Ruthenium-106 Plaque Brachytherapy for Circumscribed Choroidal Hemangioma: A Case Series and Review of Literature.

Introduction: We aim to report the anatomical and functional outcomes of ruthenium-106 brachytherapy in the management of circumscribed choroidal hemangiomas (CCH). Methods: This is a single-center, retrospective case series including patients with unilateral symptomatic CCH treated with ruthenium-106 brachytherapy at the Cairo University Ocular Oncology Service. Patient records were analyzed for patients' demographics, best corrected visual acuity (BCVA), tumor dimensions (thickness and largest base diameter), foveal subretinal fluid, radiation-related complications, and recurrence. Results: Seven patients were included in the study (including 6 males) with a mean age of 39.3 ± 15.4 years; ruthenium-106 plaque was used to deliver 50 Gray to the tumor apex. After a mean follow-up duration of 12.5 months, all patients had significant improvement in BCVA after treatment, mean tumor height decreased significantly from 4.76 ± 1.76 mm to 1.70 ± 1.2 mm (p value 0.01). The largest tumor base diameter also decreased significantly from 9.13 ± 2.68 mm to 4.65 ± 3.75 mm (p value 0.05). Subretinal fluid and exudative retinal detachment resolved in all patients, and no significant radiation-related complications were observed in any patient. None of the patients needed any further treatment or experienced recurrence within the follow-up period. Conclusion: Ruthenium-106 brachytherapy is an effective tool in the management of symptomatic CCH with a good visual prognosis and safety profile.

Retinal Pigment Epithelial Adenoma: Initial Treatment Outcomes following Episcleral Brachytherapy.

Introduction: We aim to explore the safety and efficacy of episcleral brachytherapy as a primary management option for eyes with retinal pigment epithelial (RPE) adenoma. Methods: Retrospective chart review of the demographic, clinical, ancillary, and postoperative outcome data of patients with RPE adenoma in 2 tertiary referral centers. Tumor regression, final visual acuity, and complications were assessed. Results: Five patients (3 females and 2 males) were included. Four of the 5 eyes had peripheral and mid-peripheral lesions, while one tumor was juxtapapillary. Three eyes were treated with ruthenium-106 (100 Gray), and 2 received iodine-125 episcleral plaques (85 Gray). All eyes showed clinical and imaging-based evidence of regression. Four eyes had stable or improved visual acuity, while 1 eye exhibited one line loss of visual acuity due to radiation retinopathy. Local recurrence was not observed in any eye over a median follow-up of 24 (range 6-112) months. Conclusions: Episcleral brachytherapy is an effective management option for select cases of RPE adenoma that is capable of achieving tumor regression while maintaining favorable visual acuity. The initial safety profile of brachytherapy is good without significant vision-compromising complications.

LncRNA ANRIL Promotes Glucose Metabolism and Proliferation of Colon Cancer in a High-Glucose Environment and is Associated with Worse Outcome in Diabetic Colon Cancer Patients.

BACKGROUND: The potential involvement of type 2 diabetes mellitus (T2DM) as a risk factor for colon cancer (CC) has been previously reported. Epigenetic changes, such as deregulation of long non-coding RNA (lncRNA) and microRNA (miR), have been linked to the advancement of CC; however, the effects of high glucose levels on their deregulation and, in turn, colon cancer remain unexplored. METHODS: Fifty patients had a dual diagnosis of CC and T2DM, and 60 patients with CC without diabetes mellitus were included in the study. qRT-PCR was used to examine the expression of lncRNA ANRIL and miR-186-5p in tissue samples. ANRIL, miR-186-5p, and their downstream target genes HIF-1α, PFK, HK, Bcl-2, and Bax were also determined in CC cell lines under various glucose conditions. Glucose uptake, lactate production and cells proliferation were estimated in CC cell lines. RESULTS: A significant upregulation of ANRIL expression levels (p<0.001) and a significant downregulation of miR-186-5p expression (p<0.001) in diabetic colon cancer specimens compared to those in non-diabetic colon cancer group were observed. MiR-186-5p expression levels were inversely correlated with ANRIL expression levels, blood glucose levels and HbA1c%. Concerning in vitro model, a significant upregulation of ANRIL, downregulation of miR-186-5p, upregulation of HIF-1α, glycolytic enzymes and activation of antiapoptotic pathway was detected in higher glucose concentrations than lower one. There was a significant increase of glucose uptake, lactate accumulation and proliferation of the Caco2 and SW620 cell lines in a dose dependent manner of glucose concentrations. Moreover, a significant positive correlation between glucose uptake and ANRIL expression was shown. CONCLUSIONS: A high-glucose environment can increase the tumor-promoting effect of ANRIL. ANRIL can promote glucose metabolism and colon cancer proliferation by downregulating miR-186-5p with subsequent upregulation of glycolysis enzymes expression and inhibition of apoptosis.

