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Amplitudes of 2-hydroxyglutarate (2-HG) signal for density matrix simulation of pulse acquire and semi-LASER at TE = 110 ms (TE1 =11 ms, TE2 = 65 ms and TE3 = 34 ms) acquisitions.

Legends for Supplementary Figures S1-S5.

Description of additional methods and procedures used in the study. Also includes Supplementary References.

OBJECTIVES To determine the prognostic significance of nodal yield in patients with clinically node-negative (cN0) oral cavity squamous cell carcinoma (OCSCC). METHODS This retrospective observational study included 40 patients with cN0 OCSCC who underwent treatment with at least 6 months of follow-up data from November 2012 to April 2020. We recorded the variables, including patient demographics, cancer site, tumor-node-metastasis (TNM) staging, type of treatment, lymph node yield (LNY), histopathologic diagnosis, and recurrence. The recorded data were analyzed with descriptive and interferential statistics using specific tests. RESULTS Our study cohort comprised of 27 males and 13 females with a mean age of 60.08+13.153 years. Tongue (55%) was the commonly affected site. Seventeen (42.5%) patients belonged to TNM stage II. The mean LNY in our study was 38.65±25.41 (range 7-98). Following surgery, 19 (47.5%) patients further received adjuvant therapies. Recurrence was reported only in 4 (10%) patients. There was no significant difference between LNY and recurrence rate (p=0.892). Factors including, age (p=0.121), gender (p=0.209), site (p=0.519), size of tumor (p=0.416) did not influence the LNY. CONCLUSION There is no correlation between LNY and recurrence in cN0 OCSCC patients in our study. Meticulous neck dissection and thorough pathologic reporting prevents TNM under staging and improves the overall survival and prognosis.

OBJECTIVE We conducted a meta-analysis of all randomized controlled trials (RCTs) that examined the benefits of tranexamic acid (TXA) among cancer patients undergoing head and neck (HN 265 and 275 patients were assigned to the TXA and control group, respectively. Overall, the included RCTs revealed a low risk of bias. The volume of postoperative bleeding was significantly lower in favor of the TXA group compared with the control group (n = 7 RCTs, WMD = - 51.33 ml, 95% CI [- 101.47 to - 1.2], p = 0.04). However, no significant difference was found between both groups regarding the volume of intraoperative bleeding (n = 6 RCTs, WMD = - 3.48 ml, 95% CI [- 17.11 to 10.15], p = 0.62), postoperative hemoglobin (n = 3 RCTs, WMD = 0.42 mg/dl, 95% CI [- 0.27 to 1.11], p = 0.23), duration of drainage tube removal (n = 4 RCTs, MD = - 0.41 days, 95% CI [- 1.14 to 0.32], p = 0.27), and operation time (n = 6 RCTs, WMD = 1.59 min, 95% CI [- 10.09 to 13.27], p = 0.79). TXA was safe and did not culminate in thromboembolic events or major coagulation derangements. CONCLUSION TXA administration is safe and significantly reduces the volume of postoperative bleeding. However, no difference is identified between TXA and control groups regarding the volume of intraoperative bleeding, postoperative hemoglobin level, duration of drainage tube removal, and operation time.

Objective To carry out a meta-analysis of prospective literature comparing the clinical efficacy of elective neck dissection (END) vs observation (OBS) in patients with early-stage cT1/T2N0 tongue carcinoma. Design/setting/participants/outcome measures We systematically reviewed four databases from inception to 30-October-2020. We considered all studies meeting the following PICOS conditions: (a) Patients: early-stage cT1/T2N0 tongue carcinoma, (b) Intervention: END, (c) Comparator: OBS, (d) Outcomes: local tongue recurrence, cervical nodal recurrence, disease-specific survival (DSS) rate, and disease-free survival (DFS) rate and (e) Study design: prospective reports. We pooled dichotomous data as relative risks (RRs) with 95% confidence intervals (CIs). Results Four studies (one case-control study and three randomised controlled trials) met our inclusion criteria. There were 448 eligible patients (225 and 223 patients were treated with END and OBS, respectively). END significantly correlated with improved DSS rate (RR = 1.15, 95% CI: 1.04-1.27, P = .007). Nonetheless, there were no significant differences between END and OBS groups regarding the rates of local tongue recurrence (RR = 1.23, 95% CI: 0.50-3.03, P = .65), cervical nodal recurrence (RR = 0.45, 95% CI: 0.16-1.27, P = .13) and DFS rate (RR = 1.08, 95% CI: 0.91-1.27, P = .38). Pooled analysis for cervical nodal recurrence was heterogeneous, and sensitivity analysis revealed a significantly lower cervical nodal recurrence rate in favour of END group (RR = 0.30, 95% CI: 0.13-0.67, P = .004). Conclusion END correlated with a significant decrease in cervical nodal recurrence and improved DSS rate. END might be superior to OBS in patients with early-stage cT1/T2N0 tongue cancer.

Background: Hypocalcemia is a common complication after total thyroidectomy and it is the most important factor for discharging a patient who underwent total thyroidectomy. Therefore, tools are needed to identify the risk of hypocalcemia in patients who are undergoing total thyroidectomy.Aim: The present study aimed to examine various preoperative parameters for predicting hypocalcemia.Patients and Methods: A prospective study evaluated consecutive patients who had fulfilled the surgical indications for total thyroidectomy, at two Saudi tertiary hospitals during 2017–2018. Standardized preoperative assessment that includes routine laboratory testing and measuring the corrected serum levels of calcium, vitamin D, phosphorus, and magnesium. At 6 hour after the surgery, all laboratory parameters were re-tested. The different variables were tested using Pearson's correlation analysis, the related-samples T-test, the independent-samples T-test, and repeated measures analysis of variance.Results: Total of 90 patients who underwent total thyroidectomy. The mean age of 41 ± 12 years, and included 20 men (22.2%) and 70 women (77.8%). The preoperative labs parameters (e.g., phosphorus, magnesium, albumin, vitamin D, and PTH) had poor predictive values for differentiating between the patients with and without hypocalcemia.The only significant difference was observed for postoperative PTH (p=0.037), and the postoperative magnesium and phosphorus levels were not statistically significant (p=0.200 and p=0.997, respectively).Conclusion: Our study showed that postoperative PTH levels reliably predicted postoperative hypocalcemia. We also found that hypocalcemia was not reliably predicted by age, sex disease type, or the preoperative and postoperative values for vitamin D, phosphorus, and magnesium.

