BACKGROUND: Procedural pain reduces the quality of life of cancer patients. Although there are recommendations for its prevention, there are some obstacles for its management. The purpose of this study was to analyze the barriers to procedural pain prophylaxis in cancer patients reflecting the views of the nurses.
METHODS: We used qualitative methodology based on semi-structured interviews conducted with nurses, focusing on practices of venipuncture-induced and needle change for implantable central venous access port (ICVAP) pain management in cancer patients. A thematic analysis approach informed the data analysis.
RESULTS: Interviews were conducted with 17 nurses. The study highlighted 4 main themes; technical and relational obstacles, nurses' professional recognition, the role of the team, and organizational issues. Participants understood the painful nature of venipuncture. Despite being aware of the benefits of the anesthetic patch, they did not utilize it in a systematic way. We identified several barriers at different levels: technical, relational and previous experience of incident pain. Several organizational issues were also highlighted (e.g. lack of protocol, lack of time).
CONCLUSIONS: The prevention of venipuncture-induced cancer pain requires a structured training program, which should reflect the views of nurses in clinical practice.

Background A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than with letrozole alone in the initial treatment of postmenopausal women with estrogen-receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We performed a phase 3 study that was designed to confirm and expand the efficacy and safety data for palbociclib plus letrozole for this indication. Methods In this double-blind study, we randomly assigned, in a 2:1 ratio, 666 postmenopausal women with ER-positive, HER2-negative breast cancer, who had not had prior treatment for advanced disease, to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was progression-free survival, as assessed by the investigators; secondary end points were overall survival, objective response, clinical benefit response, patient-reported outcomes, pharmacokinetic effects, and safety. Results The median progression-free survival was 24.8 months (95% confidence interval [CI], 22.1 to not estimable) in the palbociclib-letrozole group, as compared with 14.5 months (95% CI, 12.9 to 17.1) in the placebo-letrozole group (hazard ratio for disease progression or death, 0.58; 95% CI, 0.46 to 0.72; P<0.001). The most common grade 3 or 4 adverse events were neutropenia (occurring in 66.4% of the patients in the palbociclib-letrozole group vs. 1.4% in the placebo-letrozole group), leukopenia (24.8% vs. 0%), anemia (5.4% vs. 1.8%), and fatigue (1.8% vs. 0.5%). Febrile neutropenia was reported in 1.8% of patients in the palbociclib-letrozole group and in none of the patients in the placebo-letrozole group. Permanent discontinuation of any study treatment as a result of adverse events occurred in 43 patients (9.7%) in the palbociclib-letrozole group and in 13 patients (5.9%) in the placebo-letrozole group. Conclusions Among patients with previously untreated ER-positive, HER2-negative advanced breast cancer, palbociclib combined with letrozole resulted in significantly longer progression-free survival than that with letrozole alone, although the rates of myelotoxic effects were higher with palbociclib-letrozole. (Funded by Pfizer; PALOMA-2 ClinicalTrials.gov number, NCT01740427 .).

BACKGROUND: This is an update of the Cochrane systematic review of shared decision-making (SMD) making published in 2013. Children's rights to have their views heard in matters that affect their lives are now well established since the publication of the UN Convention treaty (1989). Children with cancer generally prefer to be involved in decision-making and consider it important that they have the opportunity to take part in decision-making concerning their health care, even in end-of-life decisions. There is considerable support for involving children in healthcare decision-making at a level commensurate with their experience, age and abilities. Thus, healthcare professionals and parents need to know how they should involve children in decision-making and what interventions are most effective in promoting SDM for children with cancer.
OBJECTIVES: To examine the effects of SDM interventions on the process of SDM for children with cancer who are aged four to 18 years.
SEARCH METHODS: We searched the following sources for the review: Cochrane Central Register of Controlled Studies (CENTRAL) (the Cochrane Library 2016, Issue 1); PubMed (NLM) (1946 to February 2016); Embase (Ovid) (1974 to February 2016); CINAHL (EBSCO) (1982 to February 2016); ERIC (ProQuest) (1966 to February 2016); PsycINFO (EBSCO) (1806 to February 2016); BIOSIS (Thomson Reuters) (1980 to December 2009 - subscription ceased at that date); ProQuest Dissertations and Theses (1637 to February 2016); and Sociological Abstracts (ProQuest) (1952 to February 2016). In addition we searched the reference lists of relevant articles and review articles and the following conference proceedings (2005 up to and including 2015): American Academy on Communication in Healthcare (AACH), European Society for Medical Oncology (ESMO), European CanCer Organisation (ECCO), European Association for Communication in Healthcare (EACH), International Conference on Communication in Healthcare (ICCH), International Shared Decision Making Conference (ISDM), Annual Conference of the International Society for Paediatric Oncology (SIOP) and Annual Scientific Meeting of the Society for Medical Decision Making (SMDM). We scanned the ISRCTN (International Standard Randomised Controlled Trial Number) register and the National Institutes of Health (NIH) Register for ongoing trials on 29 February 2016.
SELECTION CRITERIA: For this update, we included randomised controlled trials (RCTs) and controlled clinical trials (CCTs) of SDM interventions for children with cancer aged four to 18 years. The types of decisions included were: treatment, health care and research participation decisions. The primary outcome was SDM as measured with any validated scale.
DATA COLLECTION AND ANALYSIS: Two review authors undertook the searches, and three review authors independently assessed the studies obtained. We contacted study authors for additional information.
MAIN RESULTS: No studies met the inclusion criteria, and hence no analysis could be undertaken.
AUTHORS' CONCLUSIONS: No conclusions can be made on the effects of interventions to promote SDM for children with cancer aged four to 18 years. This review has highlighted the dearth of high-quality quantitative research on interventions to promote participation in SDM for children with cancer. There are many potential reasons for the lack of SDM intervention studies with children. Attitudes towards children's participation are slowly changing in society and such changes may take time to be translated or adopted in healthcare settings. The priority may be on developing interventions that promote children's participation in communication interactions since information-sharing is a prerequisite for SDM. Restricting this review to RCTs was a limitation and extending the review to non-randomised studies (NRS) may have produced more evidence. For this update, we included only RCTs and CCTs. Clearly more research is needed.

