Incidence and clinical profile of brain metastasis treated with whole brain radiotherapy in a tertiary hospital in eastern India: A retrospective audit.

Introduction: Management of brain metastases (BM) is witnessing marked advancement worldwide and modern technologies with better outcomes are gradually being adopted in developing countries. However, data regarding current practice in this field is lacking from the Indian subcontinent prompting us to plan the current study. Materials and Methods: A retrospective, single institutional audit was performed on 112 patients with solid tumors metastasizing to the brain treated over the last 4 years at a tertiary care center in eastern India, of which 79 were ultimately evaluable. Demography, patterns of incidence, and overall survival (OS) were determined. Results: The prevalence of BM was 5.65% among all patients with solid tumors. The median age was 55 years with a slight male preponderance. Lung followed by breast were the most common primary subsites. Multiple BM (54%), left-sided (61%), and frontal lobe lesions (54%) were the more common. Metachronous BM was found in 76% of patients. All patients received whole brain radiation therapy (WBRT). The median OS for the entire cohort was 7 months (95% confidence interval [CI]: 4 - 19 months). The median OS for lung and breast primaries were 6.5 and 8 months and for recursive partitioning analysis (RPA) classes I, II, and III the OS were 11.5, 7, and 3 months, respectively. Median OS did not differ by number of or other sites of metastases. Conclusions: The outcomes from our series about BM from solid tumors in patients from eastern Indian are in congruence to those available in the literature. Patients with BM are still largely treated with WBRT in resource-limited settings.

Perception of Oncology Evaluated by Medical Students (P.O.E.M.S)-a Single Institutional Study.

Rising incidence of cancer coupled with lack of structured oncology teaching in the undergraduate (UG) medical curriculum could be detrimental by generating unmet needs in the proper care of cancer patients in the future. To determine the orientation amongst undergraduate medical students regarding Oncology as a specialization and future career option, a cross-sectional, single institutional study was conducted amongst 950 undergraduate students by using an online survey over 2 months. The perception of the subject of Oncology as a career option and the opinion regarding the need for inclusion in the undergraduate curriculum were assessed. Students themselves or those with first-degree relatives as cancer survivors were excluded. A total of 317 responses (33.4%) met the inclusion criteria. Majority were MBBS students from semesters 6 to 9. Even though students ranked the future prospect of Oncology 7.5 on 10, only 6% of the respondents actually wanted to pursue it as a career option stating high mortality amongst cancer patients (63.6%) and emotional burnout (49.7%) as the primary limitations. On a brighter note, better job opportunity due to increasing global cancer incidence (61%) and opportunity for research (42.8%) were thought to be the promising features of the specialization. Majority (51.3%) wanted the inclusion of Oncology in the undergraduate curriculum. Due to limited exposure in the undergraduate curriculum, there is a lack of knowledge and interest regarding the scope of Oncology as a future career option. We therefore advocate revision of the undergraduate curriculum to include Oncology.

Cytogenetic Abnormalities in Multiple Myeloma: Incidence, Prognostic Significance, and Geographic Heterogeneity in Indian and Western Populations.

Multiple myeloma (MM) is a genetically complex and heterogeneous neoplasm in which cytogenetics is a major factor playing an important role in the risk stratification of disease. High-risk MM based upon cytogenetic classification includes primary IGH translocations t(4;14), t(14;16), t(14;20), and secondary progressive aberrations such as gain/amp(1q), 1p deletion, del(17p), and hypodiploidy. Several studies have proved that interphase FISH can detect primary as well as secondary cryptic aberrations very efficiently in lowest 5-10% abnormal plasma cell population. The present large-scale study was undertaken to evaluate the incidence of cytogenetic abnormalities, to analyse the correlation of conventional karyotyping with FISH, and to seek the geographic heterogeneity in the incidence of primary as well as secondary aberrations in our Indian versus Western populations. We conducted prospective studies of 1,104 patients consecutively referred from the primary, secondary, and tertiary oncology centres from all over India. Interphase FISH was performed on isolated plasma cells. Karyotype analysis was done as per ISCN 2016 and 2020. FISH could detect cytogenetic abnormalities in 67.6% of the cases with an incidence of 59% non-hyperdiploidy. The incidence of IGH translocation was 26% versus literature frequency of 40-50% which was mainly due to a low incidence (6%) of t(11;14) in contrast to 15-20% in other series. Additionally, the association of secondary progressive aberrations in the hyperdiploid group rather than the non-hyperdiploid group in our patients is not a common finding. A biallelic inactivation of TP53 as an ultra-high risk factor was detected in old-aged patients. These observations disclose the novel findings and strongly indicate the racial disparity which leads to geographic heterogeneity. In contrast to FISH, conventional karyotyping could detect MM-related aberrations in 50% of cases, of which 44% revealed highly complex karyotypes with common aberrations of chromosome 1q. Overall, FISH was found to be a novel, easy approach with high success rate and capability of detection of all cytogenetic abnormalities that add valid information for the risk stratification of disease. This, in future, in combination with mutation profile and gene expression profile will help in further refinement of disease and identification of actionable targets.