Objective Precise knowledge of facial nerve anatomy is crucial for parotid surgery. Although several surgical landmarks to identify the facial nerve have been described in literature, their position is variable, inconsistent, and difficult to follow in some cases. The purpose of this study was to prove that the facial nerve trunk (FNT) is located midway between the mastoid tip (MT) and osteocartilaginous junction of the external auditory canal (EAC). Methods A prospective study of 7 frozen cadaver specimens, of which 13 facial sides were dissected. The distances between the osteocartilaginous junction and the MT, between the FNT and the MT, and between the FNT and the osteocartilaginous junction were recorded, respectively. Results The distance between the osteocartilaginous junction and the MT ranged from 17 to 21 mm, with a mean of 19.5 mm (SD = ±1.19). The mean distances between the osteocartilaginous junction and the FNT and between the MT and the FNT were 9.2 mm (±1.58) and 10.3 mm (±1.79), respectively. Conclusion The FNT was consistently located close to the midpoint between mastoid tip inferiorly and bony‐cartilaginous junction of the EAC superiorly. Level of Evidence NA, The purpose of this study was to prove that the facial nerve trunk (FNT) is located midway between the mastoid tip (MT) and osteocartilaginous junction of the external auditory canal (EAC). We found that the mean distances between the osteocartilaginous junction and the FNT and between the MT and the FNT were 9.2 mm (±1.58) and 10.3 mm (±1.79), respectively. The FNT was consistently located close to the midpoint between mastoid tip inferiorly and bony‐cartilaginous junction of the EAC superiorly.This technique renders the whole process of identifying the main trunk of facial nerve a lot easier, less complicated and less time consuming.

Background Little is known about the model of care affecting quality of life(QoL)and treatment satisfaction among people with type 1 diabetes(PWT1D). Objectives To compare QoL, treatment satisfaction and cardiometabolic indices among PWT1D receiving different care models in Saudi Arabia. Methods QoL was measure using Audit of Diabetes Dependent Quality of Life(ADDQoL) and treatment satisfaction was measure using Diabetes Treatment Satisfaction Questionnaire status version(DTSQs). Out of 177 respondents to internet validated Arabic versions of ADDQoL and DTSQs,105 are receiving care at specialized diabetes clinics(SDC), whereas 72 are receiving traditional care at general endocrine clinics(GEC). In SDC,where care is delivered jointly by an interdisciplinary team,PWT1D are evaluated from their first visit simultaneously and thereafter as recommended by 6 care providers: diabetes specialist,educator,podiatrist,nutritionist,optometrist, and mental health specialist, while in GEC, PWT1D will be followed every 6-12months and referred to other services as needed where referrals require a long waiting period. ADDQoL and DTSQs scores,sociodemographic characteristics, and cardiometabolic indices were compared between the two groups. The association between patients’ characteristics and their ADDQoL and DTSQs scores were examined. Results Among the respondents,109(61.6%)females,132(74.6%)never married,136(76.8%) belongs to age group(18-30)years old, with a mean duration of diabetes(11.4±7.5years). Both groups are comparable across nearly all sociodemographic characteristics except for half of the SDC attendees reported higher income categories(≥10000 Saudi Riyals)(51.4%vs. 23.6%,p40years(-4.4±2.8), p=0. 013)),(being never married(-2.5±2.1)vs. married(-3.4±2.3),or divorced/window(-4.7±3.3), p=0. 010),(having bachelor degree or more (-2.4±1.9) vs. less than bachelor degrees (secondary school(-3.2±2.7),primary school(-3.9± 4.8),intermediate school(-5. 0±2.4), p=0. 005),and(being student(-2.2±1.9)vs. employed(-3.2±2.4), or unemployed(-3.2±2.5), p=0. 010). Conclusion QoL, treatment satisfaction and glycemic control among PWT1D can be enhanced by providing structured care and using devices(insulin pump and CGM). This necessitates a call for healthcare policymakers to utilize the existing health resources to optimize care for PWT1D. Presentation: No date and time listed

Purpose Early detection of thyroid cancer has reduced mortality and improved survival of patients. Increased detection has raised the incidence of early stage disease. Some physicians underestimate the suffering of these patients due to the concept of "good cancer." The unmet needs of the survivors still need to be addressed. The objective of this paper was to evaluate the long-term quality of life (QOL) of thyroid cancer survivors. Methods A cross-sectional telephone survey of 211 thyroid cancer survivors who underwent thyroidectomy performed between 2006 and 2016 in two academic tertiary care hospitals was conducted using a validated Arabic version of the European Organization for Research and Treatment of Cancer head and neck cancer specific quality of life questionnaire (EROTC QLQ) - HN43 questionnaire using a scale of 1-4, with 4 being most severe. Results On almost half (48.5%) of patients, thyroidectomy was performed in 2013 or earlier. Patients' perceptions of problems were very low, with a mean score of 1.56 ± 0.7). Worry about the test results (2.37 ± 1.19), future health (2.36 ± 1.22), tingling or numbness in hands or feet (2.32 ± 1.22), pain in the shoulder (2.04 ± 1.18), and dry, itchy skin (2.04 ± 1.18) were the only items that received a mean score of more than 2. No statistically significant differences in patients' problems were observed according to either tumor histopathology or type of thyroidectomy. Conclusion The overall QOL score for the patients was very good. The persistent problems identified need to be addressed in the long-term follow-up. Survivorship care plans need to be developed incorporating proper interventions.

