The bioassay-guided fractionation of the aril of Myristica fragrans (mace spice) yielded five phenolic compounds, one new acyclic bis phenylpropanoid (1) and four previously known phenolic compounds: compounds (1) (S) 1-(3,4,5-trimethoxyphenyl)-2-(3-methoxy-5-(prop-1-yl) phenyl)-propan-1-ol, (2) benzenemethanol; α-[1-[2,6-dimethoxy-4-(2-propen-1-yl)phenoxy]ethyl]-3,4-dimethoxy-1-acetate, (3) odoratisol A, phenol, 4-[(2S,3S)-2,3-dihydro-7-methoxy-3-methyl-5-(1E)-1-propenyl-2-benzofuranyl]-2,6-dimethoxy, (4) 1,3-benzodioxate-5-methanol,α-[1-[2,6-dimethoxy-4-(2-propenyl)phenoxy]ethyl]-acetate, (5) licarin C; benzofuran,2,3-dihydro-7-methoxy-3-methyl-5-(1E)-1-yl-2-(3,4,5-trimethoxyphenyl). An NMR tube Mosher ester reaction was used in an approach to characterize and determine the assignment of the absolute configuration of the new isolated chiral alcohol (1). The PARP-1 inhibitory activity was evaluated for compound (1) (IC50=3.04μM), compound (2) (IC50=0.001μM), compound (4) (IC50=22.07μM) and compound (5) (IC50=3.11μM). Furthermore, the isolated secondary metabolites were tested for NF-κB and K-Ras inhibitory activities. When tested in the p65 assay, compounds (2) and (4) displayed potent NF-κB inhibition (IC50=1.5 nM and 3.4nM, respectively).

Background/Aim: Effect of capsicodendrin on the NF-KB pathway was studied in MCF-7 cancer cells. Materials and Methods: The transcription factor assay was used to screen for NF-KB activity. The effect on IKK beta, ICAM-1, and caspase-7 were studied using western blot. Caspase-1 was studied using Promega Caspase-Glo (R) assay. Reactive oxygen species (ROS) were detected using the fluorescent probe DCFH-DA. The potentiometric dye JC-1 was used to assess mitochondrial membrane potential (Delta psi m) and the cell cycle was examined using a fluorescence-activated cell sorter. Results: NF-kappa B p65 inhibitory effect was IC50=8.6 mu M and cytotoxic activity was IC50=7.5 mu M. The upstream IKK and the downstream ICAM-1 were down-regulated. Sub G1-phase population increased to 81% after 12 h of treatment with capsicodendrin (10 mu M) and there was no loss of Delta psi M. Conclusion: Increased levels of intracellular ROS promoted activity of caspase-1 and induced cell death in MCF-7 cells. Capsicodendrin may be a future anticancer agent that prevents the progression of metastatic breast cancer.

Aim: The aim of this systematic review and meta-analysis was to explore and evaluate the effect of psychosocial interventions in improving sexual health outcomes among post-treatment patients with pelvic cancer.

Methods: Inclusion and exclusion criteria were pelvic cancer survivors; psychosocial interventions; studies with a control group and measures of sexual health. Five databases were searched for literature along with an inspection of the included studies' reference lists to extend the search. Risk of bias was assessed with the RoB2 tool. Standardised mean difference (SMD) with a random effects model was used to determine the effect size of psychosocial interventions for sexual health in patients with pelvic cancers.

Results: Thirteen studies were included, with a total number of 1,541 participants. There was a large heterogeneity regarding the type of psychosocial intervention used with the source found in a leave one out analysis. Six studies showed statistically significant improvements in sexual health, while three showed positive but non-significant effects. The summary effect size estimate was small SMD = 0.24 (95% confidence interval [CI]: 0.05 to 0.42, p = 0.01).

Discussion: There is limited research on psychosocial interventions for sexual health in pelvic cancer patients. There are also limitations in the different pelvic cancer diagnoses examined. Commonly, the included articles examined physical function rather than the whole sexual health spectrum. The small effect sizes may in part be due to evaluation of psychosocial interventions by measuring physical dysfunction. Future research should broaden sexual health assessment tools and expand investigations to more cancer types.

In last decade increasingly mathematical models of tumor growths have been studied, particularly on solid tumors which growth mainly caused by cellular proliferation. In this paper we propose a modified model to simulate the growth of gliomas in different stages. Glioma growth is modeled by a reaction-advection-diffusion. We begin with a model of untreated gliomas and continue with models of polyclonal glioma following chemotherapy. From relatively simple assumptions involving homogeneous brain tissue bounded by a few gross anatomical landmarks (ventricles and skull) the models have been expanded to include heterogeneous brain tissue with different motilities of glioma cells in grey and white matter. Tumor growth is characterized by a dangerous change in the control mechanisms, which normally maintain a balance between the rate of proliferation and the rate of apoptosis (controlled cell death). Result shows that this model closes to clinical finding and can simulate brain tumor behavior properly.

Background

Designing and implementation of screening programs depend on greatly epidemiologic basic data in every country. Also Variation in the incidence of various cancers in our country has been a favorite topic.

Objectives

This systematic review was conducted to provide an overall perspective about incidence, geographical and age distribution of cancers in Iran.

Methods

A comprehensive search were done according to MOOSE guideline criteria in national and international databases for selecting eligible articles from 2005 to 2015. After screening titles and abstracts, duplicated and irrelevant studies were excluded. Selected papers are written in Persian or English. The standard error of the cancer incidence was calculated based on the binomial distribution. Because of the significant heterogeneity observed among the results, we used a random-effects model combine the results of the primary studies. Moreover, a sensitivity analysis was undertaken to explore the effects of the risk of bias and other sources of heterogeneity.

Results

Overall 16 articles met eligibility criteria for inclusion. The total incidence of cancer was 19.4 and 17.2 per hundred thousand of people in males and females respectively. The five most common cancers in male were: Lymphoma, leukemia, esophagus, stomach, colorectal and in the female are: breast, colorectal, stomach, thyroid and esophagus. The highest incidence rate was seen in Golestan Province and in the age group over 65 years.

Conclusion

According to increasing incidence rate of cancers in Iran, Development, holding and accomplish of universal public cancer control program should be the first precedence for health policy.

Purpose: To describe flow as experienced by people diagnosed with and treated for head and neck cancer. Method: A descriptive design based on a deductive qualitative content analysis was used to explain Csikszentmihalyi's flow theory from the perspective of people living with head and neck cancer. Interviews were conducted with seven participants diagnosed with and treated for different forms and stages of head and neck cancer. Results: Experiences of flow were associated with people's interests, skill levels and actions involving and creating both happiness and the feeling of something worth living for. Optimal flow was a state of consciousness in which mind and body work together, and the people were completely absorbed in an activity related to nature, hobbies or family. Microflow occurred as part of everyday life, relieving stress and anxiety and helping them to focus on their daily routines. This included humming, listening to the radio or watching TV. Conclusions: The peoples inner strength and desire to feel better made flow possible, and they used unknown skills that enhanced self-satisfaction. Managing self-care activities increased feelings of control, participation and enjoyment. This calls for person-centred care with a salutogenic approach based on the peoples own interests, skill levels and actions; what makes the person feel happy.

Background

Mutations in the FMS-like tyrosine kinase 3 (FLT3) are associated with uncontrolled cellular functions that contribute to the development of acute myeloid leukaemia (AML). We performed computer simulations of the FLT3-dependent signalling network in order to study the pathways that are involved in AML development and resistance to targeted therapies.

Results

Analysis of the simulations revealed the presence of alternative pathways through phosphoinositide 3 kinase (PI3K) and SH2-containing sequence proteins (SHC), that could overcome inhibition of FLT3. Inhibition of cyclin dependent kinase 6 (CDK6), a related molecular target, was also tested in the simulation but was not found to yield sufficient benefits alone.

