COVID-19 Impact on Newly Diagnosed Breast Cancers at Regional Cancer Centre, Thiruvananthapuram-An Audit.

Geethu Babu The coronavirus pandemic has created havoc in every aspect of life including cancer care and was declared a pandemic. This audit was conducted to study the impact of the pandemic on diagnosis and treatment of newly diagnosed breast cancer patients at a tertiary cancer center in South India. A total of 1,647 patients who registered at Regional Cancer Centre (RCC), Thiruvananthapuram, Kerala, India for breast cancer during the period April 1, 2020, to September 30, 2020 (COVID-19 period) as well as April 1, 2019, to September 30, 2019 (pre-COVID-19 period) were included in the study. Data regarding the geographic distribution, stage at presentation, time factors for reporting for care, diagnosis, and treatment, referral for care elsewhere were collected and analyzed. The study was approved by the Institutional Review Board. Means and ranges were calculated for continuous type variables, and numbers and percentages for categorical variables. To determine whether there were significant differences between the two groups, independent t -test was used for continuous variables and chi-square test for categorical type of variables. A notable reduction (36%) in newly diagnosed breast cancer patients was seen in 2020 when compared with 2019. There was a significant difference in the geographic distribution of patients in both cohorts ( p = 0.001) and a notable reduction in the number of patients reporting to RCC for treatment from the northern districts of Kerala (81%) and outside Kerala (89.5%). There was no significant difference in the time (in weeks) since symptom onset and reporting to hospital or the clinical stage at diagnosis between the groups. Also, coronavirus disease 2019 (COVID-19) did not seem to negatively impact time intervals between date of registration and pathological diagnosis or start of primary treatment. More patients received neoadjuvant systemic therapy during 2020 compared with 2019, and this difference was statistically significant ( p = 0.004). There was no difference in the type of surgery (breast-conserving surgery vs. modified radical mastectomy). The results demonstrate that COVID-19 did not appear to negatively impact the diagnosis and treatment of newly diagnosed breast cancer patients. However, this is largely attributable to the significantly less number of patients who registered, for whom the departments were able to maintain timely cancer care despite the difficult pandemic times. Significantly more patients received neoadjuvant systemic therapy in 2020.

Molecular subtypes of invasive breast carcinoma of no special type, their correlation with histopathological features, Ki 67 index and tumor budding: A retrospective comparative study.

Context: Tumor budding (TB), poorly differentiated clusters (PDCs), and Ki 67 index are proven adverse prognostic factors in breast carcinoma. Though the relation of Ki 67 index with molecular subtypes of breast carcinoma have been extensively studied, there is very limited information on the role of TB and PDCs. Aims: To grade TB, PDCs, and Ki 67 index and assess histological features and relationship of all these with molecular subtypes of invasive breast carcinoma of no special type. Methods and Material: Retrospective study of 148 cases from 1/1/2019 to 30/12/2019. Division of molecular groups - Luminal A, Luminal B, Her2 neu positive, and triple-negative breast carcinomas (TNBC), and Ki 67 index grades based on St Gallen criteria, intratumoral and peritumoral TB and PDC grades as per the International Tumor Budding Consensus Conference (ITBCC) criteria for colon and correlation between these and other histological features with the molecular subtypes were done. Statistical Analysis: Chi-square test, univariate and multivariate logistic regression models were used. Results: Significant correlation was seen between TB and lymphovascular emboli, Luminal B tumors with high-grade TB and PDCs, Her 2 neu positive and TNBC tumors with low-grade TB, circumscribed tumor margins, tumor necrosis, and Luminal B, Her 2 neu positive and TNBC tumors with larger tumor size and high nuclear grades. Conclusions: TB and PDCs are useful in the prognostication of Luminal A and B tumors when the Ki 67 index values are low/intermediate. Her 2 neu positive and TNBC tumors have a high nuclear grade with necrosis and no association with TB or PDCs.

Microaneurysm turnover is a predictor of diabetic retinopathy progression.