COVID-19 VACCINE-INDUCED ACUTE EXUDATIVE POLYMORPHOUS VITELLIFORM MACULOPATHY: CASE REPORTS.

BACKGROUND: Acute exudative polymorphous vitelliform maculopathy is a presumed retinal pigment epithelium abnormality that has been reported in patients with neoplasms and under certain classes of drugs. The pathophysiology remains unclear, despite the typical clinical features. PURPOSE: To report two cases of acute exudative polymorphous vitelliform maculopathy occurring after vaccination with a COVID-19 vaccine. CASE REPORTS: Two adult patients presented with visual disturbance after inoculation with a COVID-19 vaccine. The patients were otherwise healthy and have no family history of retinal dystrophies. Both cases exhibited the following features on multimodal imaging: multifocal hyporeflective lesions involving the macula, elongated photoreceptors, accumulated vitelliform material exhibiting autofluorescence, and lack of fluorescein dye leakage. Evidence of retinal pigment epithelium dysfunction was confirmed by electrooculography. CONCLUSION: Two cases of acute exudative polymorphous vitelliform maculopathy occurring after COVID-19 vaccination were reported. A relationship between the vaccine and the retinal pigment epithelial abnormality development that led to acute exudative polymorphous vitelliform maculopathy was postulate, possibly through autoantibodies against the severe acute respiratory syndrome coronavirus 2 virus structural surface glycoprotein antigens that cross react with the normal retinal pigment epithelial cells.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY REVEALS PARADOXICALLY DECREASING CHOROIDAL THICKNESS AND INCREASING BLOOD FLOW IN REMITTING VOGT-KOYANAGI-HARADA SYNDROME.

PURPOSE: To assess changes in choroidal thickness and blood flow in active Vogt-Koyanagi-Harada syndrome and after remission using optical coherence tomography angiography. METHODS: This was a prospective study of patients with active early uveitis secondary to Vogt-Koyanagi-Harada syndrome. They underwent optical coherence tomography angiography imaging twice: at baseline and after remission on treatment. 3- × 3- and 6- × 6-mm choriocapillaris slabs were used to evaluate parafoveal adjusted flow index as a marker for choroidal blood flow. Mean choroidal thickness of 3 points (subfoveally and 2 points 300 µ m parafoveally) was also measured. RESULTS: Thirty-nine eyes of 25 patients were initially recruited. After excluding eyes with media opacity, submacular fibrosis, and choroidal neovascularization, 23 eyes of 14 patients were included. The mean follow-up period was 8.7 ± 2.5 months. Mean choroidal thickness in activity and remission was 581.65 ± 108.29 µ m and 318.34 ± 72.85 µ m respectively ( P < 0.01). Mean adjusted flow index in the 3- × 3-mm slabs activity and remission were 0.495 ± 0.027 and 0.519 ± 0.0336 ( P = 0.011), and the 6- × 6-mm slabs were 0.487 ± 0.037 and 0.517 ± 0.052 respectively ( P = 0.025). CONCLUSION: We demonstrate decreasing choroidal thickness with paradoxically increasing choroidal flow on optical coherence tomography angiography in remitting Vogt-Koyanagi-Harada syndrome. This may reflect inflammatory infiltrations or granulomas increasing choroidal thickness during activity and causing sluggish circulation of the choriocapillaris, and a reversal of this process with remission. These findings shed more light on the relationship between Vogt Koyanagi Harada syndrome and its underlying choroidal disturbances. Larger studies are needed to evaluate the efficacy of adjusted flow index in evaluating and predicting disease activity.

Prognostic value of NOTCH1 and OCT4 in gastric carcinoma.

