Innovations for the future of breast surgery.

BACKGROUND: Future innovations in science and technology with an impact on multimodal breast cancer management from a surgical perspective are discussed in this narrative review. The work was undertaken in response to the Commission on the Future of Surgery project initiated by the Royal College of Surgeons of England. METHODS: Expert opinion was sought around themes of surgical de-escalation, reduction in treatment morbidities, and improving the accuracy of breast-conserving surgery in terms of margin status. There was emphasis on how the primacy of surgical excision in an era of oncoplastic and reconstructive surgery is increasingly being challenged, with more effective systemic therapies that target residual disease burden, and permit response-adapted approaches to both breast and axillary surgery. RESULTS: Technologies for intraoperative margin assessment can potentially half re-excision rates after breast-conserving surgery, and sentinel lymph node biopsy will become a therapeutic procedure for many patients with node-positive disease treated either with surgery or chemotherapy as the primary modality. Genomic profiling of tumours can aid in the selection of patients for neoadjuvant and adjuvant therapies as well as prevention strategies. Molecular subtypes are predictive of response to induction therapies and reductive approaches to surgery in the breast or axilla. CONCLUSION: Treatments are increasingly being tailored and based on improved understanding of tumour biology and relevant biomarkers to determine absolute benefit and permit delivery of cost-effective healthcare. Patient involvement is crucial for breast cancer studies to ensure relevance and outcome measures that are objective, meaningful, and patient-centred.

This article describes how future innovations in science and technology influence the management of breast cancer from a surgical perspective. This work was undertaken in response to the Commission on the Future of Surgery project initiated by the Royal College of Surgeons of England.

Supportive care needs of patients following treatment for colorectal cancer: risk factors for unmet needs and the association between unmet needs and health-related quality of life-results from the ColoREctal Wellbeing (CREW) study.

PURPOSE: To investigate unmet needs of patients with colorectal cancer (CRC) at the end of treatment and whether unmet needs improve over time. Identify predictors of need following treatment and whether unmet need is associated with worse health-related quality of life (HRQoL). METHODS: As part of the UK ColoREctal Wellbeing (CREW) cohort study, patients treated for CRC completed the Supportive Care Needs Survey Short Form-34 (SCNS SF-34) 15 and 24 months following surgery, along with questionnaires measuring HRQoL, wellbeing, life events, social support, and confidence to manage their cancer before surgery, 3, 9, 15, and 24 months post-surgery. RESULTS: The SCNS SF-34 was completed by 526 patients at 15 months and 510 patients at 24 months. About one-quarter of patients had at least one moderate or severe unmet need at both time points. Psychological and physical unmet needs were the most common and did not improve over time. Over 60% of patients who reported 5 or more moderate or severe unmet needs at 15 months experienced the same level of unmet need at 24 months. HRQoL at the beginning of treatment predicted unmet needs at the end of treatment. Unmet needs, specifically physical, psychological, and health system and information needs, were associated with poorer health and HRQoL at the end of treatment. CONCLUSIONS: Unmet needs persist over time and are associated with HRQoL. Evaluation of HRQoL at the start of treatment would help inform the identification of vulnerable patients. Assessment and care planning in response to unmet needs should be integrated into person-centred care. IMPLICATIONS FOR CANCER SURVIVORS: Early identification of CRC patients at risk of unmet needs will help infrom personalised survivorship care plans. The implementation of personalised and tailored services are likely to confer HRQoL gains.

A comparison of three outcome measures of the impact of vasomotor symptoms on women's lives.