The presence of acquired mutations within the JAK2, CALR, and MPL genes in the majority of patients with myeloproliferative neoplasms (MPN) affords the opportunity to utilise these mutations as markers of minimal residual disease (MRD). Reduction of the mutated allele burden has been reported in response to a number of therapeutic modalities including interferon, JAK inhibitors, and allogeneic stem cell transplantation; novel therapies in development will also require assessment of efficacy. Real-time quantitative PCR has been widely adopted for recurrent point mutations with assays demonstrating the specificity, sensitivity, and reproducibility required for clinical utility. More recently, approaches such as digital PCR have demonstrated comparable, if not improved, assay characteristics and are likely to play an increasing role in MRD monitoring. While next-generation sequencing is increasingly valuable as a tool for diagnosis of MPN, its role in the assessment of MRD requires further evaluation.

Paraneoplastic retinopathy is a rare cause of painless vision loss, associated with an underlying (and often occult) systemic malignancy. Ocular examination findings are subtle, and the diagnosis is often made on the basis of electrophysiology findings. This report describes the case of a 48-year-old Caucasian man with paraneoplastic retinopathy presenting as visual disturbance, central scotomata and abnormal electrophysiology. He was subsequently diagnosed with papillary thyroid malignancy.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare but highly aggressive malignancy most often associated with exposure to asbestos. Recent evidence points to oestrogen receptor (ER)-β having a tumour-suppressor role in MPM progression, and this raises the question of whether selective modulators of ERs could play a role in augmenting MPM therapy.
MATERIALS AND METHODS: We investigated the action of tamoxifen in inhibiting the growth and modulating the cisplatin sensitivity of four MPM cell lines.
RESULTS: Tamoxifen inhibited the growth of MPM cells and also modulated their sensitivity to cisplatin. The MPM cell lines expressed ERβ, but the actions of tamoxifen were not blocked by antagonism of nuclear ERs. Tamoxifen treatment repressed the expression of cyclins by MPM cells, resulting in cell-cycle arrest and caspase-3-coupled apoptosis signaling.
CONCLUSION: The ER-independent actions of tamoxifen on MPM cell proliferation and cell-cycle progression may have clinical benefits for a subset of patients with MPM.

Spinal extradural meningeal cysts (SEMC) are uncommon causes of back pain. The literature contains only case reports of this pathology, and treatment remains controversial due to its rarity. We present a case of SEMC and describe an approach via hemilaminectomy, with the choice of side guided by radiological imaging, followed by complete excision of the cyst and repair of the underlying dural defect.

Peritoneal malignancies are a rare occurrence in children, often metastatic and rarely originating primarily in the peritoneum. The imaging findings of these entities in the pediatric age have not been recently reviewed or they have been previously described or depicted mostly as part of articles discussing each entity separately. This is a review of the most relevant peritoneal malignancies in childhood emphasizing imaging features. Knowledge of these appearances may facilitate diagnosis and staging of these neoplasms.

Background Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1). Methods In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety. Results Median progression-free survival was 10.3 months (95% confidence interval [CI], 6.7 to not reached) in the pembrolizumab group versus 6.0 months (95% CI, 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.37 to 0.68; P<0.001). The estimated rate of overall survival at 6 months was 80.2% in the pembrolizumab group versus 72.4% in the chemotherapy group (hazard ratio for death, 0.60; 95% CI, 0.41 to 0.89; P=0.005). The response rate was higher in the pembrolizumab group than in the chemotherapy group (44.8% vs. 27.8%), the median duration of response was longer (not reached [range, 1.9+ to 14.5+ months] vs. 6.3 months [range, 2.1+ to 12.6+]), and treatment-related adverse events of any grade were less frequent (occurring in 73.4% vs. 90.0% of patients), as were grade 3, 4, or 5 treatment-related adverse events (26.6% vs. 53.3%). Conclusions In patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy. (Funded by Merck; KEYNOTE-024 ClinicalTrials.gov number, NCT02142738 .).

