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Closed and open surgical techniques are two different main approaches to surgical exposure of palatally displaced canines (PDCs). Because there is insufficient evidence to support one technique over the other, there is a need for randomized controlled trials.To compare surgery time, complications and patients' perceptions between closed and open surgical techniques in PDCs.The trial was a multicentre, randomized, controlled trial with two parallel groups randomly allocated in a 1:1 ratio.Study participants were 119 consecutive patients from 3 orthodontic centres, with PDCs planned for surgical exposure, randomly allocated according to a computer-generated randomization list, using concealed allocation. Full-thickness mucoperiosteal flap was raised, and bone covering the canine was removed in both interventions. In closed exposure, an attachment with a chain was bonded to the canine and the flap was sutured back with the chain penetrating the mucosa. In open exposure, a window of tissue around the tooth was removed and glass ionomer cement placed on the canine crown, to prevent gingival overgrowth during spontaneous eruption. Patient perceptions were assessed with two questionnaires, for the evening on the day of operation and 7 days post-surgery.It was not possible to blind either patients or care providers to the interventions. The outcome assessors were blinded and were unaware of patients' intervention group.Seventy-five girls and 44 boys, mean age 13.4 years (SD 1.46) participated in the study and got either of the interventions (closed exposure, n = 60; open exposure, n = 59). Surgery time did not differ significantly between the interventions. Complications though were more severe in bilateral cases and the patients experienced more pain and impairment in the open group.There were no statistically significant differences regarding surgery time between the groups. Postoperative complications were similar between the groups in unilateral PDCs, but more common in the open group in bilateral cases. More patients in the open group experienced pain and impairment compared to the closed group.Trial registration: ClinicalTrials.gov, ID: NCT02186548 and Researchweb.org, ID: 127201.

Background Tumour stem cells are considered important to promote disease progression, recurrence and treatment resistance following chemotherapy in colon cancer. However, genomic analyses of colorectal cancer have mainly been performed on integrated tumour tissue consisting of several different cell types in addition to differentiated tumour cells. The purpose of the present study was to compare genomic alterations in two cell fractions enriched of CD133+ and CD133−/EpCAM+ cells, respectively, obtained from fresh intraoperative human tumour biopsies. Methods The tumour biopsies were fractionated into CD133+ and CD133−/EpCAM+ cells by immunomagnetic separation, confirmed by immunocytochemistry and Q-PCR. DNA were extracted and used for array comparative genome hybridization (aCGH) after whole genome amplification. Frozen tumour tissue biopsies were used for DNA/RNA extraction and Q-PCR analyses to check for DNA alterations detected in the cell fractions. Results The number and size of DNA alterations were equally distributed across the cell fractions; however, large deletions were detected on chromosome 1, 7 and 19 in CD133−/EpCAM+ cells. Deletions were frequent in both cell fractions and a deletion on chromosome 19p was confirmed in 90% of the patients. Conclusion Isolation of enriched cells derived from tumour tissue revealed mainly genomic deletions, which were not observed in tumour tissue DNA analyses. CD133+ cells were genetically heterogeneous among patients without any defined profile compared to CD133−/EpCAM+ cells. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3206-8) contains supplementary material, which is available to authorized users.

OBJECTIVES Pancreatic ductal adenocarcinomas (PDACs) are found in more than 85% of patients with pancreatic cancer and with 5-year survival of less than 10%. Effective treatment may be radical surgery, which is hampered by rapid relapse. Therefore, our aim was to compare DNA sequence alterations in patients with short and long survival to evaluate if confirmed DNA alterations predict short postoperative survival. METHODS DNA was extracted from tumor tissue from 59 PDAC patients, analyzed for KRAS mutations, and hybridized to 180 K CGH + SNP microarrays and 450 K methylation arrays. Analyses were based on postoperative survival where less than 12 months was considered to be short survival and more than 18 months was considered long survival. RESULTS Ninety-three percent of the patients had KRAS mutations in tumor DNA. Great heterogeneity of whole genome DNA sequence alterations were observed among chromosomes within the patient materials. Specific DNA sequence alterations did not directly predict postoperative survival, although short survivors had significantly more and larger DNA amplifications (P < 0.006). Amplifications on chromosome 11 and 21 and deletions on chromosome 2 predicted short postoperative survival (P < 0.03). DNA methylation was not related to survival. CONCLUSIONS Highly variable genetic differences among DNA regions in PDAC tumors were demonstrated. Postoperative short survival was related to tumor sequence DNA alterations on chromosome 2, 11, and 21.