Effect of carboplatin dose capping on survival in recurrent breast, ovary and head and neck cancers: a single institutional retrospective study.

INTRODUCTION: Carboplatin based regimens are an integral part of chemotherapy regimens for recurrent head and neck cancers (rHNC), triple negative breast cancers (rTNBC) and ovarian cancers (rOC). Dose reduction/capping of carboplatin remains a controversial aspect of such regimens in patients with moderate creatinine clearance (50 ml/min to 125 ml/min), especially in resource limited setting. The authors, therefore, looked into the magnitude of difference in outcome this makes in the above mentioned subsites. METHODS: This single institutional retrospective study was performed with a total of 120 patients divided equally into Group A (patients receiving capped dose) and Group B (patients receiving uncapped dose). Further matching was performed with respect to age, sex, body surface area, weight, and primary malignancy subsite and baseline creatinine clearance. Patients in Group A had received 450 mg (for AUC 6 regimens) and 150 mg (for AUC 2 regimens) of carboplatin while patients in Group B received the actual calculated dose of carboplatin determined by the Calvert formula. Median progression free survival (mPFS) and median overall survival (mOS) were the co-primary outcome measures. RESULTS: At a median follow-up of 24 months, compared to Group A, Group B had a higher mPFS and mOS by 4 months (p < .001) and 5.5 months (p < .001), respectively. Statistically significant difference in outcome favouring Group B extends to all primary tumour subsites, with mPFS difference being 3.1 months (rHNC), 5.1 months (rTNBC) and 4.5 months (rOC) and mOS difference being 4.2 months (rHNC), 3 months (rTNBC) and 5.6 months (rOC). It was also found that capping had a statistically significant detriment in distal failure (p = .042) compared to locoregional failure (p = .842). A higher proportion of hematotoxicity was found in Group B, however, it was not statistically significant and well manageable. CONCLUSIONS: Blatant dose capping of carboplatin should be avoided probably with more caution in patients with distant disease recurrence compared to their counterparts with locoregional failure.

Achieving Perfect Hand Washing: an Audit Cycle with Surgical Internees.

The aim of this study is to achieve 100% compliance in surgical hand antisepsis along with identification of areas of worst compliance and efficacies of various interventions best suited to deal with them. This audit was performed over 6 days in a tertiary care hospital in Calcutta, India, with 42 surgical internees. Compliance to ideal hand washing technique was recorded after each attempt with the first attempt as baseline. Video demonstration, personal demonstration by a consultant, and individual instruction were used as subsequent interventions to achieve 100% compliance. The baseline level of compliance was found to be 33.59%. A total of 6 attempts was required to achieve 100% compliance, with the increase in compliance being statistically significant (p = 0.0294). Personal instruction was found to be the most effective intervention. Hand washing technique was the criterion that needed the most number of attempts (n = 6) to rectify. This study found video-based instruction and individual guidance effective teaching tools for surgical hand disinfection and gave novel data regarding the reasons responsible for poor compliance to proper hand washing in a general surgical setting. This study demonstrated the efficiency of audit cycles in the improvement of surgical hand washing and can be the preferred mode of intervention in future studies aimed at achieving ideal hand antisepsis.

Efficacy of Chronomodulated Chemotherapy for Palliation of Hematemesis in Inoperable Gastric Cancer: A Single-Institutional Retrospective Study.

