Breast cancer hypofractionated radiotherapy in 2-weeks with 2D technique: 5-year clinical outcomes of a phase 2 trial

BACKGROUND: To report clinical outcomes and late toxicities of a 2-week hypofractionated post-operative loco-regional radiotherapy in patients with breast cancer. MATERIALS AND METHODS: This trial was approved by the Institutional Ethics Committee and registered with gov, no. NCT02460744. Between June 2013 and October 2014, 50 patients with breast cancer, post mastectomy or breast conserving surgery (BCS) were included in this study, of whom 10 had BCS. Patients were planned on a 2-dimentional (2D) simulator with 2 tangential fields and an incident supraclavicular field. Radiotherapy dose was 34 Gy/10#/2 weeks and a sequential boost of 10 Gy/5#/1 wk in BCS patients. The primary endpoint was the rate of acute skin toxicities previously reported. Here, we report the secondary end points of late toxicities, cosmesis, local recurrence, disease-free survival (DFS) and overall survival (OS). Late skin toxicities were recorded according to the Radiotherapy and Oncology Group (RTOG) scoring criteria. Cosmetic outcomes were assessed using the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/RTOG breast cosmesis and the Late Effects Normal Tissue/Subjective Objective Management Analytic (LENT/SOMA) scales for the breast and chest wall, respectively. Kaplan-Meier estimates of DFS and OS were calculated, and 5-year DFS and OS rates (with approximate 95% CIs) were estimated. RESULTS: Late grade ≥ 2 chest wall induration, hypopigmentation and subcutaneous fibrosis were seen in 3 (6%), 3 (6%) and 1 (2%) patients, respectively. Chest wall cosmesis was excellent/good in 34 (72%) and fair/bad in 13 (28%) patients. In BCS patients, grade 2 skin induration, subcutaneous fibrosis and edema was observed in 1 patient (11%) each. Cosmesis was excellent/good in 7 (78%) and fair/bad in 2 (22%) patients. Late grade ≥ 2 arm edema, pain and shoulder stiffness were reported by 1 (2%), 2 (4%) and 2 (4%) patients, respectively. No local recurrences were observed. Five patients developed distant metastases (10%). Seven patients died (14%). The 5-year DFS and OS rate was 90% (95% CI: 77–96%) and 88% (95% CI: 75–94%), respectively. CONCLUSION: Hypofractionated radiotherapy in 2 weeks in patients with breast cancer was associated with minimal late toxicity, good cosmetic outcome and excellent local control. This trial may be of relevance for developing countries where resources are limited.

GCM2 Silencing in Parathyroid Adenoma is associated with Promoter Hypermethylation and Gain of Methylation on Histone 3

PURPOSE: Glial cells missing 2 (GCM2), a zinc finger-transcription factor, is essentially required for the development of parathyroid glands. We sought to identify if the epigenetic alterations in the GCM2 transcription are involved in the pathogenesis of sporadic parathyroid adenoma. In addition, we examined the association between promoter methylation and histone modifications with disease indices. EXPERIMENTAL DESIGN: mRNA and protein expression of GCM2 were analyzed by RT-qPCR and immunohistochemistry in 33 adenomatous and 10 control parathyroid tissues. DNA methylation and histone methylation/acetylation of GCM2 promoter were measured by bisulfite sequencing and ChIP-qPCR. Additionally, we investigated the role of epigenetic modifications on GCM2 and DNA methyltransferase 1 (DNMT1) expression in PTH-C1 cells by treating with 5-aza 2\u27deoxycytidine (DAC) and BRD4770 and assessed for GCM2 mRNA and DNMT1 protein levels. RESULTS: mRNA and protein expression of GCM2 were lower in sporadic adenomatous than in control parathyroid tissues. This reduction correlated with hypermethylation (P\u3c0.001) and higher H3K9me3 levels in GCM2 promoter (P\u3c0.04) in adenomas. In PTH-C1 cells, DAC treatment resulted in increased GCM2 transcription and decreased DNMT1 protein expression, while cells treated with the BRD4770 showed reduced H3K9me3 levels but a non-significant change in GCM2 transcription. CONCLUSION: These findings suggest the concurrent association of promoter hypermethylation and higher H3K9me3 with the repression of GCM2 expression in parathyroid adenomas. Treatment with DAC restored GCM2 expression in PTH-C1 cells. Our results showed a possible epigenetic landscape in the tumorigenesis of parathyroid adenoma and also that DAC may be promising avenues of research for parathyroid adenoma therapeutics

