Intronic TP53 Polymorphisms Are Associated with Increased Δ133TP53 Transcript, Immune Infiltration and Cancer Risk.

We investigated the influence of selected TP53 SNPs in exon 4 and intron 4 on cancer risk, clinicopathological features and expression of TP53 isoforms. The intron 4 SNPs were significantly over-represented in cohorts of mixed cancers compared to three ethnically matched controls, suggesting they confer increased cancer risk. Further analysis showed that heterozygosity at rs1042522(GC) and either of the two intronic SNPs rs9895829(TC) and rs2909430(AG) confer a 2.34-5.35-fold greater risk of developing cancer. These SNP combinations were found to be associated with shorter patient survival for glioblastoma and prostate cancer. Additionally, these SNPs were associated with tumor-promoting inflammation as evidenced by high levels of infiltrating immune cells and expression of the Δ133TP53 and TP53ß transcripts. We propose that these SNP combinations allow increased expression of the Δ133p53 isoforms to promote the recruitment of immune cells that create an immunosuppressive environment leading to cancer progression.

Accuracy of the surgeons' clinical prediction of perioperative complications using a visual analog scale.

BACKGROUND: The ability to predict who will develop perioperative complications remains difficult because the etiology of adverse events is multifactorial. This study examines the preoperative and postoperative ability of the surgeon to predict complications and assesses the significance of a change in prediction. METHODS: This was a prospective study of 1013 patients. The surgeon assessed the risk of a major complication on a 100-mm visual analog scale (VAS) immediately before and after surgery. When the VAS score was changed, the surgeon was asked to document why. Patients were assessed up to 30 days postoperatively. RESULTS: Surgeons made a meaningful preoperative prediction of major complications (median score = 27 mm vs. 19 mm, p < 0.01), with an area under the receiver operating characteristic curve of 0.74 for mortality, 0.67 for major complications, and 0.63 for all complications. A change in the VAS score postoperatively was due to technical reasons in 74% of stated cases. An increased VAS score identified significantly more complications, but the improvement in the discrimination was small. When included in a multivariate model for predicting postoperative complications, the surgeon's VAS score functioned as an independent predictive variable and improved the predictive ability, goodness of fit, and discrimination of the model. CONCLUSIONS: Clinical assessment of risk by the surgeon using a VAS score independently improves the prediction of perioperative complications. Including the unique contribution of the surgeon's clinical assessment should be considered in models designed to predict the risk of surgery.

Questionnaire to aid priority and outcomes assessment in gallstone disease.

BACKGROUND: Limited health resources necessitate prioritization for access to elective cholecystectomy in New Zealand. We aimed to develop and validate a patient questionnaire for determining the effect of gallstone disease on quality of life (QOL) and evaluate its potential role in appraising prioritization and outcomes from surgery. METHODS: The Otago gallstones condition-specific questionnaire (CSQ) was designed based on review of published reports, structural equation modelling, input from experts and patient feedback. Fifty-four patients with symptomatic gallstone disease completed the CSQ including a single question asking about global condition impact, along with other QOL measures: the Gallstone Impact Checklist and the Short Form-36 Health Survey. Validity and reliability of the CSQ were assessed using standard psychometric criteria and patient acceptance was explored in a semistructured interview. Patients' priority status for surgery was determined by two participating surgeons and resulting scores were correlated with the QOL measures. RESULTS: Average CSQ completion time was 2.7 (range 1-5) min and patients found its content concise and comprehensive. Validity was supported through high correlations with the Gallstone Impact Checklist (r = 0.74), the global condition impact (r = 0.69) and related dimensions of the Short Form-36 Health Survey. CSQ questions showed satisfactory internal consistency (Cronbach's alpha = 0.94) and reproducibility (ICC = 0.93, where ICC is intraclass coefficient). Of all the QOL measures, the CSQ was the most clinically relevant, showing the strongest relationship with surgeon-rated priority (r = 0.62). CONCLUSION: Evidence is provided to support the validity of the CSQ for assessing the effect of gallstone disease on QOL. The CSQ could be particularly valuable in aiding priority decisions surgeons make and may be useful in tracking subsequent outcomes.

Internal radionuclide therapy: the ULMDOS software for treatment planning.

Before therapy with unsealed radionuclides, a dosimetry assessment must be performed for each patient. We present the interactive software tool ULMDOS, which facilitates dosimetric calculations, enhances traceability, and adequate documentation. ULMDOS is developed in IDL 6.1 (Interactive Data Language) under Windows XP/2000. First the patient data, the radiotracer data, and optionally urine and serum data are entered. After loading planar gamma camera images and drawing regions of interest, the residence times can be calculated using fits of the time activity data to exponential functions. Data can be saved in ASCII format for retrospective examination and further processing. ULMDOS allows one to process the dosimetric calculations within a standardized environment, spares the time-consuming transfer of data between different software tools, enables the documentation of ROI and raw data, and reduces intraindividual variability. ULMDOS satisfies the required conditions for traceability and documentation as a prerequisite to routine use in clinical settings.

Internal radionuclide therapy: The ULMDOS software for treatment planning.

Before therapy with unsealed radionuclides, a dosimetry assessment must be performed for each patient. We present the interactive software tool ULMDOS, which facilitates dosimetric calculations, enhances traceability, and adequate documentation. ULMDOS is developed in IDL 6.1 (Interactive Data Language) under Windows XP/2000. First the patient data, the radiotracer data, and optionally urine and serum data are entered. After loading planar gamma camera images and drawing regions of interest, the residence times can be calculated using fits of the time activity data to exponential functions. Data can be saved in ASCII format for retrospective examination and further processing. ULMDOS allows one to process the dosimetric calculations within a standardized environment, spares the time-consuming transfer of data between different software tools, enables the documentation of ROI and raw data, and reduces intraindividual variability. ULMDOS satisfies the required conditions for traceability and documentation as a prerequisite to routine use in clinical settings.

Quantitative image reconstruction in PET from emission data only using cluster analysis.

Quantitative image reconstruction in positron emission tomography requires attenuation correction. In case the attenuation correction is not measured separately, under certain conditions this can be determined from the emission data alone. We present a method based on cluster analysis that assumes only 3 empirical attenuation coefficients, i.e., 0.095 cm-1 for soft tissue, 0.02 cm-1 for lung, and 0 cm-1 for air. The subsequent image reconstruction takes place in an iterative fashion, through maximization of image likelihood. For the mathematical thorax phantom used in the present study, the results are comparable to those obtained after separate measurement of the attenuation correction.