Is simulation training effective in increasing podiatrists' confidence in foot ulcer management?

Background: Foot ulcers are a frequent reason for diabetes-related hospitalisation. Clinical training is known to have a beneficial impact on foot ulcer outcomes. Clinical training using simulation techniques has rarely been used in the management of diabetes-related foot complications or chronic wounds. Simulation can be defined as a device or environment that attempts to replicate the real world. The few non-web-based foot-related simulation courses have focused solely on training for a single skill or “part task” (for example, practicing ingrown toenail procedures on models). This pilot study aimed to primarily investigate the effect of a training program using multiple methods of simulation on participants’ clinical confidence in the management of foot ulcers. Methods: Sixteen podiatrists participated in a two-day Foot Ulcer Simulation Training (FUST) course. The course included pre-requisite web-based learning modules, practicing individual foot ulcer management part tasks (for example, debriding a model foot ulcer), and participating in replicated clinical consultation scenarios (for example, treating a standardised patient (actor) with a model foot ulcer). The primary outcome measure of the course was participants’ pre- and post completion of confidence surveys, using a five-point Likert scale (1 = Unacceptable-5 = Proficient). Participants’ knowledge, satisfaction and their perception of the relevance and fidelity (realism) of a range of course elements were also investigated. Parametric statistics were used to analyse the data. Pearson’s r was used for correlation, ANOVA for testing the differences between groups, and a paired-sample t-test to determine the significance between pre- and post-workshop scores. A minimum significance level of p < 0.05 was used. Results: An overall 42% improvement in clinical confidence was observed following completion of FUST (mean scores 3.10 compared to 4.40, p < 0.05). The lack of an overall significant change in knowledge scores reflected the participant populations’ high baseline knowledge and pre-requisite completion of web-based modules. Satisfaction, relevance and fidelity of all course elements were rated highly. Conclusions: This pilot study suggests simulation training programs can improve participants’ clinical confidence in the management of foot ulcers. The approach has the potential to enhance clinical training in diabetes-related foot complications and chronic wounds in general.

Standardising practices improves ambulatory diabetic foot management and reduces amputations : the Queensland Diabetic Foot Innovation Project, 2006 – 2009

Background Diabetic foot complications are recognised as the most common reason for diabetic related hospitalisation and lower extremity amputations. Multi-faceted strategies to reduce diabetic foot hospitalisation and amputation rates have been successful. However, most diabetic foot ulcers are managed in ambulatory settings where data availability is poor and studies limited. The project aimed to develop and evaluate strategies to improve the management of diabetic foot complications in three diverse ambulatory settings and measure the subsequent impact on ospitalisation and amputation. Methods Multifaceted strategies were implemented in 2008, including: multi-disciplinary teams, clinical pathways and training, clinical indicators, telehealth support and surveys. A retrospective audit of consecutive patient records from July 2006 – June 2007 determined baseline clinical indicators (n = 101). A clinical pathway teleform was implemented as a clinical record and clinical indicator analyser in all sites in 2008 (n = 327) and followed up in 2009 (n = 406). Results Prior to the intervention, clinical pathways were not used and multi-disciplinary teams were limited. There was an absolute improvement in treating according to risk of 15% in 2009 and surveillance of the high risk population of 34% and 19% in 2008 and 2009 respectively (p < 0.001). Improvements of 13 – 66% (p < 0.001) were recorded in 2008 for individual clinical activities to a performance > 92% in perfusion, ulcer depth, infection assessment and management, offloading and education. Hospitalisation impacts recorded reductions of up to 64% in amputation rates / 100,000 population (p < 0.001) and 24% average length of stay (p < 0.001) Conclusion These findings support the use of multi-faceted strategies in diverse ambulatory services to standardise practice, improve diabetic foot complications management and positively impact on hospitalisation outcomes. As of October 2010, these strategies had been rolled out to over 25 ambulatory sites, representing 66% of Queensland Health districts, managing 1,820 patients and 13,380 occasions of service, including 543 healed ulcer patients. It is expected that this number will rise dramatically as an incentive payment for the use of the teleform is expanded.