Penile-preserving surgery offers a revolutionary alternative to more traditional radical surgery. It offers better sexual, functional, and psychological results and evidence suggests it achieves this without sacrificing oncological outcomes. We examined the evolving nature of such surgeries, addressing controversies such as safe margins and survival outcomes and discussing more conventional techniques, including laser. At our UK center, we treat a high volume of penile cancer and here, based on such experience, we describe our glans resurfacing, glansectomy, and partial penectomy techniques; their application by disease stage; and the limitations of such surgeries.

INTRODUCTION Recent studies have advocated the use of perioperative fluid restriction in patients undergoing major abdominal surgery as part of an enhanced recovery protocol. Series reported to date include a heterogenous group of high- and low-risk procedures but few studies have focused on rectal cancer surgery alone. The aim of this study was to assess the effects of perioperative fluid volumes on outcomes in patients undergoing elective rectal cancer resection. METHODS A prospectively maintained database of patients with rectal cancer who underwent elective surgery over a 2-year period was reviewed. Total volume of fluid received intraoperatively was calculated, as well as blood products required in the perioperative period. The primary outcome was postoperative morbidity (Clavien-Dindo grade I-IV) and the secondary outcomes were length of stay and major morbidity (Clavien-Dindo grade III-IV). RESULTS Over a 2-year period (2012-2013), 120 patients underwent elective surgery with curative intent for rectal cancer. Median total intraoperative fluid volume received was 3680ml (range 1200-9670ml); 65/120 (54.1%) had any complications, with 20/120 (16.6%) classified as major (Clavien-Dindo grade III-IV). Intraoperative volume >3500ml was an independent risk factor for the development of postoperative all-cause morbidity (P=0.02) and was associated with major morbidity (P=0.09). Intraoperative fluid volumes also correlated with length of hospital stay (Pearson's correlation coefficient 0.33; P<0.01). CONCLUSIONS Intraoperative fluid infusion volumes in excess of 3500ml are associated with increased morbidity and length of stay in patients undergoing elective surgery for rectal cancer.

This UK cohort analysis of a European survey evaluated the differences between health professionals and cancer patients regarding the perceived incidence, impact and drug management of chemotherapy/radiotherapy-induced nausea/vomiting (CINV/RINV). The UK healthcare system is unique in that it has dedicated oncology clinical nurse specialists. The analysis found that more patients experienced nausea following their most recent treatment cycle than vomiting. Health professionals overestimated the incidence of CINV/RINV but underestimated its impact on patients' daily lives, particularly in cases of mild and moderate nausea/vomiting. The level of antiemetic cover initiated and degree of symptom control was often suboptimal. Patients under-reported symptoms, primarily because they considered nausea/vomiting an inevitable side effect of treatment. Altogether, 42% of patients reported full adherence to their antiemetic regimen. Leading factors for non-adherence included not having a 'preventive mindset', low symptom severity and a reluctance to increase pill burden. In conclusion, there is a perceptual gap between health professionals and patients around experiences of CINV/RINV. Advances in management depend on enhancing health professional-patient communication, and reporting and understanding nausea as a distinct issue.

This article gives a comprehensive overview of multiple myeloma (MM), a complex blood cancer involving overproduction of plasma cells. Although MM remains incurable, patients are living longer as a result of multiple treatment options. However, MM patients are also living with a higher symptom burden. The overall aims in managing MM are therefore to control disease progression, prolong survival and improve quality of life.

A 72-year-old man, on treatment for prostate cancer, attended the emergency department with his 2nd episode of spontaneous extensive bruising and haematomas. His first presentation was 2 months prior but this was thought to be because of his aspirin and he improved when aspirin was discontinued. On this occasion aspirin had been restarted 7 days before he developed his symptoms. His blood investigation was significant for a much raised activated partial thromboplastin time (aPTT). On his 3rd day of admission he deteriorated clinically with a drastic drop in his haemoglobin and worsening tense haematomas. Blood investigations confirmed the diagnosis of acquired factor VIII deficiency and he subsequently received treatment with factor VIII inhibitor bypassing activity, steroids and immunosuppresants.

