Venous thromboembolism after major gynecological cancer surgery: an analysis of cause and effect from the experience of a tertiary referral oncologic centre

Background: Patients undergoing extensive gynecological oncologic surgeries are at greater risk for developing deep vein thrombosis and pulmonary embolism than other oncological procedures. The anatomical confinement of vessels, lymphatics, and other structures in the restrictive pelvic space is contributory. We aimed to establish the etiopathogenesis of venous thromboembolism (VTE) with our practical experience. Methods: We present our experience from a tertiary referral oncologic centre in north India in patients with ovarian cancer undergoing cytoreductive surgery (CRS) with or without HIPEC, with a focus on the incidence and etiopathogenesis of deep venous thromboembolism (DVT), including anatomical barriers, restricted movement during surgical dissection, risk stratification and preventive measures. Results: Of 250 patients who underwent cytoreductive surgery (CRS) for ovarian cancer, 124 additionally underwent hyperthermic intraperitoneal chemotherapy (HIPEC). 20 (8%) patients were diagnosed with DVT within 30 days of surgery, and 3 (1.2%) were detected after 30 days. It is the most common significant postoperative morbidity. Conclusions: DVT is the most common postoperative complication in patients undergoing CRS+HIPEC for carcinoma ovary. Anatomical confinement, closed dependant spaces and more significant surgical trauma to pelvic vessels and lymphatics may be the leading cause. Detailed knowledge of anatomy and careful surgical dissection may prevent the development of DVT

An intensive audit on 250 patients of advanced ovarian cancer to improve quality of care in a tertiary referral oncology centre in India

Background: A clinical audit provides the framework to improve the quality of patient care in a systematic way. In this study, we intensively audited our 250 advanced epithelial ovarian cancer (EOC) patients aiming to improve our patient care.Methods: Ambispective study of 250 patients of advanced EOC was done from our prospectively maintained computerized database in the department of surgical oncology, AIIMS, New Delhi from 2013 to 2020.We audited the demographic profile, treatment patterns, perioperative and survival outcomes in different subgroups.Results: In this study, 83.6% stage III and 16.4% stage IV A. There was 62 (24.8%) upfront, 112 (44.8%) interval and 76 (30.4%) secondary group. 126 underwent cytoreductive surgery (CRS) and 124 CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). There was 24.8% early and 8.4% late postop complications. Median follow up 50 months. Overall, the median disease-free survival (DFS) 39 months. PFS was 12 months among 68 patients with recurrence. Attrition rate 4%. In the upfront setting, the median DFS 44 months in CRS only group and DFS not reached (p=0.032) in CRS and HIPEC group still. In the interval setting, the median DFS 39 months in CRS only group and 44 months in CRS and HIPEC group (p=0.06). In recurrent setting, the median DFS 14 months in CRS group and 23 months in CRS and HIPEC group (p=0.02)Conclusions: Audit is an integral part of any clinical practice. It teaches us to improve the quality of care and thereby better outcomes. We recommend 6 monthly clinical audits in any cancer treatment for better outcomes in future

Meigs’ syndrome: how we mistook the diagnosis in a tertiary oncology centre in India; an opinion piece on the surgeon’s responsibility in minimizing the stress of the cancer patient and family

Typical Meigs syndrome may mislead the surgeon as advanced ovarian cancer. CECT can identify the huge ovarian mass, ascites and pleural effusion. Mostly Surgeon’s mind focuses towards the pleural effusion with elevated CA 125 as stage IVa ovarian cancer because of the rarity of this syndrome. But it is Surgeon’s responsibility to diagnosis of Meigs syndrome beforehand to alleviate the pain of the patient and her family. Meigs’ syndrome typically presents with the triad of an ovarian mass, ascites and pleural effusion. The latter two resolved after removal of the mass. As this syndrome is a rare entity, this presentation of an ovarian mass may mislead the surgeon, biasing his or her mind towards advanced ovarian malignancy. Along with these if the CA-125 is also raised, the patient is usually labelled as stage IVa ovarian cancer, causing immense distress to the patient and family. This makes it even more imperative that the surgeon diagnoses this syndrome beforehand to avoid the pain of the patient and family