Exercise, appetite and weight management: understanding the compensatory responses in eating behaviour and how they contribute to variability in exercise-induced weight loss

Does exercise promote weight loss? One of the key problems with studies assessing the efficacy of exercise as a method of weight management and obesityis that mean data are presented and the individual variability in response is overlooked. Recent data have highlighted the need to demonstrate and characterise the individual variability in response to exercise. Do people who exercise compensate for the increase in energy expenditure via compensatory increases in hunger and food intake? The authors address the physiological, psychological and behavioural factors potentially involved in the relationship between exercise and appetite, and identify the research questions that remain unanswered. A negative consequence of the phenomena of individual variability and compensatory responses has been the focus on those who lose little weight in response to exercise; this has been used unreasonably as evidence to suggest that exercise is a futile method of controlling weight and managing obesity. Most of the evidence suggests that exercise is useful for improving body composition and health. For example, when exercise-induced mean weight loss is <1.0 kg, significant improvements in aerobic capacity (+6.3 ml/kg/min), systolic (−6.00 mm Hg) and diastolic (−3.9 mm Hg) blood pressure, waist circumference (−3.7 cm) and positive mood still occur. However, people will vary in their responses to exercise; understanding and characterising this variability will help tailor weight loss strategies to suit individuals.

Involvement of KLF4 in sulforaphane- and iberin-mediated induction of p21waf1/cip1

Sulforaphane (SF; 4-methylsulfinylbutyl isothiocyanate), a dietary compound derived from broccoli, may exhibit chemopreventive properties by inducing cell cycle arrest via induction of cyclin-dependent kinase inhibitor 1A (p21(waf1/cip1)), but the exact molecular mechanism has not been determined. Here we evaluate the role of the transcription factor Kruppel-like factor 4 (KLF4) in mediating the induction of p21(waf1/cip1) and cellular differentiation by SF and iberin (IB; 3-methylsulphinyl propyl isothiocyanate), also derived from broccoli. Exposure of Caco-2 and Caco-2/TC7 cells to SF and IB increased expression of both KLF4 and p21(waf1/cip1), whereas exposure of HT29 cells resulted only in induction of p21(waf1/cip1). In Caco-2 cells, small interfering RNA knock down of KLF4 expression attenuated induction of p21(waf1/cip1) in response to either SF or IB treatment. Contrary to expectation, prolonged exposure to SF reduced sucrase isomaltase activity, a marker of small intestinal differentiation in Caco-2 cells. Additional support for the SF-mediated induction of p21(waf1/cip1) by KLF4 was obtained from analyses of gastric tissue of Apc(Min/+) mice following acute intervention with SF but not from the analyses of other tissue of the intestinal tract. These results suggest that induction of p21(waf1/cip1) by SF or IB may be partly mediated by KLF4 in some colon cancer cells and tissues.

Clinical trial of the Norton Scale in acute care settings

This study investigated the effect of using Norton Scale assessment data in the nursing care of patients at risk of developing pressure ulcers. The results indicated that incorporating the Norton Scale in care planning resulted in benefits to patients through earlier and more effective nursing interventions.

Elevated uric acid correlates with wound severity

Chronic venous leg ulcers are a major health issue and represent an often overlooked area of biomedical research. Nevertheless, it is becoming increasingly evident that new approaches to enhance healing outcomes may arise through better understanding the processes involved in the formation of chronic wounds. We have for the first time shown that the terminal purine catabolite uric acid (UA) is elevated in wound fluid (WF) from chronic venous leg ulcers with relative concentrations correlating with wound chronicity. We have also shown a corresponding depletion in UA precursors, including adenosine, with increased wound severity. Further, we have shown that xanthine oxidase, the only enzyme in humans that catalyses the production of UA in conjunction with a burst of free radicals, is active in chronic WF. Taken together, this provides compelling evidence that xanthine oxidase may play a critical role in the formation of chronic wounds by prolonging the inflammatory process.