Objective: Measures of the impact of vasomotor symptoms (VMS) have been used as outcomes in clinical trials but have not been compared. This study compares the Hot Flush Rating Scale (HFRS), the Hot Flash Related Daily Interference Scale (HFRDIS), and the shorter Hot Flash Interference (HFI) scale. Methods: Baseline data were taken from two studies including healthy women (menopause transition or postmenopause) and breast cancer patients experiencing VMS. Participants completed questionnaires on sociodemographics, the HFRS, the HFRDIS, the HFI, the Work and Social Adjustment Scale (WSAS), on depression (Generalized Anxiety Disorder 7), on anxiety (Patient Health Questionnaire 9), and on use of medical services. Results: A total of 169 women (129 with history of breast cancer and 40 without) aged 54.47 (standard deviation [SD] = 9.11) years took part. They had an average of 66 (SD = 40.94) VMS per week, with a mean HFRS problem-rating of 6.53 (SD = 1.99), HFRDIS score of 5.36 (SD = 2.22), and HFI score of 6.13 (SD = 2.30). The HFRS problem-rating, HFRDIS, and HFI were significantly associated (r = 0.61-0.85), had good internal reliability (α = 0.76-0.91), and had significant concurrent validity with mood, the WSAS, and use of medical services. VMS frequency was not associated with mood, the WSAS, or use of medical services. Conclusion: The HFRS problem-rating scale and the HFI are two brief, three-item measures that measure a similar concept of VMS interference/impact, with evidence of reliability and validity.

Factors associated with intentional and unintentional non-adherence to adjuvant endocrine therapy following breast cancer.

Adherence to adjuvant endocrine therapy (AET) following breast cancer is known to be suboptimal despite its known efficacy in reducing recurrence and mortality. This study aims to investigate factors associated with non-adherence and inform the development of interventions to support women and promote adherence. A questionnaire survey to measure level of adherence, side effects experienced, beliefs about medicine, support received and socio-demographic details was sent to 292 women 2-4 years post breast cancer diagnosis. Differences between non-adherers and adherers to AET were explored, and factors associated with intentional and unintentional non-adherence are reported. Approximately one quarter of respondents, 46 (22%), were non-adherers, comprising 29 (14%) intentional non-adherers and 17 (8%) unintentional non-adherers. Factors significantly associated with intentional non-adherence were the presence of side effects (p < .03), greater concerns about AET (p < .001) and a lower perceived necessity to take AET (p < .001). Half of the sample (105/211) reported that side effects had a moderate or high impact on their quality of life. Factors associated with unintentional non-adherence were younger age (<65) (p < .001), post-secondary education (p = .046) and paid employment (p = .031). There are distinct differences between intentional non-adherence and unintentional non-adherence. Differentiation between the two types of non-adherence may help tailor support and advice interventions.

Helping Patients to Help Themselves after Breast Cancer Treatment.

There is a rise in the number of women living with the long-term consequences of cancer and continuing to suffer unmet need as breast cancer survival improves. This paper includes an introduction to self-management and a discussion of the evidence around the effectiveness of the key intervention types that could help patients to help themselves after treatment. Self-management interventions are particularly beneficial in reducing bother from symptoms, without patients having to take on the additional burden of more unwanted side-effects frequently seen with pharmacological interventions. There is a need to prioritise the funding of these financially viable self-management strategies to ensure equity of access and that these interventions are available for those in need.

Managing fatigue after cancer treatment: development of RESTORE, a web-based resource to support self-management.

OBJECTIVE: The aim of this study is to co-create an evidence-based and theoretically informed web-based intervention (RESTORE) designed to enhance self-efficacy to live with cancer-related fatigue (CRF) following primary cancer treatment. METHODS: A nine-step process informed the development of the intervention: (1) review of empirical literature; (2) review of existing patient resources; (3) establish theoretical framework; (4) establish design team with expertise in web-based interventions, CRF and people affected by cancer; (5) develop prototype intervention; (6) user testing phase 1; (7) refinement of prototype; (8) user testing phase 2; and (9) develop final intervention. RESULTS: Key stakeholders made a critical contribution at every step of intervention development, and user testing, which involved an iterative process and resulted in the final intervention. The RESTORE intervention has five sessions; sessions 1 and 2 include an introduction to CRF and goal setting. Sessions 3-5 can be tailored to user preference and are designed to cover areas of life where CRF may have an impact: home and work life, personal relationships and emotional adjustment. CONCLUSIONS: It is feasible to systematically 'co-create' an evidence-based and theory-driven web-based self-management intervention to support cancer survivors living with the consequences of cancer and its treatment. This is the first account of the development of a web-based intervention to support self-efficacy to manage CRF. An exploratory trial to test the feasibility and acceptability of RESTORE is now warranted.

Cancer survivors' self-efficacy to self-manage in the year following primary treatment.