Conclusions

The PI3K pathway provided a basis for resistance to treatments. Alternative signalling pathways could not, however, restore cancer growth signals (proliferation and loss of apoptosis) to the same levels as prior to treatment, which may explain why FLT3 resistance mutations are the most common resistance mechanism. Finally, sensitivity analysis suggested the existence of optimal doses of FLT3 and CDK6 inhibitors in terms of efficacy and toxicity.

Background: The smoothened (SMO) receptor is an essential component of the Sonic hedgehog (SHH) signalling, which is associated with the development of skin basal cell carcinoma (BCC). SMO inhibitors are indicated for BCC patients when surgical treatment or radiation therapy are not possible. Unfortunately, SMO inhibitors are not always well tolerated due to severe side effects, and their therapeutical success is limited by resistance mutations. Methods: We investigated how common are resistance-causing mutations in two genomic databases which are not linked to BCC or other cancers, namely 1000 Genomes and ExAC. To examine the potential for combination therapy or other treatments, we further performed knowledge-based simulations of SHH signalling, in the presence or absence of SMO and PI3K/Akt inhibitors. Results: The database analysis revealed that of 18 known mutations associated with Vismodegib-resistance, three were identified in the databases. Treatment of individuals carrying such mutations is thus liable to fail a priori. Analysis of the simulations suggested that a combined inhibition of SMO and the PI3K/Akt signalling pathway may provide an effective reduction in tumour proliferation. However, the inhibition dosage of SMO and PI3K/Akt depended on the activity of phosphodiesterases (PDEs). Under high PDEs activities, SMO became the most important control node of the network. By applying PDEs inhibition, the control potential of SMO decreased and P13K appeared as a significant factor in controlling tumour proliferation. Conclusions: Our systems biology approach employs knowledge-based computer simulations to help interpret the large amount of data available in public databases, and provides application-oriented solutions for improved cancer resistance treatments.

A large subset of anaplastic large cell lymphoma (ALCL) patients harbour a somatic aberration in which anaplastic lymphoma kinase (ALK) is fused to nucleophosmin (NPM) resulting in a constitutively active signalling fusion protein, NPM-ALK. We computationally simulated the signalling network which mediates pathological cell survival and proliferation through NPM-ALK to identify therapeutically targetable nodes through which it may be possible to regain control of the tumourigenic process. The simulations reveal the predominant role of the VAV1-CDC42 (cell division control protein 42) pathway in NPM-ALK-driven cellular proliferation and of the Ras / mitogen-activated ERK kinase (MEK) / extracellular signal-regulated kinase (ERK) cascade in controlling cell survival. Our results also highlight the importance of a group of interleukins together with the Janus kinase 3 (JAK3) / signal transducer and activator of transcription 3 (STAT3) signalling in the development of NPM-ALK derived ALCL. Depending on the activity of JAK3 and STAT3, the system may also be sensitive to activation of protein tyrosine phosphatase-1 (SHP1), which has an inhibitory effect on cell survival and proliferation. The identification of signalling pathways active in tumourigenic processes is of fundamental importance for effective therapies. The prediction of alternative pathways that circumvent classical therapeutic targets opens the way to preventive approaches for countering the emergence of cancer resistance.

Bakgrund: Varje år drabbas flera kvinnor i Sverige av gynekologisk cancer. Behandlingarna leder till många biverkningar och kvinnorna tvingas leva med dessa följder i resten av sitt liv. Detta problem är viktigt att belysa för att kunna hjälpa kvinnor i framtiden att bli mer förberedda på förändringarna och för att sjuksköterskorna ska kunna ge de bästa stödet. 

Syfte: Syftet var att beskriva kvinnors erfarenheter av hur livet förändrats efter att ha behandlats för gynekologisk cancer. 

Metod: En litteraturstudie med kvalitativ design, med en induktivansats.  Analysen av de 10 vetenskapliga artiklarna är gjord utifrån Graneheim & Lundmans manifesta innehållsanalys.  

Resultat: Resultatet visade att kvinnor upplever en förändring på flera olika sätt. Kategorier som togs fram var upplevelsen av att vara kvinna, upplevelser av sexualitetens förändringar och att inte känna igen sig själv och sin kropp. Kvinnor pratade exempelvis om informationsbrist, inkontinensbesvär, temperaturförändringar och smärta och oro i samband med sexuella relationer. 

Slutsats: Cancer kan påverka en människa på många olika sätt både fysiskt och emotionellt. Kvinnor som går igenom och överlevt gynekologisk cancer är i stort behov av stöd. Information är en av de viktigaste delarna för att kunna förstå den förändrade kroppen.

Two new glycerol esters, (S)-2-hydroxy-3-(octanoyloxy)propyl tetracosanoate (1) and (S)-3-(((S)-11-acetoxy octadecanoyl)oxy)propane-1,2-diyl diacetate (2), and eight known compounds, docosanedioic acid (3), 2,5-dimethylnonadecane (4), lupeol (5), stigmasterol (6), β-sitosterol (7), heptadecanoic acid (8), hexanedioic acid, 1,6-bis[(2R)-ethylhexyl] ester (9), and 1,3-di-O-[2',2'-di-(p-phenylene)] (10) were isolated from the leaves of Garcinia daedalanthera Pierre, collected from Indonesia. Structural analysis of the isolates was performed using 1 D- and 2 D-NMR, LC- and GC-MS, IR, polarimetry, and UV-visible spectroscopic methods. Cytotoxicity assessments, as well as reactive oxygen species (ROS) analysis of the isolates, were also completed. Lupeol was the only compound found active with an IC₅₀ value of 19.2 µM against HT-29 colon cancer cells. Significant ROS inhibition and induction activity was observed for compounds 4 and 8, respectively.

Targeted therapies have revolutionized cancer treatment. Unfortunately, their success is limited due to the development of drug resistance within the tumor, which is an evolutionary process. Understanding how drug resistance evolves is a prerequisite to a better success of targeted therapies. Resistance is usually explained as a response to evolutionary pressure imposed by treatment. Thus, evolutionary understanding can and should be used in the design and treatment of cancer. In this article, drug-resistance to targeted therapies is reviewed from an evolutionary standpoint. The concept of apoptosis-induced compensatory proliferation (AICP) is developed. It is shown that AICP helps to explain some of the phenomena that are observed experimentally in cancers. Finally, potential drug targets are suggested in light of AICP.

Acute myeloid leukemia is an aggressive cancer, which, in spite of increasingly better understanding of its genetic background remains difficult to treat. Mutations in the FLT3 gene are observed in ≈30% of the patients. Most of these mutations are internal tandem duplications (ITDs) of a sequence within the protein coding region, an activation mechanism that is almost non-existent with other genes and cancers. As patients each carry their own unique set of mutations, it is challenging to understand how ITDs activate the protein, and ascertain the risk for each individual patient. Available treatment options are limited due to development of drug resistance. Here, recent studies are reviewed that help to better understand the molecular mechanism behind activation of the FLT3 protein due to mutations. It is argued that difference in mutation sequences and especially location might be coupled to prognosis. When it comes to FLT3 inhibitors, key differences between them can be attributed to the mode of inhibition (type-1 and type-2 inhibitors), effective inhibitory coefficient in the blood plasma and off-target binding. Accounting for the position and length of insertions may in the future be used to predict prognosis and rationalise treatment. Development of new inhibitors must take into account the potential for resistance mutations. Inhibitors aimed at multiple specific targets are currently being developed. These, and as well as combination therapies will hopefully lead to longer periods during which targeted FLT3 therapy will remain effective.