Image-guided radiotherapy (IGRT) is an essential tool in the accurate delivery of modern radiotherapy techniques. Prostate radiotherapy positioned using skin marks or bony anatomy may be adequate for delivering a relatively homogeneous whole-pelvic radiotherapy dose, but these surrogates are not reliable when using reduced margins, dose escalation or hypofractionated stereotactic radiotherapy. Fiducial markers (FMs) for prostate IGRT have been in use since the 1990s. They require surgical implantation and provide a surrogate for the position of the prostate gland. A variety of FMs are available and they can be used in a number of ways. This review aimed to establish the evidence for using prostate FMs in terms of feasibility, implantation procedures, types of FMs used, FM migration, imaging modalities used and the clinical impact of FMs. A search strategy was defined and a literature search was carried out in Medline. Inclusion and exclusion criteria were applied, which resulted in 50 articles being included in this review. The evidence demonstrates that FMs provide a more accurate surrogate for the position of the prostate than either external skin marks or bony anatomy. A combination of FM alignment and soft-tissue analysis is currently the most effective and widely available approach to ensuring accuracy in prostate IGRT. FM implantation is safe and well tolerated. FM migration is possible but minimal. Standardization of all techniques and procedures in relation to the use of prostate FMs is required. Finally, a clinical trial investigating a non-surgical alternative to prostate FMs is introduced.

BACKGROUND: Head and neck cancer treatment has developed over the last decade, with improved mortality and survival rates, but the treatments often result in dysphagia (a difficulty in swallowing) as a side effect. This may be acute, resolving after treatment, or remain as a long-term negative sequela of head and neck cancer (HNC) treatment. Interventions to counteract the problems associated with dysphagia include swallowing exercises or modification of diet (bolus texture, size), or both.
OBJECTIVES: To determine the effects of therapeutic exercises, undertaken before, during and/or immediately after HNC treatment, on swallowing, aspiration and adverse events such as chest infections, aspiration pneumonia and profound weight loss, in people treated curatively for advanced-stage (stage III, stage IV) squamous cell carcinoma of the head and neck.
SEARCH METHODS: The Cochrane ENT Information Specialist searched the ENT Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 6); MEDLINE; PubMed; Embase; CINAHL; LILACS; KoreaMed; IndMed; PakMediNet; Web of Science; ClinicalTrials.gov; ICTRP; speechBITE; Google Scholar; Google and additional sources for published and unpublished trials. The date of the search was 1 July 2016.
SELECTION CRITERIA: We selected randomised controlled trials (RCTs) of adults with head and neck cancer (stage III, stage IV) who underwent therapeutic exercises for swallowing before, during and/or immediately after HNC treatment to help produce safe and efficient swallowing. The main comparison was therapeutic exercises versus treatment as usual (TAU). Other possible comparison pairs included: therapeutic exercises versus sham exercises and therapeutic exercises plus TAU versus TAU. TAU consisted of reactive management of a patient's dysphagia, when this occurred. When severe, this included insertion of either a percutaneous endoscopic gastroscopy or nasogastric tube for non-oral feeding.
DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: safety and efficiency of oral swallowing, as measured by reduced/no aspiration; oropharyngeal swallowing efficiency (OPSE) measures, taken from videofluoroscopy swallowing studies; and adverse events, such as chest infections, aspiration pneumonia and profound weight loss. Secondary outcomes were time to return to function (swallowing); self-reported changes to quality of life; changes to psychological well-being - depression, anxiety and stress; patient satisfaction with the intervention; patient compliance with the intervention; and cost-effectiveness of the intervention.
MAIN RESULTS: We included six studies (reported as seven papers) involving 326 participants whose ages ranged from 39 to 83 years, with a gender bias towards men (73% to 95% across studies), reflecting the characteristics of patients with HNC. The risk of bias in the studies was generally high.We did not pool data from studies because of significant differences in the interventions and outcomes evaluated. We found a lack of standardisation and consistency in the outcomes measured and the endpoints at which they were evaluated.We found no evidence that therapeutic exercises were better than TAU, or any other treatment, in improving the safety and efficiency of oral swallowing (our primary outcome) or in improving any of the secondary outcomes.Using the GRADE system, we classified the overall quality of the evidence for each outcome as very low, due to the limited number of trials and their low quality. There were no adverse events reported that were directly attributable to the intervention (swallowing exercises).
AUTHORS' CONCLUSIONS: We found no evidence that undertaking therapeutic exercises before, during and/or immediately after HNC treatment leads to improvement in oral swallowing. This absence of evidence may be due to the small participant numbers in trials, resulting in insufficient power to detect any difference. Data from the identified trials could not be combined due to differences in the choice of primary outcomes and in the measurement tools used to assess them, and the differing baseline and endpoints across studies.Designing and implementing studies with stronger methodological rigour is essential. There needs to be agreement about the key primary outcomes, the choice of validated assessment tools to measure them and the time points at which those measurements are made.