Preclinical data, and an increasing list of clinical investigations, show anti-inflammatory agents to favourably influence the biology of colorectal tumor. We have earlier reported on re-expression of activated immune cells after three days preoperative treatment of patients with colorectal carcinoma, randomized to receive oral NSAID (indomethacin or celebrex). Antisecretory prophylaxis (esomeprasol) was provided to all patients and served as sham treatment. Concomittant to MHC locus activation, Prominin1/CD133, a marker associated with stemness and poor prognosis in several solid tumors, was downregulated. The aim of the present study was to evaluate expression of additional regulators belonging to the stem cell niche, OCT4, SOX2 and BMP7, as well as some microRNAs, reported to act as tumor suppressors or oncomiRs. Peroperative tumor biopsies were analyzed by microarrays, quantitative real-time PCR and immunohistochemistry (IHC). The stem cell master regulator SOX2 was increased by NSAIDs (p

Alterations in eicosanoid metabolism is well established in a variety of malignant tumors, particularly colorectal carcinoma. Recent studies in our laboratory have emphasized a role for EP subtype receptors in progression of colorectal cancer and disease specific mortality. Therefore, the aim of the present study was to extend our knowledge to include additional receptor expression (DP1, DP2, FP, IP, TP) for prostanoids (PGD2, TXA2, PGF2alpha, PGI2) in relationship to tumor stage, differentiation and progression of colorectal cancer.Total RNA from 62 tumors and adjacent normal colon tissue (n = 48) was extracted. Quantification of receptor expression was performed by realtime PCR and related to the expression of an appropriate housekeeping gene (GAPDH). Tumors were assessed according to Dukes A-D (stage I-IV).DP1, DP2, FP and IP receptor subtypes displayed significantly reduced overall expression in tumor tissue compared to normal colon tissue, while the TP receptor subtype showed significantly higher expression in tumor tissue. Overall expression of the prostanoid receptors in tumor tissue was not related to clinical indexes as tumor stage and tumor cell differentiation evaluated by multivariate analyses. Cultured colorectal cancer cell lines with low (HT-29) and high (HCA-7) intrinsic PGE2 production at confluent state did not express DP1 and IP receptor subtypes, but displayed low expression of DP2, FP and TP receptor subtypes.The results in the present study indicate imbalanced expression of prostanoid receptors in colorectal cancer compared to normal colon tissue without clear cut relationship to disease progression. Therefore, future studies should be performed on defined cells within the tumor tissue compartment determining whether any prostanoid receptor(s) is useful as a molecular target in treatment or prevention of colorectal cancer.

Background Cyclooxygenase (COX) and epidermal growth factor receptor (EGFR) activities promote progression of colorectal cancer. Combined treatment against these targets has not been more effective than single treatments alone. Therefore, our aim was to analyze relationships between COX and EGFR in peroperative colorectal tumor biopsies. Method Tumor and colon mucosa tissue were collected at primary intended curative operations in patients according to well-recognized statistical distributions of tumor stages in colorectal cancer. COX-1, COX-2 and EGFR content in tumor and colon mucosa tissue were quantified by western blot and Q-PCR. Results COX-2 protein appeared as two bands, one at 66 kDa in almost all tumor and mucosa samples and one at 74 kDa in 73% of the tumors and in 23% of the mucosa samples. Tumor COX-2 mRNA was not different from the content in mucosa samples, while COX-2 protein was increased in tumor tissue (p < 0.0003). A correlation between 74 kDa COX-2 protein and COX-2 mRNA occurred in tumor tissue, with significantly increasing COX-2 mRNA across tumor stages. EGFR mRNA content was lower in tumor tissue (p < 0.0001), while EGFR protein was similar in tumor and mucosa samples. COX-2 and EGFR proteins showed a positive correlation in mucosa, while a negative correlation occurred in tumor tissue. Tumor tissue with high COX-2 74 kDa protein lacked EGFR protein. Conclusion Our present results are compatible with the theory that COX-2 and EGFR signalling pathways are inversely related in colorectal cancer tissue. This may explain why combinatorial clinical treatments have been less rewarding.

