Abstract This study investigated the diagnostic accuracy of cone beam computed tomography (CBCT) compared to panoramic radiography in determining the anatomical position of the impacted third molar ...in relation with the mandibular canal. The study sample comprised 53 third molars from 40 patients with an increased risk of inferior alveolar nerve (IAN) injury. The panoramic and CBCT features (predictive variables) were correlated with IAN exposure and injury (outcome variables). Sensitivity and specificity of modalities in predicting IAN exposure were compared. The IAN was exposed in 23 cases during third molar removal and injury occurred in 5 patients. No significant difference in sensitivity and specificity was found between both modalities in predicting IAN exposure. To date, lingual position of the mandibular canal was significantly associated with IAN injury. CBCT was not more accurate at predicting IAN exposure during third molar removal, however, did elucidate the 3D relationship of the third molar root to the mandibular canal; the coronal sections allowed a bucco-lingual appreciation of the mandibular canal to identify cases in which a lingually placed IAN is at risk during surgery. This observation dictates the surgical approach how to remove the third molar, so the IAN will not be subjected to pressure.
Introduction
The field of tumor-specific fluorescence-guided surgery has seen a significant increase in the development of novel tumor-targeted imaging agents. Studying patient benefit using ...intraoperative fluorescence-guided imaging for cancer surgery is the final step needed for implementation in standard treatment protocols. Translation into phase III clinical trials can be challenging and time consuming. Recent studies have helped to identify certain waypoints in this transition phase between studying imaging agent efficacy (phase I–II) and proving patient benefit (phase III).
Trial initiation
Performing these trials outside centers of expertise, thus involving motivated clinicians, training them, and providing feedback on data quality, increases the translatability of imaging agents and the surgical technique. Furthermore, timely formation of a trial team which oversees the translational process is vital. They are responsible for establishing an imaging framework (camera system, imaging protocol, surgical workflow) and clinical framework (disease stage, procedure type, clinical research question) in which the trial is executed. Providing participating clinicians with well-defined protocols with the aim to answer clinically relevant research questions within the context of care is the pinnacle in gathering reliable trial data.
Outlook
If all these aspects are taken into consideration, tumor-specific fluorescence-guided surgery is expected be of significant value when integrated into the diagnostic work-up, surgical procedure, and follow-up of cancer patients. It is only by involving and collaborating with all stakeholders involved in this process that successful clinical translation can occur.
Aim
Here, we discuss the challenges faced during this important translational phase and present potential solutions to enable final clinical translation and implementation of imaging agents for image-guided cancer surgery.
Barrett's esophagus is the only known mucosal precursor for the highly malignant esophageal adenocarcinoma. Malignant degeneration of non-dysplastic Barrett's esophagus occurs in < 0.6% per year in ...Dutch surveillance cohorts. Therefore, it has been proposed to increase the surveillance intervals from 3 to 5 years, potentially increasing development of advanced stage interval cancers. To prevent such cases robust biomarkers for more optimal stratification over longer follow up periods for non-dysplastic Barrett's patients are required. In this multi-center study, aberrations for chromosomes 7, 17, and structural abnormalities for c-MYC, CDKN2A, TP53, Her-2/neu and 20q assessed by DNA fluorescence in situ hybridization on brush cytology specimens, were used to determine marker scores and to perform clonal diversity measurements, as described previously. In this study, these genetic biomarkers were combined with clinical variables and analyzed to obtain the most efficient cancer prediction model after an extended period of follow-up (median time of 7 years) by applying Cox regression modeling, bootstrapping and leave-one-out analyses. A total of 334 patients with Barrett's esophagus without dysplasia from 6 community hospitals (n = 220) and one academic center (n = 114) were included. The annual progression rate to high grade dysplasia and/or esophageal adenocarcinoma was 1.3%, and to adenocarcinoma alone 0.85%. A prediction model including age, Barrett circumferential length, and a clonicity score over the genomic set including chromosomes 7, 17, 20q and c-MYC, resulted in an area under the curve of 0.88. The sensitivity and specificity of this model were 0.91 and 0.38. The positive and negative predictive values were 0.13 (95% CI 0.09 to 0.19) and 0.97 (95% CI 0.93 to 0.99). We propose the implementation of the model to identify non-dysplastic Barrett's patients, who are required to remain in surveillance programs with 3-yearly surveillance intervals from those that can benefit from less frequent or no surveillance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
MicroRNAs are small non-coding RNA molecules, which regulate central mechanisms of tumorigenesis. In colorectal tumours, the combination of gain of 8q and 13q is one of the major factors associated ...with colorectal adenoma to adenocarcinoma progression. Functional studies on the miR-17-92 cluster localised on 13q31 have shown that its transcription is activated by c-myc, located on 8q, and that it has oncogenic activities. We investigated the contribution of the miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression.
