Chemotherapeutic Management Research Articles

Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of chemotherapeutic management and antiangiogenic treatment of newly diagnosed glioblastoma in adults.

What is the role of temozolomide in the management of adult patients (aged 65 and under) with newly diagnosed glioblastoma? These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. Level I: Concurrent and post-irradiation Temozolomide (TMZ) in combination with radiotherapy and post-radiotherapy as described by Stupp et al. is recommended to improve both PFS and OS in adult patients with newly diagnosed GBM. There is no evidence that alterations in the dosing regimen have additional beneficial effect. Is there benefit to adjuvant temozolomide treatment in elderly patients (> 65years old?). These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. Level III: Adjuvant TMZ treatment is suggested as a treatment option to improve PFS and OS in adult patients (over 70years of age) with newly diagnosed GBM. What is the role of local regional chemotherapy with BCNU biodegradable polymeric wafers in adult patients with newly diagnosed glioblastoma? These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. Level III: There is insufficient evidence for the use of BCNU wafers following resection in patients with newly diagnosed glioblastoma who undergo the Stupp protocol after surgery. Further studies of higher quality are suggested to understand the role of BCNU wafer and other locoregional therapy in the setting of Stupp Protocol. What is the role of bevacizumab in the adult patient with newly diagnosed glioblastoma? These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. Level I: Bevacizumab in general is not recommended in the initial treatment of adult patients with newly diagnosed GBM. It continues to be strongly recommended that patients with newly diagnosed GBM be enrolled in properly designed clinical trials to assess the benefit of novel chemotherapeutic agents compared to standard therapy.

Chemo-Therapeutic Management of An Acute Abscess in a Male Asian Elephant (Elephas maximus)

A 40-year-old male Asian elephant was presented to the Veterinary Polyclinic, North Paravur with right pelvic limb lameness and a swelling in the right ilial region, which had developed after darting one month previously. The swelling was diagnosed as a unilateral acute abscess, which was lanced, drained and lavaged. Topical treatments, systemic antibiotic therapy and an analgesic were administered, and the animal made an uneventful recovery.

Identification of key genes for guiding chemotherapeutic management in ovarian cancer using translational bioinformatics

The emergence of resistance to chemotherapy drugs in patients with ovarian cancer is still the main cause of low survival rates. The present study aimed to identify key genes that may provide treatment guidance to reduce the incidence of drug resistance in patients with ovarian cancer. Original data of chemotherapy sensitivity and chemoresistance of ovarian cancer were obtained from the Gene Expression Omnibus dataset GSE73935. Differentially expressed genes (DEGs) between sensitive and resistant ovarian cancer cell lines were screened by Empirical Bayes methods. Overlapping DEGs between four chemoresistant groups were identified by Venn map analysis. Protein-protein interaction networks were also constructed, and hub genes were identified. The hub genes were verified by in vitro experiments as well as The Cancer Genome Atlas data. Results from the present study identified eight important genes that may guide treatment decisions regarding chemotherapy regimens for ovarian cancer, including epidermal growth factor-like repeats and discoidin I-like domains 3, NRAS proto-oncogene, hyaluronan and proteoglycan link protein 1, activated protein C receptor, CD53, cyclin-dependent kinase inhibitor 2A, insulin-like growth factor 1 receptor and roundabout guidance receptor 2 genes. Their expressions were found to have an impact on the prognosis of different treatment groups (cisplatin, paclitaxel, cisplatin + paclitaxel, cisplatin + doxorubicin and cisplatin + topotecan). The results indicated that these genes may minimise the occurrence of ovarian cancer drug resistance and may provide effective treatment options for patients with ovarian cancer.

