentiality). The paper discusses five themes about the formation of collective identity and concludes that mental health nurses are theoretically well positioned to develop and rethink social recovery models, ideas about fragmented selves and multiple histories that the postmodern age now curates.

I spy with my little eye something beginning with O: looking at what the myth of 'doing the observations' means in mental health nursing culture.

Those who are familiar with psychiatric inpatient settings will be aware of the expressions 'doing the obs', 'being on checks' and 'special observations'. That is because the task of observing patients is seen as being pivotal to the mental health nursing role. This paper describes an ethnographic research project that offers a rethinking of psychiatric observation. The author uses data from an ethnographic research project to provide an examination of the structure, process and outcome of this seemingly straightforward nursing task and explores how 'doing the obs' has additional symbolic and cultural meaning similar to what Barthes terms myth. The symbolic connotations are numerous and wide-ranging and expose a practice that could be said to punctuate daily activities and an ordering of relationships between nurses and services users. The classic sociological issues of status, power and containment are all relevant, yet rethought. The use of ethnographic research allowed the author to focus on the more symbolic cultural dynamics and develop five initial ethnographic themes concerning the constituting experience of watching and being watched.

Using transactional analysis to understand the supervisory process.

Most literature on supervision praises its ability to create space for reflection, but seldom explores the disabling effects. Using the experiences of four nurses, this article makes use of Berne's Transactional Analysis model as a method for illuminating patterns within supervision. The article concludes that the confessional nature of clinical supervision reflects contemporary practice and the implications of supervision really appear to be an undercover policing or enforcement of cultural/management objectives.

Who's the boss? Children's perception of hospital hierarchy.

Young people in an in-patient mental health unit seemed to recognise that a hierarchy existed within the multidisciplinary team and that it had an effect upon their care and treatment. A literature review suggested that the prevailing culture perpetuated a hierarchy and those who get things done ('the bosses') have power while nurses have 'relational' power (Souminen et al 1997). The views of 35 in-patients aged between 13 and 17 years were obtained using a questionnaire and discussion. These young people believed that doctors (and possibly psychologists) make the important decisions, with nurses perceived as being 'all rounders' with no particular authority. Other professionals had distinct roles but were also subordinate. The findings of this exploratory study are relevant for the multidisciplinary team but further studies are needed to identify more specific implications for practice.

Favourite patients: exploring labelling in inpatient culture.

In this article, the author reports on a research study into the issue of favouritism in nursing, exploring theory relevant to the topic. The study focused on the nature of favouritism in nursing. Its explorative and descriptive nature allowed interviews to be conducted with nurses. They acknowledged that attachment and boundaries seem to be the most important issues related to favouritism. However, some of the participants pondered on the notion that personal characteristics of both patients and nurses affect the nature of nurse-patient interaction and attachment. The study has enabled discussion about these various aspects of practice and provides some tentative conclusions.

PAT: advanced nursing interventions for eating disorders.

Passive activity time (PAT) is a nursing intervention that was developed for young people with eating disorders. This development was a pioneering attempt to examine the nursing care for this client group and improve treatment programmes. Nursing practice before PAT was dominated by a biomedical model which directed a set procedure of care for all patients, focusing primarily on weight restoration. The prominent interventions were bed rest for any patient who was under weight and a strict dietary regimen. PAT was the result of a change in nursing practice towards a more holistic philosophy of care. This article will describe the rationale behind its development and discuss its potential in future nursing practice for people experiencing anorexia nervosa.

A little lady called Pandora: an exploration of philosophical traditions of humanism and existentialism in nursing ill children.

This article battles its way through the contemporary philosophical assumptions regarding interactions with traumatized young people. That is, interaction by nurses as they attempt to provide 'a shoulder to cry on', 'someone to trust' or just simply 'a hand to hold'. The young people that are nursed in the hospital setting have experienced illness, surgery and recovery to name just a few, but when confronted with being separated from their families, being frightened and needing a friend the role of nursing takes on many different facets. The child (Pandora) a traumatized child taken from home to a new strange place, is warmly accepted by carers who seem to share a set of beliefs and assumptions about relationships and interaction. This article aims to explore the effects humanist and existentialist philosophy has had in guiding current nursing practice using extracts from his own practice and observations.

Observing nurse-patient interaction.

This article describes an observational study of nurses' interactions with mentally ill young people in a regional adolescent unit. Nurses initiated more than twice as many interactions as patients and were consistent in the average length of time they interacted with the young people. The author recommends that future studies include more qualitative data on the nature of interactions.