The colorectal adenoma-carcinoma sequence has provided a paradigmatic framework for understanding the successive somatic genetic changes and consequent clonal expansions that lead to cancer
. ...However, our understanding of the earliest phases of colorectal neoplastic changes-which may occur in morphologically normal tissue-is comparatively limited, as for most cancer types. Here we use whole-genome sequencing to analyse hundreds of normal crypts from 42 individuals. Signatures of multiple mutational processes were revealed; some of these were ubiquitous and continuous, whereas others were only found in some individuals, in some crypts or during certain periods of life. Probable driver mutations were present in around 1% of normal colorectal crypts in middle-aged individuals, indicating that adenomas and carcinomas are rare outcomes of a pervasive process of neoplastic change across morphologically normal colorectal epithelium. Colorectal cancers exhibit substantially increased mutational burdens relative to normal cells. Sequencing normal colorectal cells provides quantitative insights into the genomic and clonal evolution of cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Amaç: Parotis bezi tümörleri, tüm baş boyun tümörlerinin yaklaşık % 2-3' ünü oluşturmaktadır ve % 80-85' i benign natürdedir. Bu çalışmamızda, parotis kitlesi ile kliniğimize başvuran olguları ...retrospektif olarak inceleyerek; uygulanan cerrahi tedavileri, histopatolojik sonuçları, görülme oranlarını ve cerrahi sonrası komplikasyonları değerlendirmeyi amaçladık. Gereç ve Yöntem: Ocak 2013 ile Ocak 2019 tarihleri arasında, kliniğimize parotis kitlesi ile başvuran hastalar çalışmaya dahil edildi. Hastalar; cinsiyet, operasyon yöntemi, histopatolojik sonuçları ve post-operatif komplikasyonları açısından retrospektif olarak incelendi. Bulgular: 75 hastanın 52’ si erkek, 23’ si kadındı. Yaş ortalaması 49,7 min:23 max:94 σ:5.083 olarak tespit edildi. Cerrahi tedavi sonrası histopatoloji sonuçlarına göre olguların 62’ si benign % 82,5 , 13’ i habis % 17,5 idi. Selim tümör olarak en sık pleomorfik adenom 33 olgu saptandı. İkinci en sık selim tümör olarak ise Whartin tümörü olduğu görüldü 27 olgu . Cerrahi yöntem olarak 67 hastaya yüzeyel parotidektomi, 8 hastaya total parotidektomi uygulandı. İki olguda geçici fasiyal parezi, bir olguda tümör invazyonundan dolayı fasiyal sinirin rezeke edilmesine bağlı kalıcı fasiyal paralizi, bir hastada fasiyel sinirin bukkal dalından kaynaklanan sellüler schwannoma nedeniyle kalıcı parsiyel fasiyal paralizi, iki olguda ise post-operatif hematom izlendi. Sonuç: Parotis tümörlerinin tedavisi genel olarak cerrahidir. Histopatolojik tanı, tümörün evresi ve derecesi önemlidir. Gerektiğinde boyun diseksiyonu uygulanmalıdır.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Plasma hsa-miR-483-5p was significantly overexpressed in adrenocortical cancer patients relative to patients with adenomas.•Hsa-miR-483-5p can be detected in the urine.•No significant difference in ...the expression of urinary hsa-miR-483-5p was found between patients with adrenocortical adenoma or cancer.•No correlation between cortisol secretion and plasma or urinary hsa-miR-483-5p could be established.
Minimally invasive circulating microRNAs might be used for the preoperative differentiation of adrenocortical carcinoma (ACC) and adrenocortical adenoma (ACA). So far, the best blood-borne microRNA biomarker of ACC is circulating hsa-miR-483-5p. The expression of urinary hsa-miR-483-5p as a non-invasive marker of malignancy and its correlation with plasma hsa-miR-483-5p, has not been investigated, yet.
Our aim was to investigate the expression of urinary hsa-miR-483-5p and its correlation with its plasma counterpart.
Plasma and urinary samples from 23 ACC and 23 ACA patients were analysed using real-time RT-qPCR. To evaluate the diagnostic applicability of hsa-miR-483-5p, ROC-analysis was performed.
Significant overexpression of hsa-miR-483-5p was observed in carcinoma patients’ plasma samples compared to adenoma patients’ (p < 0.0001, sensitivity: 87%, specificity: 78.3%). In urinary samples, however, no significant difference could be detected between ACC and ACA patients.
