Longitudinal diffusion and volumetric kinetics of head and neck cancer magnetic resonance on a 1.5T MR-Linear accelerator hybrid system: A prospective R-IDEAL Stage 2a imaging biomarker characterization/ pre-qualification study.

Objectives: We aim to characterize the serial quantitative apparent diffusion coefficient (ADC) changes of the target disease volume using diffusion-weighted imaging (DWI) acquired weekly during radiation therapy (RT) on a 1.5T MR-Linac and correlate these changes with tumor response and oncologic outcomes for head and neck squamous cell carcinoma (HNSCC) patients as part of a programmatic R-IDEAL biomarker characterization effort. Methods: Thirty patients with pathologically confirmed HNSCC who received curative-intent RT at the University of Texas MD Anderson Cancer Center, were included in this prospective study. Baseline and weekly Magnetic resonance imaging (MRI) (weeks 1-6) were obtained, and various ADC parameters (mean, 5 th , 10 th , 20 th , 30 th , 40 th , 50 th , 60 th , 70 th , 80 th , 90 th and 95 th percentile) were extracted from the target regions of interest (ROIs). Baseline and weekly ADC parameters were correlated with response during RT, loco-regional control, and the development of recurrence using the Mann-Whitney U test. The Wilcoxon signed-rank test was used to compare the weekly ADC versus baseline values. Weekly volumetric changes (Δvolume) for each ROI were correlated with ΔADC using Spearman's Rho test. Recursive partitioning analysis (RPA) was performed to identify the optimal ΔADC threshold associated with different oncologic outcomes. Results: There was an overall significant rise in all ADC parameters during different time points of RT compared to baseline values for both gross primary disease volume (GTV-P) and gross nodal disease volumes (GTV-N). The increased ADC values for GTV-P were statistically significant only for primary tumors achieving complete remission (CR) during RT. RPA identified GTV-P ΔADC 5 th percentile >13% at the 3 rd week of RT as the most significant parameter associated with CR for primary tumor during RT (p <0.001). Baseline ADC parameters for GTV-P and GTV-N didn't significantly correlate with response to RT or other oncologic outcomes. There was a significant decrease in residual volume of both GTV-P & GTV-N throughout the course of RT. Additionally, a significant negative correlation between mean ΔADC and Δvolume for GTV-P at the 3 rd and 4 th week of RT was detected (r = -0.39, p = 0.044 & r = -0.45, p = 0.019, respectively). Conclusion: Assessment of ADC kinetics at regular intervals throughout RT seems to be correlated with RT response. Further studies with larger cohorts and multi-institutional data are needed for validation of ΔADC as a model for prediction of response to RT.

Mutation-Agnostic Detection of Colorectal Cancer Using Liquid Biopsy-Based Methylation-Specific Signatures.

Detection of methylation patterns in circulating tumor DNA (ctDNA) can offer a novel approach for cancer diagnostics given the unique signature for each tumor type. We developed a next-generation sequencing (NGS)-based assay targeting 32 CpG sites to detect colorectal cancer-specific ctDNA. NGS was performed on bisulfite-converted libraries and status dichotomization was done using median methylation ratios at all targets. We included plasma samples from patients with metastatic colorectal (n = 20) and non-colorectal cancers (n = 8); and healthy volunteers (n = 4). Median methylation ratio was higher in colorectal cancer compared with non-colorectal cancers (P = .001) and normal donors (P = .005). The assay detected ctDNA in 85% of patients with colorectal cancer at a specificity of 92%. Notably, we were able to detect methylated ctDNA in 75% of patients in whom ctDNA was not detected by other methods. Detection of methylated ctDNA was associated with shorter median progression-free survival compared to non-detection (8 weeks versus 54 weeks; P = .027).

Laparoscopic management of infantile hydrocele in pediatric age group.