Introduction Children can present with a wide variety of parotid diseases. However, most of them do not require surgical treatment. The indications of parotid surgery in children may differ from those in adults. In this study, we aim to review the indications and outcomes of parotidectomy in our pediatric population. Methods Retrospective review of the medical records of patients who underwent parotid surgery at age

BACKGROUND: Thyroid malignancy, the most diagnosed cancer of the endocrine system, represents 2% of all malignancies worldwide. The increasing incidence of thyroid cancer has been linked to the increasing sensitivity of modern diagnostic methods which overdiagnosis small thyroid tumors. OBJECTIVES: Assess the distribution and trends in thyroid cancer among thyroidectomy patients. DESIGN: Descriptive, based on medical record review. SETTINGS: Two tertiary care centers in Riyadh. PATIENTS AND METHODS: We included patients who underwent thyroid surgery from January 1, 2004 to December 31, 2016 who ranged in age from 9–90 years regardless of initial diagnosis. MAIN OUTCOME MEASURES: Distribution of thyroid carcinomas by type, age and sex and trends over the time period. SAMPLE SIZE: 979 patients. RESULTS: Of 979 patients, 84.5% were

PURPOSE: The diagnostic criteria of allergic fungal rhinosinusitis focus on characteristic clinical, radiographic, histopathologic findings and immunologic characteristics of the disease. None of these are useful for a prompt outpatient diagnosis of the condition. No clear endoscopic signs (pathognomonic) of polyps in allergic fungal rhinosinusitis are mentioned in the literature. OBJECTIVE: The objective of this study is to describe and evaluate the sensitivity and specificity of an endoscopic sign the intrapolypoidal white particles for the diagnosis of allergic fungal rhinosinusitis in outpatient setting. METHODOLOGY: In a descriptive, cross-sectional study, 46 chronic rhinosinusitis patients were examined by endoscope in the outpatient clinic. The endoscopic images of the nasal polypi were captured preoperatively. During endoscopic surgery, a sample of nasal polypi was taken for fungal staining and culture. Results of histopathology were compared to the impression of rhinologist on the images of nasal polypi captured preoperatively. RESULTS: The most common endoscopic features were the expansion of sinus (24, 52.2%) and intrapolypoidal white particles (50%). Intrapolypoidal white particles were calculated to have 85.71% sensitivity, 65.63% specificity, 52.17% positive predictive value, 91.3% negative predictive value and 71.74% diagnostic accuracy. CONCLUSION: This study offers a new endoscopic sign, intrapolypoidal white particles for diagnosing allergic fungal rhinosinusitis.

Precise identification and preservation of the facial nerve is mandatory to avoid dysfunction of the facial nerve during parotidectomy. In this article, the authors are introducing a new landmark to identify the facial nerve for parotidectomy that is more protective for the facial nerve. The authors use a simple approach to predict the position of facial nerve main trunk intraoperatively without geometric calculations and a lot of landmarks. An imaginary almost 2 cm line is drawn between mastoid tip inferiorly and bony-cartilaginous junction of the external auditory canal superiorly. The main trunk of the facial nerve can be visualized at the midpoint of this line. The authors have been using this landmark successfully for the last 10 years, without any functional deficit of the parotid nerve. Identifying the facial nerve at the trunk level by this landmark renders following the branches forward in the glandular parenchyma less complicated.

Introduction Increased body mass index is known to be associated with the high prevalence of differentiated thyroid cancers; however data on its impact on survival outcome after thyroidectomy and adjuvant therapy is scanty. Objective We aimed to evaluate the impact of body mass index on overall survival and disease free survival rates in patients with differentiated thyroid cancers. Methods Between 2000 and 2011, 209 patients with differentiated thyroid cancers (papillary, follicular, hurthle cell) were treated with thyroidectomy followed by adjuvant radioactive iodine-131 therapy and thyroid-stimulating hormone suppression. Based on body mass index, patients were divided into five groups; (a) 40 kg/m2 (morbid obese). Various demographic, clinical and treatment characteristics and related toxicity and outcomes (overall survival, and disease free survival) were analyzed and compared. Results Median follow up period was 5.2 years (0.6-10). Mean body mass index was 31.3 kg/m2 (17-72); body mass index 31-40 kg/m2 was predominant (89 patients, 42.6%) followed by 26-30 kg/m2 seen in 58 patients (27.8%). A total of 18 locoregional recurrences (8.6%) and 12 distant metastasis (5.7%) were seen. The 10 year disease free survival and overall survival rates were 83.1% and 58.0% respectively. No significant impact of body mass index on overall survival or disease free survival rates was found (p = 0.081). Similarly, multivariate analysis showed that body mass index was not an independent prognostic factor for overall survival and disease free survival. Conclusion Although body mass index can increase the risk of thyroid cancer, it has no impact on treatment outcome; however, further trials are warranted.

Background: Incidental parathyroidectomy with subsequent hypoparathyroidism and postoperative hypocalcemia is thought to be one of the common complications of thyroidectomy. Current literature reports wide discrepancy in incidence and risk factors. Objectives: The aim of our study was to evaluate the incidence and risk factors of incidental parathyroidectomy in thyroid surgery. Methods: A retrospective study included 270 patients who had thyroid surgery that was performed over two years from January 2017 to December 2018 in two tertiary care hospitals. Preoperative and postoperative records were assessed. Factors such as gender, diagnosis, type of surgery, and usage of surgical loupes during the procedure were evaluated and were compared to find the association with incidental parathyroidectomy in thyroid surgery. Results: Incidental parathyroidectomy was noticed in 62 (23%) surgical specimens during histopathologic examination. There was no significant association between incidental parathyroidectomy and sex of patient, use of surgical loupes, pathology of thyroid disease, or neck dissection. Conclusion: Although the risk of incidental parathyroidectomy is inevitable, careful dissection and meticulous intraoperative identification of parathyroid gland during thyroidectomy can reduce the incidence of incidental parathyroidectomy, thereby minimizing the risk of postoperative hypoparathyroidism and hypocalcemia.

Background Tumors of salivary glands are enlarged as a low-risk mass and mostly benign in nature. The treatment of salivary gland malignancy remains quite challenging because of its relative infrequency, unreliable biological manners, and risk of re-emergence. For effective treatment planning, prediction of factors associated with the recurrence of salivary gland malignancy is essential. Aim The objective of this study was to identify the factors associated with recurrence of salivary gland malignancy at two tertiary hospitals in Saudi Arabia. Material and methods A cross-sectional study was conducted at two tertiary hospitals in Saudi Arabia, where data of patients were recorded from the medical records of hospitals from 2012 to 2018. 63 patients who were diagnosed with salivary gland malignancy, whether originated from parotid, submandibular, sublingual, and minor salivary glands were included in the study. Descriptive statistics are shown in mean, frequency, and percentages, while comparative analysis was done using the Chi-square test, where p < 0.05 is considered significant. Results This study included 63 participants. The majority of malignant salivary gland cancers arise from the parotid gland (47.6%), and mucoepidermoid carcinoma was the commonest form of malignancy in 36.5% of the studied population. Out of 63 patients, 17 had a recurrence of cancer, and the initial advanced stage of the disease is apparently associated with the re-emergence of salivary gland cancer. Conclusion The initial advanced stage of cancer has a significant role in the recurrence of salivary gland malignancy. As salivary gland malignancy is rare and has unreliable behavior, establishing an adequate treatment plan prediction for recurrence is essential.