Studies on Capacity Fade of Spinel-Based Li-Ion Batteries

The performance of Cell-Batt® Li-ion cells using nonstoichiometric spinel as the positive electrode material has been studied at different charging rates. The capacity of the cell was optimized based on varying the charging current and the end potential. Subsequent to this, the capacity fade of these batteries was studied at different charge currents. During cycling, cells were opened at intermittent cycles and extensive material and electrochemical characterization was done on the active material at both electrodes. For all charge currents, the resistance of both the electrodes does not vary significantly with cycling. This result is in contrast with cells made with LiCoO2 cathode where the increase in cathode resistance with cycling causes the fade in capacity. Comparison of cyclic voltammograms of spinel and carbon electrode before and after 800 cycles reveals a decrease in capacity with cycling. Low rate charge-discharge studies confirmed this loss in capacity. The capacity loss was approximately equally distributed between both electrodes. On analyzing the X-ray diffraction patterns of the spinel electrode that were charged and discharged for several cycles, it can be seen that apart from the nonstoichiometric spinel phase, an additional phase slowly starts accumulating with cycling. This is attributed to the formation of defect spinel product -MnO2 according to a chemical reaction, which also leads to MnO dissolution in the electrolyte. Energy dispersive analysis by X-ray of the carbon samples shows an increase in Mn content with cycling. These studies indicate that capacity fade of spinel-based Li-ion cells can be attributed to (i) structural degradation at the cathode and (ii) loss of active materials at both electrodes due to electrolyte oxidation

Differential expression of collectins in human placenta and role in inflammation during spontaneous Labor.

© 2014 Yadav et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Collectins, collagen-containing Ca2+ dependent C-type lectins and a class of secretory proteins including SP-A, SP-D and MBL, are integral to immunomodulation and innate immune defense. In the present study, we aimed to investigate their placental transcript synthesis, labor associated differential expression and localization at feto-maternal interface, and their functional implication in spontaneous labor. The study involved using feto-maternal interface (placental/decidual tissues) from two groups of healthy pregnant women at term (≥37 weeks of gestation), undergoing either elective C-section with no labor ('NLc' group, n = 5), or normal vaginal delivery with spontaneous labor ('SLv' group, n = 5). The immune function of SP-D, on term placental explants, was analyzed for cytokine profile using multiplexed cytokine array. SP-A, SP-D and MBL transcripts were observed in the term placenta. The 'SLv' group showed significant up-regulation of SP-D (p = 0.001), and down-regulation of SP-A (p = 0.005), transcripts and protein compared to the 'NLc' group. Significant increase in 43 kDa and 50 kDa SP-D forms in placental and decidual tissues was associated with the spontaneous labor (p<0.05). In addition, the MMP-9-cleaved form of SP-D (25 kDa) was significantly higher in the placentae of 'SLv' group compared to the 'NLc' group (p = 0.002). Labor associated cytokines IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α and MCP-1 showed significant increase (p<0.05) in a dose dependent manner in the placental explants treated with nSP-D and rhSP-D. In conclusion, the study emphasizes that SP-A and SP-D proteins associate with the spontaneous labor and SP-D plausibly contributes to the pro-inflammatory immune milieu of feto-maternal tissues.Funding provided by BT/PR15227/BRB/10/906/2011) Department of Biotechnology (DBT), Government of India http://dbtindia.nic.in/index.asp (TM) and Indian Council of Medical Research (ICMR) Junior Research Fellowship (JRF)/Senior Research Fellowship (SRF), Government of India, www.icmr.nic.in (AKY)

The Oncoprotein EVI1 and the DNA Methyltransferase Dnmt3 Co-Operate in Binding and De Novo Methylation of Target DNA