Expression levels of the miR-17-92 cluster were determined in 55 colorectal tumours and in 10 controls by real-time RT-PCR. Messenger RNA c-myc expression was also determined by real-time RT-PCR in 48 tumours with array comparative genomic hybridisation (aCGH) data available.
From the six members of the miR-17-92 cluster, all except miR-18a, showed significant increased expression in colorectal tumours with miR-17-92 locus gain compared with tumours without miR-17-92 locus gain. Unsupervised cluster analysis clustered the tumours based on the presence of miR-17-92 locus gain. Significant correlation between the expression of c-myc and the six miRNAs was also found.
Increased expression of miR-17-92 cluster during colorectal adenoma to adenocarcinoma progression is associated to DNA copy number gain of miR17-92 locus on 13q31 and c-myc expression.
Abstract This prospective study evaluated the role of cone beam computed tomography (CBCT) in the treatment of patients with impacted mandibular third molars at increased risk of inferior alveolar ...nerve (IAN) injury. Subjects with an increased risk of IAN injury, as diagnosed on panoramic radiographs, were enrolled in this study and underwent additional CBCT imaging. Two oral maxillofacial surgeons independently planned the surgical technique and estimated the risk of IAN injury on panoramic radiographs and on CBCT images. A test of symmetry and the McNemar test were executed to calculate the differences between the two imaging modalities. The study sample comprised 40 patients (mean age 27.6 years) presenting 53 mandibular third molars. Risk assessment for IAN injury based on panoramic radiography compared with CBCT imaging differed significantly ( P < 0.005). After reviewing the CBCT images, significantly more subjects were reclassified to a lower risk for IAN injury compared with the panoramic radiograph assessments. This change in risk assessment also resulted in a significantly different surgical approach ( P < 0.03). The results of this study show that CBCT contributes to optimal risk assessment and, as a consequence, to more adequate surgical planning, compared with panoramic radiography.
This study aimed to identify the oncogenes at 20q involved in colorectal adenoma to carcinoma progression by measuring the effect of 20q gain on mRNA expression of genes in this amplicon.
...Segmentation of DNA copy number changes on 20q was performed by array CGH (comparative genomic hybridisation) in 34 non-progressed colorectal adenomas, 41 progressed adenomas (ie, adenomas that present a focus of cancer) and 33 adenocarcinomas. Moreover, a robust analysis of altered expression of genes in these segments was performed by microarray analysis in 37 adenomas and 31 adenocarcinomas. Protein expression was evaluated by immunohistochemistry on tissue microarrays.
The genes C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5, mapping at 20q, were significantly overexpressed in carcinomas compared with adenomas as a consequence of copy number gain of 20q.
This approach revealed C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5 genes to be important in chromosomal instability-related adenoma to carcinoma progression. These genes therefore may serve as highly specific biomarkers for colorectal cancer with potential clinical applications.
Cushing’s disease (CD) is a rare and severe endocrine disease characterized by hypercortisolemia. Previous studies have found structural brain alterations in remitted CD patients compared to healthy ...controls, specifically in the anterior cingulate cortex (ACC). However, potential mechanisms through which these persistent alterations may have occurred are currently unknown.
Structural 3T MRI’s from 25 remitted CD patients were linked with gene expression data from neurotypical donors, derived from the Allen Human Brain Atlas. Differences in gene expression between the ACC and an unaffected control cortical region were examined, followed by a Gene Ontology (GO) enrichment analysis. A cell type enrichment analysis was conducted on the differentially expressed genes, and a disease association enrichment analysis was conducted to determine possible associations between differentially expressed genes and specific diseases. Subsequently, cortisol sensitivity of these genes in existing datasets was examined.
The gene expression analysis identified 300 differentially expressed genes in the ACC compared to the cortical control region. GO analyses found underexpressed genes to represent immune function. The cell type specificity analysis indicated that underexpressed genes were enriched for deactivated microglia and oligodendrocytes. Neither significant associations with diseases, nor evidence of cortisol sensitivity with the differentially expressed genes were found.
Underexpressed genes in the ACC, the area vulnerable to permanent changes in remitted CD patients, were often associated with immune functioning. The specific lack of deactivated microglia and oligodendrocytes implicates protective effects of these cell types against the long-term effects of cortisol overexposure.
•Underexpressed genes in the ACC of CD patients associated with immune functioning.•Fewer deactivated microglia and oligodendrocytes markers in the ACC of CD patients.•These cell types may protect against the effects of chronic cortisol overexposure.
Background
Health‐related quality of life (QoL) is of major importance in pancreatic cancer, owing to the limited life expectation. The aim of this prospective longitudinal study was to describe QoL ...in patients undergoing resection for pancreatic or periampullary malignancy.