Background Tumors of salivary glands are enlarged as a low-risk mass and mostly benign in nature. The treatment of salivary gland malignancy remains quite challenging because of its relative infrequency, unreliable biological manners, and risk of re-emergence. For effective treatment planning, prediction of factors associated with the recurrence of salivary gland malignancy is essential. Aim The objective of this study was to identify the factors associated with recurrence of salivary gland malignancy at two tertiary hospitals in Saudi Arabia. Material and methods A cross-sectional study was conducted at two tertiary hospitals in Saudi Arabia, where data of patients were recorded from the medical records of hospitals from 2012 to 2018. 63 patients who were diagnosed with salivary gland malignancy, whether originated from parotid, submandibular, sublingual, and minor salivary glands were included in the study. Descriptive statistics are shown in mean, frequency, and percentages, while comparative analysis was done using the Chi-square test, where p < 0.05 is considered significant. Results This study included 63 participants. The majority of malignant salivary gland cancers arise from the parotid gland (47.6%), and mucoepidermoid carcinoma was the commonest form of malignancy in 36.5% of the studied population. Out of 63 patients, 17 had a recurrence of cancer, and the initial advanced stage of the disease is apparently associated with the re-emergence of salivary gland cancer. Conclusion The initial advanced stage of cancer has a significant role in the recurrence of salivary gland malignancy. As salivary gland malignancy is rare and has unreliable behavior, establishing an adequate treatment plan prediction for recurrence is essential.

Ahmed Marzouk Maklad,1,2 Yasser Bayoumi,2,3 Mohamed Abdalazez SenosyHassan,2,4 AbuSaleh A Elawadi,5,6 Hussain AlHussain,2 Ashraf Elyamany,7,8 Saleh F Aldhahri,9 Khalid Hussain Al-Qahtani,10 Mubarak AlQahtani,11 Mutahir A Tunio12 1Clinical Oncology, Sohag University, Sohag, Egypt; 2Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 3Radiation Oncology, NCI, Cairo University, Cairo, 4Radiation Oncology, Minia Oncology Center, Minia, 5Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 6Medical Physics, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 7Medical Oncology, SECI-Assiut University, Assiut, Egypt; 8Medical Oncology, Comprehensive Cancer Center, King Fahad Medical City, 9Department of Otolaryngology, Head and Neck Surgery, King Saud University, 10Department of Otolaryngology-Head and Neck Surgery, College of Medicine, King Saud University, 11Department of ENT, King Fahad Medical City, 12Radiation Oncology, King Fahad Medical City, Riyadh, Saudi Arabia Background: We aimed to investigate the patterns of failure (locoregional and distant metastasis), associated factors, and treatment outcomes in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy (IMRT) combined with chemotherapy. Patients and methods: From April 2006 to December 2011, 68 nasopharyngeal carcinoma patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume and positive neck nodes were 66–70Gy, 63Gy to clinical target volume, and 50.4–56Gy to clinically negative neck. The clinical toxicities, patterns of failures, locoregional control, distant metastasis control, disease-free survival, and overall survival were observed. Results: The median follow-up time was 52.2months (range: 11–87months). Epstein–Barr virus infection was positive in 63.2% of patients. Overall disease failure developed in 21 patients, of whom 85.8% belonged to stage III/IV disease. Among these, there were seven locoregional recurrences, three regional recurrences with distant metastases, and eleven distant metastases. The median interval from the date of diagnosis to failure was 26.5months (range: 16–50months). Six of ten (60%) locoregional recurrences were treated with reirradiation ± concurrent chemotherapy. The 5-year locoregional control, distant metastasis control, disease-free survival, and overall survival rates of whole cohort were 81.1%, 74.3%, 60.1%, and 73.4%, respectively. Cox regression analyses revealed that neoadjuvant chemotherapy, age, and Epstein–Barr virus were independent predictors for disease-free survival. Conclusion: Neoadjuvant chemotherapy followed by IMRT with or without chemotherapy improves the long-term survival of Saudi patients with nasopharyngeal carcinoma. Distant metastasis was the main pattern of treatment failure. Neoadjuvant chemotherapy, age, and Epstein–Barr virus status before IMRT were important independent prognostic factors. Keywords: nasopharyngeal carcinoma, treatment outcomes, patterns of failures, prognostic factors

Patient: Female, 36-year-old Final Diagnosis: Thyroglossal duct cyst Symptoms: Dysphagia • neck mass Medication:— Clinical Procedure: Sistrunk’s procedure Specialty: Otolaryngology Objective: Unusual clinical course Background: Thyroglossal duct cysts are the most common congenital neck cysts. They typically present in childhood and early adulthood, and average a size of 2–4 cm, but can also present in later adult life. Case Report: We present a case of a 36-year-old female patient with a very large midline neck mass, reaching the mandible superiorly. Patient history and physical examination, as well as computed tomography scan of her neck, confirmed the diagnosis of large thyroglossal duct cyst. She underwent Sistrunk procedure for thyroglossal duct cyst excision, and the specimen was sent for histopathological evaluation, which confirmed the diagnosis. Conclusions: Thyroglossal duct cyst should be considered as a differential diagnosis in older patients and in patients with a relatively large neck mass.