CONTEXT: Aside abdominal discomfort and pain, upper gastrointestinal bleeding (UGIB) significantly disgraces the quality of life (QoL), especially in inoperable gastric cancer patients. Although, in early stages, it is infrequent and often ignored, but in advanced stages, its aggressiveness often deteriorates patient's hemoglobin (Hb) level and performing status. AIM: The aim of this study is to correlate the change in (1) the frequency of episodes of UGIB, (2) its severity in terms of Common Terminology Criteria for Adverse Events (CTCAE) grade for UGIB, and (3) Hb level with the successful completion of successive cycles of palliative chemotherapy where it becomes invariably the only modality to palliate the cancer disease. SETTING AND DESIGN: This single-institutional retrospective observational study included seventy gastric carcinoma patients with a chief complaint of frequent hematemesis. They were divided according to the cause behind inoperability or irresectability: (1) Metastatic disease, (2) locally advanced irresectable disease, (3) uncontrolled comorbidities, (4) poor GC (PGC), and (5) refused to give surgical consent. SUBJECTS AND METHODS: Following baseline evaluation and prechemotherapy workups, patients were subjected to three-weekly chronomodulated modified EOX regimen. Relevant parameters, i.e., (1) average episodes per-week (AEP) score, (2) Hb, and (3) average CTCAE grade value for UGIB were recorded after every cycle. RESULTS: At 12-week follow-up, there was a significant decrease in mean AEP score from baseline (from 2.6691 ± 0.7047 to 1.5033 ± 0.6272) for the entire cohort (P < 0.001). Maximum benefit in terms of mean Hb (increase by 1.0737% above baseline) took place for PGC group (P < 0.001). Mean CTCAE grade value for the entire cohort decreased from baseline by 0.6428, which was statistically significant with a P < 0.001. CONCLUSIONS: PGC group was maximally benefited considering all three parameters. Though surgery defines the mainstay of treatment for gastric carcinoma, yet in inoperable cases, only chronomodulated chemotherapy significantly affects the severity of UGIB and thus may improve QoL.

A Field Fire Ulcer.

Basal cell carcinoma (BCC) is the most common skin cancer, mostly affecting areas of the skin exposed to UV radiation. Though metastasis is rare, the tumour may be locally invasive with a high recurrence rate. Pathophysiology involves neoplastic transformation of the pluripotent cells of the epidermis and follicular epithelium. 'Field fire BCC' is an uncommon type of BCC, showing concomitant crusting, ulceration and scarring which spreads peripherally with a central area of regression.

Stratification of phaco-trabectome surgery results using a glaucoma severity index in a retrospective analysis.

BACKGROUND: To stratify the outcomes of phacoemulsification combined with trabectome surgery using a new glaucoma severity index. METHODS: This is a retrospective, observational cohort study that included open angle glaucoma patients with visually significant cataract that had phacoemulsification combined with trabectome surgery. Exclusion criteria were follow-up less than 12 months, any other surgeries or diagnosis of neovascular or active uveitic glaucoma. Patients were stratified into four groups according to the Glaucoma Index (GI) that incorporated preoperative intraocular pressure (IOP), number of medications and visual field status. The primary outcome measures were IOP reduction and the success rate at 12 months. We examined the relationship between GI group and IOP and medications at one year with a linear regression analysis and survival with log-rank testing. RESULTS: Of 1374 patients, a total of 498 cases with 12 month follow-up were included in the study after applying the exclusion criteria. At one year, IOP of GI groups 1 through 4 was reduced by 2.9 ± 4.4, 3.6 ± 5.0, 3.9 ± 5.3, and 9.2 ± 7.6 mmHg for. Individuals in the next higher GI group had a 1.69 ± 0.2 mmHg larger IOP decrease. The success rate was 98%, 93%, 96% and 88% at one year for GI groups 1 to 4 (p < 0.05). CONCLUSIONS: A substantial IOP reduction was seen in subjects with more advanced glaucoma suggesting that the trabecular meshwork is the primary impediment to outflow and its ablation benefits those eyes relatively more than in mild glaucoma. A larger IOP reduction can be expected in individuals with a higher GI group that indicates a clinically more challenging glaucoma.

Gene transfer to the outflow tract.