Association between ambient ultraviolet radiation and risk of esophageal cancer

OBJECTIVES: Ecological studies have suggested an inverse relationship between latitude and risks of some cancers. However, associations between solar ultraviolet radiation (UVR) exposure and esophageal cancer risk have not been fully explored. We therefore investigated the association between nevi, freckles, and measures of ambient UVR over the life-course with risks of esophageal cancers. METHODS: We compared estimated lifetime residential ambient UVR among Australian patients with esophageal cancer (330 esophageal adenocarcinoma (EAC), 386 esophago-gastric junction adenocarcinoma (EGJAC), and 279 esophageal squamous cell carcinoma (ESCC)), and 1471 population controls. We asked people where they had lived at different periods of their life, and assigned ambient UVR to each location based on measurements from NASA's Total Ozone Mapping Spectrometer database. Freckling and nevus burden were self-reported. We used multivariable logistic regression models to estimate the magnitude of associations between phenotype, ambient UVR, and esophageal cancer risk. RESULTS: Compared with population controls, patients with EAC and EGJAC were less likely to have high levels of estimated cumulative lifetime ambient UVR (EAC odds ratio (OR) 0.59, 95% confidence interval (CI) 0.35-0.99, EGJAC OR 0.55, 0.34-0.90). We found no association between UVR and risk of ESCC (OR 0.91, 0.51-1.64). The associations were independent of age, sex, body mass index, education, state of recruitment, frequency of reflux, smoking status, alcohol consumption, and H. pylori serostatus. Cases with EAC were also significantly less likely to report high levels of nevi than controls. CONCLUSIONS: These data show an inverse association between ambient solar UVR at residential locations and risk of EAC and EGJAC, but not ESCC.

How much do residential aged care staff members know about the nutritional needs of residents?

Background Undernutrition, weight loss and dehydration are major clinical issues for people with dementia in residential care, with excessive weight loss contributing to increased risk of frailty, immobility, illness and premature morbidity. This paper discusses a nutritional knowledge and attitudes survey conducted as part of a larger project focused on improving nutritional intake of people with dementia within a residential care facility in Brisbane, Australia. Aims The specific aims of the survey were to identify (i) knowledge of the nutritional needs of aged care facility residents; (ii) mealtime practices; and (iii) attitudes towards mealtime practices and organisation. Methods A survey based on those used in other healthcare settings was completed by 76 staff members. The survey included questions about nutritional knowledge, opinions of the food service, frequency of feeding assistance provided and feeding assessment practices. Results Nutritional knowledge scores ranged from 1 to 9 of a possible 10, with a mean score of 4.67. While 76% of respondents correctly identified risk factors associated with malnutrition in nursing home residents, only 38% of participants correctly identified the need for increased protein and energy in residents with pressure ulcers, and just 15% exhibited correct knowledge of fluid requirements. Further, while nutritional assessment was considered an important part of practice by 83% of respondents, just 53% indicated that they actually carried out such assessments. Identified barriers to promoting optimal nutrition included insufficient time to observe residents (56%); being unaware of residents' feeding issues (46%); poor knowledge of nutritional assessments (44%); and unappetising appearance of food served (57%). Conclusion An important step towards improving health and quality of life for residents of aged care facilities would be to enhance staff nutritional awareness and assessment skills. This should be carried out through increased attention to both preservice curricula and on-the-job training. Implications for practice The residential facility staff surveyed demonstrated low levels of nutrition knowledge, which reflects findings from the international literature. This has implications for the provision of responsive care to residents of these facilities and should be explored further.

Nurse staffing levels and the incidence of mortality and morbidity in the adult intensive care unit : a literature review