Objective: To evaluate the outcomes of radical intent radiation therapy in early glottic carcinoma (EGC), including local control rate (LCR), disease-free survival (DFS), death specific free survival (DSFS), and overall survival (OS) rates, in Saudi patients treated at a single institution. Materials and methods: This is an institutional review board (IRB) approved, retrospective study of 27 patients with T1-2 N0 M0, early glottic carcinoma (EGC) who were treated from 2010 to 2015 at our institution with different radiotherapy (RT) fractionation regimens. The regimens included six different fractionation schedules of radiotherapy (RT): 50 Gy (20 x 2.5 Gy) dose prescribed to 95% isodose line, 52.4 Gy (20 x 2.52 Gy), 63 Gy (28 x 2.25 Gy), 66 Gy (33 x 2 Gy), and 70 Gy (35 x 2 Gy). The cohort was stratified into two groups, ≤ 52.5 Gy (n=15) and > 52.5 Gy (n=12). The median follow-up of all patients was 31.7 months (range 7-82). Results: The mean age of the cohort was 64.5 years (median 65, range: 41-83). Eleven patients (40.7%) had a history of smoking. The majority of the cohort was with T1a EGC (70.4%, n=19), and anterior commissure invasion was seen in three patients (11.1%). The mean RT doses were 55.6 Gy (range: 50-70). The five-year LCR, DFS, DSFS, and OS rates were 83.1%, 80.0%, 96.2%, and 92.6%, respectively. The LCR rates for those receiving a dose of 52.5 Gy or less were 61.3 months compared to 89.5 months for those who received more than 52.5 Gy (p=0.994). Non-smokers and patients with an unknown smoking history achieved a five-year LCR of 100%, while patients with a positive smoking history achieved a five-year LCR of 60.6% (p=0.044). Conclusion: Radiation therapy for EGC in our patients showed reasonable five-year LCR with larynx preservation at 83.1%, DFS 80.0%, five-year OS rate 92.6%, and DSFS rate 96.2%. We found that smoking had a significant correlation with LCR. However, large prospective trials are warranted to evaluate the efficacy of overall treatment time, dose per fraction of above 2 Gy, and smoking effect.

Mutahir A Tunio,1 Mushabbab Al Asiri,2 Khalid Hussain Al-Qahtani,3 Sadiq Aldandan,4 Khalid Riaz,5 Yasser Bayoumi,6 1Radiation Oncology, King Fahad Medical City, Riyadh, Saudi Arabia; 2Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 3Department of Otolaryngology - Head and Neck Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 4Department of Histopathology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 5Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 6Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt Abstract: Skull base metastasis from differentiated thyroid carcinoma, including papillary and follicular thyroid carcinoma, is a rare manifestation. Herein, we present three cases of skull base metastasis of papillary thyroid carcinoma. The mean age of the patients was 68.6 (65–74) years, and the mean interval between initial diagnosis and skull base metastasis was 56.3 (28–89) months. Cranial nerve palsies were seen in all patients. Intensity modulated radiation therapy to deliver 6,000–6,600 cGy to the skull base metastasis was given to all patients, in addition to partial resection in one patient. At the time of last follow-up, all skull base metastases were well controlled. Keywords: papillary thyroid carcinoma, skull base metastasis, treatment

Introduction Controversy exists about the prognosis of squamous cell carcinoma of the tongue between young and older patients. Our objective was to evaluate age as a prognostic factor in oral tongue cancer. Materials and methods A retrospective study was conducted by reviewing charts of 61 patients. They were divided into two age groups, below 40 years and above 40 years. Data regarding epidemiology pathology report, tumor differentiation, staging, treatment and outcome were obtained. The length of survival and disease recurrence was calculated and compared in this two age group. Statistical analysis was performed using student, t-test. Results The result showed no significant difference in prognosis, tumor differentiation or staging related to age in oral tongue cancer. Conclusion Although age is not a significant prognostic factor in oral tongue cancer, the disease etiology is likely different, we recommend prompt and aggressive treatment of young patients. How to cite this article Al-Qahtani K, Brousseau V, Islam T. prognosis of patients less than 40 Years of Age with Squamous Cell Cancer of the Oral Tongue. Int J Head Neck Surg 2015;6(2): 53-56.

Objectives: To evaluate the clinicopathologic features, and explore the treatment outcomes of synchronous, or metachronous second primary malignancies (SPM) in conjunction with differentiated thyroid cancers (DTC). Methods: This retrospective study was conducted on 823 DTC patients treated between 2000 and 2012 at 2 tertiary care hospitals (King Fahad Medical City and King Khalid University Hospital) in Riyadh, Kingdom of Saudi Arabia. Forty-one (5%) DTC patients were found to have SPM (61% metachronous and 39% synchronous). These patients with SPM were studied for clinicopathological features and treatment outcomes. Results: The patients with DTC and SPM were older (median age: 54.3 years) than those without SPM (median age: 43.2 years); p =0.04. The frequency of SPM was breast (51.2%), colon (12.2%), kidney (7.3%), astrocytoma (7.3%), parotid (7.3%), rectum (4.9%), lymphoma (4.9%), nasopharynx (2.4%), and stomach (2.4%). Median follow-up was 8.05 years. Ten-year disease free survival, and overall survival (OS) rates were lower in DTC patients with SPM (56.1% for 10-year survival, and 71.7% for OS) than without SPM (95.5% for 10-year survival, and 97.8% for OS); p =0.0001. Metachronous SPM had better 10-year disease free survival rates (60.2%) than synchronous SPM (45%). Conclusion: The co-occurrence of SPM with DTC affects long-term disease free survival and OS rates. Saudi Med J 2015; Vol. 36 (4): 442-448 doi: 10.15537/smj.2015.4.10341

Objectives The study evaluates the hearing result, complication rate and parental satisfaction following two different approaches in the management of external auditory canal atresia. Methods A retrospective chart review of 30 patients with external auditory canal atresia was conducted. Twenty of them underwent external canal atresia surgery and 10 had Bone Anchored Hearing Aid ( BAHA ). Hearing results, pre- and post-intervention, complications, parental satisfaction rate and speech improvement were measured. Results Closure of the air-bone gap (ABG) to 30 dB was seen in less than 50% in the surgery group. The BAHA group had closure of the ABG to less than 15 dB. Parental satisfaction was higher in BAHA group. The most common complications in the surgical and BAHA groups were group was soft tissue stenosis and adverse skin reactions for the BAHA group. Conclusion In the treatment of auditory canal atresia, BAHA provides superior hearing results, greater parental satisfaction and fewer complications as compared to surgery.