Testicular Lymphoma: A Rare Entity

Testicular malignancy in old age men should be thoroughly studied because of low rate of incidence. Incidence of testicular lymphomas have been shown to be nearly 9% among all testicular malignancies and 1-2% of all lymphomas found in human body. The most common hisopathological pattern among lymphomas is B-cell type and of these diffuse large B-cell subtype is commonest; however, less commonly, Burkitt’s lymphoma, anaplastic lymphoma or Hodgkin’s lymphoma may primarily involve the testis. Testicular lymphoma is rare whether as a primary or as a secondary origin. Diffuse Large B-Cell Lymphomas (DLBCL) is the most common histopathological type if primary in origin; however aggressive patterns like, Burkitt’s lymphoma, are more common when there is secondary involvement of testis. Stage of the lymphoma (Ann Arbor staging) determines the prognosis of the disease. Other prognostic factors include presence of B symptoms and International Prognostic Index (IPI) score, involvement of spermatic cord and other testis. Immunohistochemistry should be done after histopathological diagnosis for effective treatment of variants of testicular lymphoma. High inguinal orchiectomy along with chemotherapy with or without radiotherapy is current treatment of choice for these tumours. In this article, the case of testicular lymphoma is presented in a 61-year-old male patient, clinical presentation, investigations and surgical and chemotherapeutic management with discussion with respect to previous clinical studies. In this case report, patient presented with swelling of left scrotum for which he underwent the radiological and biochemical investigations. He was further planned for frozen section biopsy. The histopathological and immunohistochemical analysis was suggestive of DLBCL, as final diagnosis.

EGCG maintained Nrf2-mediated redox homeostasis and minimized etoposide resistance in lung cancer cells

Abstract Lung adenocarcinomas exhibit chemoresistance mostly due to deregulation of nuclear factor erythroid-derived 2-like 2 (Nrf2). Epigallocatechin gallate (EGCG), was investigated for altering Nrf2 mediated etoposide resistance in different lung adenocarcinoma cells. In A549, EGCG downregulated nuclear Nrf2 by upregulating the nuclear localization of Keap1 whereas in NCIH23, EGCG augmented Nrf2 by reducing Keap1. In Keap-1 independent mode EGCG increased p53, and decreased p21, in A549 but in NCIH23 vice versa was observed. EGCG enhanced retinoid X receptor (RXR) in both A549 and NCIH23 but retinoid acid receptor (RAR) was aggravated in A549 and suppressed in NCIH23. Though the direction of Nrf2 regulation was opposite in two cell lines, optimum level of Nrf2 was maintained which increased responsiveness towards etoposide. EGCG sensitized/potentiated lung adenocarcinoma cells towards chemotherapy by inducing G2/M arrest and suppressing the multi-drug resistance. Thus, EGCG might have a novel implication in chemotherapeutic management of lung cancer cells.

Trastuzumab in the Treatment of Pregnant Breast Cancer Patients - an Overview of the Literature.

Breast cancer is one of the most common malignancies which appear during pregnancy. Since women are increasingly not giving birth until they are at a more advanced age, it can be assumed that the incidence of pregnancy-related breast cancers will continue to increase in the future. Because of pregnancy-induced changes and conservative diagnosis, these carcinomas are frequently not detected until they are at an advanced stage and thus generally require systemic adjuvant therapy. The available data on optimal chemotherapeutic management are limited. Particularly for the use of the target agent trastuzumab which could crucially contribute to improving the prognosis in the therapy of HER2-overexpressing breast cancer in non-pregnant women, there is a lack of definitive information regarding the profile of action and safety in pregnancy as well as with regard to any long-term effects on the child. Thirty-eight pregnancies on trastuzumab for the treatment of breast cancer were able to be analysed in the literature currently available. Information can be gained from this and conclusions can be drawn which can individualise and decisively improve therapeutic options in the future for the pregnant breast cancer patient.