Plasma hsa-miR-483-5p has been confirmed as significantly overexpressed in adrenocortical cancer patients and thus might be exploited as a minimally invasive preoperative marker of malignancy. The applicability of urinary hsa-miR-483-5p for the diagnosis of adrenocortical malignancy could not be confirmed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Two‐dimensional gel electrophoresis (2DE) in proteomics is traditionally assumed to contain only one or two proteins in each 2DE spot. However, 2DE resolution is being complemented by the rapid ...development of high sensitivity mass spectrometers. Here we compared MALDI‐MS, LC‐Q‐TOF MS and LC‐Orbitrap Velos MS for the identification of proteins within one spot. With LC‐Orbitrap Velos MS each Coomassie Blue‐stained 2DE spot contained an average of at least 42 and 63 proteins/spot in an analysis of a human glioblastoma proteome and a human pituitary adenoma proteome, respectively, if a single gel spot was analyzed. If a pool of three matched gel spots was analyzed this number further increased up to an average of 230 and 118 proteins/spot for glioblastoma and pituitary adenoma proteome, respectively. Multiple proteins per spot confirm the necessity of isotopic labeling in large‐scale quantification of different protein species in a proteome. Furthermore, a protein abundance analysis revealed that most of the identified proteins in each analyzed 2DE spot were low‐abundance proteins. Many proteins were present in several of the analyzed spots showing the ability of 2DE‐MS to separate at the protein species level. Therefore, 2DE coupled with high‐sensitivity LC‐MS has a clearly higher sensitivity as expected until now to detect, identify and quantify low abundance proteins in a complex human proteome with an estimated resolution of about 500 000 protein species. This clearly exceeds the resolution power of bottom‐up LC‐MS investigations.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Early and comprehensive endoscopic detection of colonic dysplasia—the most clinically significant precursor lesion to colorectal adenocarcinoma—provides an opportunity for timely, minimally invasive ...intervention to prevent malignant transformation. Here, the development and evaluation of biodegradable near‐infrared fluorescent silica nanoparticles (FSN) that have the potential to improve adenoma detection during fluorescence‐assisted white‐light colonoscopic surveillance in rodent and human‐scale models of colorectal carcinogenesis is described. FSNs are biodegradable (t1/2 of 2.7 weeks), well‐tolerated, and enable detection and delineation of adenomas as small as 0.5 mm2 with high tumor‐to‐background ratios. Furthermore, in the human scale, APC1311/+ porcine model, the clinical feasibility and benefit of using FSN‐guided detection of colorectal adenomas using video‐rate fluorescence‐assisted white‐light endoscopy is demonstrated. Since nanoparticles of similar size (e.g., 100–150 nm) or composition (i.e., silica and silica/gold hybrid) have already been successfully translated to the clinic, and clinical fluorescent/white‐light endoscopy systems are becoming more readily available, there is a viable path towards clinical translation of the proposed strategy for early colorectal cancer detection and prevention in high‐risk patients.
Conventional white‐light colonoscopy has a relatively high adenoma miss rate, particularly in high‐risk patients. Biodegradable fluorescent silica nanoparticles (FSNs) have the potential to improve the detection of colorectal adenomas during endoscopic surveillance. Since FSNs are fully biodegradable and well‐tolerated, there is a viable path towards clinical translation of FSN‐guided colonoscopy for improved adenoma detection endoscopy in high‐risk patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
MicroRNAs (miRNAs) are proposed as potential biomarkers for the diagnosis of numerous diseases. Here, we performed a meta-analysis to evaluate the utility of faecal miRNAs as a non-invasive tool in ...colorectal cancer (CRC) screening. A systematic literature search, according to predetermined criteria, in five databases identified 17 research articles including 6475, 783 and 5569 faecal-based miRNA tests in CRC, adenoma patients and healthy individuals, respectively. Sensitivity, specificity, positive/negative likelihood and diagnostic odds ratios, area under curve (AUC), summary receiver operator characteristic (sROC) curves, association of individual or combinations of miRNAs to cancer stage and location, subgroup, meta-regression and Deeks' funnel plot asymmetry analyses were employed. Pooled miRNAs for CRC had an AUC of 0.811, with a sensitivity of 58.8% (95% confidence interval CI: 51.7-65.5%) and specificity of 84.8% (95% CI: 81.1-87.8%), whilst for colonic adenoma, it was 0.747, 57.3% (95% CI: 40.8-72.3%) and 76.1% (95% CI: 66.1-89.4%), respectively. The most reliable individual miRNA was miR-21, with an AUC of 0.843, sensitivity of 59.3% (95% CI: 26.3-85.6%) and specificity of 85.6% (95% CI: 72.2-93.2%). Paired stage analysis showed a better diagnostic accuracy in late stage CRC and sensitivity higher in distal than proximal CRC. In conclusion, faecal miR-21, miR-92a and their combination are promising non-invasive biomarkers for faecal-based CRC screening.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Kalsiyum pirofosfat dihidrat depolanma hastalığı KPPD olarak bilinen psödogut eklem aralığında kristal birikimi ile seyreden romatolojikbir hastalıktır. KPPD kristal depolanma hastalığı sıklıkla ...ileri yaşta aralıklı artrite neden olan bir hastalıktır. KPPD en sık olarak diz, el bileği, omuz ve kalça eklemlerini tutar. Hiperparatiroidizm, hemokromatozis, hipomagnezemi, hipofosfatemi KPPD ile ilişkilidir. İleri yaşta monoartritle başvuran hastalarda KPPD ayırıcı tanıda düşünülmelidir. Bu çalışmada KPPD ve paratiroid adenomu saptanan olgu sunulmaktadır