BACKGROUND: Studies have shown that nurse staffing levels, among many other factors in the hospital setting, contribute to adverse patient outcomes. Concerns about patient safety and quality of care have resulted in numerous studies being conducted to examine the relationship between nurse staffing levels and the incidence of adverse patient events in both general wards and intensive care units. AIM: The aim of this paper is to review literature published in the previous 10 years which examines the relationship between nurse staffing levels and the incidence of mortality and morbidity in adult intensive care unit patients. METHODS: A literature search from 2002 to 2011 using the MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and Australian digital thesis databases was undertaken. The keywords used were: intensive care; critical care; staffing; nurse staffing; understaffing; nurse-patient ratios; adverse outcomes; mortality; ventilator-associated pneumonia; ventilator-acquired pneumonia; infection; length of stay; pressure ulcer/injury; unplanned extubation; medication error; readmission; myocardial infarction; and renal failure. A total of 19 articles were included in the review. Outcomes of interest are patient mortality and morbidity, particularly infection and pressure ulcers. RESULTS: Most of the studies were observational in nature with variables obtained retrospectively from large hospital databases. Nurse staffing measures and patient outcomes varied widely across the studies. While an overall statistical association between increased nurse staffing levels and decreased adverse patient outcomes was not found in this review, most studies concluded that a trend exists between increased nurse staffing levels and decreased adverse events. CONCLUSION: While an overall statistical association between increased nurse staffing levels and decreased adverse patient outcomes was not found in this review, most studies demonstrated a trend between increased nurse staffing levels and decreased adverse patient outcomes in the intensive care unit which is consistent with previous literature. While further more robust research methodologies need to be tested in order to more confidently demonstrate this association and decrease the influence of the many other confounders to patient outcomes; this would be difficult to achieve in this field of research.

A prospective observational study of patient positioning in a Saudi intensive care unit

Aim: To describe the positioning of patients managed in an intensive care unit (ICU); assess how frequently these patients were repositioned; and determine if any specific factors influenced how, why or when patients were repositioned in the ICU. Background: Alterations in body position of ICU patients are important for patient comfort and are believed to prevent and/or treat pressure ulcers, improve respiratory function and combat the adverse effects of immobility. There is a paucity of research on the positioning of critically ill patients in Saudi Arabian ICUs. Design and Methods: A prospective observational study was undertaken. Participant demographic data were collected as were clinical factors (i.e. ventilation status, primary diagnosis, co-morbidities and Ramsay sedation score) and organizational factors (i.e. time of day, type of mattress or beds used, nurse/patient ratio and the patient's position). Clinical and some organization data were recorded over a continuous 48 hour period. Result: Twenty-eight participants were recruited to the study. No participant was managed in either a flat or prone position. Obese participants were most likely to be managed in a supine position. The mean time between turns was two hours. There was no significant association between the mean time between turns and the recorded variables related to patients' demographic and organizational considerations. Conclusion: Results indicate that patient positioning in the ICU was a direct result of unit policy - it appeared that patients were not repositioned based upon evaluation of their clinical condition but rather according to a two-hour ICU timetable