Chemotherapeutic Management of Hemangiosarcoma in Canines – An Update

Chemotherapeutic Management of Hemangiosarcoma in Canines – An Update

Thymoquinone‐induced antitumor and apoptosis in human lung adenocarcinoma cells

Lung cancer has been associated with the highest cancer-associated mortality rate in the world. Chemotherapeutic management of cancer necessitates introducing new promising agents. Plants represent a rich source of new antineoplastic and chemotherapeutic agents. Thymoquinone (TQ), the main constituent of Nigella sativa (black seed or black cumin), has shown potent antioxidant and anti-inflammatory activities so far. The purpose of the current study was to evaluate the antineoplastic potential of TQ and their underlying mechanisms in A549 cells (human lung cancer cell line). The A549 cells were treated with the different concentrations of TQ for three following days. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Necrosis and apoptosis were assessed by fluorescence-activated cell sorter analysis through propidium iodide and annexin V staining and also by assessing caspase-3 and -9 activation. DNA fragmentation was monitored by gel electrophoresis. TQ decreased the viability and increased apoptotic cell death in A549 human lung tumor cells. TQ treatment significantly elevated the Bax/ Bcl-2 ratio in the lung cancer cells. TQ also upregulated p53 expression, another apoptotic modulator in A549 cancer cells. TQ also activated caspase-dependent apoptosis by the activation of caspases-3 and -9. Our results proposed that TQ may be a potential new therapeutic agent for the management of lung cancer. TQ promoted apoptosis in A546 lung cancer cells by the activation of p53 and caspase cascade dependent pathways.

Reengineering Critical Laboratory Testing for Timely Chemotherapeutic Management.

Delivery of cytotoxic therapy is a complex multifaceted process that involves harmonized collaboration between all systems involved. Optimizing laboratory turnaround time (TAT) ensures timely delivery of chemotherapy, which potentially translates into improved patient outcomes and satisfaction. In this study, we aimed to reduce the laboratory TAT for key laboratory tests to optimize the timely administration of chemotherapy. TAT data for complete blood count (CBC) and comprehensive metabolic panel (CMP) included specimen collection to receipt (Col-Rcv), specimen receipt to result release (Rcv-Res), and the overall TAT from specimen collection to result release (Col-Res). Work flows were reconfigured to transport CBC specimens directly to the hematology laboratory after collection and to treat all CMP samples from chemotherapy clinics as urgent [i.e., shortest turnaround time (STAT)]. From the CMP, total bilirubin and creatinine-the 2 key analytes for liver and renal toxicity assessment before chemotherapy drug administration-were analyzed on ABL 800 whole blood analyzers to further improve the laboratory TAT. CBC showed a significant reduction in the median (Col-Res) TAT to 16 min (P < 0.0001). For CMP, by processing all specimens as STAT samples, the median (Col-Res) TAT was reduced from 74 min to 54 min (P < 0.0001), and it was further reduced to 9 min (P < 0.0001) for total bilirubin and creatinine. Careful work flow analysis and reengineering of preanalytical and analytical process for key laboratory tests significantly reduced median overall TAT to <20 min, which helped facilitate more timely delivery of chemotherapy, without necessitating the construction of a satellite laboratory.

Chemotherapeutic Management in a Labrador Retriever with Cutaneous Nonepitheliotropic B-cell Lymphoma

Chemotherapeutic Management in a Labrador Retriever with Cutaneous Nonepitheliotropic B-cell Lymphoma

Cost-effectiveness of newer anti-emetics in the prevention of chemotherapy induced nausea and vomiting: a pharmaco-economic study analysis