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Individuals diagnosed with colorectal adenomas with high-risk features during screening colonoscopy have increased risk for the development of subsequent adenomas and colorectal cancer. While US ...guidelines recommend surveillance colonoscopy at 3 years in this high-risk population, surveillance uptake is suboptimal. To inform future interventions to improve surveillance uptake, we sought to assess surveillance rates and identify facilitators of uptake in a large integrated health system. We utilized a cohort of patients with a diagnosis of ≥ 1 tubular adenoma (TA) with high-risk features (TA ≥ 1 cm, TA with villous features, TA with high-grade dysplasia, or ≥ 3 TA of any size) on colonoscopy between 2013 and 2016. Surveillance colonoscopy completion within 3.5 years of diagnosis of an adenoma with high-risk features was our primary outcome. We evaluated surveillance uptake over time and utilized logistic regression to detect factors associated with completion of surveillance colonoscopy. The final cohort was comprised of 405 patients. 172 (42.5%) patients successfully completed surveillance colonoscopy by 3.5 years. Use of a patient reminder (telephone, electronic message, or letter) for due surveillance (adjusted odds = 1.9; 95%CI = 1.2-2.8) and having ≥ 1 gastroenterology (GI) visit after diagnosis of an adenoma with high-risk features (adjusted odds = 2.6; 95%CI = 1.6-4.2) significantly predicted surveillance colonoscopy completion at 3.5 years. For patients diagnosed with adenomas with high-risk features, surveillance colonoscopy uptake is suboptimal and frequently occurs after the 3-year surveillance recommendation. Patient reminders and visitation with GI after index colonoscopy are associated with timely surveillance completion. Our findings highlight potential health system interventions to increase timely surveillance uptake for patients diagnosed with adenomas with high-risk features.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective
To compare the diagnostic accuracy of dual-energy (DE) virtual non-contrast computed tomography (vNCT) to non-contrast CT (NCT) for the diagnosis of adrenal adenomas.
Methods
Search of ...multiple databases and grey literature was performed. Two reviewers independently applied inclusion criteria and extracted data. Risk of bias was assessed using QUADAS-2. Summary estimates of diagnostic accuracy were generated and sources of heterogeneity were assessed.
Results
Five studies (170 patients; 192 adrenal masses) were included for diagnostic accuracy assessment; all used dual-source dual-energy CT. Pooled sensitivity for adrenal adenoma on vNCT was 54% (95% CI: 47–62%). Pooled sensitivity for NCT was 57% (95% CI: 45–69%). Pooling of specificity was not performed since no false positives were reported. There was a trend for overestimation of HU density on vNCT as compared to NCT which appeared related to contrast timing. Potential sources of bias were seen regarding the index test and reference standard for the included studies. Potential sources of heterogeneity between studies were seen in adenoma prevalence and intravenous contrast timing.
Conclusions
vNCT images generated from dual-energy CT demonstrated comparable sensitivity to NCT for the diagnosis of adenomas; however the included studies are heterogeneous and at high risk for some types of bias.
Key points
• Similar sensitivity of vNCT to NCT for diagnosis of adenoma
• Heterogeneity could be related to vNCT from early (<=60 sec) CECT studies
• Could not pool specificity as there were no false positives
• Small number of heterogeneous studies at high risk of bias
Diabetes is associated with an increased risk of colorectal cancer (CRC). We conducted a retrospective analysis of adenoma detection rates (ADR) in initial screening colonoscopies to further ...investigate the role of diabetes in adenoma detection.
A chart review was performed on initial average risk screening colonoscopies (ages 45-75) during 2012-2015. Data collected included basic demographics, insurance, BMI, family history of CRC, smoking, diabetes, and aspirin use. Multivariable generalized linear mixed models for binary outcomes were used to examine the relationship between diabetes and variables associated with CRC risk and ADR.
Of 2865 screening colonoscopies, 282 were performed on patients with type 2 diabetes (T2DM). Multivariable analysis suggested that T2DM (OR = 1.49, 95% CI:1.13-1.97, p = 0.0047) was associated with an increased ADR, as well as smoking, older age, higher BMI and male sex (all p < 0.05). For patients with T2DM, those not taking diabetes medications were more likely to have an adenoma than those taking medication (OR = 2.38, 95% CI:1.09-5.2, p = 0.03).
T2DM has an effect on ADR after controlling for multiple confounding variables. Early interventions for prevention of T2DM and prescribing anti-diabetes medications may reduce development of colonic adenomas and may contribute to CRC prevention.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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