The function and mechanisms of action of ghrelin and obestatin in ovarian cancer

In this study, we have demonstrated that the preproghrelin derived hormones, ghrelin and obestatin, may play a role in ovarian cancer. Ghrelin and obestatin stimulated an increase in cell migration in ovarian cancer cell lines and may play a role in cancer progression. Ovarian cancer is the leading cause of death among gynaecological cancers and is the sixth most common cause of cancer-related deaths in women in developed countries. As ovarian cancer is difficult to diagnose at a low tumour grade, two thirds of ovarian cancers are not diagnosed until the late stages of cancer development resulting in a poor prognosis for the patient. As a result, current treatment methods are limited and not ideal. There is an urgent need for improved diagnostic markers, as well better therapeutic approaches and adjunctive therapies for this disease. Ghrelin has a number of important physiological effects, including roles in appetite regulation and the stimulation of growth hormone release. It is also involved in regulating the immune, cardiovascular and reproductive systems and regulates sleep, memory and anxiety, and energy metabolism. Over the last decade, the ghrelin axis, (which includes the hormones ghrelin and obestatin and their receptors), has been implicated in the pathogenesis of many human diseases and it may t may also play an important role in the development of cancer. Ghrelin is a 28 amino acid peptide hormone that exists in two forms. Acyl ghrelin (usually referred to as ghrelin), has a unique n-octanoic acid post-translational modification (which is catalysed by ghrelin O-acyltransferase, GOAT), and desacyl ghrelin, which is a non-octanoylated form. Octanoylated ghrelin acts through the growth hormone secretagogue receptor type 1a (GHSR1a). GHSR1b, an alternatively spliced isoform of GHSR, is C-terminally truncated and does not bind ghrelin. Ghrelin has been implicated in the pathophysiology of a number of diseases Obestatin is a 23 amino acid, C-terminally amidated peptide which is derived from preproghrelin. Although GPR39 was originally thought to be the obestatin receptor this has been disproven, and its receptor remains unknown. Obestatin may have as diverse range of roles as ghrelin. Obestatin improves memory, inhibits thirst and anxiety, increases pancreatic juice secretion and has cardioprotective effects. Obestatin also has been shown to regulate cell proliferation, differentiation and apoptosis in some cell types. Prior to this study, little was known regarding the functions and mechanisms of action ghrelin and obestatin in ovarian cancer. In this study it was demonstrated that the full length ghrelin, GHSR1b and GOAT mRNA transcripts were expressed in all of the ovarian-derived cell lines examined (SKOV3, OV-MZ-6 and hOSE 17.1), however, these cell lines did not express GHSR1a. Ovarian cancer tissue of varying stages and normal ovarian tissue expressed the coding region for ghrelin, obestatin, and GOAT, but not GHSR1a, or GHSR1b. No correlations between cancer grade and the level of expression of these transcripts were observed. This study demonstrated for the first time that both ghrelin and obestatin increase cell migration in ovarian cancer cell lines. Treatment with ghrelin (for 72 hours) significantly increased cell migration in the SKOV3 and OV-MZ-6 ovarian cancer cell lines. Ghrelin (100 nM) stimulated cell migration in the SKOV3 (2.64 +/- 1.08 fold, p <0.05) and OV-MZ-6 (1.65 +/- 0.31 fold, p <0.05) ovarian cancer cell lines, but not in the representative normal cell line hOSE 17.1. This increase in migration was not accompanied by an increase in cell invasion through Matrigel. In contrast to other cancer types, ghrelin had no effect on proliferation. Ghrelin treatment (10nM) significantly decreased attachment of the SKOV3 ovarian cancer cell line to collagen IV (24.7 +/- 10.0 %, p <0.05), however, there were no changes in attachment to the other extracellular matrix molecules (ECM) tested (fibronectin, vitronectin and collagen I), and there were no changes in attachment to any of the ECM molecules in the OV-MZ-6 or hOSE 17.1 cell lines. It is, therefore, unclear if ghrelin plays a role in cell attachment in ovarian cancer. As ghrelin has previously been demonstrated to signal through the ERK1/2 pathway in cancer, we investigated ERK1/2 signalling in ovarian cancer cell lines. In the SKOV3 ovarian cancer cell line, a reduction in ERK1/2 phosphorylation (0.58 fold +/- 0.23, p <0.05) in response to 100 nM ghrelin treatment was observed, while no significant change in ERK1/2 signalling was seen in the OV-MZ-6 cell line with treatment. This suggests that this pathway is unlikely to be involved in mediating the increased migration seen in the ovarian cancer cell lines with ghrelin treatment. In this study ovarian cancer tissue of varying stages and normal ovarian tissue expressed the coding region for obestatin, however, no correlation between cancer grade and level of obestatin transcript expression was observed. In the ovarian-derived cell lines studied (SKOV3, OV-MZ-6 and hOSE 17.1) it was demonstrated that the full length preproghrelin mRNA transcripts were expressed in all cell lines, suggesting they have the ability to produce mature obestatin. This is the first study to demonstrate that obestatin stimulates cell migration and cell invasion. Obestatin induced a significant increase in migration in the SKOV3 ovarian cancer cell line with 10 nM (2.80 +/- 0.52 fold, p <0.05) and 100 nM treatments (3.12 +/- 0.68 fold, p <0.05) and in the OV-MZ-6 cancer cell line with 10 nM (2.04 +/- 0.10 fold, p <0.01) and 100 nM treatments (2.00 +/- 0.37 fold, p <0.05). Obestatin treatment did no affect cell migration in the hOSE 17.1normal ovarian epithelial cell line. Obestatin treatment (100 nM) also stimulated a significant increase in cell invasion in the OV-MZ-6 ovarian cancer cell line (1.45 fold +/- 0.13, p <0.05) and in the hOSE17.1 normal ovarian cell line cells (1.40 fold +/- 0.04 and 1.55 fold +/- 0.05 respectively, p <0.01) with 10 nM and 100 nM treatments. Obestatin treatment did not stimulate cell invasion in the SKOV3 ovarian cancer cell line. This lack of obestatin-stimulated invasion in the SKOV3 cell line may be a cell line specific result. In this study, obestatin did not stimulate cell proliferation in the ovarian cell lines and it has previously been shown to have no effect on cell proliferation in the BON-1 pancreatic neuroendocrine and GC rat somatotroph tumour cell lines. In contrast, obestatin has been shown to affect cell proliferation in gastric and thyroid cancer cell lines, and in some normal cell lines. Obestatin also had no effect on attachment of any of the cell lines to any of the ECM components tested (fibronectin, vitronectin, collagen I and collagen IV). The mechanism of action of obestatin was investigated further using a two dimensional-difference in gel electrophoresis (2D-DIGE) proteomic approach. After treatment with obestating (0, 10 and 100 nM), SKOV3 ovarian cancer and hOSE 17.1 normal ovarian cell lines were collected and 2D-DIGE analysis and mass spectrometry were performed to identify proteins that were differentially expressed in response to treatment. Twenty-six differentially expressed proteins were identified and analysed using Ingenuity Pathway Analysis (IPA). This linked 16 of these proteins in a network. The analysis suggested that the ERK1/2 MAPK pathway was a major mediator of obestatin action. ERK1/2 has previously been shown to be associated with obestatin-stimulated cell proliferation and with the anti-apoptotic effects of obestatin. Activation of the ERK1/2 signalling pathway by obestatin was, therefore, investigated in the SKOV3 and OV-MZ-6 ovarian cancer cell lines using anti-active antibodies and Western immunoblots. Obestatin treatment significantly decreased ERK1/2 phosphorylation at higher obestatin concentrations in both the SKOV3 (100 nM and 1000 nM) and OV-MZ-6 (1000 nM) cell lines compared to the untreated controls. Currently, very little is known about obestatin signalling in cancer. This thesis has demonstrated for the first time that the ghrelin axis may play a role in ovarian cancer migration. Ghrelin and obestatin increased cell migration in ovarian cancer cell lines, indicating that they may be a useful target for therapies that reduce ovarian cancer progression. Further studies investigating the role of the ghrelin axis using in vivo ovarian cancer metastasis models are warranted.