AIM: To analyse retinopathy phenotypes and microaneurysm (MA) turnover in mild non-proliferative diabetic retinopathy (NPDR) as predictors of progression to diabetic central-involved macular oedema (CIMO) in patients with type 2 diabetes mellitus (DM) in two different ethnic populations. METHODS: 205 patients with type 2 DM and mild NPDR were followed in a prospective observational study for 2 years or until development of CIMO, in two centres from different regions of the world. Ophthalmological examinations, including best-corrected visual acuity (BCVA), fundus photography with RetmarkerDR analysis, and optical coherence tomography (OCT), were performed at baseline and 6 12 and 24 months. RESULTS: 158 eyes/patients reached either the study endpoint, CIMO (24) or performed the last study visit (24-month visit) without developing CIMO (134). From the eyes/patients in analysis, 27 eyes (17.1%) progressed to more advanced ETDRS (Early Treatment Diabetic Retinopathy Study) levels: 6 progressed to mild NPDR (level 35), 15 progressed to moderate NPDR (level 43), 5 progressed to moderately severe NPDR (level 47) and 1 progressed to high risk PDR (level 71). Worsening in ETDRS level is associated with phenotype C (p=0.005). From the 130 eyes/patients with a low MA turnover, 18 (13.8%) eyes/patients had an increase in ETDRS level, and from the 19 eyes/patients with a high MA turnover, 9 (47.4%) had an increase in ETDRS level (p<0.001). CONCLUSION: Eyes in the initial stages of diabetic retinopathy show different phenotypes with different risks for progression to CIMO. In phenotype C, MA turnover correlates with ETDRS grading worsening and development of CIMO.

A comparative study of set up variations and bowel volumes in supine versus prone positions of patients treated with external beam radiation for carcinoma rectum.

PURPOSE: A prospective study was undertaken to evaluate the influence of patient positioning on the set up variations to determine the planning target volume (PTV) margins and to evaluate the clinical relevance volume assessment of the small bowel (SB) within the irradiated volume. MATERIALS AND METHODS: During the period of months from December 2011 to April 2012, a computed tomography (CT) scan was done either in supine position or in prone position using a belly board (BB) for 20 consecutive patients. All the patients had histologically proven rectal cancer and received either post- or pre-operative pelvic irradiation. Using a three-dimensional planning system, the dose-volume histogram for SB was defined in each axial CT slice. Total dose was 46-50 Gy (2 Gy/fraction), delivered using the 4-field box technique. The set up variation of the study group was assessed from the data received from the electronic portal imaging device in the linear accelerator. The shift along X, Y, and Z directions were noted. Both systematic and random errors were calculated and using both these values the PTV margin was calculated. RESULTS: The systematic errors of patients treated in the supine position were 0.87 (X-mm), 0.66 (Y-mm), 1.6 (Z-mm) and in the prone position were 1.3 (X-mm), 0.59 (Y-mm), 1.17 (Z-mm). The random errors of patients treated in the supine positions were 1.81 (X-mm), 1.73 (Y-mm), 1.83 (Z-mm) and in prone position were 2.02 (X-mm), 1.21 (Y-mm), 3.05 (Z-mm). The calculated PTV margins in the supine position were 3.45 (X-mm), 2.87 (Y-mm), 5.31 (Z-mm) and in the prone position were 4.91 (X-mm), 2.32 (Y-mm), 5.08 (Z-mm). The mean volume of the peritoneal cavity was 648.65 cm 3 in the prone position and 1197.37 cm 3 in the supine position. CONCLUSION: The prone position using BB device was more effective in reducing irradiated SB volume in rectal cancer patients. There were no significant variations in the daily set up for patients treated in both supine and prone positions.

Different phenotypes of the appearance of the outer plexiform layer on optical coherence tomography.

PURPOSE: To present a selected case series of different phenotypes of the normal outer plexiform layer (OPL) visualized by optical coherence tomography (OCT). METHODS: Five cases were selected to represent the spectrum of appearances of the OPL in this case series. Categorical descriptions of each manifestation were then developed. Additional SD-OCT scans were obtained from a normal volunteer to further support the hypothesis. RESULTS: The inner one-third of the OPL typically appears hyperreflective on OCT, while the outer two-thirds (Henle fiber layer) may have a more varied appearance. Six different phenotypes of Henle fiber layer reflectivity were noted in this series, and classified as: bright, columnar, dentate, delimited, indistinct, and dark. The brightness of the Henle fiber layer appears to depend on the geometric angle between the OCT light beam and the axonal fibers in this portion of the OPL. This angle appears to be a function of the natural orientation of the Henle fiber layer tissue (θN), the existence of subretinal pathology that alters the angle of the neurosensory retina (θ(P)), and the tilt angle of the tissue on the B-scan (θ(T)) due to decentered OCT acquisition. CONCLUSIONS: Since accurate interpretation of the OPL/ONL boundary is of vital importance to study the thickness of ONL, location of cystoid lesions, hyperreflective crescents over drusen, et al., our case series may aid better understanding of the OPL appearance in SD-OCT. In the absence of clear delineation, it may be most correct to refer to indistinct OPL and ONL together as the photoreceptor nuclear axonal complex (PNAC).