The complexity of cancer and the vast amount of experimental data available have made computer-aided approaches necessary. Biomolecular modelling techniques are becoming increasingly easier to use, whereas hardware and software are becoming better and cheaper. Cross-talk between theoretical and experimental scientists dealing with cancer-research from a molecular approach, however, is still uncommon. This is in contrast to other fields, such as amyloid-related diseases, where molecular modelling studies are widely acknowledged. The aim of this review paper is therefore to expose some of the more common approaches in molecular modelling to cancer scientists in simple terms, illustrating success stories while also revealing the limitations of computational studies at the molecular level.

Breast cancer is the most common cancer among women in Sweden and globally. Socio-demographic, genetic and productive factors together with some endogenous and exogenous hormones and lifestyle are some of the risk factors that can cause this type of cancer. There is no cure for metastatic breast cancer but the treatment goal is to control the disease and prolong the survival. Treatment options in metastatic breast cancer are exactly like the ones in primary breast cancer. Targeted cancer therapy is a treatment that targets either one or some specific characters of the cancer. Serine-threonine kinases called CDK4/6 inhibitors like Ibrance with chemical name palbociclib, Kisqali with chemical name ribociclib and Verzenios with chemical name abemaciclib are used for target therapy against metastatic breast cancer. CDK4/6 inhibitors in combination with aromatase inhibitors, estrogen receptor down regulators or selective receptor modulators are also used to address the treatment resistant metastatic breast cancers. The aim of this thesis is to investigate the role and the effect of CDK4/6 inhibitors in the treatment of metastatic breast cancer. Six randomized controlled trial studies were selected from the PubMed data base. Results from the trial analysis showed equal effects and relative same adverse event profiles between those three mentioned CDK4/6 inhibitors. The primary endpoint, progression free survival and secondary endpoints including overall survival, clinical benefit rate, overall response rate and safety were investigated in these studies. The duration of progression free survival (PFS) and overall response rate (ORR) was longer and improved in most studies however improvement in overall survival (OS) was not achieved. More research studies are needed to determine optimal treatment for patients with metastatic breast cancer who are medicated by CDK4/6 inhibitors.

Bakgrund: Cancerfallen i Sverige har fördubblats sedan 1970-talet och om cirka 20 år uppskattas 100 000 nya personer insjukna i cancer per år. Att drabbas av cancer anses vara en av de mest stressfyllda situationer en person kan uppleva och sjukdomen påverkar patienten både fysiskt, psykiskt och existentiellt. För att lättare hantera sin nya vardag kan patienten behöva tillämpa olika copingstrategier som används för att hantera svåra påfrestningar. 

Syfte: Syftet med studien var att utifrån ett patientperspektiv beskriva copingstrategier som kan hjälpa patienter med avancerad cancer. 

Metod: En litteraturstudie med 14 kvalitativa vetenskapliga artiklar genomfördes. Artiklarna analyserades utifrån Lundman och Hällgren-Graneheims (2017) manifesta innehållsanalys. 

Resultat: Resultatet delades in i fyra kategorier och tretton underkategorier. Kategorierna som framkom var; Viljan att styra över sitt liv, uppmuntrande känslor, socialt stöd samt andligt stöd.

Slutsats: Sjuksköterskan behöver agera på ett sådant sätt att patientens hälsa ökar och lidandet minskar. Sjuksköterskan behöver också utgå ifrån patientens unika och subjektiva livsvärld eftersom det är först då som patientens copingstrategier kan identifieras och stärkas. Tillgodosedda copingstrategier leder till att patientens vardag och liv kan genomsyras av en känsla av hanterbarhet, begriplighet och meningsfullhet.

SAMMANFATTNING

Bakgrund: Årligen dör ett av fyra cancerdiagnostiserade barn i Sverige. Föräldrarnas liv efter förlusten förändras för alltid och reaktionerna kan variera. Efter förlusten är föräldrarna i stort behov av stöd från sina nätverk. De måste lära sig att leva med förlusten och de får kämpa för att komma tillbaka till vardagen. Syfte: Syftet med studien var att beskriva hur föräldrarna upplevde välbefinnande respektive lidande upp till två år efter att deras barn avlidit i cancer. Metod: Studien utgår från fem självbiografier som analyserades med kvalitativ innehållsanalys. Resultat: Att förlora sitt barn skapar många blandade känslor hos föräldrarna, allt från sorg till lättnad. Föräldrarna är i behov av stöd efter den livsomvälvande upplevelsen. Barnen är en del av familjerna då minnena alltid lever kvar. Syskonen är en avgörande faktor för föräldrarnas kamp att fortsätta den nya vardagen. Föräldrarna lär sig att leva med saknaden och sorgen. Slutsats: Att förlora ett barn är en traumatisk händelse som skapar många olika känslor. Att få bra stöd är viktigt för föräldrarna som bearbetar händelsen på olika sätt. Minnena av barnen finns alltid hos föräldrarna så länge de lever och de genomgår förändringar efter att barnen har avlidit.

OBJECTIVE: European cancer survival rates vary widely. System factors, including whether or not primary care physicians (PCPs) are gatekeepers, may account for some of these differences. This study explores where patients who may have cancer are likely to present for medical care in different European countries, and how probability of presentation to a primary care clinician correlates with cancer survival rates.

DESIGN: Seventy-eight PCPs in a range of European countries assessed four vignettes representing patients who might have cancer, and consensus groups agreed how likely those patients were to present to different clinicians in their own countries. These data were compared with national cancer survival rates.

SETTING: A total of 14 countries.

SUBJECTS: Consensus groups of PCPs.

MAIN OUTCOME MEASURES: Probability of initial presentation to a PCP for four clinical vignettes.

RESULTS: There was no significant correlation between overall national 1-year relative cancer survival rates and the probability of initial presentation to a PCP (r  = -0.16, 95% CI -0.39 to 0.08). Within that there was large variation depending on the type of cancer, with a significantly poorer lung cancer survival in countries where patients were more likely to initially consult a PCP (lung r = -0.57, 95% CI -0.83 to -0.12; ovary: r = -0.13, 95% CI -0.57 to 0.38; breast r = 0.14, 95% CI -0.36 to 0.58; bowel: r = 0.20, 95% CI -0.31 to 0.62).

CONCLUSIONS: There were wide variations in the degree of gatekeeping between countries, with no simple binary model as to whether or not a country has a "PCP-as-gatekeeper" system. While there was case-by-case variation, there was no overall evidence of a link between a higher probability of initial consultation with a PCP and poorer cancer survival. KEY POINTS European cancer survival rates vary widely, and health system factors may account for some of these differences. The data from 14 European countries show a wide variation in the probability of initial presentation to a PCP. The degree to which PCPs act as gatekeepers varies considerably from country to country. There is no overall evidence of a link between a higher probability of initial presentation to a PCP and poorer cancer survival.

Background National European cancer survival rates vary widely. Prolonged diagnostic intervals are thought to be a key factor in explaining these variations. Primary care practitioners (PCPs) frequently play a crucial role during initial cancer diagnosis; their knowledge could be used to improve the planning of more effective approaches to earlier cancer diagnosis. Objectives This study sought the views of PCPs from across Europe on how they thought the timeliness of cancer diagnosis could be improved. Design In an online survey, a final open-ended question asked PCPs how they thought the speed of diagnosis of cancer in primary care could be improved. Thematic analysis was used to analyse the data. Setting A primary care study, with participating centres in 20 European countries. Participants A total of 1352 PCPs answered the final survey question, with a median of 48 per country. Results The main themes identified were: patient-related factors, including health education; care provider-related factors, including continuing medical education; improving communication and interprofessional partnership, particularly between primary and secondary care; factors relating to health system organisation and policies, including improving access to healthcare; easier primary care access to diagnostic tests; and use of information technology. Re-allocation of funding to support timely diagnosis was seen as an issue affecting all of these. Conclusions To achieve more timely cancer diagnosis, health systems need to facilitate earlier patient presentation through education and better access to care, have well-educated clinicians with good access to investigations and better information technology, and adequate primary care cancer diagnostic pathway funding.