This study aimed to identify potential predictors of non-attendance among children and adolescents with dental behaviour management problems (DBMP). A group of 179 patients, 7.5-19 yr of age, was grouped into 56 'non-attenders' (discontinued treatment, missed appointments, oror= 20% cancellations) and 123 'attenders'. In addition to data from an introductory interview and dental recordings, baseline data from psychometric measures of fear and other personal and parental characteristics were included in logistic regression analyses and tree-based modelling. The non-attenders had higher scores on impulsivity and sociability and lower socio-economic status (SES) than the attenders, and they lived more often in single-parent families. Logistic regression analyses and tree-based modelling point to SES and parental anxiety as important predictors for non-attendance within this group of children and adolescents. To predict, and possibly to prevent, non-attendance among children and adolescents referred for specialized dental care because of DBMP, we must consider their lives and family situations as well as their personal characteristics and oral health status. Further research should focus on whether the observed associations between non-attendance and factors such as personal characteristics, family and psychosocial factors, and previous dental experiences, also hold for those who remain in regular dental care.

This study aimed to investigate the role of dental fear (DF) and other personal characteristics in relation to dental behaviour management problems (DBMP).A study group of 230 patients (7.5-19 years old; 118 girls), referred because of DBMP, was compared to a reference group of 248 same-aged patients (142 girls) in ordinary dental care. Patients and their parents independently filled in questionnaires including measures of fear and anxiety, behavioural symptoms, temperamental reactivity, and emotion regulation.Study group patients referred because of DBMP differed from the reference group in all investigated aspects of personal characteristics. In the multivariate analyses, DF was the only variable with consistent discriminatory capacity through all age and gender subgroups. Aspects of anxiety, temperament, and behavioural symptoms contributed, but differently for different subgroups and at different levels of dental fear.Among older children and adolescents, DF deserves to be re-established as the single most important discriminating variable for DBMP at clearly lower scores than commonly used. Further research should focus on the different patterns of DBMP development, considering various personal characteristics that may trigger, maintain, or exacerbate young patients' vulnerability to DF and DBMP.

The primary aim of this thesis was to study dental fear, personal characteristics and psychosocial concomitants in relation to dental behaviour management problems (DBMP) and dental attendance. The study sample consisted of children (8-12 yrs) and adolescents (13-19 yrs) referred to the Specialized Paediatric Dental Clinic because of DBMP. They were compared to a reference group of same aged dental patients in ordinary dental care. A methodological study explored the Dental Subscale of the Children's Fear Survey Schedule (CFSS-DS) in terms of agreement between self and parental ratings and age- and gender-differentiated cut-off scores as compared to the commonly used. Baseline data on children's and adolescents' dental fear, psychosocial situation and everyday life, and personal characteristics were analysed according to a variable-based approach using logistic regression analyses and tree-based modelling of group differences. From the frequency of missed or/and cancelled appointments or interruption of dental treatment the group of referred children was separated into two groups (non-attendees vs. attendees). The differences between the groups were analysed using logistic regression analyses and tree-based modelling. It was found that children and adolescents referred because of DBMP differ in several ways from children and adolescents in ordinary dental care. These differences concerns dental fear, emotional and behavioural problems and temperamental aspects, as well as psychosocial concomitants. The results indicated an overall more negative and complex picture for the children and adolescents referred because of DBMP. The occurrence of single-parent families, child-parent separations, and professional support actions were clearly more frequent among patients referred because of DBMP. Dental fear was the only variable with consistent discriminatory capacity for DBMP through all age and gender subgroups. Aspects of anxiety, temperament, and behavioural symptoms contributed to the prediction of DBMP, but differently for different subgroups and at different levels of dental fear. A non-attending behaviour within the DBMP group was predicted by family factors and a temperamental profile indicating an out-going and somewhat impulsive personal profile. The results indicate further need to establish and validate age and gender differentiated cut-off scores and that self-rating on the CFSS-DS should complement parental ratings, since DF was the single best predictor of DBMP at clearly lower scores than commonly used. Avoidance may be seen as the extreme of DBMP, varying from irregular dental attendance to dropping out entirely from dental treatment. Therefore deeper knowledge and understanding of DBMP, will help the dental staff to meet and treat children and adolescents according to their individual need and act for the prevention of DBMP and irregular dental attendance.

