Predictive risk factors for distant metastasis in pediatric differentiated thyroid cancer from Saudi Arabia

BackgroundDespite their excellent prognosis, children and young adults (CAYA) with differentiated thyroid cancer (DTC) tend to have more frequent occurrence of distant metastasis (DM) compared to adult DTC. Data about DM in CAYA from Middle Eastern ethnicity is limited.MethodsMedical records of 170 patients with DTC ≤18 years were retrospectively reviewed. Clinico-pathological factors associated with lung metastasis in CAYA, their clinical presentation and outcome were analyzed. Rick factors related to distant metastasis-free survival (DMFS) for the whole cohort were evaluated.ResultsDM was observed in 27 patients and all were lung metastasis. Lung metastasis was significantly associated with younger age (≤15 years), extrathyroidal extension (ETE), multifocal tumors, bilaterality, presence of lymph node (LN) disease and high post-operative stimulated thyroglobulin (sTg). Highest negative predictive values were seen with low post-operative sTg (97.9%), absence of LN disease (93.8%), absence of ETE (92.2%) and age older than 15 years (92.9%). Post-therapy whole body scan (WBS) identified most of the lung metastasis (21 of 27; 77.8%). Upon evaluating patients response according to ATA guidelines, excellent response was seen in only one patient, while biochemical persistence and structural persistence were seen in 11.1% (3/27) and 77.8% (21/27), respectively. Elevated post-operative sTg (>10ng/ml) was the only risk factor found to be significantly associated with both biochemical persistence (with or without structural persistence (p = 0.0143)) and structural persistence (p = 0.0433). Cox regression analysis identified age and post-operative sTg as independent risk factors related to DMFS. Based on these two risk factors for DMFS, patients were divided into 3 groups: low risk (no risk factors), intermediate risk (1 risk factor) and high risk (both risk factors). 20-year DMFS rates in the low-, intermediate- and high-risk groups were 100.0%, 81.3% and 23.7% respectively (p < 0.0001).ConclusionHigher suspicion for metastatic pediatric DTC should be considered in patients who are young, have LN disease, extrathyroidal extension and elevated post-operative sTg. Persistent disease, despite therapy, is very common and it appears to be related to post-operative sTg level. Hence, risk adaptive management is desirable in CAYA with DTC

PD-L1 Expression Is an Independent Marker for Lymph Node Metastasis in Middle Eastern Endometrial Cancer

Programmed death ligand 1 (PD-L1) expression in endometrial cancer (EC) tumor cells have been reported in several studies with inconsistent results. Furthermore, there is scarcity of data on the prevalence and prognostic significance of PD-L1 expression in EC from Middle Eastern ethnicity. We aimed to assess PD-L1 expression in a large cohort of Middle Eastern EC and to correlate this with clinico-pathological factors, as well as mismatch repair (MMR) protein status and patients’ outcome. PD-L1 expression was investigated using immunohistochemistry on tissue microarray in an unselected cohort of 440 EC. Kaplan–Meier and logistic regression analysis were used to compare the outcome and prognostic factors. PD-L1 expression in tumor tissue was detected in 18.9% (83/440) EC cases with no impact on survival. When stratified for MMR protein status, PD-L1 expression was similar for both MMR deficient and MMR proficient ECs. However, the expression of PD-L1 in tumor cells was significantly associated with type II (non-endometrioid) histology (p = 0.0005) and lymph node metastasis (p = 0.0172). Multivariate analysis showed PD-L1 expression to be an independent risk factor for lymph node metastasis (odds ratio: 2.94; 95% CI: 1.26–6.84; p = 0.0123). In conclusion, PD-L1 was strongly associated with non-endometrioid EC and was an independent prognostic marker of lymph node metastasis

The prevalence of allergic rhinitis and atopic markers in obstructive sleep apnea

Allergic rhinitis (AR) related inflammation might worsen the severity of obstructive sleep apnea (OSA), however, the relationship between the two disorders remains controversial. Our aim was to determine the prevalence of AR and atopic markers in OSA. This cross-sectional study recruited participants with sleep-related complaints referred to a sleep center from February 2013 to June 2014. The diagnosis of OSA was based on the Berlin questionnaire (BQ) followed by confirmatory polysomnography (PSG). The diagnosis of AR was made via focused history and clinical examination and was confirmed by measuring atopic markers. OSA was diagnosed in 97 out of 157 adults attending the sleep clinic (61.8%). There was a high prevalence of AR (52.6%) among OSA individuals. This was not significantly different from the frequency in the non-OSA individuals (p = 0.5). Elevated total immunoglobulin E (IgE; >100 K/μL), eosinophil count, and positive Phadiatop tests were found in individuals with OSA to be 37.1%, 11.3%, and 41.2%, respectively. Individuals without OSA have shown similar percentages. In our cohort, there was no significant difference in frequency of AR and atopy among participants with OSA compared to those without OSA