Background: Chemotherapy induced Nausea and Vomiting (CINV) is one the most common adverse effects associated with chemotherapeutic management of carcinoma breast. Preventing CINV becomes a vital part in treatment of these cancer patients for better compliance. The conventional regimen of newer 5-HT3 receptor antagonist and dexamethasone along with newer agents - Aprepitant, a NK-1 receptor antagonist and a recently approved atypical antipsychotic, Olanzapine have shown better control of CINV. These newer agents are effective but also very expensive.Methods: The study included carcinoma breast patients scheduled for chemotherapy (n = 55 in each group) who either received aprepitant or olanzapine or a combination of both as the anti-emetic regimen. Considering Cost-Effectiveness Analysis (CEA), the cost included was the cost of anti-emetic agents (sponsor’s perspective) and outcome measured as control of nausea and vomiting - as Complete Protection (CP), Complete Response to Best (CRB) and Incomplete Response (IR) for acute (0-24 hours) and delayed (24-120 hours) phases. The cost effectiveness(CE) ratio for emesis and CINV free days were calculated.Results: CP was seen better during the acute period than the delayed period. With Aprepitant, delayed CRB and IR was seen with 13 (23.6%) and 10 (18.2%) subjects. 16 (29.1%) showed IR with Olanzapine during the delayed period.The average number of Emesis and CINV free days were 4.65, 4.51, 4.89 and 3.38, 3.96, 4.15 for the three groups respectively. The cost required to achieve 1 emesis and 1 CINV free day per subject in the 3 groups was INR 351.19, INR 27.20, INR 339.54 and INR 483.36, INR 30.94, INR 400.60 respectively.Conclusions: The newer anti-emetic even though being expensive at cost, pharmacoeconomically provide better outcomes and seem to have better control rates than the conventional regimen.

Geographical Distribution of Visceral Leishmaniasis Among Children in Dhamar Governorate, Yemen

This is a retrospective study to describe the geographical distribution of <i>visceral leishmaniasis</i> among children in Dhamar governorate, Yemen and to assess the outcomes of the chemotherapeutic management. It was conducted at Al -Wahdah University Hospital, Mabar, Dhamar governorate from April 2015 to March 2016. The study population were all the patients admitted to the hospital having the disease and the data sourced from the patients ‘charts using a performa sheet. Fifty-seven pediatric patients with confirmed <i>visceral leishmaniasis</i> were registered during the study period. The mean age was 3.51±2.4 years and all cases were from Dhamar governorate. All cases presented with fever and splenomegaly. All children were severely anemic and the mean haemoglobin concentration was (6.51±2.82 g/dl). The mean duration of symptoms prior to admission was 98.28±10.6 days and the mean hospital stay was 22.07±15.3 days. The cure rate after hospital management was 94.7%. Death had occurred in 3 cases (5.2%) mostly seen among younger age, and with prolonged illness prior to hospitalization. This study confirmed the presence of VL cases in Dhamar governorate, most frequently affected children below four years of age with excellent response to chemotherapeutic drug. The extension of <i>visceral leishmaniasis</i> infection to involve the highest central regions indicates that the disease tend to spread to other unusual parts of the country. Such a new distribution combined with lack of vital recording and reporting make the efforts to approximate the figure of true incidence difficult.

Inhibitory growth evaluation and apoptosis induction in MCF-7 cancer cells by new 5-aryl-2-butylthio-1,3,4-oxadiazole derivatives.

Cancer has become one of the global health issues and it is the life-threatening disease characterized by unrestrained growth of cells. Despite various advances being adopted by chemotherapeutic management, the use of the current anticancer drugs such as Doxorubicin, Asparginase, Methotrexate, Vincristine remains limited due to high toxicity, side effects and developing drug resistance. Apoptosis is a crucial cellular process and improper regulation of apoptotic signaling pathways may lead to cancer formation. Subsequently, the synthesis of effective chemotherapeutic agents that can induce apoptosis in tumor cell has emerged as a significant approach in cancer drug discovery. The goal of this work is to develop a potential antitumor agent exerting significant inhibitory effects on cancer cell and low cytotoxicity, for which we focused on the structural features of 1,3,4-oxadiazoles as it a privileged scaffold in modern medicinal chemistry and have the ability to inhibit growth factors, enzymes and kinases potentially involved in the attainment of cellular immortality and carcinogenesis. In vitro MTT screening assay showed the compound 5-aminophenyl-2-butylthio-1,3,4-oxadiazole (5e) showing the highest inhibitory effect against MCF-7 cancer cell with IC50 value 10.05±1.08µM while it is much safer and less toxic on normal cell line (HEK-293). The dose-dependent treatment of MCF-7 cells with 5e resulted in inhibition of cell migration in the wound healing assay. The flow-cytometry analysis showed the cells arrested in G0/G1 phase of the cell cycle. Compound 5e induced apoptosis of MCF-7 cells was characterized using DAPI staining and Annexin V-PE/7-AAD dual binding assay. Reduction of NBT by compound 5e showed a reduced generation of ROS. Western blotting studies showed high activation of apoptotic protein Caspase3 and decrease in expression of anti-apoptotic protein BCL-2. Based on the results of in vitro studies, it could be concluded that compound 5e showed a significant inhibitory growth effect on MCF-7 cells and have the potential to be developed as lead molecule and further structural modifications may result in promising new anticancer agents.