Chemotherapy-induced nausea and vomiting : a review to inform clinical practice

Chemotherapy-induced nausea and vomiting (CINV) is a common sideeffect of cytotoxic treatment and despite the widespread use of anti-emetic medication, it continues to affect a significant proportion of patients with up to 23% and 73% of chemotherapy patients still experiencing vomiting and nausea symptoms, respectively. This is of particular concern in oncology patients as nausea and vomiting may result in malnutrition, decreased quality of life and in extreme cases, treatment stoppage. Therefore, the primary aim of this paper was to inform clinicians on the current literature regarding CINV including its effect on the patient, its pathophysiology, and current treatment options. In addition, this review will also discuss the usage of dietetic interventions as well as less utilised, novel interventions such as oral ginger extracts in the treatment of CINV. In order to address these issues, a systematic literature search was conducted using Pubmed, CINAHL, MEDLINE, Embase, and Health Source (Nursing/Academic Edition). A key finding of this review was that common dietary strategies (e.g. eating slowly, avoiding fatty foods) seem to be solely based on professional opinion as no clinical trials investigating these strategies were identified. In contrast, ginger extracts were found to possess several viable mechanisms that interact with CINV progression including 5-HT3, Substance P and acetylcholine receptor antagonism; anti-inflammatory and antioxidant properties; and gastrointestinal motility and gastric emptying modulation. In conclusion, research investigating dietetic interventions in the management of CINV is sparse and requires further investigation while novel intervention such as ginger, possess multiple mechanisms that may benefit CINV management. This review will discuss the prevalence and significance of CINV, dietetic and novel treatment options, and provide implications for clinical practise and future research.