Background: NOTCH1 pathway activation has been recently described to be a key player in gastric carcinogenesis, enhance the survival and proliferation of cancer stem cells (CSCs) and mediate chemoresistance in several malignancies. Aim: This study investigated the correlation between NOTCH1 and CSC marker OCT4 (octamer binding transcription factor-4) expression and the clinicopathological properties, survival and treatment outcome in patients with gastric carcinoma (GC) receiving adjuvant chemotherapy. Materials and. Methods: NOTCH1 and OCT4 were immunohistochemically detected in 50 post-operated specimens of GC. Patients' data regarding disease-free survival (DFS), overall survival (OS), and the response to the chemotherapy was statistically analyzed. Results: NOTCH1 and OCT4 overexpression was detected in 60% and 52% of GC tissues, respectively, and that was significantly higher than the rates in adjacent non-neoplastic gastric mucosa (P < 0.05). A significant correlation was detected between overexpression of NOTCH1 and OCT4 in GC and aggressive clinicopathological features; poor differentiation (P = 0.021, P = 0.037, respectively), depth of tumor invasion (P < 0.001 for both), TNM stage (P < 0.001 for both), lymph node metastasis (P = 0.002, P = 0.003, respectively) and distant metastasis (P < 0.001 for both). NOTCH1 was positively correlated with OCT4 (P = 0.002). Survival analysis disclosed that upregulation of NOTCH1 and OCT4 was associated with worse DFS (P = 0.013, P < 0.001, respectively) and OS (P < 0.001 for both). Overexpression of NOTCH1 and OCT4 correlated with poor response to chemotherapy (P = 0.013, P = 0.005, respectively) and worse clinical outcome. Conclusion: Combined detection of these proteins might disclose even better predictive value for shorter survival and resistance to chemotherapy.

Bilateral Morning Glory Syndrome with Bilateral Persistent Fetal Vasculature in a Patient with Joubert's Syndrome.

Purpose. We report a case of a 1-year-old girl who was referred to us with a cerebellar anomaly and delayed growth and development for bilateral ptosis and poor fixation. Based on our ophthalmologic examination, we concluded that she has bilateral persistent fetal vasculature (PFV) with morning glory syndrome (MGS). A closer look into her neurologic condition revealed that she has Joubert's syndrome. Observations. External examination revealed bilateral symmetrical ptosis with syndromic facies and her fundus examination revealed a large dysplastic optic disc with anomalous radiating vessels and a fibrous tissue tuft originating from the disc. The left eye showed similar findings in addition to a central excavation and a fibrovascular stalk extending from the optic disc. These findings were consistent with bilateral MGS and bilateral PFV. The brain imaging included a computed tomography scan and magnetic resonance imaging, both of which revealed a "molar tooth appearance" of the midbrain and an anomalous cerebellum suggestive of Joubert's syndrome. Conclusions and Importance. This is the first case report of a case of bilateral MGS and bilateral PFV associated with Joubert's syndrome. This case report documents the associated optic nerve disease in these patients, not previously described, which are additive causes of visual compromise in addition to the brain insult.

Effect of KRAS mutational status on disease behavior and treatment outcome in patients with metastatic colorectal cancer: intratumor heterogeneity and mutational status.

BACKGROUND: Nowadays, the outcomes of metastatic colorectal cancer (mCRC) have considerably improved. Genetic studies evaluating KRAS mutational status are important in the personalized therapy era to understand disease heterogeneity, disease behaviors, and treatment outcomes. METHODS: This multicenter retrospective study evaluated 360 patients with mCRC treated at three oncology centers in Saudi Arabia and Egypt between February 2011 and December 2015. Patients were treated with bevacizumab and cetuximab according to guidelines. Therapy outcome, time to progression, and disease-associated death were assessed. KRAS mutational status was evaluated by testing exons 12 and 13. RESULTS: Approximately 220 (61.1%) cases were of wild-type KRAS, whereas KRAS mutation was noted in 38.9%. KRAS mutation was common in the descending colon, whereas a low incidence of the KRAS mutation was observed in the ascending colon (P<0.001). Among patients with KRAS mutation, 64.3% initially presented as emergency cases with obstruction/perforation (P=0.002), and 62.9% had hepatic or pulmonary metastasis. The progression-free survival (PFS) was 10.7 months. Cases without KRAS mutation showed a higher PFS than did those with KRAS mutation (mean PFS: 11.5 vs. 9.6 months, P=0.001). The overall survival was 23.2 months. The survival varied considerably according to KRAS type: patients without mutation survived for 25.0 months and those with mutation survived for 19.6 months (P<0.001). Disease-related death occurred in 132 (36.7%) cases, approximately 57.1% of them (80 cases) had KRAS mutations (P=0.001). CONCLUSIONS: A major association between KRAS mutational status and both disease behavior and treatment outcomes was found in this study. Patients with KRAS mutation show advanced disease presentation, with lower PFS and overall survival.

Projection resolved optical coherence tomography angiography to distinguish flow signal in retinal angiomatous proliferation from flow artifact.