PURPOSE: Cancer survivors are increasingly expected to manage the consequences of cancer and its treatment for themselves. There is evidence that self-efficacy is important for successful self-management and that this can be enhanced with support. The purpose of this study was to assess self-efficacy to manage problems in the year following primary treatment. METHODS: This cross-sectional online survey included cancer survivors who had completed their treatment within the past 12 months. Self-efficacy was assessed and variables expected to be associated with self-efficacy were measured using validated scales including quality of life, well-being, illness perceptions, depression and social support. RESULTS: One hundred eighty-two respondents (mean age 50; 81% female) completed the survey. They had been treated for a range of cancers; most commonly breast (45%). Self-efficacy scores varied between individuals and according to the illness-related task to be managed. Respondents were least confident in managing fatigue and most confident in accessing information about their cancer. Individuals most likely to report low self-efficacy were women, those experiencing higher levels of pain and/or depression, lower well-being scores, lower socio-economic status, low levels of social support, or a more negative perception of cancer. CONCLUSIONS: Self-efficacy to self-manage problems faced as a consequence of cancer and its treatment can vary widely in the year following treatment. Fatigue may be particularly difficult to manage. IMPLICATIONS FOR CANCER SURVIVORS: Variations in self-efficacy highlight the importance of assessing specific problems faced and people's confidence to manage them in order to tailor appropriate self-management support.

Recovery and self-management support following primary cancer treatment.

BACKGROUND: Around 2 million people are living with or beyond cancer in the UK. However, experiences and needs following primary treatment are relatively neglected. Following treatment, survivors may feel particularly vulnerable and face threats to their identity. We present a conceptual framework to inform areas of self-management support to facilitate recovery of health and well-being following primary cancer treatment. METHODS: To explain the framework, we draw on data from two studies: UK-wide consultation about cancer patients' research priorities and survivors' self-management in the year following primary cancer treatment. RESULTS: Self-confidence may be low following treatment. Recovery includes rebuilding lost confidence. Support to manage the impact of cancer on everyday life was a priority. Self-management support included health professionals, peers, employers, family, friends and online resources. However, support was not always available and confidence to access support could be low. CONCLUSION: Cancer survivors may struggle to self-manage following primary treatment where confidence is low or support is lacking. Low confidence may be a significant barrier to accessing support. Supporting recovery of self-confidence is an important aspect of recovery alongside physical and psychosocial problems in the context of changing health care and cancer follow-up.

A survey of provision of breast care nursing for patients with metastatic breast cancer--implications for the role.

The role of the breast care nurse was developed in the UK and is now being adopted internationally. Although evidence is available to suggest that the role is beneficial in the care of women with primary breast cancer, it is emerging that women with metastatic breast cancer do not receive the same level of support. This study aimed to develop an understanding of the role of the breast care nurse in the provision of care for patients with metastatic breast cancer. A cross-sectional survey of 276 breast care nurses in the UK found that 91% of breast care nurses stated that they provided care for patients with metastatic disease and 81% provided ongoing information and support. However 57% of breast care nurses acknowledged that the provision of care for this population was inadequate and many reported feeling ill equipped to care for women with progressive disease. Care pathways for this patient group are unstructured and ill defined complicating the efforts of breast care nurses to identify and provide care for them. In conclusion, the current nursing service for women with metastatic breast cancer is inadequate but many breast care nurses are working to address this.

Menopausal hot flushes after breast cancer.

The study aimed to improve understanding of the natural history and impact of hot flushes after breast cancer. Data were collected from women participating in an RCT of relaxation to reduce the incidence of flushes from breast cancer follow-up clinics from two hospitals in South-East England. Repondents were 150 women experiencing hot flushes following completion of primary treatment for breast cancer. This study utilized a flush diary, the Hot Flushes and Night Sweats Questionnaire (HFNSQ), Functional Assessment of Cancer Therapy with Endocrine Subscale (FACT-ES) and Spielberger State/Trait Anxiety Index (STAI) as the main outcome measures. The study found that in this sample, 51 (34%) women experienced flushes more than five years after diagnosis and 75 (50%) more than 5 years after menopause. Sleep disruption occurred in 90 women (72% of those that returned diaries), affecting half of the nights they recorded. The mean problem rating on the HFNSQ was 4.85 out of 10. A peak incidence of flushes was apparent around 10 a.m. in women taking tamoxifen. It was concluded that hot flushes after breast cancer may be long-lasting and cause sleeping difficulties for many women. Tamoxifen may affect the diurnal pattern of flushes. After breast cancer, the duration of flushes, potential distress and disruption to women's lives should not be underestimated and appropriate interventions should be offered.