AIM: To review all surveillance breast magnetic resonance imaging (MRI) examinations performed over a 6-year period at an Irish national centre to determine the recall rate, biopsy rate, and cancer-detection rates.
MATERIALS AND METHODS: All breast MRI examinations performed for surveillance purposes in women at high risk of developing breast cancer between January 2009 and December 2014 were reviewed. The Breast Imaging-Reporting and Data System (BI-RADS) score for each MRI examination was determined, the type of additional imaging performed, and the method of biopsy, if performed, was recorded. Histology of the biopsy specimens was reviewed.
RESULTS: Data for 715 women undergoing 1445 surveillance MRI examinations were identified. Of the examinations, 10.9% (157/1445) had MRI BI-RADS scores that required recall for further imaging and 6.3% (91/1445) required a biopsy. Recall rates were 14.2% (86/607) and 8.5% (71/838) in the prevalent and incident rounds, respectively. The overall cancer detection rate was 17 per 1000.
CONCLUSION: The current UK guideline was not achieved and no studies to date have achieved the target of <7%. Aiming for this target could risk lowering the cancer-detection rate. The authors would suggest a target rate of <15% and <10% for the prevalent round and incident rounds, respectively.

PURPOSE: Radiofrequency ablation (RFA) is one of the most popular and well-standardized minimally invasive cancer treatments (MICT) for liver tumours, employed where surgical resection has been contraindicated. Less-experienced interventional radiologists (IRs) require an appropriate planning tool for the treatment to help avoid incomplete treatment and so reduce the tumour recurrence risk. Although a few tools are available to predict the ablation lesion geometry, the process is computationally expensive. Also, in our implementation, a few patient-specific parameters are used to improve the accuracy of the lesion prediction.
METHODS: Advanced heterogeneous computing using personal computers, incorporating the graphics processing unit (GPU) and the central processing unit (CPU), is proposed to predict the ablation lesion geometry. The most recent GPU technology is used to accelerate the finite element approximation of Penne's bioheat equation and a three state cell model. Patient-specific input parameters are used in the bioheat model to improve accuracy of the predicted lesion.
RESULTS: A fast GPU-based RFA solver is developed to predict the lesion by doing most of the computational tasks in the GPU, while reserving the CPU for concurrent tasks such as lesion extraction based on the heat deposition at each finite element node. The solver takes less than 3 min for a treatment duration of 26 min. When the model receives patient-specific input parameters, the deviation between real and predicted lesion is below 3 mm.
CONCLUSION: A multi-centre retrospective study indicates that the fast RFA solver is capable of providing the IR with the predicted lesion in the short time period before the intervention begins when the patient has been clinically prepared for the treatment.

BACKGROUND: It is estimated that up to 75% of cancer survivors may experience cognitive impairment as a result of cancer treatment and given the increasing size of the cancer survivor population, the number of affected people is set to rise considerably in coming years. There is a need, therefore, to identify effective, non-pharmacological interventions for maintaining cognitive function or ameliorating cognitive impairment among people with a previous cancer diagnosis.
OBJECTIVES: To evaluate the cognitive effects, non-cognitive effects, duration and safety of non-pharmacological interventions among cancer patients targeted at maintaining cognitive function or ameliorating cognitive impairment as a result of cancer or receipt of systemic cancer treatment (i.e. chemotherapy or hormonal therapies in isolation or combination with other treatments).
SEARCH METHODS: We searched the Cochrane Centre Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PUBMED, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and PsycINFO databases. We also searched registries of ongoing trials and grey literature including theses, dissertations and conference proceedings. Searches were conducted for articles published from 1980 to 29 September 2015.
SELECTION CRITERIA: Randomised controlled trials (RCTs) of non-pharmacological interventions to improve cognitive impairment or to maintain cognitive functioning among survivors of adult-onset cancers who have completed systemic cancer therapy (in isolation or combination with other treatments) were eligible. Studies among individuals continuing to receive hormonal therapy were included. We excluded interventions targeted at cancer survivors with central nervous system (CNS) tumours or metastases, non-melanoma skin cancer or those who had received cranial radiation or, were from nursing or care home settings. Language restrictions were not applied.
DATA COLLECTION AND ANALYSIS: Author pairs independently screened, selected, extracted data and rated the risk of bias of studies. We were unable to conduct planned meta-analyses due to heterogeneity in the type of interventions and outcomes, with the exception of compensatory strategy training interventions for which we pooled data for mental and physical well-being outcomes. We report a narrative synthesis of intervention effectiveness for other outcomes.
MAIN RESULTS: Five RCTs describing six interventions (comprising a total of 235 participants) met the eligibility criteria for the review. Two trials of computer-assisted cognitive training interventions (n = 100), two of compensatory strategy training interventions (n = 95), one of meditation (n = 47) and one of physical activity intervention (n = 19) were identified. Each study focused on breast cancer survivors. All five studies were rated as having a high risk of bias. Data for our primary outcome of interest, cognitive function were not amenable to being pooled statistically. Cognitive training demonstrated beneficial effects on objectively assessed cognitive function (including processing speed, executive functions, cognitive flexibility, language, delayed- and immediate- memory), subjectively reported cognitive function and mental well-being. Compensatory strategy training demonstrated improvements on objectively assessed delayed-, immediate- and verbal-memory, self-reported cognitive function and spiritual quality of life (QoL). The meta-analyses of two RCTs (95 participants) did not show a beneficial effect from compensatory strategy training on physical well-being immediately (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.59 to 0.83; I(2)= 67%) or two months post-intervention (SMD - 0.21, 95% CI -0.89 to 0.47; I(2) = 63%) or on mental well-being two months post-intervention (SMD -0.38, 95% CI -1.10 to 0.34; I(2) = 67%). Lower mental well-being immediately post-intervention appeared to be observed in patients who received compensatory strategy training compared to wait-list controls (SMD -0.57, 95% CI -0.98 to -0.16; I(2) = 0%). We assessed the assembled studies using GRADE for physical and mental health outcomes and this evidence was rated to be low quality and, therefore findings should be interpreted with caution. Evidence for physical activity and meditation interventions on cognitive outcomes is unclear.
AUTHORS' CONCLUSIONS: Overall, the, albeit low-quality evidence may be interpreted to suggest that non-pharmacological interventions may have the potential to reduce the risk of, or ameliorate, cognitive impairment following systemic cancer treatment. Larger, multi-site studies including an appropriate, active attentional control group, as well as consideration of functional outcomes (e.g. activities of daily living) are required in order to come to firmer conclusions about the benefits or otherwise of this intervention approach. There is also a need to conduct research into cognitive impairment among cancer patient groups other than women with breast cancer.