Successful Chemotherapy of Canine Transmissible Venereal Tumor in a Bitch

Transmissible venereal tumor (TVT), also referred to as Sticker’s tumor, venereal granuloma, transmissible venereal sarcoma, infective venereal tumor, and transplantable lymphosarcoma, is a tumor that primarily affects the genitalia of sexually mature dogs, and is usually transmitted during coitus (Rogers, 1997). In India, it is the most common tumor of dogs owing to uncontrolled breeding practices (Singh et al ., 1991). The transmissible nature is suggestive of an infectious etiology; however, no infectious particles have ever been detected within the tumor cells (Rogers, 1997). These tumor cells are not the patient’s own cells transformed into cancer cells. The TVT is a tumor that grafts itself from one dog’s body onto another dog’s body (Richardson, 1981). The present communication reports a case of TVT and its successful chemotherapeutic management in a bitch.

Asn-Gly-Arg-modified polydopamine-coated nanoparticles for dual-targeting therapy of brain glioma in rats.

The blood-brain barrier (BBB) is the major clinical obstacle in the chemotherapeutic management of brain glioma. Here we synthesized a pH-sensitive dual-targeting doxorubicin (DOX) carrier to compromise tumor endothelial cells, enhance BBB transportation, and improve drug accumulation in glioma cells. The drug delivery system was constructed with polydopamine (PDA)-coated mesoporous silica nanoparticles (NPs, MSNs) and the PDA coating was functionalized with Asn-Gly-Arg (NGR), a ligand with specific affinity for cluster of differentiation 13 (CD13). MSN-DOX-PDA-NGR showed a higher intracellular accumulation in primary brain capillary endothelial cells (BCECs) and C6 cells and greater BBB permeability than the non-targeting NPs (MSN-DOX-PDA) did in vitro. Ex vivo and in vivo tests showed that MSN-DOX-PDA-NGR had a higher accumulation in intracranial tumorous tissue than the undecorated NPs did. Furthermore, the antiangiogenesis and antitumor efficacy of MSN-DOX-PDA-NGR were stronger than that of MSN-DOX-PDA. Therefore, these results indicate that the dual-targeting vehicles are potentially useful in brain glioma therapy.

Abstract 2090: Evaluation of the cytotoxic profile of Metformin and Y15 in platinum resistant ovarian cancer cells