OBJECTIVES: Cancer survival and stage of disease at diagnosis and treatment vary widely across Europe. These differences may be partly due to variations in access to investigations and specialists. However, evidence to explain how different national health systems influence primary care practitioners' (PCPs') referral decisions is lacking.This study analyses health system factors potentially influencing PCPs' referral decision-making when consulting with patients who may have cancer, and how these vary between European countries.

DESIGN: Based on a content-validity consensus, a list of 45 items relating to a PCP's decisions to refer patients with potential cancer symptoms for further investigation was reduced to 20 items. An online questionnaire with the 20 items was answered by PCPs on a five-point Likert scale, indicating how much each item affected their own decision-making in patients that could have cancer. An exploratory factor analysis identified the factors underlying PCPs' referral decision-making.

SETTING: A primary care study; 25 participating centres in 20 European countries.

PARTICIPANTS: 1830 PCPs completed the survey. The median response rate for participating centres was 20.7%.

OUTCOME MEASURES: The factors derived from items related to PCPs' referral decision-making. Mean factor scores were produced for each country, allowing comparisons.

RESULTS: Factor analysis identified five underlying factors: PCPs' ability to refer; degree of direct patient access to secondary care; PCPs' perceptions of being under pressure; expectations of PCPs' role; and extent to which PCPs believe that quality comes before cost in their health systems. These accounted for 47.4% of the observed variance between individual responses.

CONCLUSIONS: Five healthcare system factors influencing PCPs' referral decision-making in 20 European countries were identified. The factors varied considerably between European countries. Knowledge of these factors could assist development of health service policies to produce better cancer outcomes, and inform future research to compare national cancer diagnostic pathways and outcomes.

Background: Although there has been a steady increase in intervention studies aimed toward supporting family caregivers in palliative cancer care, they often report modest effect sizes and there is a lack of knowledge about possible barriers to intervention effectiveness. Objective: The aim of this study is to explore the characteristics of family caregivers who did not benefit from a successful psychoeducational group intervention compared with the characteristics of those who did. Intervention/Methods: A psychoeducational intervention for family caregivers was delivered at 10 palliative settings in Sweden. Questionnaires were used to collect data at baseline and following the intervention. The Preparedness for Caregiving Scale was the main outcome for the study and was used to decide whether or not the family caregiver had benefited from the intervention (Preparedness for Caregiving Scale difference score <= 0 vs >= 1). Results: A total of 82 family caregivers completed the intervention and follow-up. Caregivers who did not benefit from the intervention had significantly higher ratings of their preparedness and competence for caregiving and their health at baseline compared with the group who benefited. They also experienced lower levels of environmental burden and a trend toward fewer symptoms of depression. Conclusions: Family caregivers who did not benefit from the intervention tended to be less vulnerable at baseline. Hence, the potential to improve their ratings was smaller than for the group who did benefit. Implications for Practice: Determining family caregivers in cancer and palliative care who are more likely to benefit from an intervention needs to be explored further in research.

Background: The significance of metaphors for the experience of cancer has been the topic of extensive previous research, with “Battle” and “Journey” metaphors standing out as key. Adaptation to the patient’s use of metaphor is generally believed to be an important aspect of person-centered care, especially in palliative care. The aim of this study was to investigate the use of metaphors in blogs written in Swedish by people living with advanced cancer and explore possible patterns associated with individuals, age and gender.

Methods: The study is based on a dataset totaling 2 602 479 words produced some time during the period 2007–2016 by 27 individuals diagnosed with advanced cancer. Both qualitative and quantitative procedures were used, and the findings are represented as raw frequencies as well as normalized frequencies per 10 000 words. Our general approach was exploratory and descriptive. The Mann-Whitney U test was used to analyze statistical significance.

Results: Our results confirm the strong foothold of “Journey” and “Battle” metaphors. “Imprisonment” and “Burden” metaphors were also used by the majority of the individuals. The propensity to use metaphors when describing the cancer experience was found to differ extensively across the individuals. However, individuals were not found to opt for one conceptualization over the other but tended to draw on several different metaphor domains when conceptualizing their experience. Socio-demographic factors such as age or gender were not found to be strong predictors of metaphor choice in this limited study.

Conclusions: Using a range of different metaphors allows individuals with advanced cancer to highlight different aspects of their experience. The presence of metaphors associated with “Journey”, “Battle”, “Imprisonment” and “Burden” across individuals could be explained by the fact that the bloggers are part of a culturally consistent cohort, despite variations in age, sex and cancer form. Awareness of metaphors commonly used by patients can enhance health professionals’ capacity to identify metaphorical patterns and develop a common language grounded in the patients’ own metaphor use, which is an important requisite for person-centered palliative care.

Background Evidence is increasing for the use of faecal immunochemical tests (FITs) for occult blood as diagnostic tools when colorectal cancer can be suspected. FITs have been used for this purpose in Swedish primary care since around 2005 despite absence of supporting guidelines. To our knowledge, the extent of this use has not been studied. Objective To investigate the use of FITs as diagnostic tools, and if the use was related to patient age, sex and travel time from primary care to diagnostic facilities in secondary care. Design Population-based retrospective study using data from electronic health records. Setting and subjects Patients >= 18 years that provided FITs in primary care in five Swedish health care regions during 2015. Driving times from their primary care centres to secondary care were calculated. Main outcome measures The proportion of patients that provided FITs was calculated for each region, different age intervals and grouped driving times. Results 18,913 patients provided FITs. The proportion of listed patients in the five regions that provided FITs increased with age: 0.86-1.2% for ages <65 years, 3.6-4.1% for ages 65-79 years and 3.8-6.1% for ages >= 80 years. Differences between the regions were small. There was no overall correlation between the proportion of patients that provided FITs and driving time to secondary care. Conclusion FITs were used extensively in Swedish primary care with a higher use in older age groups. There was no tendency towards a higher use of FITs at primary care centres with longer driving times to secondary care.

Background Rectal bleeding is considered an alarm symptom for colorectal cancer (CRC) but it is common and mostly caused by benign conditions. Qualitative faecal immunochemical tests (FITs) for occult blood have been used as diagnostic aids for many years in Sweden when CRC is suspected. The study aimed to evaluate the usefulness of FITs requested by primary care physicians for patients with and without histories of rectal bleeding, in the diagnosis of CRC. Methods Results of all FITs requested in primary care for symptomatic patients in the orebro region during 2015 were retrieved. Data on each patient's history of rectal bleeding was gathered from electronic health records. Patients diagnosed with CRC within 2 years were identified from the Swedish Cancer Register. The analysis focused on three-sample FITs, the customary FIT in Sweden. Results A total of 4232 patients provided three-sample FITs. Information about the presence/absence of rectal bleeding was available for 2027 patients, of which 59 were diagnosed with CRC. For 606 patients with the presence of rectal bleeding, the FIT showed sensitivity 96.2%, specificity 60.2%, positive predictive value 9.8% (95% CI 6.1-13.4) and negative predictive value 99.7% (95% CI 99.2-100) for CRC. For 1421 patients without rectal bleeding, the corresponding figures were 100%, 73.6%, 8.3% (95% CI 5.6-10.9) and 100% (95% CI 99.6-100). Conclusion The diagnostic performance of a qualitative three-sample FIT provided by symptomatic patients in primary care was similar for those with and without a history of rectal bleeding. FITs seem useful for prioritising patients also with rectal bleeding for further investigation.