An exploration of the causal factors making an online course content popular & engaging

An education system consists of imparting knowledge, assessing the learners, collecting feedback, analysing it, and taking proper measures to improve it. All these measures ultimately improve learner satisfaction which gets reflected in the learner performance and makes the course popular. Due to the corona pandemic, educational institutes and universities have shifted their activities online. In such a scenario, it is challenging to identify a course's popularity and the factors that make it popular. In this work, the authors have performed aspect-based sentiment analysis of learner feedback to identify the essential aspects of creating a popular course. The traditional methods for analysing feedback for sentiment analysis require manual intervention and are tedious. The authors have proposed a framework that identifies learner reviews' aspect level sentiment polarity and selected the significant aspects impacting a course's popularity. Experimental work is conducted over a large-scale real-world education dataset containing around 110 K learner comments (referred to as Educational Dataset now onwards) collected from Coursera1 and learner data from academic institution MSIT2. Different word embeddings viz., FastText, Word2Vec (Word2Vector), GloVe (Global representation of Vectors), and user-created embeddings are used for CNN (Convolution Neural Network) and LSTM (Long Short Term Memory) models. These models are further compared with BERT (Bidirectional Encoder Representation from Transformers), EvoMSA (Evolutionary Multilingual Sentiment Analysis) and ELMo (Embeddings from Language Model) classifiers to find the method that works best for identifying the aspects that impact the popularity of a course. Based on the experimental results over the collected Dataset, BERT based model provides the best results with an accuracy of 94.27

Tuberculosis of gall-bladder mimicking malignancy – a case report

A correct preoperative diagnosis of gall-bladder tuberculosis is exceptionally unusual in the absence of pathognomic features both on clinical presentation and on imaging. Herein we present a case of 50 year female who was operated with a provisional diagnosis of gall-bladder malignancy and was found to have tuberculosis of gall-bladder on histopatholog

Prevalence of non-alcoholic fatty liver disease and hypercholesterolemia in patients with gallstone disease undergoing laparoscopic cholecystectomy

Background: Gallstone disease (GSD) and nonalcoholic fatty liver disease (NAFLD) are connected with a high prevalence in the general population and they share common risk factors for their occurrence. Limited literature with inconsistent results is available, suggesting a potential association between these lifestyle-induced diseases. Liver biopsy is the gold standard for diagnosing NAFLD. The aim of this study was (1) to identify the prevalence of asymptomatic NAFLD or NASH in liver biopsy; (2) to identify the association of hypercholesterolemia with NAFLD in patients undergoing laparoscopic cholecystectomy (LC). Methods: This is a prospective observational study conducted on patients who underwent LC for symptomatic gallstones in the Department of General Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India, from 1st July 2013 to 31st December 2014. All included patients had ultrasonography (USG) and the following parameters tested: serum triglycerides (TG), cholesterol, low density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). A wedge liver biopsy was obtained from free edge of the right liver lobe during LC and all biopsy specimens were analyzed by a single pathologist. Results: Among 101 patients included in the study, dyslipidemia was present in 49.50%. There was no association between NAFLD and serum cholesterol, TG or LDL-C (P, 0.428, 0.848, 0.371 respectively). NAFLD was confirmed in liver biopsy in 21.8% of patients but none had fibrosis or cirrhosis on biopsy. No complications were observed following liver biopsy. Conclusions: Liver biopsy during LC gives an opportunity to diagnose the disease at an early and reversible stage. It is feasible, safe and cost effective

Gruźlica pęcherzyka żółciowego imitująca nowotwór złośliwy – opis przypadku

Niezwykle rzadko udaje się poprawnie przedoperacyjnie rozpoznać gruźlicę pęcherzyka żółciowego przy braku patognomonicznych cech w obrazie klinicznym i badaniach obrazowych. W niniejszej pracy przedstawiono przypadek 50-letniej chorej, którą zoperowano po wstępnym rozpoznaniu nowotworu złośliwego pęcherzyka żółciowego, a następnie w badaniu histopatologicznym stwierdzono gruźlicę pęcherzyka żółcioweg

Częstość występowania niealkoholowej stłuszczeniowej choroby wątroby i hipercholesterolemii u chorych z kamicą pęcherzyka żółciowego poddawanych cholecystektomii laparoskopowej