Although the UK National Institute for Health and Care Excellence guidelines recommend that in patients with biopsy-proven invasive lobular carcinoma (ILC), preoperative MRI scan is considered, the accuracy of diagnosis of ILC in core biopsy of the breast has not been previously investigated. Eleven pathology laboratories from the UK and Ireland submitted data on 1112 cases interpreted as showing features of ILC, or mixed ILC and IDC/no special type (NST)/other tumour type, on needle core biopsy through retrieval of histology reports. Of the total 1112 cases, 844 were shown to be pure ILC on surgical excision, 154 were mixed ILC plus another type (invariably ductal/NST) and 113 were shown to be ductal/NST. Of those lesions categorised as pure ILC on core, 93% had an element of ILC correctly identified in the core biopsy sample and could be considered concordant. Of cores diagnosed as mixed ILC plus another type on core, complete agreement between core and excision was 46%, with 27% cases of pure ILC, whilst 26% non-concordant. These data indicate that there is not a large excess of expensive MRIs being performed as a result of miscategorisation histologically.

BACKGROUND: Fine needle aspiration biopsy (FNAB) is the tool of choice for evaluating thyroid nodules with the majority classified as benign following initial assessment. However, concern remains about false negative results and some guidelines have recommended routine repeat aspirates. We aimed to assess the utility of routine repeat FNAB for nodules classified as benign on initial biopsy and to examine the impact of establishing a multidisciplinary team for the care of these patients.
METHODS: We performed a retrospective review of 400 consecutive patients (413 nodules) who underwent FNAB of a thyroid nodule at our hospital between July 2008 and July 2011. Data recorded included demographic, clinical, histological and radiological variables.
RESULTS: Three hundred and fifty seven patients (89 %) were female. Median follow-up was 5.5 years. Two hundred and fifty eight (63 %) nodules were diagnosed as benign. The rate of routine repeat biopsy increased significantly over the time course of the study (p for trend = 0.012). Nine Thy 2 nodules were classified differently on the basis of routine repeat biopsy; one patient was classified as malignant on repeat biopsy and was diagnosed with papillary thyroid carcinoma. Eight were classified as a follicular lesions on repeat biopsy-six diagnosed as benign following lobectomy; two declined lobectomy and were followed radiologically with no nodule size increase.
CONCLUSIONS: The false negative rate of an initial benign cytology result, from a thyroid nodule aspirate, is low. In the setting of an experienced multidisciplinary thyroid team, routine repeat aspiration is not justified.

Ileal pouch-related adenocarcinoma remains a rarity; thus, guidelines on treatment are currently lacking. We present this case of a 54-year-old man who underwent restorative proctocolectomy with stapled ileal pouch-anal anastomosis formation for familial adenomatous polyposis during the 1980s. Despite undergoing annual surveillance endoscopy, the patient was noted to be anaemic and passing fresh blood per anus Endoscopy and radiological investigation revealed the presence of a pouch-related adenocarcinoma. This was subsequently treated with short-course radiotherapy and pouch excision. The patient remains well until now and will follow six-monthly surveillance protocols with a transition to annual surveillance after 2 years.