Background Colorectal cancer (CRC) diagnostics are challenging in primary care and reliable diagnostic aids are desired. Qualitative faecal immunochemical tests (FITs) have been used for suspected CRC in Sweden since the mid-2000s, but evidence regarding their effectiveness is scarce. Anaemia and thrombocytosis are both associated with CRC. Aim To evaluate the usefulness of qualitative FITs requested for symptomatic patients in primary care, atone and combined with findings of anaemia and thrombocytosis, in the diagnosis of CRC. Design and setting A population-based cohort study using electronic health records and data from the Swedish Cancer Register, covering five Swedish regions. Method Patients aged >= 18 years in the five regions who had provided FITs requested by primary care practitioners from 1 January 2015 to 31 December 2015 were identified. FIT and blood-count data were registered and all CRC diagnoses made within 2 years were retrieved. Diagnostic measurements were calculated. Results In total, 15 789 patients provided FITs (four different brands); of these patients, 304 were later diagnosed with CRC. Haemoglobin levels were available for 13 863 patients, and platelet counts for 10 973 patients. Calculated for the different FIT brands only, the sensitivities for CRC were 81.6%-100%; specificities 65.7%-79.5%: positive predictive values 4.7%-8.1%; and negative predictive values 99.5%-100%. Calculated for the finding of either a positive FIT or anaemia, the sensitivities increased to 88.9-100%. Adding thrombocytosis did not further increase the diagnostic performance. Conclusion Qualitative FITs requested in primary care seem to be useful as rule in tests for referral when CRC is suspected. A negative FIT and no anaemia indicate a low risk of CRC.

Bakgrund: I Sverige insjuknar ungefär ett barn om dagen i cancer. När ett barn drabbas av cancer påverkas hela familjen. Föräldrarna upplever en rädsla över bieffekter, behandling samt att förlora sitt barn och diskuterar oftast inte sina upplevelser med vårdpersonalen vilket leder till ökad oro och onödigt lidande. Föräldrarna har ofta en stor roll i barnets möjlighet att finna välbefinnande och det är därför viktigt att tillvarata deras erfarenheter och upplevelser. Syfte: Syftet med studien var att belysa föräldrars upplevelse av att leva med ett cancersjukt barn. Metod: Studien grundades på en kvalitativ metod utifrån fem bloggar. En kvalitativ manifest innehållsanalys utifrån Lundman och Hällgren Graneheims (2012) användes för att finna det centrala i materialet. Resultat: Föräldrars upplevelser av att leva med ett cancersjukt barn innebar en stor emotionell påverkan där oro och rädsla var de främsta fynden. Genom att tillämpa copingstrategier samt leva i nuet kunde föräldrarna bättre hantera vardagen. Sjukhusmiljön frambringade både positiva och negativa känslor hos föräldrarna och en känsla av utsatthet i samband med vårdmiljön framkom. Slutsats: Föräldrars upplevelser bör uppmärksammas och de behöver stöd från vårdpersonalen. Bättre samordning och kommunikation samt en kontaktperson kan vara lämpliga åtgärder för att främja föräldrarnas välbefinnande.

Background: It is 50-75% of the women in Sweden who suffer from menopausal problems. Common problems include vasomotor symptoms such as hot flashes, sweating and palpitations, but also urogenital atrophy, osteoporosis, urination and depression. A third of all menopausal women are in need of treatment to maintain their quality of life. Hormone therapy with estrogen of menopausal women started in the United States in 1942. International guidelines today are that estrogen should be used in conjunction with a progestagen if the woman has an intact uterus in order for the estrogen's stimulation of the endometrium to be inhibited. A large randomized study, the Women's Health Initiative, showed that conventional hormones increase the risk of breast cancer and it was therefore stopped prematurely in 2002. After that, the demand for bioidentical hormones rose as these are considered safer by many, but opinions are controversial. Studies have shown that bioidentical progesterone may be associated with a lower risk of breast cancer than synthetic progestin when given together with estrogen, but there is currently no conclusive evidence that this is true. On the other hand, studies show that progesterone increases the risk of endometrial cancer compared to progestin when combined with estrogen.

Aim: The aim of the present work was to investigate the risk of breast and endometrial cancer during treatment with bioidentical hormones of menopausal women in comparison to conventional hormone therapy. 

Method: A literature study was conducted in which six scientific articles were reviewed. The articles were retrieved from the PubMed database and were all randomised and not older than 10 years. They all investigated treatment with bioidentical or conventional hormones of menopausal women. 

Results: Conventional hormones showed an increased risk of breast cancer compared to placebo and bioidentical hormones, while they reduced the risk of endometrial cancer compared to placebo. Bioidentical hormones increased the risk of endometrial cancer compared to placebo in one study, while another study showed that there was no increased risk. 

Conclusion: The studies analyzed in this thesis show clearly that bioidentical hormones are associated with a lower risk of breast cancer than conventional ones. However, the risk of endometrial cancer may increase with bioidentical hormones compared to the conventional ones, but the results are inconclusive. Follow-up studies for bioidentical hormones are currently lacking and are needed to determine the long-term effect they have on breasts and endometrium. In conclusion, a woman in the choice of hormone therapy should be carefully considered with the benefit of risks.

Bcr-Abl1 kinase domain mutations are the most prevalent cause of treatment resistance in chronic myeloid leukaemia (CML). Alternate resistance pathways nevertheless exist, and cell line experiments show certain patterns in the gain, and loss, of some of these alternate adaptations. These adaptations have clinical consequences when the tumour develops mechanisms that are beneficial to its growth under treatment, but slow down its growth when not treated. The results of temporarily halting treatment in CML have not been widely discussed in the clinic and there is no robust theoretical model that could suggest when such a pause in therapy can be tolerated. We constructed a dynamic model of how mechanisms such as Bcr-Abl1 overexpression and drug transporter upregulation evolve to produce resistance in cell lines, and investigate its behaviour subject to different treatment schedules, in particular when the treatment is paused ('drug holiday'). Our study results suggest that the presence of additional resistance mechanisms creates an environment which favours mutations that are either preexisting or occur late during treatment. Importantly, the results suggest the existence of tumour drug addiction, where cancer cells become dependent on the drug for (optimal) survival, which could be exploited through a treatment holiday. All simulation code is available at https://github.com/Sandalmoth/dual-adaptation.

Targeted therapies are a mainstay of modern cancer treatments. Rather than harming rapidly dividing cells in general, targeted therapies work by directly interfering with oncogenic molecular pathways present in a tumour. Consequently, a targeted therapy typically has less severe side effects. However, specificity comes at a price as comparatively small changes to the target can render the treatment ineffective. Much like the natural selection among plants and animals, individual cancer cells compete with one another for space and resources. Hence, if a single cancer cell acquires a resistance adaptation, the forces of evolution can turn that advantage in a single cell into an untreatable resistant cancer.

This thesis is principally concerned with chronic myeloid leukaemia (CML), characterized by a chromosomal translocation called the Philadelphia chromosome which creates the constitutively active tyrosine kinase Bcr-Abl1. The discovery of tyrosine kinase inhibitors (TKIs) targeting Bcr-Abl1 greatly improved treatment outcomes. Eventually however, resistance emerges. An important mechanism in CML is mutations in the kinase domain of Bcr-Abl1 that affect how well the drugs bind. A number of drugs have been developed that target the mutated kinase to varying degrees, but it is still desirable to prevent drug resistance from occurring in the first place, as the accumulation of multiple mutations is almost certain to create untreatable resistance.

The fitness effects of a drug resistance adaptation depend on the drug treatment, so it may be possible to alter the fitness landscape by modifying the treatment. This work examines different approaches, mainly in CML, to delay or prevent the onset of resistance through modifying the treatment protocol.