PURPOSE: To evaluate laparoscopic management of hydroceles in pediatrics, with evaluation of the internal inguinal ring (IIR) and the PPV (patent processus vaginalis) in different types of hydroceles, and the incidence of the contralateral PPV. METHODS: The IIR and the type of hydrocele on the same side of 93 patients with 106 infantile hydroceles were evaluated and managed, in addition to contralateral side. RESULTS: The IIR on same side was closed in 8.5% (Type I) and patent in 91.5% (Type II and III) with different shapes. Contralateral IIR was open in 88.7% of cases. The operative time was 30.99 ± 7.23 min, with no intra-operative complication. The vas deferens and testicular vessels were secured and there were no injuries or bleeding. The conversion rate was zero, and all procedures (Type II and II) were completed totally laparoscopic. No post-operative complications except a case of tense hydrocele developed scrotal edema that managed conservatively. CONCLUSION: Laparoscopic hydrocelectomy is safe, applicable and feasible for management of different types of hydroceles in pediatrics. The IIR is patent in nearly all cases with/out communication to the hydrocele. The contralateral IIR can be managed in the same session. Laparoscopic hydrocelectomy with/out hydrocelectomy and IIR closure is essential in preventing recurrence.

The Effect of Antrum Size on Weight Loss, Glucagon-Like Peptide-1 (GLP-1) Levels, and Glycemic Control Following Laparoscopic Sleeve Gastrectomy in Adolescents with Obesity and Type 2 Diabetes.

PURPOSE: The aim of this study was to compare the effect of antral resection versus antral preservation sleeve gastrectomy on the post-operative GLP-1, glycemic control, and weight loss in adolescents suffering from severe obesity and type 2 diabetes (T2D). MATERIALS AND METHODS: This study included 36 adolescents. Patients were randomly divided into 2 groups: group (A) and group (B). Each group included 18 patients who underwent LSG, starting transection at 2 cm or 5 cm from the pyloric ring in group (A) and group (B), respectively. They were followed up at 1, 3, 6, 12, and 24 months post-operatively. The outcomes were the post-operative GLP-1 response, glycemic control, weight loss, and safety. RESULTS: The improvements in the body mass index and the percentage of excess weight loss (%EWL) were statistically significant within each group. The mean GLP-1 levels showed significant increase at the 1, 3, and 6 months but not in the 12 and 24 months in all the studied samples within each group. The mean HbA1c levels and post-prandial serum C-peptide significantly improved within each group (P < 0.05). No statistical differences in the weight loss, %EWL, GLP-1, HbA1c, C-peptide changes, and complication rates were observed between both groups. Diabetic remission was significantly higher (88.9%) in group (A). CONCLUSIONS: LSG resulted in generalized significant GLP-1 initial response that decreased over time. The reduced antrum size did not influence the GLP-1 response, glycemic control, or insulin resistance, but resulted in significantly better T2D remission. Since the study examines a small number of patients, further studies are needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04388059.

Breast-Gynaecological & Immuno-Oncology International Cancer Conference (BGICC) Consensus and Recommendations for the Management of Triple-Negative Breast Cancer.

Background: The management of patients with triple-negative breast cancer (TNBC) is challenging with several controversies and unmet needs. During the 12th Breast-Gynaecological & Immuno-oncology International Cancer Conference (BGICC) Egypt, 2020, a panel of 35 breast cancer experts from 13 countries voted on consensus guidelines for the clinical management of TNBC. The consensus was subsequently updated based on the most recent data evolved lately. Methods: A consensus conference approach adapted from the American Society of Clinical Oncology (ASCO) was utilized. The panellists voted anonymously on each question, and a consensus was achieved when ≥75% of voters selected an answer. The final consensus was later circulated to the panellists for critical revision of important intellectual content. Results and conclusion: These recommendations represent the available clinical evidence and expert opinion when evidence is scarce. The percentage of the consensus votes, levels of evidence and grades of recommendation are presented for each statement. The consensus covered all the aspects of TNBC management starting from defining TNBC to the management of metastatic disease and highlighted the rapidly evolving landscape in this field. Consensus was reached in 70% of the statements (35/50). In addition, areas of warranted research were identified to guide future prospective clinical trials.

The first BGICC consensus and recommendations for breast cancer awareness, early detection and risk reduction in low- and middle-income countries and the MENA region.