The first aim of this methodological study was to investigate the agreement between self-ratings of Children's Fear Survey Schedule (CFSS-DS). The second aim was to explore using differentiated cut-off scores, and to compare these cut-off scores with those commonly used.Three different data collections included study groups (n = 497) of children and adolescents who had been referred to specialized pediatric dentistry clinics, and reference groups (n = 499) of dental patients and children rating the analyses were limited to the Östergötland sample (n = 210 + 228). Patients and their accompanying parents (mainly mothers) were asked to fill in the CFSS-DS independently. Cut-off scores on the CFSS-DS scale were determined using receiver-operating characteristic analysis; patient-parent agreement was illustrated with Bland-Altman plots.The patient-parent agreement was modest, particularly among those who were referred because of dental behaviour management problems (DBMP). Cut-off scores differentiated by age and gender, suggested by exploration according to two different methods, were with few exceptions clearly below the standard cut-off score.[corrected] The validity of parental ratings of their children dental fear should be questioned, particularly in high-fear populations. Self-ratings should, as far as possible, be used to complement parental ratings. One consequence of using the standard cut-off score is the risk of overlooking some patients needs for special attention. Further research is needed to establish and validate age-and gender-differentiated cut-off scores on the CFSS-DS.

Prostaglandins support progression of colorectal cancer by several mechanisms. This conclusion is based on epidemiological and drug intervention long-term studies or retrieved from animal and cell culture experiments. The aim of the present study was to map receptor and enzyme expression for prostanoid metabolism in the presence of high or low PGE2 content within colon cancer tissue at primary tumor operation and after short-term preoperative provision of non-steroidal anti-inflammatory drug (NSAID). Twenty-three unselected patients with colon cancer were randomly selected to receive indomethacin (NSAID) or sham treatment for 3 days before surgery. Normal colon and tumor tissue were collected at operation for RNA extraction. Tissue PGE2 levels were measured by radioimmunoassay. Gene expression was quantified by microarray and real-time PCR. COX-1 expression increased proportionally to COX-2 expression in colon cancer tissue from untreated patients. Indomethacin reduced PGE2 content in normal and tumor tissue with subsequently decreased IP, HPGD and PPARgamma receptor expression in both tumor and normal colon tissue, while subtype EP1-4 receptors were not significantly influenced by indomethacin treatment. MPGES-1 expression was not related to overall PGE2 content in tumor and colon tissue, but decreased significantly in normal tissue during indomethacin exposure. Reduction of tumor tissue PGE2 was related to significant alteration in expression of several hundred genes indicating decreased cell cycling and increased apoptosis during indomethacin treatment, probably related to upregulation of acute phase reactants in tumor tissue. Increased prostanoid activity in colon cancer tissue is related to cross-talk between tumor and stroma cells.

Children with dental behavioural management problems (DBMP) form a heterogeneous group, where personal characteristics play significant roles. Attention to everyday life and family situation as additional background facets may help to better understand and treat these patients.This study describes everyday life and family situation in child/adolescent patients referred because of DBMP, as compared to patients in ordinary dental care.A study group of 230 referred patients (8-19 years old; 118 girls) was compared to a reference group of 248 same-aged patients (142 girls) without DBMP. Patients and parents were interviewed according to a semistructured protocol.Patients referred because of DBMP more often lived in low socioeconomic status families, had parents not living together, fewer leisure-time activities, and were assessed as doing worse in social interactions compared to the reference group. Half of the study group had personal professional support, and some had experienced interventions by the social authorities. Whether these findings apply also to children/adolescents with DBMP who are not referred to specialist care remains to study.Many children and adolescents referred because of DBMP have a burdensome life and family situation. This should be paid attention to in research and in clinical care.

The objectives were to study the progression rate of approximal caries in 14 to 19-year-old adolescents and to assess the influence of experience of previous caries as a predictor of caries progression during the following years. The study population comprised 100 adolescents, all 19 years old, randomly selected. In all, there were 93 adolescents included in the study, for whom all sets of bitewing radiographs from 14 up to and including the age of 19 were assessed with respect to approximal caries. It could be noted that 32% of the adolescents had had at least one bitewing examination every year from 14 to 19 years of age. At the age of 14, 38% of the males and 24% of the females were radiographically without any sign of caries lesions (caries-free). The median survival time of initial caries in the present study was >5 years, while for manifest caries it was 3.2 years. It was found that 37% of the surfaces with manifest caries in males and 18% of the corresponding surfaces in females were restored within a year. The results show that experience of previous caries does not seem to be a significant indicator and does not influence when the next radiographic examination should be performed. It is thus concluded that individualized bitewing examination is the exception rather than the rule.

Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.