OBJECTIVE: To establish whether CT dose variation occurs in breast cancer localization procedures between radiation therapy (RT) centres in Ireland and to propose diagnostic reference levels (DRLs) for this procedure.
METHODS: All RT centres in Ireland were invited to participate in a dose audit survey, providing data on the CT dose index volume (CTDIvol), dose-length product (DLP), current-time product (mAs), tube potential, scan length, slice thickness, scanning margins, use of automated exposure control (AEC) and scanner technology for 10 patients with breast cancer who were average sized. DRLs were derived for each dose descriptor by calculation of the rounded 75th percentile of the distribution of mean doses.
RESULTS: Data were returned for 60 patients from 6 RT centres (50% response rate). Significant variation in mean CTDIvol and mean DLP was observed between centres (p < 0.0001). Mean scan lengths and mean mAs differed significantly between centres (p < 0.0001). Tube potential was 120 kV for all sequences across centres. AEC was employed in all but one centre. Proposed DRLs for breast localization are 26 mGy and 732 mGy cm for CTDIvol and DLP, respectively.
CONCLUSION: CT dose variation occurs between centres, establishing a need for optimization. DRLs for breast cancer localization have been proposed with the potential for reduction in CT dose.
ADVANCES IN KNOWLEDGE: This article provides the first reported DRL for breast cancer CT localization procedure in RT and can be used as a benchmark for comparison for other RT centres.

OBJECTIVE: Beneficial effects of adrenalectomy on cardiovascular risk factors in patients with subclinical Cushing's syndrome (SCS) are uncertain. We sought to conduct a systematic review and meta-analysis with the following objectives: (i) determine the effect of adrenalectomy compared with conservative management on cardiovascular risk factors in patients with SCS and (ii) compare the effect of adrenalectomy on cardiovascular risk factors in patients with SCS vs those with a nonfunctioning (NF) adrenal tumor.
METHODS: MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trial were searched on 17 November 2015. Reviewers extracted data and assessed methodological quality in duplicate.
RESULTS: We included 26 studies reporting on 584 patients with SCS and 457 patients with NF adrenal tumors. Studies used different definitions of SCS. Patients with SCS undergoing adrenalectomy demonstrated an overall improvement in cardiovascular risk factors (61% for hypertension, 52% for diabetes mellitus, 45% for obesity and 24% for dyslipidemia). When compared with conservative management, patients with SCS undergoing adrenalectomy experienced improvement in hypertension (RR 11, 95% CI: 4.3-27.8) and diabetes mellitus (RR 3.9, 95% CI: 1.5-9.9), but not dyslipidemia (RR 2.6, 95% CI: 0.97-7.2) or obesity (RR 3.4, 95% CI: 0.95-12). Patients with NF adrenal tumors experienced improvement in hypertension (21/54 patients); however, insufficient data exist for comparison to patients with SCS.
CONCLUSIONS: Available low-to-moderate-quality evidence from heterogeneous studies suggests a beneficial effect of adrenalectomy on cardiovascular risk factors in patients with SCS overall and compared with conservative management.

Resection of the submandibular gland is generally undertaken as an integral component of level I neck dissection for oral cancer. However, it is unclear whether lymph nodes are present within the submandibular gland which may form the basis of lymphatic spread. Our purpose was to investigate the frequency of lymph nodes within the submandibular gland, and the incidence and mechanism of submandibular gland involvement in floor of mouth cancer. Retrospective review of 177 patients with oral cancer undergoing neck dissection. Original pathology slides of floor of mouth cases were re-reviewed by two pathologists to determine frequency of intraglandular lymph nodes, and incidence and mechanism of submandibular gland involvement by cancer. The overall incidence of cervical metastases was 36.4 %, of whom 44 % had level I metastases. Level I metastases were significantly more common in floor of mouth than tongue cancers (p = 0.004). Among 50 patients with floor of mouth cancer undergoing re-review of pathology slides, intraglandular lymph nodes were not found in any of 69 submandibular glands. Submandibular gland involvement by cancer was present in two patients, representing 1 % of all oral cancers, and 4 % FOM cases. Mechanisms of involvement were direct extension, and by an apparent novel mechanism of carcinoma growing along bilateral Wharton's ducts. Despite the high incidence of level I metastasis in floor of mouth, lymphatic metastases to submandibular gland are unlikely based on absence of intraglandular lymph nodes. We describe a previously unreported mechanism of submandibular gland involvement.

This study aimed to collect data on the oral health status of patients undergoing treatment for head and neck oncology across Northern Ireland. Data were collected on all patients referred to the Northern Ireland Multidisciplinary Head and Neck Oncology Team for discussion and treatment planning. Each patient underwent pre-treatment dental assessment in the Centre for Dentistry, Queen's University Belfast, between June 2013 and November 2014. Data were collected from clinical oral examinations supplemented with intra-oral radiographs. During the course of the study 96 patients were assessed and the levels of dental disease observed in this cohort were high. On clinical examination 43% were diagnosed with caries and 46% with periodontal disease. Ten patients were completely edentate. The disease profile of this patient group presents significant challenges to dental services tasked with rendering patients dentally fit prior to undergoing oncology treatment.