The experience of hot flushes after breast cancer.

As survival from breast cancer increases, there is a corresponding rise in the number of women living with the long-term consequences of its treatment. Distressing menopausal hot flushes occur in many of these women. This article reports on interviews conducted with 8 women, exploring the experience of hot flushes after breast cancer. Women's accounts of hot flushes varied from being a mild sensation to an intensely unpleasant sensation affecting the whole body and accompanied by drenching perspiration. Flushes affected all aspects of the women's lives, including sleeping, clothing, social situations, intimate relationships, and ability to work. Emotionally, women talked about being out of control. Having cancer and menopause simultaneously made it more difficult for the women to cope, and cancer treatment could cause flushing. The women used many strategies to help relieve their difficulties. Some resorted to hormone replacement therapy, whereas others turned to herbal medications and other alternative interventions such as acupuncture. Most women adopted behavioral strategies to try to regain control. Ultimately, they found that control was gained by attitude of mind. Cognitive behavioral techniques may enhance the sense of control and contribute to coping during hot flushes.

Preoperative chemotherapy for resectable thoracic esophageal cancer.

BACKGROUND: Surgery has been the treatment of choice for localized esophageal cancer. A number of studies have investigated whether preoperative chemotherapy followed by surgery leads to an improvement in cure rates but the individual reports have been conflicting. An explicit systematic update of the role of preoperative chemotherapy in the treatment of resectable thoracic esophageal cancer is, therefore, warranted. OBJECTIVES: The objective of this review is to determine the role of preoperative chemotherapy on patients with resectable thoracic esophageal carcinomas. SEARCH STRATEGY: Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to 2006), EMBASE (1988 to 2006) and CANCERLIT (1993 to 2002). There were no language restrictions. SELECTION CRITERIA: All trials of patients with potentially resectable carcinomas of the esophagus (of any histologic type) who were randomised to having either chemotherapy or no chemotherapy before surgery. DATA COLLECTION AND ANALYSIS: The primary outcome was survival, which was assessed using hazard ratios. This is an amendment to the original review which used relative risks to assess survival at yearly intervals. Hazard ratios (HR) have now been introduced to summarise the complete survival experience in a single analysis. The risk ratio (relative risk; RR) was used to compare rates of resections, tumour recurrences and treatment morbidity and mortality. MAIN RESULTS: There were eleven randomised trials involving 2019 patients. Eight trials (1729 patients) reported sufficient detail on survival to be included in a meta-analysis for the primary outcome. There was some evidence to suggest that preoperative chemotherapy improves survival, but this was inconclusive (HR 0.88; 95% CI 0.75 to 1.04). There was no evidence to suggest that the overall rate of resections (RR 0.96, 95% CI 0.92 to 1.01) or the rate of complete resections (R0) (RR 1.05; 95% CI 0.97 to 1.15) differ between the preoperative chemotherapy arm and surgery alone. There is no evidence that tumour recurrence (RR 0.81, 95% CI 0.54 to 1.22) or non-fatal complication rates (RR 0.90; 95% CI 0.76 to 1.06) differ for preoperative chemotherapy compared to surgery alone. Trials reported risks of toxicity with chemotherapy that ranged from 11% to 90%. AUTHORS' CONCLUSIONS: In summary, preoperative chemotherapy plus surgery may offer a survival advantage compared to surgery alone for resectable thoracic esophageal cancer, but the evidence is inconclusive. There is some evidence of toxicity and preoperative mortality associated with chemotherapy.

Distribution of Escherichia coli O157 in bovine fecal pats and its impact on estimates of the prevalence of fecal shedding.