PURPOSE: To investigate whether hyperreflective foci (HRF) exhibit flow projection artifact on OCTA, and study the efficacy of commercial projection artifact removal software (PAR-OCTA, Optovue, Inc), and a custom projection resolved OCTA (PR-OCTA) in distinguishing artifacts from true flow in retinal angiomatous proliferation (RAP). METHODS: The study included five eyes with HRF representing pigment migration in dry age-related macular degeneration (AMD), five eyes with leaking treatment-naïve RAP, and ten eyes with diabetic hard exudates. We examined flow signal on OCTA cross-sections using PAR, and performed PR-OCTA to study the effect of increasingly stringent projection removal thresholds. Flow signal intensity was analyzed and quantified using imageJ (NIH, Bethesda, MD, USA), by calculating the percentage of red pixels (R) representing flow, compared to green (G) and blue (B) pixels. RESULTS: PAR-OCTA cross sections revealed persistent flow signal in all HRF, including RAP, hard exudates and pigment migration. In RAP, PR-OCTA detected intransigent flow, irrespective of the flow removal threshold. Mean R in the five RAP lesions remained higher than mean G and B at the most stringent PR-OCTA threshold (40.96% vs 29.52 and 29.52%, respectively), denoting persistence of flow. In contrast, increasing the PR-OCTA threshold in pigment migration and hard exudates removed the flow signal, with a statistically significant decrease in mean R with increasing threshold. (p = 0.017 and 0.0029, respectively). CONCLUSION: Commercial PAR-OCTA is not completely effective at removing artifactual flow in hard exudates and HRF related to pigment migration. Custom built PR-OCTA, using a sliding scale of threshold, allowed us to distinguish true flow in RAP from artifactual flow in avascular HRF. Further studies are needed to validate the optimum threshold for projection artifact removal, which would preserve true flow in RAP and the small intraretinal capillaries.

Prognostic significance of the genetic and the immunohistochemical expression of epithelial-mesenchymal-related markers in colon cancer.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is one of the main events in colorectal cancer (CRC) spread. Snail-1 is a zinc transcription factor that mediates EMT in tumor cells probably by down-regulation of E-cadherin and claudin-1. OBJECTIVES: To detect the expression of epithelial markers (claudin-1 and E-cadherin) and mesenchymal markers (snail-1 and vimentin) in primary cancer colon. Also, to select stage II cancer patients of a high risk that can benefit from postoperative adjuvant chemotherapy. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analysis were performed to investigate snail-1, claudin-1, E-cadherin and vimentin expressions at mRNA and protein levels in fresh tissues of cancer colon and normal colonic mucosa. The correlations between the expression of these markers and clinicopathological parameters were performed. RESULTS: Normal colonic mucosa revealed complete membranous expression of claudin-1, preserved E-cadherin and negative snail-1 and vimentin expressions. Compared to control, the expression of snail-1 and vimentin mRNA in cancer colon was significantly up-regulated while the expression of claudin-1 and E-cadherin mRNA was significantly down-regulated. These changes were significantly associated with stage and lymph node involvement at both mRNA and protein levels (p< 0.05). There were significant negative correlations between vimentin and each of E-cadherin and claudin-1 gene expression and between snail-1 and each of E-cadherin and claudin-1 gene expression. Moreover, these changes were independent predictors of recurrence of stage II cancer colon cases. CONCLUSION: There is a clinical significance of snail-1, claudin-1, E-cadherin and vimentin as possible markers for recognizing patients with lymph node involvement, advanced stage and high incidence of tumor recurrence in cancer colon.

Comparison of high-dose-rate and low-dose-rate brachytherapy in the treatment of endometrial carcinoma.

PURPOSE: To compare the outcomes for endometrial carcinoma patients treated with either high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy. METHODS AND MATERIALS: This study included 1,179 patients divided into LDR (1,004) and HDR groups (175). Patients with International Federation of Gynecology and Obstetrics (FIGO) surgical Stages I-III were included. All patients were treated with postoperative irradiation. In the LDR group, the postoperative dose applied to the vaginal cuff was 60-70 Gy surface doses to the vaginal mucosa. The HDR brachytherapy prescription was 6 fractions of 2 Gy each to a depth of 0.5 cm from the surface of the vaginal mucosa. Overall survival, disease-free survival, local control, and complications were endpoints. RESULTS: For all stages combined, the overall survival, disease-free survival, and local control at 5 years in the LDR group were 70%, 69%, and 81%, respectively. For all stages combined, the overall survival, disease-free survival, and local control at 5 years in the HDR group were 68%, 62%, and 78%, respectively. There were no significant differences in early or late Grade III and IV complications in the HDR or LDR groups. CONCLUSION: Survival outcomes, pelvic tumor control, and Grade III and IV complications were not significantly different in the LDR brachytherapy group compared with the HDR group.