Abstract Platinum resistance remains a major challenge in the chemotherapeutic management of ovarian cancer. The anti-diabetic drug metformin has been previously shown to induce cytotoxicity in platinum resistant ovarian cancer cells and overexpression and increased phosphorylation of a tyrosine kinase called Focal Adhesion Kinase (FAK) has been implicated in the development of this platinum resistance. Therefore, in the present study we evaluated the combined cytotoxic efficacy of Metformin and the focal adhesion kinase inhibitor 1,2,4,5-Benzenetetraamine tetrahydrochloride (Y15) in platinum resistant OVCAR3 ovarian cancer cells. Cells were initially treated with concentrations of Y15 ranging from 10-100 μM, and metformin from 10-100mM to determine 1C50 values. Subsequently, cells were treated with Y15 (80 μM) and metformin (26mM) alone and in combination. All treatments were triplicated with duration of 24hrs and control cells exposed to media only. The cytotoxic profile of each treatment was assessed using the automated trypan blue assay. DNA fragmentation and poly ADP ribose polymerase (PARP) cleavage assays were performed to evaluate the mechanism of cell death and we further evaluated the expression of phosphorylated FAK, p53 and p21 in response to treatments using western blot. Y15 alone produced 48% cell death. In combination, Y15 significantly increased the cytotoxic efficacy of metformin by 22%, when compared to the metformin only treatment. Cell death by apoptosis was confirmed by PARP cleavage and the presence of DNA fragments in Y15, metformin, and metformin +Y15 treatment groups. The Metformin +Y15 combination significantly downregulated the expression of phosphorylated FAK when compared to the individual treatments and control and this confirmed reduced FAK activity. Reduced FAK auto phosphorylation also correlated with increased expression of p53 AND p21 in metformin and Y15 treatment groups. Our findings show that Y15 significantly enhances the cytotoxic profile of metformin in platinum resistant OVCAR-3 cells. Furthermore, a FAK dependent apoptotic mechanism appears to underlie the cytotoxic effect of metformin as well as Y15 as both drugs significantly reduced the phosphorylation of FAK alone, and in combination. Reduced FAK activity also correlated with increased p53 and p21 expression. This study is the first to report a FAK dependent cytotoxic mechanism of metformin in ovarian cancer and in further work we will evaluate the mechanisms why which metformin cooperates with Y15 to inhibit FAK activity in platinum resistant ovarian cancer. Citation Format: Arkene S. Levy, Zara Khan, Samuel Batko, Keerthi Thallapureddy, Robert Smith, Thanigaivelan Kanagasabai, Julie Torruellas Garcia, Appu Rathinavelu. Evaluation of the cytotoxic profile of Metformin and Y15 in platinum resistant ovarian cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2090.

Abstract A53: Antiproliferative, antiangiogenic and proapoptotic actions qualify Nigella sativa as taxane therapy adjuvant in ovarian cancer

Abstract Taxane {Docetaxel (DTX), Paclitaxel (PTX)} based standard chemotherapeutic management of ovarian cancer faces the limitations of resistant phenotype and systemic toxicity. To explore potential agents for adjuvant drug therapy, ethanolic extract of seeds of medicinal plant-Nigella sativa (NS) and Thymoquinone (THM), an isolated volatile oil from its seeds are investigated here against Human Epithelial Ovarian Cancer cell line (SKOV3). Using SKOV3 cells, grown and maintained under standardised protocols of cell culture, the anti-proliferative effect of DTX, PTX, NS and THM was evaluated individually at 4µM, 4µM, 100µg and 100µM respectively. Combination of DTX(2µM)/PTX(2µM)+NS(50µg)/THM(50µM) were evaluated at sub IC50 for anti-proliferative activity and putative mechanistic basis (IL-8, TNFα, VEGF, Bcl2, Bax). Here, IC50 value of DTX, PTX, NS and THM is reported as 4.7µM, 5.3µM, 71.8µg and 0.11pM, respectively. Cytotoxicity of DTX+NS/THM and PTX+NS/THM was 54.22,59.85, 55.5 and 60.36%, respectively that was greater than either DTX , PTX, NS or THM at 48.24, 47.18, 59.4 and 48.35% respectively. Following 24 hr treatment, DTX, PTX, NS, THM and DTX/PTX+NS/THM significantly induced levels of IL-8 and pro-apoptotic protein Bax, but, reduced secretion of TNF-α, VEGF and anti-apoptotic protein Bcl-2 vs control. Agents that interact synergistically or additively with chemotherapeutic drugs can be used as adjuvants in cancer chemotherapy to act by multi-targeted therapeutic approach so as to reduce dose, side effects and resistance. Cytokines such as IL-8, TNF-α, VEGF are important components of tumor microenvironment and play major role in cancer invasion, angiogenesis and metastasis. Bax and Bcl-2 are proteins of apoptotic pathway that check for cell survival and senescence. Anti-proliferative, anti-angiogenic and pro-apoptotic activities of NS and THM, unequivocally demonstrates their potential as adjuvants for taxane therapy in ovarian cancer. Combination of NS and THM with DTX and PTX stalls SKOV3 growth through IL-8, TNF-α, VEGF and Bax/Bcl-2 mediated pathways. Citation Format: Rajani Mathur, Mukesh Tiwari. Antiproliferative, antiangiogenic and proapoptotic actions qualify Nigella sativa as taxane therapy adjuvant in ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr A53.