The distribution of Escherichia coli O157 in bovine feces was examined by testing multiple samples from fecal pats and determining the density of E. coli O157 in immunomagnetic separation (IMS)-positive fecal samples. The density of E. coli O157 in bovine feces was highly variable, differing by as much as 76,800 CFU g(-1) between samples from the same fecal pat. The density in most positive samples was <100 CFU g(-1), the limit of reliable detection by IMS. Testing only one 1-g sample of feces per pat with IMS may result in a sensitivity of detection as low as 20 to 50%. It is therefore probable that most surveys have greatly underestimated the prevalence of E. coli O157 shedding in cattle and the proportion of farms with shedding cattle. The sensitivity of the detection of E. coli O157 in bovine feces can be as much as doubled by testing two 1-g samples per pat rather than one 1-g sample.

Preoperative chemotherapy for resectable thoracic esophageal cancer.

BACKGROUND: Surgery has been the treatment of choice for localized esophageal cancer. A number of studies have investigated whether preoperative chemotherapy followed by surgery leads to an improvement in cure rates, but the individual reports have been conflicting. An explicit systematic update of the role of preoperative chemotherapy in the treatment of resectable thoracic esophageal cancer is therefore warranted. OBJECTIVES: The objective of this review is to determine the role of preoperative chemotherapy on patients with resectable thoracic esophageal carcinomas. SEARCH STRATEGY: Trials were identified by searching the Cochrane Controlled Trials Register, MEDLINE (1966 - 2003), EMBASE (1988 - 2003) and CancerLit (1993 - 2003). There were no language restrictions. SELECTION CRITERIA: Types of studies. Studies that randomised patients with potentially resectable carcinomas of the esophagus (of any histologic type) to chemotherapy or no chemotherapy before surgeries were included in this review. Types of participants. The participants consisted of patients with localized potentially resectable thoracic esophageal carcinomas. Trials involving patients with carcinomas of the cervical esophagus were excluded. Types of interventions. Trials that compared chemotherapy before surgery (esophagectomy) with surgical resections alone (esophagectomy) were included. Types of outcome measures. The primary outcome was overall survival at yearly intervals after randomisation. Secondary outcomes of interest included rates of resections, response to chemotherapy, rates of local and distant recurrences, quality-of-life, and treatment morbidity and mortality. DATA COLLECTION AND ANALYSIS: All analyses were carried out on intention-to-treat. Survival at 1, 2, 3, 4 and five years were used as endpoints of clinical relevance along with the median survival. The risk ratio (relative risk; RR) was the primary measure of effect for survival, rates of resections, and tumour recurrences. The risk difference (RD) was used to describe differences in response to chemotherapy, treatment morbidity and mortality. MAIN RESULTS: There were 11 randomised trials involving 2051 patients. At 1- year and 2-year the risk ratios showed no difference in survival between preoperative chemotherapy and surgery alone. The 3-year risk ratios found a 21% increase in survival (RR = 1.21; 95% CI 0.88 to 1.68; p = 0.25) and a 24% increase in survival with preoperative chemotherapy at 4 years (RR = 1.24; 95% CI 0.92 to 1.68; p = 0.15) but they did not reach statistical significance. Only at 5 years did the results become significant (RR = 1.44; 95% CI 1.05 to 1.97; p = 0.02). The overall rate of resections and the rate of complete resections (R0) did not differ between the preoperative chemotherapy arm and surgery alone. The pooled clinical response to chemotherapy was about 36% (RD = 0.36; 95% CI 0.26 to 0.47) but the complete pathologic response was a disappointing 3% (RD = 0.03; 95% CI 0.01 to 0.04). No single agent or combination of chemotherapeutic agents was found to be superior to the others. There was a 19% reduction in local recurrence with preoperative chemotherapy, but this was not significant (RR = 0.81; 95% CI 0.54 to 1.22; p = 0.3). Preoperative chemotherapy was somewhat more harmful to patients than surgery alone. REVIEWER'S CONCLUSIONS: In summary, preoperative chemotherapy plus surgery appears to offer a survival advantage at 3, 4, and 5 years, which reached significance only at 5 years compared to surgery alone for resectable thoracic esophageal cancer of any histologic type. The number needed to treat for one extra survivor at five years is eleven patients. The results are tempered by the increased toxicity and mortality associated with chemotherapy. The most beneficial chemotherapy combination appears to be cisplatin and 5-flurouracil based, however, the dosing is unclear.

Transfer of antibiotic resistance between commensal and pathogenic members of the Enterobacteriaceae under ileal conditions.