Elevated intraocular pressure is the primary cause of open angle glaucoma. Outflow resistance exists within the trabecular meshwork but also at the level of Schlemm's canal and further downstream within the outflow system. Viral vectors allow to take advantage of naturally evolved, highly efficient mechanisms of gene transfer, a process that is termed transduction. They can be produced at biosafety level 2 in the lab using protocols that have evolved considerably over the last 15-20 years. Applied by an intracameral bolus, vectors follow conventional as well as uveoscleral outflow pathways. They may affect other structures in the anterior chamber depending on their transduction kinetics which can vary among species when using the same vector. Not all vectors can express long-term, a desirable feature to address the chronicity of glaucoma. Vectors that integrate into the genome of the target cell can achieve transgene function for the life of the transduced cell but are mutagenic by definition. The most prominent long-term expressing vector systems are based on lentiviruses that are derived from HIV, FIV, or EIAV. Safety considerations make non-primate lentiviral vector systems easier to work with as they are not derived from human pathogens. Non-integrating vectors are subject to degradation and attritional dilution during cell division. Lentiviral vectors have to integrate in order to express while adeno-associated viral vectors (AAV) often persist as intracellular concatemers but may also integrate. Adeno- and herpes viral vectors do not integrate and earlier generation systems might be relatively immunogenic. Nonviral methods of gene transfer are termed transfection with few restrictions of transgene size and type but often a much less efficient gene transfer that is also short-lived. Traditional gene transfer delivers exons while some vectors (lentiviral, herpes and adenoviral) allow transfer of entire genes that include introns. Recent insights have highlighted the role of non-coding RNA, most prominently, siRNA, miRNA and lncRNA. SiRNA is highly specific, miRNA is less specific, while lncRNA uses highly complex mechanisms that involve secondary structures and intergenic, intronic, overlapping, antisense, and bidirectional location. Several promising preclinical studies have targeted the RhoA or the prostaglandin pathway or modified the extracellular matrix. TGF-ß and glaucoma myocilin mutants have been transduced to elevate the intraocular pressure in glaucoma models. Cell based therapies have started to show first promise. Past approaches have focused on the trabecular meshwork and the inner wall of Schlemm's canal while new strategies are concerned with modification of outflow tract elements that are downstream of the trabecular meshwork.

Combined analysis of trabectome and phaco-trabectome outcomes by glaucoma severity.

Prior glaucoma severity staging systems were mostly concerned with visual field function and retinal nerve fiber layer, but did not include intraocular pressure or medications to capture resistance to treatment. We recently introduced a simple index that combines pressure, medications, and visual field damage and applied it to stratify outcomes of trabectome surgery. In the analysis presented here, we combined data of trabectome alone and trabectome with same session cataract surgery to increase testing power and chances of effect discovery. This microincisional glaucoma surgery removes the primary resistance to outflow in glaucoma, the trabecular meshwork, and has been mostly used in mild glaucoma. Traditional glaucoma surgeries have a relatively high complication rate and have been reserved for more advanced disease stages. In the analysis presented here we include our data of trabectome combined with cataract surgery. This is a common practice pattern as both occur in the same age group with increasing frequency. For patients in higher glaucoma index (GI) groups, the intraocular pressure (IOP) reduction was 2.34+/-0.19 mmHg more than those in a GI group one level lower while holding everything else constant. Those who had undergone trabectome combined with phacoemulsification had an IOP reduction that was 1.29+/-0.39 mmHg less compared to those with trabectome alone. No statistically significant difference was found between genders and age groups while holding everything else constant. Hispanics had a 3.81+/-1.08 mmHg greater IOP reduction. Pseudoexfoliation and steroid glaucoma patients had an IOP reduction that was greater by 2.91+/-0.56 and 3.86+/-0.81 mmHg, respectively, than those with primary open angle glaucoma. These results suggest a role for trabectome-mediated ab interno trabeculectomy beyond mild forms of glaucoma. Additionally, the multifactorial glaucoma index demonstrates a role in staging patients when comparing glaucoma surgical modalities.

Steroid-induced glaucoma treated with trabecular ablation in a matched comparison with primary open-angle glaucoma.

BACKGROUND: To evaluate the outcomes of trabectome-mediated ab interno trabeculectomy in patients with steroid-induced glaucoma (SIG). DESIGN: A retrospective, observational cohort study performed in the Department of Ophthalmology, University of Pittsburgh Medical Center. PARTICIPANTS: The data of 60 patients with SIG and 484 controls with primary open-angle glaucoma (POAG) matched by age, gender and glaucoma index were collected from the Trabectome Study Group database. METHODS: Reduction of intraocular pressure (IOP) and medications were compared between POAG and SIG by multivariate regression. Kaplan-Meier was used for survival analysis. Success was defined as IOP ≤21 mmHg and at least 20% IOP reduction from baseline for any two consecutive visits after 3 months without secondary glaucoma surgery. Postoperative IOP and number of medications were compared with baseline in the SIG subgroups by the Wilcoxon test. MAIN OUTCOME MEASURES: Intraocular pressure reduction and 1-year success rate. RESULTS: Patients with SIG had a higher baseline IOP (31.4 ± 10.4 vs. 24.1 ± 7.6 mmHg, P < 0.01) and obtained a greater IOP reduction than controls with POAG (48.4% vs. 31.5%, P < 0.01). Multivariate regression showed that patients with SIG had an IOP reduction of 6.7 ± 1.1 mmHg more than those with POAG. Survival rates at 12 months were comparable at 86% in the SIG group and 85% in the POAG group (P = 0.47). Patients with SIG with a high baseline IOP, younger age and advanced glaucoma experienced a larger IOP drop. CONCLUSION: Trabectome appears to be an effective surgical treatment in reducing IOP for patients with SIG.