A biosimilar is a biologic that is highly similar to a licensed biologic (the reference product) in terms of purity, safety and efficacy. If the reference product is licensed to treat multiple therapeutic indications, extrapolation of indications, i.e., approval of a biosimilar for use in an indication held by the reference product but not directly studied in a comparative clinical trial with the biosimilar, may be possible but has to be scientifically justified. Here, we describe the data required to establish biosimilarity and emphasize that indication extrapolation is based on scientific principles and known mechanism of action.

The importance of ion channels in the hallmarks of many cancers is increasingly recognised. This article reviews current knowledge of the expression of members of the voltage-gated calcium channel family (CaV) in cancer at the gene and protein level and discusses their potential functional roles. The ten members of the CaV channel family are classified according to expression of their pore-forming α-subunit; moreover, co-expression of accessory α2δ, β and γ confers a spectrum of biophysical characteristics including voltage dependence of activation and inactivation, current amplitude and activation/inactivation kinetics. CaV channels have traditionally been studied in excitable cells including neurones, smooth muscle, skeletal muscle and cardiac cells, and drugs targeting the channels are used in the treatment of hypertension and epilepsy. There is emerging evidence that several CaV channels are differentially expressed in cancer cells compared to their normal counterparts. Interestingly, a number of CaV channels also have non-canonical functions and are involved in transcriptional regulation of the expression of other proteins including potassium channels. Pharmacological studies show that CaV canonical function contributes to the fundamental biology of proliferation, cell-cycle progression and apoptosis. This raises the intriguing possibility that calcium channel blockers, approved for the treatment of other conditions, could be repurposed to treat particular cancers. Further research will reveal the full extent of both the canonical and non-canonical functions of CaV channels in cancer and whether calcium channel blockers are beneficial in cancer treatment.

PURPOSE: The purpose of this study was to evaluate the accuracy of multidetector computed tomography (MDCT) in the preoperative assessment of renal sinus fat invasion (RSFI) in patients with renal cell carcinoma (RCC) and to assess imaging features that improve detection of RSFI on CT.
METHODS: This is a single-institution retrospective review of 53 consecutive patients with histologically proven RCC who underwent triple-phase preoperative contrast MDCT prior to partial or radical nephrectomy. Two experienced radiologists (R1 and R2), blinded to the final histology result, independently reviewed the preoperative MDCT studies to assess for RSFI. Histopathology was used as the gold standard for the presence of RSFI.
RESULTS: Of 55 surgically resected RCCs that were evaluated with contrast-enhanced MDCT, 34.5% (19/55) of RCCs had RSFI on final histopathology. Multidetector CT demonstrated high sensitivity (R1, 100%; R2, 93.7%) for the detection of RSFI, but a low positive predictive value (R1, 40%; R2, 53%) and specificity (R1, 38.4%; R2, 66.6%). Interreader agreement for RSFI was moderate (κ = 0.56). Renal tumors were significantly larger in cases with RSFI (6.3 ± 3.219 cm) than tumors without RSFI (4.1 ± 2.9 cm) (P = 0.0275). Renal sinus fat invasion was more commonly associated to an irregular tumor margin at the tumor renal sinus fat interface (P < 0.001).
CONCLUSIONS: Multidetector computed tomography demonstrates a high sensitivity but low positive predictive value in diagnosing RSFI with implications for prognosis and treatment planning. Tumor size, location, irregular tumor margin at the tumor/renal sinus interface, and invasion into pelvicaliceal structures can aid in the diagnosis of RSFI on preoperative MDCT.

Background The incidence of thyroid cancer is increasing in men and women. Fine needle aspiration (FNA) is an accepted technique to assess thyroid nodules but is associated with a high rate of non-diagnostic sampling. Purpose To assess the diagnostic performance of ultrasound-guided FNA of thyroid nodules and identify factors associated with non-diagnostic sampling. Material and Methods A retrospective review of thyroid FNAs was performed between 2006 and 2013. Patient demographics, nodule characteristics, procedural technique, cytology, and complications were recorded. Cytology was categorized THY1-5 based on the British Thyroid Association guidelines. Descriptive and multivariable analysis were conducted to identify factors associated with non-diagnostic sampling. Results A total of 724 procedures were identified with 597 (82.5%) in women, and an overall mean age of 40 years (age range, 17-87 years). Factors associated with a non-diagnostic outcome in the multivariable regression analysis included increasing lesion depth (OR, 1.05 per mm; 95% confidence interval [CI], 1.007-1.10), age (OR, 1.012 per year; 95% CI, 1.0-1.025) and number of FNA passes (1 vs. 4+; OR, 6.07; 95% CI, 2.27-16.21). The complication rate was 1.1% related to perilesional hematomas and vaso-vagal episodes. Conclusion Thyroid FNA is a safe and reliable procedure for cytological assessment of thyroid nodules. Deeper nodules and older patients are more likely to have non-diagnostic samples.