Periodically switching between different TKIs, i.e. drug rotations, was shown through modelling to increase the expected time to resistance and seems to have some protective benefits in vitro. Also apparently promising were drug combinations involving a novel inhibitor asciminib, currently in phase III trials, which can reduce overall drug burden while also being seemingly effective against known resistance mutations. Finally, a model of the interaction between resistance mutations and less potent alternate resistance mechanisms revealed how a drug holiday may have resensitizing, or even beneficial effects.

BackgroundResistance towards targeted cancer treatments caused by single nucleotide variations is a major issue in many malignancies. Currently, there are a number of available drugs for chronic myeloid leukaemia (CML), which are overcome by different sets of mutations. The main aim of this study was to explore if it can be possible to exploit this and create a treatment protocol that outperforms each drug on its own.MethodsWe present a computer program to test different treatment protocols against CML, based on available resistance mutation growth data. The evolution of a relatively stable pool of cancer stem cells is modelled as a stochastic process, with the growth of cells expressing a tumourigenic protein (here, Abl1) and any emerging mutants determined principally by the drugs used in the therapy.ResultsThere can be some benefit to Bosutinib-Ponatinib rotation therapy even if the mutation status is unknown, whereas Imatinib-Nilotinib rotation is unlikely to improve the outcomes. Furthermore, an interplay between growth inhibition and selection effects generates a non-linear relationship between drug doses and the risk of developing resistance.ConclusionsDrug rotation therapy might be able to delay the onset of resistance in CML patients without costly ongoing observation of mutation status. Moreover, the simulations give credence to the suggestion that lower drug concentrations may achieve better results following major molecular response in CML.

Targeted therapies for chronic myeloid leukaemia (CML) are effective, but rarely curative. Patients typically require treatment indefinitely, which gives ample time for drug resistance to evolve. Drug resistance issues are one of the main causes of death owing to CML, thus any means of preventing resistance are of importance. Drug rotations, wherein treatment is switched periodically between different drugs are one such option, and have been theorized to delay the onset of resistance. In vitro testing of drug rotation therapy is a first step towards applying it in animal or human trials. We developed a method for testing drug rotation protocols in CML cell lines based around culturing cells with a moderate amount of inhibitors interspersed with washing procedures and drug swaps. Drug rotations of imatinib and ponatinib were evaluated in a CML specific cell line, KCL-22. The growth of KCL-22 cells was initially reduced by a drug rotation, but the cells eventually adapted to the protocol. Our results show that ponatinib in a drug rotation temporarily sensitizes the cells to imatinib, but the effect is short-lived and is eventually lost after a few treatment cycles. Possible explanations for this observation are discussed.

Background: Chronic myeloid leukaemia is in principle a treatable malignancy but drug resistance is lowering survival. Recent drug discoveries have opened up new options for drug combinations, which is a concept used in other areas for preventing drug resistance. Two of these are (I) Axitinib, which inhibits the T315I mutation of BCR-ABL1, a main source of drug resistance, and (II) Asciminib, which has been developed as an allosteric BCR-ABL1 inhibitor, targeting an entirely different binding site, and as such does not compete for binding with other drugs. These drugs offer new treatment options. Methods: We measured the proliferation of KCL-22 cells exposed to imatinib–dasatinib, imatinib–asciminib and dasatinib–asciminib combinations and calculated combination index graphs for each case. Moreover, using the median–effect equation we calculated how much axitinib can reduce the growth advantage of T315I mutant clones in combination with available drugs. In addition, we calculated how much the total drug burden could be reduced by combinations using asciminib and other drugs, and evaluated which mutations such combinations might be sensitive to. Results: Asciminib had synergistic interactions with imatinib or dasatinib in KCL-22 cells at high degrees of inhibition. Interestingly, some antagonism between asciminib and the other drugs was present at lower degrees on inhibition. Simulations revealed that asciminib may allow for dose reductions, and its complementary resistance profile could reduce the risk of mutation based resistance. Axitinib, however, had only a minor effect on T315I growth advantage. Conclusions: Given how asciminib combinations were synergistic in vitro, our modelling suggests that drug combinations involving asciminib should allow for lower total drug doses, and may result in a reduced spectrum of observed resistance mutations. On the other hand, a combination involving axitinib was not shown to be useful in countering drug resistance.

Background

Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacologicaltreatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is stillunclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-toheadtrial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadinevs. placebo in patients with advanced cancer.

Methods

The 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will usea parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidatevs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0–10 scale. The study periodincludes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcomeis the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illnesstherapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, whichwill be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for AdverseEvents in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learningalgorithm will be employed for the clinical prediction of different agents in homogeneous subgroups.

Discussion

The findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatmentapproach, design of future trials, as well as the development of CRF management guidelines.

Trial registration IRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.

Background: Rural-dwellers have poorer cancer outcomes than urban counterparts, for reasons which are unclear. At healthcare institution level, poorer access to investigations and different clinical decision-making by rural primary healthcare practitioners (PCPs) could be important. Aim: To compare access to investigations, attitudes to cancer diagnosis and clinical decision-making between rural and urban PCPs. Setting: A vignette-based cross-sectional survey of rural and urban PCPs in 20 European countries. Methods: Data on PCPs' decision-making and attitudes to cancer diagnosis were based on clinical scenarios. Comparisons were made using tests of proportion, univariable and multivariable binary logistic regression. Results: Of the 1779 PCPs completing the survey 541 30.4 %) practiced rurally. Rural PCPs had significantly less direct access to all investigative modalities: ultrasound; endoscopy; x-ray and advanced screening (all p<0.001). Rural PCPs were as likely as urban PCPs to take diagnostic action (investigation and/or referral) at the index consultation in all four clinical vignettes ((OR, 95 % CI) for lung: 0.90, 0.72-1.12; ovarian: 0.95, 0.75-1.19; breast: 0.87, 0.69-1.09; colorectal: 0.98, 0.75-1.30). Rural PCPs were less likely to refer to a specialist at the index consultation for ovarian cancer (OR 0.71 95 % CI 0.51-0.99). Rural PCPs were significantly more likely to report that their patients faced barriers to accessing specialist care, but practitioners did not report greater difficulties making specialist referral than their urban counterparts Conclusions: European rural PCPs report poorer access to investigations but are at least as likely as urban PCPs to investigate or refer patients that might have cancer at the index consultation.

The aim of this population-based registry study was to explore how cancer influences the health of partners, by examining the onset of new diagnoses for partners, health care use and health care costs among partners living with patients with cancer. The sample consisted of partners of patients with cancer (N = 10 353) and partners of age- and sex-matched controls who did not have cancer (N = 74 592). Diagnoses, health care use and health care costs were studied for a continuous period starting 1 year before the date of cancer diagnosis and continued for 3 years. One year after cancer diagnosis, partners of patients with cancer had significantly more mood disorders, reactions to severe stress and ischaemic heart disease than they exhibited in the year before the diagnosis. Among partners of patients with cancer, the type of cancer was associated with the extent and form of increased health care use and costs; both health care use and costs increased among partners of patients with liver cancer, lung cancer, colon cancer and miscellaneous other cancers. The risk of poorer health varied according to the type of cancer diagnosed, and appeared related to the severity and prognosis of that diagnosis.

BACKGROUND: It is unclear to what extent primary care practitioners (PCPs) should retain responsibility for follow-up to ensure that patients are monitored until their symptoms or signs are explained.

AIM: To explore the extent to which PCPs retain responsibility for diagnostic follow-up actions across 11 international jurisdictions.

DESIGN AND SETTING: A secondary analysis of survey data from the International Cancer Benchmarking Partnership.