Impact of a Glaucoma Severity Index on Results of Trabectome Surgery: Larger Pressure Reduction in More Severe Glaucoma.

PURPOSE: To stratify outcomes of trabectome-mediated ab interno trabeculectomy (AIT) by glaucoma severity using a simple and clinically useful glaucoma index. Based on prior data of trabectome after failed trabeculectomy, we hypothesized that more severe glaucoma might have a relatively more reduced facility compared to mild glaucoma and respond with a larger IOP reduction to trabecular meshwork ablation. METHODS: Patients with primary open angle glaucoma who had undergone AIT without any other same session surgery and without any second eye surgery during the following 12 months were analyzed. Eyes of patients that had less than 12 months follow up or were diagnosed with neovascular glaucoma were excluded. A glaucoma index (GI) was created to capture glaucoma severity based on visual field, number of preoperative medications, and preoperative IOP. Visual field (VF) was separated into 3 categories: mild, moderate, and advanced (assigned 1, 2, and 3 points, respectively). Preoperative number of medications (meds) was divided into 4 categories: ≤1, 2, 3 or ≥4, and assigned with a value of 1 to 4. Baseline IOP (IOP) was divided into 3 categories: <20 mmHg, 20-29 mmHg, and greater than 30 mmHg and assigned with 1 to 3 points. GI was defined as IOP × meds × VF and separated into 4 groups: <6 (Group 1), 6-12 (Group 2), >12-18 (Group 3) and >18 (Group 4). Linear regression was used to determine if there was an association between GI group and IOP reduction after one year or age, gender, race, diagnosis, cup to disc (C/D) ratio, and Shaffer grade. RESULTS: Out of 1340 patients, 843 were included in the analysis. The GI group distribution was GI1 = 164, GI2 = 202, GI3 = 260, and GI4 = 216. Mean IOP reduction after one year was 4.0±5.4, 6.4±5.8, 9.0±7.6, 12.0±8.0 mmHg for GI groups 1 to 4, respectively. Linear regression showed that IOP reduction was associated with GI group after adjusting for age, gender, race, diagnosis, cup to disc ratio, and Shaffer grade. Each GI group increase of 1 was associated with incremental IOP reductions of 2.95±0.29 mmHg. Success rate at 12 months was 90%, 77%, 77%, and 71% for GI groups 1 to 4. The log-rank test suggested significant differences between GI groups. CONCLUSION: A simple glaucoma index, GI, was created to capture glaucoma severity and a relative resistance to treatment. A higher GI was associated with a larger IOP reduction in trabectome surgery. This indicates that there is a role for AIT beyond mild glaucoma and ocular hypertension.

Regionally Discrete Aqueous Humor Outflow Quantification Using Fluorescein Canalograms.

PURPOSE: To visualize and quantify conventional outflow directly in its anatomic location. METHODS: We obtained fluorescein canalograms in six porcine whole eyes and six porcine anterior segment cultures. Eyes were perfused with a constant pressure of 15 mmHg using media containing 0.017 mg/ml fluorescein. Flow patterns were visualized using a stereo dissecting microscope equipped for fluorescent imaging. Images were captured every 30 seconds for 20 minutes for time lapse analysis. Anterior chamber cultures were imaged again on day three of culture. Canalograms were first analyzed for filling time per quadrant. We then wrote a program to automatically compute focal flow fits for each macropixel and to detect convergent perilimbal flow patterns with macropixels grouped into 3 equal-radial width rings around the cornea. A generalized additive model was used to determine fluorescence changes of individual macropixels. RESULTS: The resulting imaging algorithm deployed 1024 macropixels that were fit to determine maximum intensity and time to fill. These individual fits highlighted the focal flow function. In whole eyes, significantly faster flow was seen in the inferonasal (IN) and superonasal (SN) quadrants compared to the superotemporal (ST) and inferotemporal (IT) ones (p<0.05). In anterior chamber cultures, reduced flow on day 1 increased in all quadrants on day 3 except in IT (p<0.05). Perilimbal ring analysis uncovered convergent perilimbal flow. CONCLUSIONS: An algorithm was developed that analyzes regional and circumferential outflow patterns. This algorithm found flow patterns that changed over time and differ in whole eyes and anterior segment cultures.