AIM: To determine the rate of antibiotic resistance transmission between commensal and pathogenic representatives of the Enterobacteriaceae. METHODS AND RESULTS: Through the use of a validated in vitro simulation of the porcine ileum, the transmission of antibiotic resistance was detected between commensal Escherichia coli, E. coli O157 and Salmonella spp. Countable transconjugant populations arose readily and, in one example, proved capable of indefinite persistence. CONCLUSIONS: Genetic material conferring antibiotic resistance is readily transmissible between members of the Enterobacteriaceae under ileal conditions. Recipient phenotype influences the persistence of multi-resistant transconjugants. SIGNIFICANCE AND IMPACT OF THE STUDY: The observation that the conjugal transmission of antibiotic resistance is commonplace under ileal conditions impacts primarily on the risk of food contamination by multi-resistant bacteria. The establishment of a multi-resistant transconjugant population as a dominant member of the microflora maintains a genetic reservoir of antimicrobial resistance.

Influence of tetracycline exposure on tetracycline resistance and the carriage of tetracycline resistance genes within commensal Escherichia coli populations.

AIMS: To assess the influence of incremental tetracycline exposure on the genetic basis of tetracycline resistance within faecal Escherichia coli. METHODS AND RESULTS: Through the adoption of a novel combination of multiple breakpoint selection, phenotypic characterization and the application of a polymerase chain reaction based gene identification system it proved possible to monitor the influence of antibiotic exposure on resistance gene possession. Using tetracycline as a case study a clear hierarchy was revealed between tet genes, strongly influenced by host antimicrobial exposure history. CONCLUSIONS: The antimicrobial exposure regime under which an animal is produced affects both the identity and magnitude of resistance gene possession of a selected bacterial population within its enteric microflora. Among the ramifications associated with such resistance gene selection is the degree of resistance conferred and the carriage of linked resistance determinants. This selection is applied by exposure to antibiotic concentrations well below recognized minimum inhibitory tetracycline concentration breakpoints widely adopted to characterize bacterial 'susceptibility'. SIGNIFICANCE AND IMPACT OF THE STUDY: This study confirms the ability of minimal antibiotic exposure to select for the continued persistence of resistance genes within the enteric microflora. It is clearly demonstrated that different antimicrobial regimes select for different resistance genes, the implications of which are discussed.

The quantitative measurement of antimicrobial resistance in Escherichia coli at the meta-population level (meta-population analysis).

AIMS: To define a method that describes antimicrobial resistance of meta-populations of bacteria in both a quantitative and biologically meaningful way. METHODS AND RESULTS: Using spiral plating and colony counting technology we obtained, from animal faecal samples, the density of Escherichia coli that grow at different concentrations of antibiotic. A mathematical description of this dose-response curve fitted the data well. The parameters of this model have biological meaning and the model allowed subtle differences between meta-populations to be detected. CONCLUSIONS: This method, termed MPA (meta-population analysis), is practical and provides a useful quantitative description of antimicrobial resistance in a bacterial meta-population. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that resistance can be defined quantitatively. The method may be used in many epidemiological and clinical studies of antimicrobial resistance in animals and humans.

Long-term survival of Escherichia coli O157 on pasture following an outbreak associated with sheep at a scout camp.

AIMS: To monitor the decay of E. coli O157 in soil (loamy sand) on a scout campsite following an outbreak in humans. METHODS AND RESULTS: Samples of soil and sheep faeces were collected from the campsite and tested for the presence of E. coli O157 by immunomagnetic separation (IMS) after enrichment in buffered peptone water + vancomycin at 42 degrees C for 6 h. Enumeration of target was carried out by direct plating onto sorbitol MacConkey agar plates supplemented with cefixime and tellurite (CTSMAC) incubated at 37 degrees C for 24 h. Low numbers (< 100 g(-1)) were estimated by the most probable number (3-tube MPN) technique. CONCLUSIONS: Survival was observed for 15 weeks. SIGNIFICANCE AND IMPACT OF THE STUDY: A number of laboratory studies have followed the decay of E. coli O157 in soil, animal faeces and water. This study follows (for the first time) the decay of the organism in soil after an outbreak associated with sheep. It demonstrates the long-term persistence of the organism in the environment and the results will be potentially important in performing risk assessments for both human and animal infection.