Methods
QoL was measured on a scale of 0–100 in patients who underwent pancreatic resection for malignancy or premalignancy at the University Medical Centre Utrecht before resection, and 1, 3, 6 and 12 months after surgery. Measures consisted of the RAND‐36, the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ‐C30) and the EORTC pancreatic cancer‐specific module (QLQ‐PAN26).
Results
Between March 2012 and November 2013, 68 consecutive patients with a malignancy (59 patients) or premalignancy (9) were included. Physical role restriction, social and emotional domains showed a significant and clinically relevant deterioration directly after operation in 53 per cent (RAND‐36, P < 0·001), 63 and 78 per cent (QLQ‐C30 and RAND‐36 respectively, P < 0·001) and 37 per cent (RAND‐36, P < 0·001) of patients respectively. Most domains demonstrated recovery to preoperative values or better at 3 months, except for physical functioning. Emotional functioning at 3, 6 and 12 months was better than at baseline (P < 0·001). Symptom scores revealed a deterioration in vitality, pain (P = 0·002), fatigue (P < 0·001), appetite loss (P < 0·001), altered bowel habit (P = 0·001) and side‐effects (P < 0·001) after 1 month. After 3 months, only side‐effects were worse than preoperative values (P < 0·001).
Conclusion
QoL after pancreatic resection for malignant and premalignant tumours decreased considerably in the early postoperative phase. Full recovery of QoL took up to 6 months after the operation.
Quality of life recovers in 6 months
Aims/hypothesis
Vasopressin plays a role in osmoregulation, glucose homeostasis and inflammation. Therefore, plasma copeptin, the stable C-terminal portion of the precursor of vasopressin, has strong ...potential as a biomarker for the cardiometabolic syndrome and diabetes. Previous results were contradictory, which may be explained by differences between men and women in responsiveness of the vasopressin system. The aim of this study was to evaluate the usefulness of copeptin for prediction of future type 2 diabetes in men and women separately.
Methods
From the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 4,063 women and 3,909 men without diabetes at baseline were included. A total of 208 women and 288 men developed diabetes during a median follow-up of 7.7 years.
Results
In multivariable-adjusted models, we observed a stronger association of copeptin with risk of future diabetes in women (OR 1.49 95% CI 1.24, 1.79) than in men (OR 1.01 95% CI 0.85, 1.19) (
p
interaction
< 0.01). The addition of copeptin to the Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) clinical model improved the discriminative value (C-statistic,+0.007,
p
= 0.02) and reclassification (integrated discrimination improvement IDI = 0.004,
p
< 0.01) in women. However, we observed no improvement in men. The additive value of copeptin in women was maintained when other independent predictors, such as glucose, high sensitivity C-reactive protein (hs-CRP) and 24 h urinary albumin excretion (UAE), were included in the model.
Conclusions/interpretation
The association of plasma copeptin with the risk of developing diabetes was stronger in women than in men. Plasma copeptin alone, and along with existing biomarkers (glucose, hs-CRP and UAE), significantly improved the risk prediction for diabetes in women.
Despite the fact that primary percutaneous catheter drainage has become standard practice, some patients with pancreatic fistula after pancreatoduodenectomy ultimately undergo a relaparotomy. The aim ...of this study was to compare completion pancreatectomy with a pancreas-preserving procedure in patients undergoing relaparotomy for pancreatic fistula after pancreatoduodenectomy.
This retrospective cohort study of nine institutions included patients who underwent relaparotomy for pancreatic fistula after pancreatoduodenectomy from 2005-2018. Furthermore, a systematic review and meta-analysis were performed according to the PRISMA guidelines.
From 4877 patients undergoing pancreatoduodenectomy, 786 (16 per cent) developed a pancreatic fistula grade B/C and 162 (3 per cent) underwent a relaparotomy for pancreatic fistula. Of these patients, 36 (22 per cent) underwent a completion pancreatectomy and 126 (78 per cent) a pancreas-preserving procedure. Mortality was higher after completion pancreatectomy (20 (56 per cent) versus 40 patients (32 per cent); P = 0.009), which remained after adjusting for sex, age, BMI, ASA score, previous reintervention, and organ failure in the 24 h before relaparotomy (adjusted odds ratio 2.55, 95 per cent c.i. 1.07 to 6.08). The proportion of additional reinterventions was not different between groups (23 (64 per cent) versus 84 patients (67 per cent); P = 0.756). The meta-analysis including 33 studies evaluating 745 patients, confirmed the association between completion pancreatectomy and mortality (Mantel-Haenszel random-effects model: odds ratio 1.99, 95 per cent c.i. 1.03 to 3.84).
Based on the current data, a pancreas-preserving procedure seems preferable to completion pancreatectomy in patients in whom a relaparotomy is deemed necessary for pancreatic fistula after pancreatoduodenectomy.
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