Wstęp: Kamica żółciowa i niealkoholowa stłuszczeniowa choroba wątroby (NAFLD) często występują w populacji ogólnej i mają wspólne czynniki ryzyka pojawienia się. Dostępne są nieliczne publikacje ze sprzecznymi wynikami sugerującymi potencjalny związek między chorobami związanymi ze stylem życia. Złotym standardem w rozpoznaniu NAFLD pozostaje biopsja wątroby. Cel: Celem badania było: (1) określenie częstości występowania bezobjawowej NAFLD lub NASH w biopsji wątroby, (2) zbadanie związku hipercholesterolemii z NAFLD u pacjentów poddawanych laparoskopowej cholecystektomii (LC). Metody: Przeprowadzono prospektywne badanie obserwacyjne u pacjentów poddanych LC z powodu objawowej kamicy żółciowej w Klinice Chirurgii Ogólnej Podyplomowego Instytutu Edukacji i Nauki w Chandigarh w Indiach od 1 lipca 2013 r. do 31 grudnia 2014 r. U wszystkich osób wykonano: badanie ultrasonograficzne jamy brzusznej, oznaczenie triglicerydów w surowicy (TG), cholesterolu, cholesterolu lipoprotein o niskiej gęstości (LDL-C) i cholesterolu lipoprotein o dużej gęstości. Klinową biopsję wątroby uzyskano z wolnej krawędzi prawego płata wątroby w czasie LC. Wszystkie próbki biopsji były analizowane przez tego samego patomorfologa. Wyniki: Wśród 101 pacjentów objętych badaniem dyslipidemia występowała u 49,5%. Nie stwierdzono związku między NAFLD a stężeniem cholesterolu w surowicy, TG lub LDL-C (odpowiednio p = 0,428; 0,848; 0,371). NAFLD potwierdzono na podstawie biopsji wątroby u 21,8% osób, przy czym u żadnej nie zaobserwowano włóknienia ani marskości tego narządu w bioptacie. Po biopsji wątroby nie wystąpiły powikłania. Wnioski: Biopsja wątroby w czasie LC daje możliwość rozpoznania choroby wątroby na wczesnym i odwracalnym etapie. Badanie to jest: łatwe do wykonania, bezpieczne i ekonomicznie uzasadnione

Hypofractionated radiotherapy in young versus older women with breast cancer: a retrospective study from India

Background: Young women with breast cancer (BC) are not represented in the trials on hypofractionation. In this study we compared outcomes in young patients with BC to their older counterparts treated with hypofractionated radiotherapy (RT) in a regional cancer centre in India. Materials and methods: Between January 1990 to December 2010, women with BC, treated with hypofractionated RT dose of 35–40 Gy/15#/3 weeks were divided into two groups, ≤ 35 years and > 35 years. Outcomes compared were locoregional recurrence rate (LRR), locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), overall survival (OS) and toxicities. LRRFS, DFS and OS were estimated using the Kaplan-Meier method. Results: Of total 2244 patients, 359 were ≤ 35 years of age and 1885 were > 35 years. Patient and disease characteristics were comparable between the two groups, except that comorbidities were significantly higher in the > 35 years age group, more patients aged ≤ 35 years had nodal N3 disease, received chemotherapy and RT to internal mammary nodes and more patients in the > 35 years group received hormonal therapy. Median follow up was 10 years (range 1–30 years). LRR and distant metastases were comparable between the two groups. However, synchronous LRR and distant metastases were significantly higher in the ≤ 35 years group 18 (5.1%) as compared to the > 35 years group 39 (2.1%) with p = 0.018. Estimated 10-year LRRFS, DFS and OS were 92% vs. 94% (p = 0.95), 68% vs. 73%(p = 0.058) and 78% vs. 76% (p = 0.10) in ≤ 35 years and > 35 years, respectively. OS for stage 1 was comparable between the two groups. However, for stage 2 and 3 it was 77% vs. 82%(p = 0.048) and 53% vs. 62% (p = 0.045) in the ≤ 35 years and > 35 years group, respectively. Acute and late toxicity were similar in the two groups. Conclusion: Young BC patients had higher LRR and distant metastases. LRRFS, DFS and toxicities were comparable between the two groups. However, OS was poorer in young BC patients with stage 2 and 3 disease