Background Assessing surgical competency in otolaryngology is challenging, and residency programs are now responsible for ensuring the surgical competency of their graduates. Therefore, more objective assessment tools are being incorporated into the evaluation process. Objective structured assessment of technical skills (OSATSs) tools have been developed for multiple otolaryngology procedures. These include tonsillectomy, endoscopic sinus surgery, thyroidectomy, mastoidectomy, direct laryngoscopy, and rigid bronchoscopy. The purpose of this study was to develop and test a new assessment tool for septoplasty surgery and ensuring its feasibility, reliability, and construct validity. This study was designed develop an test a valid, reliable, and feasible evaluation tool designed to measure the development of trainees’ surgical skills in the operating room for septoplasty surgery. Methods A new OSATSs-based instrument form for septoplasty was developed. During the study period of 2 years, 21 otolaryngology–head and neck surgery residents (ranging from postgraduate year 2 to 5) were evaluated intraoperatively by on faculty member obtaining al of 175 evaluations. Surgical performance was rated using a seven-item task-specific checklist (TSC) and a global rating scale (GRS). The TSC assessed specific septoplasty technical skills, and the GRS assessed the overall surgical performance. Results Our tool showed construct validity for both components of the assessment instrument, with increasing mean scores with advancing clinical levels. Cronbach's α, a measure of internal consistency, was 0.911 for TSC and 0.898 for GRS. Strong correlation between the TSC and GRS was established (r = 0.955; p < 0.01). Conclusion This study proved our educational tool to be a valid, reliable, and feasible method for assessing competency in septoplasty surgery. It can be integrated into surgical training programs to facilitate direct formative feedback. Assessing trainees’ learning curves enables insight into their progression, ensuring their appropriate development.

Kimura's disease is a rare, chronic inflammatory condition of unknown etiology; with a predilection in the head and neck region. However, the involvement of the lip and epiglottis is extremely rare, and poses a diagnostic challenge. Here, we report a case of a 32-year-old Saudi male presenting with lip mass and epiglottic swelling without any history of hoarse voice or airway compromise. Serology showed elevated immunoglobulin E levels, and histopathological examination of biopsied lesions revealed well-developed lymphoid follicles with eosinophilic infiltration confirming Kimura's disease. At the time of last follow-up, his condition was satisfactory without any signs of recurrence.

Introduction Selective neck dissection (SND) is performed to prevent head and neck cancers metastasis. We tried to determine the incidence of level IIb lymph nodes metastasis and it is associations in head and neck cancers for selection of patients requiring SND. Materials and methods A retrospective study was conducted on 57 patients who underwent surgical removal of the head and neck tumor by 84 neck dissections. Fisher exact test was used to measure the association between positive IIb nodes and the other variables. Results Nine (15.8%) of 57 patients showed level IIb lymph nodes metastasis comprising 10.71% of the 84 neck dissections. Six (66.66%) were associated with oral cavity cancers, 8 (88.9%) with squamous cell carcinoma (SCC), 6 (66.66%) with T4 tumor. Five (55.6%) were N2b, and 7 (77.8%) were found in N+ necks. All (100%) positive IIb nodes were associated with metastatic level IIa. Significant associations were found betweenpositive IIbnodesand N2b (p= 0.005), clinically N+ necks (p = 0.005) and IIa (p < 0.01). Conclusion The incidence of level IIb nodes metastasis is high so they should be removed in any oral tumor, SCC, advanced staging, N+ necks or positive IIa lymph nodes metastasis. How to cite this article Al zahrani F, Al-Qahtani K, Alshahrani m, Almufargi K, Alkhudhayri A, Obad l, Islam T. Incidence of lymphatic metastasis to Neck Nodes level IIb in Neck Dissection for Head and Neck Cancers: A Retrospective Study. Int J Head Neck Surg 2014;5(3):99-103.

Background Fibular free flap (FFF) bone has thick cortical bone surrounding a fatty marrow. The cortex has sufficient density for dental implantation, but the marrow limits bone stock. A novel technique was devised to increase bone density: the bone-impacted fibular free flap (BIFFF). The purpose of this study was to: (1) describe the BIFFF technique; (2) evaluate the bone density of BIFFF; and (3) evaluate the stability/success of implants placed in BIFFFs. Methods Patients undergoing maxillary/mandibular reconstruction with FFFs were prospectively enrolled from 1998 to 2008. Two cohorts were compared: BIFFF and nonmodified FFF. The main outcome was bone density as seen on CT scans. Primary dental implant stability was determined via Periotest. Results Thirty-eight patients were included in this study. BIFFFs achieved higher bone density versus unmodified FFFs (p < .05). Greater primary dental implant stability occurred in BIFFFs (p < .05). One hundred percent of BIFFF and 59% of nonmodified FFF implants were successful at 1 year. Conclusion BIFFF increases reconstructed bone density, initial dental implant stability, and 1-year implant success. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1648–1653, 2014

Objectives: To evaluate the clinicopathological features and treatment outcomes of papillary thyroid carcinoma tall cell variant (PTC-TCV) in Saudi population. Methods: This retrospective study were medical records of 776 treated PTC patients between December 2007 and 2015, at King Fahad Medical City and King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia was probed for PTC-TCV. Total 42 (5.4%) patients were found to have PTC-TCV, which were investigated for demographic, symptoms, histopathological features, and treatment outcomes locoregional control (LRC), distant metastasis control (DMC), disease free survival (DFS), and overall survival (OS) rates. Results: Mean age of cohort was 52.3 years (range: 46-80), with female predominance (73.8%). Mean tumor size was 3.62 cm (range: 0.4-10). Rates of LVSI (59.5%), positive pathological lymph nodes (66.7%), multifocality (42.9%) and extrathyroidal extension , (45.3%). Median follow-up was 37.4 months (range: 6-60). Local recurrence rate were seen in 6/42 (14.2%) patients and 8/42 (19%) developed distant metastasis. The 5 year rates of LRC (82.3%), DMC (77.8%), DFS (69.2%), and OS (86.7%) multivariate analysis showed PTC-TVC as an important independent prognosticator (odds ratio: 4.2; 95% confidence interval: 1.79-7.3; p =0.03) Conclusion: Papillary thyroid carcinoma tall cell variant is associated with aggressive biological behavior. Saudi Med J 2016; Vol. 37 (11): 1220-1224 doi: 10.15537/smj.2016.11.15480 How to cite this article: Al-Qahtani KH, Tunio MA, Al Asiri M, Bayoumi Y, Alshehri WA, Aljohani NJ, Ali AA, Fatani H. Tall Cell Variant Papillary Thyroid Carcinoma in Saudi Patients: A clinicopathological and Outcomes Analysis. Saudi Med J . 2016 Nov;37(11):1220-1224. doi: 10.15537/smj. 2016 .11.15480.