Evaluation of the axial location of cystoid spaces in retinal vein occlusion using optical coherence tomography.

PURPOSE: To analyze the axial distribution of intraretinal cystoid changes in patients with retinal vein occlusion (RVO), incorporating a new hypothesis about the optical coherence tomographic boundary between the outer nuclear layer and the outer plexiform layer. METHODS: Data were collected from patients with RVO who underwent spectral domain coherence tomography imaging. For each image set, certified graders evaluated each retinal layer for cystoid macular edema, defined as hyporeflective intraretinal cystoid spaces. Subretinal fluid, if present, was also noted. RESULTS: Forty-eight eyes were evaluated (24 branch RVO, 18 central RVO, 6 hemiretinal vein occlusion). Cystoid macular edema was present in 30.8% of eyes in outer nuclear layer, 77.9 % in outer plexiform layer, 77.9 % in inner nuclear layer, 36.9 % in inner plexiform layer, 48.8 % in ganglion cell layer, and 4.9% in nerve fiber layer. Subretinal fluid was assessed as present in 23.8% of patients. The presence of subretinal fluid correlated most strongly with cystoid changes in the outer nuclear layer (r = 0.514, P = 0.001) but was not significantly correlated with these changes in the superficial retina. CONCLUSION: Use of spectral domain coherence tomography allows precise characterization of the axial location of cystoid spaces in RVO and highlights the frequency of fluid accumulation in the outer plexiform layer and inner nuclear layer. Using updated definitions, cystoid macular edema seems to occur less frequently in the outer nuclear layer, but when it does so, it is often associated with subretinal fluid. Future longitudinal studies, documenting the axial progression of such changes, and their response to treatment, may be of clinical relevance as pharmacotherapeutic options evolve.

Juxtapapillary pigment epithelium detachment observed in asymptomatic participants using optical coherence tomography.

PURPOSE: To use three-dimensional optical coherence tomography (3D-OCT) to assess the prevalence of juxtapapillary retinal pigment epithelial detachments (jPED) in an asymptomatic population. METHODS: Asymptomatic participants (i.e., family members of patients) were prospectively recruited over a 6-month period. Each subject completed a questionnaire prior to the acquisition of two undilated 45° fundus images and two undilated raster 3D-OCT scans (512 × 128) covering the macula and optic nerve from each eye using 3D-OCT-1000. Fundus images were graded for the presence of peripapillary atrophy (PPA), peripapillary pigment (PPP), drusen in the macula, and drusen elsewhere, whereas 3D-OCT scans were assessed for the presence of jPED, drusen in the macula, and drusen elsewhere. RESULTS: In all, 276 eyes from 138 participants were evaluated. Mean participant age was 37.6 years (range: 18-74 years; SD: 15.5 years). In all, 87 jPEDs were detected in 26.1% (36/138) of asymptomatic participants (25 bilateral and 11 unilateral) or 17.0% (47/276) of asymptomatic eyes (23 in the right eye and 24 in the left). The maximum height of jPED was 198.3 ± 53.8 (range: 101.8-376.0) µm. The minimum distance of jPED to the border of optic nerve head (OPN) was 2.6 ± 11.1 (range: 0-61.9) µm. The occurrence of jPEDs or drusen elsewhere by subjects increased statistically with increasing age (P < 0.001, respectively). CONCLUSIONS: In this study, definite jPEDs were observed by OCT in asymptomatic participants, which were not seen with fundus photography. jPEDs were seen more commonly with increasing age, although it is not known whether these lesions represent deposition of drusen-like material or aborted choroidal neovascularization adjacent to the natural break in Bruch's membrane at the optic disc.