Loss of CDH16 expression is a strong independent predictor for lymph node metastasis in Middle Eastern papillary thyroid cancer

Abstract Papillary Thyroid Cancer (PTC) is the most common type of thyroid cancer. The membrane-associated glycoprotein cadherin-16 (CDH16) plays a significant role in the embryonal development of thyroid follicles and cell adhesion. Previous studies have indicated a substantial downregulation of CDH16 in PTC. However, its role in Middle Eastern PTC has not been elucidated. We analyzed a tissue microarray comprising 1606 PTC and 240 normal thyroid tissues using immunohistochemistry to assess CDH16 expression and determine its clinico-pathological associations. We also conducted BRAF and TERT mutations analyses through Sanger sequencing. Disease-free survival (DFS) was assessed using Kaplan–Meier curves. CDH16 immunostaining was seen in 100% of normal thyroid tissues but only in 9.4% of PTC tissues (p < 0.0001). The loss of CDH16 expression was associated with aggressive PTC characteristics including bilaterality, multifocality, extrathyroidal extension, tall cell variant, lymph node metastasis (LNM) and distant metastasis. Additionally a correlation between loss of CDH16 expression and BRAF and TERT mutations was identified. Intriguingly, upon conducting multivariate logistic regression analysis, CDH16 was determined to be an independent predictor for LNM (Odds ratio = 2.46; 95% confidence interval = 1.60–3.79; p < 0.0001). Furthermore, CDH16 loss was associated with a shorter DFS (p = 0.0015). However, when we further subdivided CDH16 negative patients based on the co-existence of TERT and/or BRAF mutations, we found that patients with both CDH16 negative expression and TERT mutation exhibited the shortest DFS (p < 0.0001). In conclusion, our results suggest that CDH16 protein expression could serve as a valuable diagnostic tool for PTC. Furthermore, these findings demonstrate that the loss of CDH16 expression is an independent predictor of LNM and may contribute to the aggressiveness of PTC. Therefore, downregulation of CDH16 in PTC might be a potential target for designing novel therapeutic strategies to treat PTC

Prevalence of obstructive sleep apnea among patients with coronary artery disease in Saudi Arabia

Background: Despite the association between obstructive sleep apnea (OSA) and coronary artery disease (CAD), few studies have investigated this issue in Saudi Arabia. Objectives: This study aimed to identify the prevalence of OSA among CAD patients. Subjects and methods: This was a cross-sectional (descriptive) study conducted at King Abdul-Aziz University Hospital in Jeddah, Saudi Arabia from April 2012 to December 2013. All consecutive patients referred to the cardiac catheterization lab for coronary angiography who exhibited evidence of CAD were included in this study. This study was conducted in two stages. During the first stage, each participant was interviewed individually. The administered interview collected data pertaining to demographics, comorbidities, and the STOP-BANG questionnaire score. The second stage of this study consisted of a diagnostic overnight polysomnography (PSG) of 50% of the subjects at high risk for OSA according to the STOP-BANG questionnaire. Results: Among the patients with CAD (N = 156), 128 (82%) were categorized as high risk for developing OSA. PSG was conducted on 48 patients. The estimated prevalence of OSA in the study sample was 56.4%. Approximately 61% of the documented sleep apnea patients suffered from moderate to severe OSA. Conclusion: This local study concurs with reports in the literature indicating that OSA is very common among CAD patients

The prevalence of obstructive sleep apnea in adult patients with sickle cell disease

Purpose: Although few previous studies suggested an increased prevalence of obstructive sleep apnea (OSA) among children with sickle cell disease (SCD) compared to others, there are little data regarding this association in adults. In this study, we aimed to investigate the prevalence of OSA among the patients with SCD and its risk factors. Materials And Methods: This cross-sectional, observational study was conducted at a specialty hematology clinic. From December 2013 to July 2014, all the patients with SCD and chronic anemia were approached. Data were collected on the risk of OSA using the Berlin questionnaire, and the data on daytime sleepiness were collected using the Epworth sleepiness scale (ESS); medical history of the patients was also obtained. The objective diagnosis of OSA using polysomnography was performed in a subsample of the study population. Results: The study included 106 patients, 44.3% with SCD and 55.7% with other types of anemia being used as a comparison group. Among the patients with SCD, 14.9% were at a high risk of OSA, and 23% were confirmed to have OSA, whereas 10.1% and 16.7% of those in the comparison group did, respectively. However, there were no statistically significant differences between the two groups. Mean scores of risk factors for OSA among the patients with SCD with OSA were 28 years for age, 22.1 kg/m2for body mass index, 14.5 inches for neck circumference, 122 mmHg for systolic blood pressure, and 6.67 for ESS score. Conclusion: Although not different from chronic anemia, the OSA is a common, coexisting disease in the patients with SCD. Furthermore, it is suspected that the traditional screening tools may miss potential cases of OSA in the SCD population