METHOD: The authors counted the proportion of 2879 PCPs who retained responsibility for each area of follow-up (appointments, test results, and non-attenders). Proportions were weighted by the sample size of each jurisdiction. Pooled estimates were obtained using a random-effects model, and UK estimates were compared with non-UK ones. Free-text responses were analysed to contextualise quantitative findings using a modified grounded theory approach.

RESULTS: PCPs varied in their retention of responsibility for follow-up from 19% to 97% across jurisdictions and area of follow-up. Test reconciliation was inadequate in most jurisdictions. Significantly fewer UK PCPs retained responsibility for test result communication (73% versus 85%, P = 0.04) and non-attender follow-up (78% versus 93%, P<0.01) compared with non-UK PCPs. PCPs have developed bespoke, inconsistent solutions to follow-up. In cases of greatest concern, 'double safety netting' is described, where both patient and PCP retain responsibility.

CONCLUSION: The degree to which PCPs retain responsibility for follow-up is dependent on their level of concern about the patient and their primary care system's properties. Integrated systems to support follow-up are at present underutilised, and research into their development, uptake, and effectiveness seems warranted.

Objective. Non-neuronal acetylcholine (ACh) has been suggested to be a mediator for the development of various types of cancer. We analyzed a possible role for this molecule in carcinogenesis and/or progression of human colon cancer, in patient biopsies harvested from the colon during surgery. We addressed whether ACh synthesis (by choline acetyltransferase) and/or degradation (by ACh esterase), as well as the expression of the α7-subtype of the nicotinic ACh receptors, and the peptide ligand at the α7 receptors, secreted mammalian Ly6/urokinase-type plasminogen activator receptor-related protein-1, respectively, are deranged in tumor tissue as compared with macroscopically tumor-free colon tissue. Methods. A total of 38 patients were grouped for analysis based on their respective Dukes stage (either Dukes A + B or C + D). A mucosal tissue sample was harvested from macroscopically tumor-free colon tissue (i.e. control tissue), as well as from the tumor, and protein lysates were prepared for quantitative Western blotting. Full-thickness specimens were taken for immunohistochemistry. Results. For all the above named markers, there was a significant difference between control and tumor tissue with regard to protein levels, and there was, in addition, a significant difference in protein levels between the Dukes A + B and C + D groups. Conclusion. The current findings may suggest a role for ACh in colon carcinogenesis/cancer progression; the data obtained could have prognostic and/or therapeutic significance for this disease.

Background: To suffer from a tumor disease starts both physical and mental processes in the patient. These patients often need some form of surgical treatment or action. It is a group of patients who have often been through a lot, before, during, and after the surgery.

Aim: To describe patients' perceptions of encounters with healthcare professionals after undergoing cancer surgery in the gastrointestinal tract.

Methods: The study was an empirical study with a qualitative design and a phenomenographic approach. Eight patients recruited from a surgical department in a hospital in southern Sweden were interviewed, and data were analyzed according to a phenomenographic method.

Results: Patients described what the encounter means after undergoing cancer surgery, which resulted in three descriptive categories – creating an adequate environment for care, paying attention to individual needs for care, and facilitating patient participation in care. Patients perceived that the healthcare professionals are committed to the patient's situation and that their commitment has a positive effect on the patients' mood postoperatively when they felt seen.

Conclusion: The healthcare professionals’ ability to be sensitive to the different needs of the patients was important for how the patient perceived their care in the ward. The possibility of some kind of activity that could help dispel negative thoughts and the patient's need for active participation in their own care were important aspects.

About 12 to 17 percent of all breast cancers are triple-negative breast cancer (TNBC). In TNBC, estrogen, progesterone, and human epidermal growth factor receptor two are not expressed, or copies of the HER2 gene are decreased (or both). This makes TNBC hard to treat in comparison with other kinds of breast cancers. New studies have made some interesting observations on how some monoclonal antibodies can help to treat TNBC. One of the monoclonal antibodies that can be useful for treating TNBC is pembrolizumab. Pembrolizumab inhibits programmed death ligand 1 (PD-1), which is located on the surface of T cells from connecting to immune checkpoint proteins such as programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) located on the surface of the cancer cell. Breaking this connection enables continued activation of T cells and attack of the cancer cells.

This thesis aimed to evaluate if pembrolizumab was safe and effective as monotherapy or as a combination therapy with chemotherapy for patients with different stages of TNBC. This study was based on scientific articles identified from the database PubMed. Five randomized controlled trial studies were selected for further study in this project. Two publications were chosen from keynote-355, which studied the effect and safety of Pembrolizumab in combination with chemotherapy and compared it to chemotherapy monotherapy in patients with metastatic TNBC. The first study included patients from different countries as it was a multi-center study, and the second one focused only on patients who enrolled in Japan. One study was chosen from keynote-119 studies, which compared health-related quality of life for patients who were treated with pembrolizumab monotherapy or with monotherapy of chemotherapy. The last two articles which were chosen were about keynote-522. The first article about keynote-522 compared was a multicenter study enrolled in 21 countries. In this study, patients had early-stage TNBC and received neoadjuvant placebo chemotherapy or pembrolizumab chemotherapy. After the breast operation, either adjuvant pembrolizumab or placebo was received. The other study looked at Asian patients who enrolled in keynote-522.

Results showed that monotherapy with pembrolizumab did not make a massive difference in overall survival compared to chemotherapy. Still, it led to better health- related quality of life for patients (Combined Positive Score (CPS) ≥ 10) treated with pembrolizumab. Results from keynote-355 showed that combination therapy with pembrolizumab and chemotherapy led to better and longer progression-free survival and overall survival in patients with CPS ≥ 10 treated with pembrolizumab. The analysis of Japanese patients showed even better progression-free survival and overall survival results than the global population. The study from keynote-522 showed that neoadjuvant pembrolizumab and chemotherapy followed by adjuvant pembrolizumab had a better effect than only neoadjuvant chemotherapy. The second keynote-522 study showed the same results as the global study and better results at event-free survival for the Asian population than the overall population.

After reviewing the articles, it was found that pembrolizumab proves to be a safe and effective treatment for TNBC. To enhance understanding of the drug's effects, measures such as extending follow-up periods, conducting further studies to assess its effectiveness, and exploring new research methodologies are proposed.

Background: Survival rates following a diagnosis of cancer vary between countries. The International Cancer Benchmarking Partnership (ICBP), a collaboration between six countries with primary care led health services, was set up in 2009 to investigate the causes of these differences. Module 3 of this collaboration hypothesised that an association exists between the readiness of primary care physicians (PCP) to investigate for cancer - the 'threshold' risk level at which they investigate or refer to a specialist for consideration of possible cancer - and survival for that cancer (lung, colorectal and ovarian). We describe the development of an international survey instrument to test this hypothesis. Methods: The work was led by an academic steering group in England. They agreed that an online survey was the most pragmatic way of identifying differences between the jurisdictions. Research questions were identified through clinical experience and expert knowledge of the relevant literature. A survey comprising a set of direct questions and five clinical scenarios was developed to investigate the hypothesis. The survey content was discussed and refined concurrently and repeatedly with international partners. The survey was validated using an iterative process in England. Following validation the survey was adapted to be relevant to the health systems operating in other jurisdictions and translated into Danish, Norwegian and Swedish, and into Canadian and Australian English. Results: This work has produced a survey with face, content and cross cultural validity that will be circulated in all six countries. It could also form a benchmark for similar surveys in countries with similar health care systems. Conclusions: The vignettes could also be used as educational resources. This study is likely to impact on healthcare policy and practice in participating countries.