Khalid Hussain AL-Qahtani,1 Mutahir A Tunio,2 Mushabbab Al Asiri,2 Yasser Bayoumi,3 Ali Balbaid,2 Naji J Aljohani,4 Hanadi Fatani5 1Department of Otolaryngology-Head & Neck Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2Department of Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 3Department of Radiation Oncology, NCI, Cairo University, Cairo, Egypt; 4Department of Endocrinology and Thyroid Oncology, 5Histopathology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia Introduction: The aim of this study was to evaluate the treatment outcomes of differentiated thyroid cancer in Saudi patients aged above 60 years. Materials and methods: Comparative analysis was performed in 252 patients aged 46–60 years (Group A) and 118 patients aged above 60 years (Group B), who had thyroidectomy, radioactive iodine-131, and thyroid-stimulating hormone suppression therapy between July 2000 and December 2012. Different clinicopathological features, treatment, complications, disease-free survival, and overall survival rates were compared. Results: Mean age of patients in Group A was 51.9 years (range: 46–60), and mean age of those in Group B was 68.6 years (range: 62–97). Group B patients had higher positive lymph nodes (43.2%), P=0.011. The frequency of extrathyroidal extension, multifocality, and lymphovascular space invasion was seen more in Group B than in Group A. Postsurgical complications (permanent hypoparathyroidism, bleeding, and wound infections) were also seen more in Group B (P=0.043, P=0.011, and P=0.021, respectively). Group B patients experienced more locoregional recurrences (11.0%, P=0.025); similarly, more distant metastases were observed in Group B (15.3%, P=0.003). The 10-year disease-free survival rates were 87.6% in Group A and 70.8% in Group B (P

Background Salivary ductal carcinoma (SDC) of parotid gland is a rare and aggressive entity; accounting for 1–3 % of all malignant salivary gland tumors, 0.2 % of epithelial salivary gland neoplasms, 0.5 % of salivary gland carcinomas, and 1.1 % of parotid gland carcinomas. Here in we aimed to evaluate the clinico-pathological features and treatment outcomes of parotid gland SDC in Saudi population. Methods Among 38 patients with parotid malignancies, who were treated in two major tertiary care referral cancer centers between December 2007 and December 2014, seven cases (18.4 %) were found to have SDC, which were investigated for clinicopathological features, locoregional recurrences (LRRs), distant metastasis (DM) and survival rates. Results Mean age of cohort was 62.3 years (range: 41–83) and female predominant (71.4 %). All patients underwent total parotidectomy and ipsilateral neck dissection. Mean tumor size was 3.4 cm (range: 2.1–5.3); perineural invasion (85.8 %); lymph node involvement (42.9 %); and HER-2 neu overexpression (28.6 %). Postoperative radiation therapy (PORT) was given to six patients (dose: 50–66 Gy). Median follow-up was 20.2 months (range: 11–48). LRRs were seen in five (71.4 %) patients (base of skull, 3 patients; cervical nodes, one patient; parotid bed, one patient). LRRs were salvaged with resection (two patients) and re-irradiation (one patient with base of skull). DM in lungs was seen in three patients (42.8 %); one treated with carboplatin/paclitaxel based chemotherapy. The 4-year disease free and overall survival rates were 16.7 % and 40 % respectively. Conclusion SDC of parotid gland is a rare and aggressive entity, and most of LRRs were seen in the base of skull, which warrants inclusion of base of skull in clinical target volume in PORT planning. Role of anti HER-2 targeted therapy in SDC with HER-2 neu overexpression needs further investigations.

Background: The objective of this study was to evaluate the safety of preserving the submandibular gland in early-stage oral cavity cancer. Materials and Methods: We retrospectively collected the data for all patients who present with early-stage oral cavity cancer and underwent local wide excision with concomitant neck dissection over 8 years from 2008 to 2016 at two tertiary oncology centers in Saudi Arabia. Results: Forty-seven patients, comprising 26 males (55.3%) and 21 females (44.7%), were included in the study; the primary presentation, documented risk factors, and postoperative pathological results were evaluated. Conclusion: The present study showed that risk of submandibular gland metastasis in clinically early-stage oral cavity squamous cell carcinoma was almost nil.

Introduction: Thyroid disease is a common medical disorder. And thyroid cancer considered the second-most common cancer among the young Saudi females. Ultrasonography (US) and computed tomography (CT) are used in the diagnosis of thyroid nodules. However, US has its limitations, and CT scan is superior in detecting important details that would affect patient care and prevents possible complications. Objective: The study evaluates the benefits of CT scans implementation together with the US as a preoperative evaluation of any thyroid diseases which can improve thyroid patient care. Methodology: The retrospective study was conducted on a total of 207 patients, in a tertiary center, Riyadh, Saudi Arabia. Results: A total of 207 patients with thyroid diseases who had both US and CT scan done despite thyroid surgery done or not (164 females and 43 males; mean age, 44.6 ± 14.5 years) were included in our study, and any patient with improper imaging protocol or poor US or CT image quality was excluded. From there, 207 patients, we had 88 patients with benign and 85 with malignant pathology (+34 patients no surgery done for them). The present study showed that US had better specificity and accuracy in the prediction of thyroid malignancy comparing to the CT scan. Furthermore, CT had a significant P

Background Head and neck oncologists are often confronted with the difficult challenge of balancing cancer cure with the preservation of function when deciding the patient's best treatment protocol. This task is especially difficult in cancer of the base of tongue. The purpose of this manuscript is to describe the beavertail modification of the radial forearm-free flap in base of tongue reconstruction. Methods Thirty-one consecutive patients treated for base of tongue cancer with primary surgery were followed prospectively. The technique of the beavertail modification is described. Swallowing and speech function were assessed preoperatively and postoperatively. Results All the flaps survived. Thirty (97%) patients started consuming oral diet within 1 year, and all had normal speech intelligibility. Conclusions The beavertail modification of the radial forearm arm flap seems to provide the reconstructive elements that allow patients with large base of tongue extirpations to develop functional swallowing and speech production postoperatively. © 2008 Wiley Periodicals, Inc. Head Neck, 2009