Ginger - mechanism of action in chemotherapy-induced nausea and vomiting: A review

Despite advances in anti-emetic therapy, chemotherapy-induced nausea and vomiting (CINV) still poses a significant burden to patients undergoing chemotherapy. Nausea, in particular, is still highly prevalent in this population. Ginger has been traditionally used as a folk remedy for gastrointestinal complaints and has been suggested as a viable adjuvant treatment for nausea and vomiting in the cancer context. Substantial research has revealed ginger to possess properties that could exert multiple beneficial effects on chemotherapy patients who experience nausea and vomiting. Bioactive compounds within the rhizome of ginger, particularly the gingerol and shogaol class of compounds, interact with several pathways that are directly implicated in CINV in addition to pathways that could play secondary roles by exacerbating symptoms. These properties include 5-HT3, substance P and acetylcholine receptor antagonism; anti-inflammatory properties; and modulation of cellular redox signalling, vasopressin release, gastrointestinal motility, and gastric emptying rate. This review outlines these proposed mechanisms by discussing the results of clinical, in vitro and animal studies both within the chemotherapy context and in other relevant fields. The evidence presented in this review indicates that ginger possesses multiple properties that could be beneficial in reducing chemotherapy-induced nausea and vomiting.

A phase II study of mitomycin C and oral etoposide for advanced adenocarcinoma of the upper gastrointestinal tract

Background: Mitomycin C and etoposide have both demonstrated activity against gastric carcinoma. Etoposide is a topoisomerase II inhibitor with evidence for phase-specific and schedule-dependent activity. Patients and method. Twenty-eight consecutive patients with advanced upper gastrointestinal adenocarcinoma were treated with intravenous (i.v.) bolus mitomycin C 6 mg/m2 on day 1 every 21 days to a maximum of four courses. Oral etoposide capsules 50 mg b.i.d. (or 35 mg b.i.d. liquid) were administered days 1 to 10 extending to 14 days in subsequent courses if absolute neutrophil count >1.5 x 109/l on day 14 of first course, for up to six courses. Results: Twenty-six patients were assessed for response of whom 12 had measurable disease and 14 evaluable disease. Four patients had a documented response (one complete remission, three partial remissions) with an objective response rate of 15% (95% confidence interval (95% CI) 4%-35%). Eight patients had stable disease and 14 progressive disease. The median survival was six months. The schedule was well tolerated with no treatment-related deaths. Nine patients experienced leucopenia (seven grade II and two grade III). Nausea and vomiting (eight grade II, one grade III), fatigue (eight grade II, two grade III) and anaemia (seven grade II, two grade III) were the predominant toxicities. Conclusion: This out-patient schedule is well tolerated and shows modest activity in the treatment of advanced upper gastrointestinal adenocarcinoma. Further studies using protracted schedules of etoposide both orally and as infusional treatment should be developed.

Differential pathologic variables and outcomes across the spectrum of adenocarcinoma of the esophagogastric junction

Background Adenocarcinoma of the esophagogastric junction (AEG) as described by Siewert et al. is classified as one entity in the latest (7th Edition) American Joint Cancer Committee/International Union Against Cancer (AJCC/UICC) manual, compared with the previous mix of esophageal and gastric staging systems. The origin of AEG tumors, esophageal or gastric, and their biology remain controversial, particularly for AEG type II (cardia) tumors. Methods We adapted a large prospective database (n = 520: 180 type I, 182 type II, 158 type III) to compare AEG tumors under the new TNM system Pathological variables associated with prognosis were compared (pT, pN, stage, differentiation, R status, lymphovascular invasion, perineural involvement, number of positive nodes, percent of positive nodes, and tumor length), as well as overall survival. Results Compared with AEG type I tumors, type II and type III tumors had significantly (p\0.05) more advanced pN stages, greater number and percentage of positive nodes, poorer differentiation, more radial margin involvement, and more perineural invasion. In AEG type I, 14/180 patients (8%) had[6 involved nodes (pN3), compared with 16 and 30% of patients classified type II and III, respectively. Median survival was significantly (p = 0.03) improved for type I patients (38 months) compared with those with tumors classified as type II (28 months) and type III (24 months). In multivariate analysis node positivity and pN staging but not AEG site had an impact on survival. Conclusions In this series AEG type I is associated with more favorable pathologic features and improved outcomes compared with AEG type II and III. This may reflect earlier diagnosis, but an alternative possibility, that type I may be a unique paradigm with more favorable biology, requires further study. © Société Internationale de Chirurgie 2010.