Objectives: The International Cancer Benchmarking Partnership (ICBP) is a collaboration between 6 countries and 12 jurisdictions with similar primary care-led health services. This study investigates primary care physician (PCP) behaviour and systems that may contribute to the timeliness of investigating for cancer and subsequently, international survival differences. Design: A validated survey administered to PCPs via the internet set out in two parts: direct questions on primary care structure and practice relating to cancer diagnosis, and clinical vignettes, assessing management of scenarios relating to the diagnosis of lung, colorectal or ovarian cancer. Participants: 2795 PCPs in 11 jurisdictions: New South Wales and Victoria (Australia), British Columbia, Manitoba, Ontario (Canada), England, Northern Ireland, Wales (UK), Denmark, Norway and Sweden. Primary and secondary outcome measures: Analysis compared the cumulative proportion of PCPs in each jurisdiction opting to investigate or refer at each phase for each vignette with 1-year survival, and conditional 5-year survival rates for the relevant cancer and jurisdiction. Logistic regression was used to explore whether PCP characteristics or system differences in each jurisdiction affected the readiness to investigate. Results: 4 of 5 vignettes showed a statistically significant correlation (p<0.05 or better) between readiness to investigate or refer to secondary care at the first phase of each vignette and cancer survival rates for that jurisdiction. No consistent associations were found between readiness to investigate and selected PCP demographics, practice or health system variables. Conclusions: We demonstrate a correlation between the readiness of PCPs to investigate symptoms indicative of cancer and cancer survival rates, one of the first possible explanations for the variation in cancer survival between ICBP countries. No specific health system features consistently explained these findings. Some jurisdictions may consider lowering thresholds for PCPs to investigate for cancer-either directly, or by specialist referral, to improve outcomes.

Bakgrund: Ordet cancer kan vara ett väldigt laddat ord för många människor, cancer hos barn är ännu mer laddat eftersom det gäller just ett barn. Då ett barn får diagnosen cancer är det inte bara barnet som drabbas, utan även familjen och stora delar av omgivningen såsom skola och kompisar. Idag finns det goda chanser att barn överlever sin cancersjukdom och det finns välgjorda riktlinjer för hur vården ska bedrivas under aktiv behandling och hur uppföljningen av barnet ska ske efter avslutad behandling. Men finns det någon plan för att uppföljning av föräldrarna och hur är deras mående tas omhand efter en påfrestande tid som denna?

Syfte: Syftet var att undersöka föräldrars erfarenheter av livet efter att barnet har avslutat en lyckad cancerbehandling.

Metod: En litteraturstudie genomfördes och resultatet baseras på åtta

vetenskapliga kvalitativa och kvantitativa artiklar.

Resultat: Fyra övergripande kategorier identifierades: Erfarenhet av känslomässiga reaktioner; Erfarenhet av påverkan på livet; Betydelsen av stöd och relationer; Att återgå till det normala.

Slutsats: Resultat i studien visade att många föräldrar upplever ständig närvaro av oro, ångest eller depression även efter barnets avslutade behandling. De föräldrar som uppfattar sina barn som mer sårbara och bräckliga blir mer påverkade av den negativa stress som sjukdomen och dess behandling har utgjort. Vidare gick att utläsa att den ständiga jakten efter eventuella symtom blir ett stresspåslag och utgör en påminnelse i det vardagliga livet. Allt detta bidrar till okontrollerbara tankar om återfall eller död vilket leder till ett hinder för familjen att bearbeta det de varit med om och gå vidare. En förlorad nära kontakt med vårdpersonal efter avslutad behandling får vissa föräldrar att känna ångest.

PURPOSE: The technocratic and medicalized model of healthcare is rarely optimal for patients. By connecting two different studies we explore the possibilities of increasing quality of life in cancer care.

METHODS: The first study captures survival strategies in a historically isolated Arctic village in Norway resulting in Momentary contentment theory, which emerged from analysing four years of participant observation and interview data. The second study conceptualizes everyday life of cancer patients based on in-depth interviews with 19 cancer patients; this was conceptualized as Navigating a new life situation. Both studies used classic grounded theory methodology. The connection between the studies is based on a health design approach.

RESULTS: We found a fit between cancer patients challenging life conditions and harsh everyday life in an Arctic village. Death, treatments and dependence have become natural parts of life where the importance of creating spaces-of-moments and a Sense of Safety is imminent to well-being. While the cancer patients are in a new life situation, the Arctic people show a natural ability to handle uncertainties.

CONCLUSION: By innovation theories connected to design thinking, Momentary contentment theory modified to fit cancer care would eventually be a way to improve cancer patients' quality of life.

This study reports the results of a university course aimed at exploring and improving cooperation in healthcare with both cancer survivors, loved ones and healthcare professionals as students.

Central to the course was the understanding of and moving between each other's perspectives. Operating within a framework inspired by problem-based learning (PBL), small groups consisting of at least one cancer survivor, one loved one and one healthcare professional, collaboratively created scenarios based on their personal experiences. The students developed, elaborated, and identified problems and potential solutions. The pedagogical framing illustrated an empowering process of defining and elaborating a problem of their combined concerns, using their different knowledge. Although cooperation presented challenges, most students were able to explore and appreciate each other's perspectives when provided with a safe environment. Our experiences highlight the importance of both contextual safety and personal development as key factors in addressing power imbalances in healthcare.

Självundersökning efter operation för malignt melanom kan reducera mortaliteten.

44 patienter, varav hälften förutom muntlig information fick en video om självundersökning efter malignt melanom, kontrollerades sex månader efter operation avseende kunskap om hur en korrekt självundersökning ska utföras. De fick även skatta sitt välbefinnande före och efter operation.

Resultatet visade att de som erhöll videon hade bättre resultat vid kunskapskontrollen och förbättrade sitt välbefinnande jämfört med dem som erhöll endast muntlig information.

Videon tycks vara ett verktyg i vården av dessa patienter som bidrar till att minska återbesöken och frigöra tid för nybesök.

Ductal carcinoma of the breast is the most common form of invasive breast tumours. The grading system for breast cancer is defined by Elston and Ellis and is based on three criterions. One of these criterions is the mitotic count in pathological sections of breast carcinomas stained with Hematoxylin Eosin. A common method often applied as a complement in diagnosis of breast carcinoma is immunohistochemical staining with use of antibodies directed against Ki67, a proliferation marker. Phosphohistone H3 is a histone protein that is located in the cell nucleus. The protein is believed to be a specific marker for mitosis since it only is phosphorylated during mitosis, and to some extent at the end of the G2-phase. The purpose of this study was to evaluate pHH3 as a potential marker for mitosis when diagnosing ductal breast cancer. The purpose was also to compare the method to mitotic figuring and the count of Ki67-positive cells, and to study the inter-individual variability when assessing the histological sections. The material consisted of 20 biopsies containing invasive ductal breast cancer. The sections were stained using IHC and all sections were evaluated microscopically. Cells positive for pHH3, Ki67 and mitotic cells were quantified, by three doctors. From the doctors results an average value was determined for each case and method. To be able to compare the methods the coefficient of variation was calculated. The average value of the coefficient of variation was determined for each method and also the standard deviation (SD). The coefficient of variation showed average values of 0,21 for Ki67 +/- 0,10 SD, 0,33 for pHH3 +/- 0,14 SD and 0,46 for mitotic figuring +/- 0,34 SD. The correlation coefficients for the methods and each doctor showed dispersion. The correlations showed average values of r = 0,78 for Ki67 and pHH3, r = 0,74 for Ki67 and mitosis and r = 0,83 for pHH3 and mitosis. According to this study it seems as though anti-pHH3 could complement the other methods. However explicit criteria which defines a threshold value of which cells should be considered pHH3-positive needs to be established. The inter-individual differences seem to decrease using antipHH3 compared with mitotic counting, which is more time consuming. Although the minimum difference can be seen when assessing anti-Ki67 as a proliferation marker.