DataSheet_1_Predictive risk factors for distant metastasis in pediatric differentiated thyroid cancer from Saudi Arabia.docx

BackgroundDespite their excellent prognosis, children and young adults (CAYA) with differentiated thyroid cancer (DTC) tend to have more frequent occurrence of distant metastasis (DM) compared to adult DTC. Data about DM in CAYA from Middle Eastern ethnicity is limited.MethodsMedical records of 170 patients with DTC ≤18 years were retrospectively reviewed. Clinico-pathological factors associated with lung metastasis in CAYA, their clinical presentation and outcome were analyzed. Rick factors related to distant metastasis-free survival (DMFS) for the whole cohort were evaluated.ResultsDM was observed in 27 patients and all were lung metastasis. Lung metastasis was significantly associated with younger age (≤15 years), extrathyroidal extension (ETE), multifocal tumors, bilaterality, presence of lymph node (LN) disease and high post-operative stimulated thyroglobulin (sTg). Highest negative predictive values were seen with low post-operative sTg (97.9%), absence of LN disease (93.8%), absence of ETE (92.2%) and age older than 15 years (92.9%). Post-therapy whole body scan (WBS) identified most of the lung metastasis (21 of 27; 77.8%). Upon evaluating patients response according to ATA guidelines, excellent response was seen in only one patient, while biochemical persistence and structural persistence were seen in 11.1% (3/27) and 77.8% (21/27), respectively. Elevated post-operative sTg (>10ng/ml) was the only risk factor found to be significantly associated with both biochemical persistence (with or without structural persistence (p = 0.0143)) and structural persistence (p = 0.0433). Cox regression analysis identified age and post-operative sTg as independent risk factors related to DMFS. Based on these two risk factors for DMFS, patients were divided into 3 groups: low risk (no risk factors), intermediate risk (1 risk factor) and high risk (both risk factors). 20-year DMFS rates in the low-, intermediate- and high-risk groups were 100.0%, 81.3% and 23.7% respectively (p ConclusionHigher suspicion for metastatic pediatric DTC should be considered in patients who are young, have LN disease, extrathyroidal extension and elevated post-operative sTg. Persistent disease, despite therapy, is very common and it appears to be related to post-operative sTg level. Hence, risk adaptive management is desirable in CAYA with DTC.</p

POLE and POLD1 germline exonuclease domain pathogenic variants, a rare event in colorectal cancer from the Middle East

Abstract Background Colorectal cancer (CRC) is a major contributor to morbidity and mortality related to cancer. Only ~5% of all CRCs occur as a result of pathogenic variants in well‐defined CRC predisposing genes. The frequency and effect of exonuclease domain pathogenic variants of POLE and POLD1 genes in Middle Eastern CRCs is still unknown. Methods Targeted capture sequencing and Sanger sequencing technologies were employed to investigate the germline exonuclease domain pathogenic variants of POLE and POLD1 in Middle Eastern CRCs. Immunohistochemical analysis of POLE and POLD1 was performed to look for associations between protein expression and clinico‐pathological characteristics. Results Five damaging or possibly damaging variants (0.44%) were detected in 1,135 CRC cases, four in POLE gene (0.35%, 4/1,135) and one (0.1%, 1/1,135) in POLD1 gene. Furthermore, low POLE protein expression was identified in 38.9% (417/1071) cases and a significant association with lymph node involvement (p = .0184) and grade 3 tumors (p = .0139) was observed. Whereas, low POLD1 expression was observed in 51.9% (555/1069) of cases and was significantly associated with adenocarcinoma histology (p = .0164), larger tumor size (T3 and T4 tumors; p = .0012), and stage III tumors (p = .0341). Conclusion POLE and POLD1 exonuclease domain pathogenic variants frequency in CRC cases was very low and these exonuclease domain pathogenic variants might be rare causative events of CRC in the Middle East. POLE and POLD1 can be included in multi‐gene panels to screen CRC patients