We describe a new approach applicable to the determination of organic acids that serve as diagnostic markers for several inherited metabolic disorders. We utilized liquid chromatography/tandem mass spectrometry for analysis of organic acid derivatives of a recently described benzofurazan reagent. The derivatization step was necessary to obtain organic acid derivatives suitable for analysis by reversed-phase liquid chromatography with high ionization efficiency for mass spectrometry in the positive-ion mode. In this work, a group of related dicarboxylic acid markers containing five or six carbon atoms were analyzed and validation was performed for glutaric and 3-hydroxyglutaric acids, the specific markers for glutaric acidemia type 1. Derivatization was achieved by reacting untreated urine with the derivatization reagent under mild conditions. The reaction mixture was analyzed on a C18 ultra-performance liquid chromatography (UPLC) column (50x2.1 mm, 1.7 microm) and detected in the multiple reaction monitoring mode in 5 min. Calibration curves were linear up to at least 1000 microM with detection limits for glutaric and 3-hydroxyglutaric acids of 0.025 and 0.02 microM, respectively (signal-to-noise ratio of 3). Intra-day (n=11) and inter-day (n=6) coefficients of variation were better than 11.2%. The assay was successfully applied to control (n=134) and glutaric acidemia type 1 (n=55) urine samples.

Summary Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1R132H in the subventricular zone (SVZ) of the adult mouse brain. The mice developed hydrocephalus and grossly dilated lateral ventricles, with accumulation of 2-hydroxyglutarate and reduced α-ketoglutarate. Stem and transit amplifying/progenitor cell populations were expanded, and proliferation increased. Cells expressing SVZ markers infiltrated surrounding brain regions. SVZ cells also gave rise to proliferative subventricular nodules. DNA methylation was globally increased, while hydroxymethylation was decreased. Mutant SVZ cells overexpressed Wnt, cell-cycle and stem cell genes, and shared an expression signature with human gliomas. Idh1R132H mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis., Graphical Abstract, Highlights • Idh1R132H knockin in the mouse brain SVZ recapitulates features of gliomagenesis • Self-renewal and proliferation of neural stem cells and progenitors increase • SVZ cells proliferate ectopically, infiltrate the brain parenchyma, and form nodules • Increases occur in 2HG levels, Wnt and telomere pathway activity, and DNA methylation, Bardella et al. report that expression of IDH1R132H in the subventricular zone of the adult mouse brain causes features of gliomagenesis, including increased numbers of neural stem cells, cellular infiltration into surrounding brain regions, and a gene expression profile overlapping that of human gliomas.

Background Dacrocystorhinostomy (DCR) is an operation used to treat nasolacrimal duct obstruction. Essentially there are two approaches: external and endoscopic. Several modalities are used in endoscopic DCR; all aiming to improve success rate, reduce complications, and shorten operative time. Both kerrison punch and drill are widely used in endoscopic DCR with non-conclusive knowledge about differences in operative details as well as on the outcome. The aim of this study is to compare between powered (drill) and non-powered (kerrison punch) DCR to clarify the superiority of one over the other. Methods A retrospective chart review of 59 patients who underwent endoscopic DCR procedure at our institution from June 2013 until July 2014 (34 kerrison punch and 32 powered drill). Operative details, surgical outcome and complications were compared between both groups. Results A total of 66 endoscopic DCRs were performed on 59 patients. Procedure success rate among kerrison punch group was 87.88 % vs. 90.9 % in powered drill group (p = 0.827), while complications for both groups were statistical not significant (p = 0.91). The mean operating time among kerrison punch group was significantly lower than in powered drill group (75 min vs. 125 min, p = 0.0001). Conclusion Kerrison punch showed significant reduction in operating time when compared to powered drill for endoscopic DCR. No statistically significant difference was found between both groups regarding procedures’ success rate and complication.

Introduction Age is an important prognostic factor in differentiated thyroid cancer (DTC). Our aim was to evaluate differences in clinicopathological features and treatment outcomes among children and adult patients with DTC. Materials and methods We studied 27 children (below 18 years) with DTC treated during the period 2000–2012 and were compared with (a) 78 adults aged 19–25 years and (b) 52 adults aged 26–30 years treated during the same period in terms of their clinicopathological features and long term treatment outcomes. Locoregional recurrence (LRR), locoregional control (LRC), distant metastasis (DM), distant metastasis control (DMC), disease free survival (DFS) and overall survival (OS) rates were evaluated. Results Mean age of children was 13.5 years (range: 5–18), while mean age of adults was 24.6 years (range: 19–30). In children, female: male ratio was 2.85:1, and in adults female: male ratio was 7.1:1 (P = 0.041). No significant difference in tumor size was seen between the two groups (P = 0.653). According to American Thyroid Association (ATA) risk stratification classification, the children (85.2 %) were found to have at high risk as compared to adults P = 0.001. Post-thyroidectomy complications and RAI induced toxicities were observed more in children than adults (P = 0.043 and P = 0.041 respectively). LRR occurred in 6 (22.2 %), 9 (11.5 %) and 3 (5.8 %) in age groups of

2-Oxoglutarate (2OG) and ferrous iron dependent oxygenases are involved in many biological processes in organisms ranging from humans (where some are therapeutic targets) to plants. These enzymes are of significant biomedicinal interest because of their roles in hypoxic signaling and epigenetic regulation. Synthetic N-oxalylglycine (NOG) has been identified as a broad-spectrum 2OG oxygenase inhibitor and is currently widely used in studies on the hypoxic response and chromatin modifications in animals. We report the identification of NOG as a natural product present in Rheum rhabarbarum (rhubarb) and Spinach oleracea (spinach) leaves; NOG was not observed in Escherchia coli or human embryonic kidney cells (HEK 293T). The finding presents the possibility that NOG plays a natural role in regulating gene expression by inhibiting 2OG dependent oxygenases. This has significance because tricarboxylic acid cycle (TCA) intermediate inhibition of 2OG dependent oxygenases has attracted major interest in cancer research.