EVI1 has pleiotropic functions during murine embryogenesis and its targeted disruption leads to prenatal death by severely affecting the development of virtually all embryonic organs. However, its functions in adult tissues are still unclear. When inappropriately expressed, EVI1 becomes one of the most aggressive oncogenes associated with human hematopoietic and solid cancers. The mechanisms by which EVI1 transforms normal cells are unknown, but we showed recently that EVI1 indirectly upregulates self-renewal and cell-cycling genes by inappropriate methylation of CpG dinucleotides in the regulatory regions of microRNA-124-3 (miR-124-3), leading to the repression of this small gene that controls normal differentiation and cell cycling of somatic cells. We used the regulatory regions of miR-124-3 as a read-out system to investigate how EVI1 induces de novo methylation of DNA. Here we show that EVI1 physically interacts with DNA methyltransferases 3a and 3b (Dnmt3a/b), which are the only de novo DNA methyltransferases identified to date in mouse and man, and that it forms an enzymatically active protein complex that induces de novo DNA methylation in vitro. This protein complex targets and binds to a precise region of miR-124-3 that is necessary for repression of a reporter gene by EVI1. Based on our findings, we propose that in cooperation with Dnmt3a/b EVI1 regulates the methylation of DNA as a sequence-specific mediator of de novo DNA methylation and that inappropriate EVI1 expression contributes to carcinogenesis through improper DNA methylation

Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas : expert recommendations from the World Sarcoma Network

Sarcomas are a heterogeneous group of malignancies with mesenchymal lineage differentiation. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as tissue-agnostic oncogenic drivers has led to new personalized therapies for a subset of patients with sarcoma in the form of tropomyosin receptor kinase (TRK) inhibitors. NTRK gene rearrangements and fusion transcripts can be detected with different molecular pathology techniques, while TRK protein expression can be demonstrated with immunohistochemistry. The rarity and diagnostic complexity of NTRK gene fusions raise a number of questions and challenges for clinicians. To address these challenges, the World Sarcoma Network convened two meetings of expert adult oncologists and pathologists and subsequently developed this article to provide practical guidance on the management of patients with sarcoma harboring NTRK gene fusions. We propose a diagnostic strategy that considers disease stage and histologic and molecular subtypes to facilitate routine testing for TRK expression and subsequent testing for NTRK gene fusions.Peer reviewe

Curcuminoid Binding to Embryonal Carcinoma Cells: Reductive Metabolism, Induction of Apoptosis, Senescence, and Inhibition of Cell Proliferation

Curcumin preparations typically contain a mixture of polyphenols, collectively referred to as curcuminoids. In addition to the primary component curcumin, they also contain smaller amounts of the co-extracted derivatives demethoxycurcumin and bisdemethoxycurcumin. Curcuminoids can be differentially solubilized in serum, which allows for the systematic analysis of concentration-dependent cellular binding, biological effects, and metabolism. Technical grade curcumin was solubilized in fetal calf serum by two alternative methods yielding saturated preparations containing either predominantly curcumin (60%) or bisdemethoxycurcumin (55%). Continual exposure of NT2/D1 cells for 4–6 days to either preparation in cell culture media reduced cell division (1–5 µM), induced senescence (6–7 µM) or comprehensive cell death (8–10 µM) in a concentration-dependent manner. Some of these effects could also be elicited in cells transiently exposed to higher concentrations of curcuminoids (47 µM) for 0.5–4 h. Curcuminoids induced apoptosis by generalized activation of caspases but without nucleosomal fragmentation. The equilibrium binding of serum-solubilized curcuminoids to NT2/D1 cells incubated with increasing amounts of curcuminoid-saturated serum occurred with apparent overall dissociation constants in the 6–10 µM range. However, the presence of excess free serum decreased cellular binding in a hyperbolic manner. Cellular binding was overwhelmingly associated with membrane fractions and bound curcuminoids were metabolized in NT2/D1 cells via a previously unidentified reduction pathway. Both the binding affinities for curcuminoids and their reductive metabolic pathways varied in other cell lines. These results suggest that curcuminoids interact with cellular binding sites, thereby activating signal transduction pathways that initiate a variety of biological responses. The dose-dependent effects of these responses further imply that distinct cellular pathways are sequentially activated and that this activation is dependent on the affinity of curcuminoids for the respective binding sites. Defined serum-solubilized curcuminoids used in cell culture media are thus suitable for further investigating the differential activation of signal transduction pathways