In low-middle income countries (LMICs) and the Middle East and North Africa (MENA) region, there is an unmet need to establish and improve breast cancer (BC) awareness, early diagnosis and risk reduction programs. During the 12th Breast, Gynecological & Immuno-oncology International Cancer Conference - Egypt 2020, 26 experts from 7 countries worldwide voted to establish the first consensus for BC awareness, early detection and risk reduction in LMICs/MENA region. The panel advised that there is an extreme necessity for a well-developed BC data registries and prospective clinical studies that address alternative modalities/modified BC screening programs in areas of limited resources. The most important recommendations of the panel were: (a) BC awareness campaigns should be promoted to public and all adult age groups; (b) early detection programs should combine geographically distributed mammographic facilities with clinical breast examination (CBE); (c) breast awareness should be encouraged; and (d) intensive surveillance and chemoprevention strategies should be fostered for high-risk women. The panel defined some areas for future clinical research, which included the role of CBE and breast self-examination as an alternative to radiological screening in areas of limited resources, the interval and methodology of BC surveillance in women with increased risk of BC and the use of low dose tamoxifen in BC risk reduction. In LMICs/MENA region, BC awareness and early detection campaigns should take into consideration the specific disease criteria and the socioeconomic status of the target population. The statements with no consensus reached should serve as potential catalyst for future clinical research.

Overexpression of Carbonic Anhydrase IX is a Dismal Prognostic Marker in Breast Carcinoma in Egyptian Patients.

Carbonic anhydrase IX (CAIX) is an enzyme whose expression is very limited in normal tissues and it is highly expressed in various cancers. Therefore, inhibition of CAIX is considered as a promising therapeutic target for the treatment of solid tumors where hypoxic environment has developed. The aim of the current work is to evaluate the immunohistochemical (IHC) expression of CAIX in breast cancer (BC) of Egyptian patients and to investigate the associations of CAIX expression with the standard clinicopathologic features, IHC subtypes of BC, and overall survival. This retrospective study was conducted on 56 archival cases of Egyptian BC patients. Fifty-one of 56 cases (91.1%) showed positive expression of CAIX with cytoplasmic localization, whereas 5 cases (8.9%) showed negative expression. CAIX IHC overexpression is significantly associated with advanced stage and presence of coagulative tumor cell necrosis (P=0.03 and 0.02, respectively). Multivariate analysis revealed Ki67 labeling index and CAIX H-score grouping (P=0.03 and 0.02, respectively) as independent prognostic factors affecting BC patients' overall survival. We concluded that CAIX could play a role in the progression of the studied BC cases. CAIX is a good candidate for target therapy.

Relationship of CK8/18 expression pattern to breast cancer immunohistochemical subtyping in Egyptian patients.

The immunohistochemical (IHC) subtyping of breast cancer can be a useful substitute for gene expression analysis. The aim of this study was to investigate the relationship of CK8/18 to the biology of breast carcinoma (BC) represented by its IHC subtypes. The IHC expression of CK8/18 was correlated with IHC subtypes of BC using ER, PR, HER2/neu, and Ki67 LI (with cutoff 14%). All cases showed CK 8/18 expression in tumour cells with varying degree of intensities; 49/70 cases (70%) showed diffuse cytoplasmic expression (loss of membranous pattern), while 21/70 cases (30%) showed membrano-cytoplasmic pattern. Adjacent non-neoplastic breast lobules showed membrano-cytoplasmic pattern in 58% of cases, which was significantly different from the pattern in invasive cancer (P = 0.002). A loss of membranous pattern in malignant tumours was significantly associated with higher tumour grade (P = 0.02), higher mitotic count (P = 0.03), and negative HER2/neu status (P = 0.04). CK 8/18 H score ranged between 1 and 290 with mean ± SD was 181 ± 70.54. Tumours with lower CK 8/18 H score were in the advanced stage group (P = 0.04). Low CK8/18 H score and loss of membranous pattern were significantly associated with triple negative (TN) subtype as compared with luminal subtype (P = 0.006 and P = 0.026, respectively). In addition, CK8/18 with lost membranous pattern was significantly associated with TN subtype compared with HER2/neu positive subtype (P = 0.001). However, there was no significant difference between luminal A and B subtypes regarding CK8/18 H score or pattern of expression. This study concluded that low CK8/18 H score and loss of membranous pattern of CK8/18 are associated with worse prognostic features and TN subtype.