Changing Times for the IJHBT.

I welcome you to 2016 with the latest 120-page issue of our journal, up from the 70 pages previously. In this issue too, we maintain our focus on original articles and reviews for the printed journal, and increasingly hope to move towards special online editions for case reports and letters to the Editor. The invited reviews in his issue focus on the old and the new. On one hand, they deliberate on how the advent of genomics and personalized medicine is revolutionizing the way we diagnose and manage hematological malignancies [1, 2]. On the other, they remind us that good medicine is based on astute evaluation of all evidence, be it from fashionable new techniques or from conventional ones that have stood the test of time. In that regard, the diverse monoclonal protein electrophoretic patterns reviewed by Misra et al. [3] reveal myeloma to be as intriguingly heterogeneous a disease at the paraprotein level as it is at the genomic, morphological and clinical levels. As chemotherapeutic management and acute care of hematological malignancies improve across the country, quality-of-life issues are assuming greater importance. In this issue, Kumar et al. [4] investigate growth impairment and short stature among children treated for acute lymphoblastic leukemia, while Rohilla et al. [5] report on obstetric outcomes in women with chronic myelogeneous leukemia. Another tricky management issue is the judicious management of elderly AML or high-risk MDS, and this is addressed by a Turkey study which looks at epigenetic modifiers alone as well as in combination with low-dose cytosine arabinoside in such patients. New technologies often bring with them new and unexpected complications. Among the benign disorders, Dubey et al. [6] investigate how life-saving intra-uterine blood transfusions to Rh-negative fetuses of Rh-positive mothers may carry the risk of inducing additional maternal antibodies against fetal antigens, thereby aggravating Rhisoimmunization. Sen et al. [7] similarly caution that highpressure carbon dioxide insufflation, commonly used in laparoscopic surgeries, may depress natural anticoagulant systems as well as fibrinolysis thus contributing to surgeryassociated thrombophilia. In the midst of these rapidly changing times for hematology in general and the journal in particular, the coming of the New Year offers us an opportunity to pause, reflect and take stock. The entire Editorial Board welcomes your inputs on what you think the IJHBT’s goals for the future should be, and how best can they be realized. Comments, suggestions and letters from readers on published articles and ongoing events are, as always, welcome. Wishing everyone a very happy new year ahead.

Multifractal analysis of tumour microscopic images in the prediction of breast cancer chemotherapy response.

Due to the individual heterogeneity, highly accurate predictors of chemotherapy response in invasive breast cancer are needed for effective chemotherapeutic management. However, predictive molecular determinants for conventional chemotherapy are only emerging and still incorporate a high degree of predictive variability. Based on such pressing need for predictive performance improvement, we explored the value of pre-therapy tumour histology image analysis to predict chemotherapy response. Fractal analysis was applied to hematoxylin/eosin stained archival tissue of diagnostic biopsies derived from 106 patients diagnosed with invasive breast cancer. The tissue was obtained prior to neoadjuvant anthracycline-based chemotherapy and patients were subsequently divided into three groups according to their actual chemotherapy response: partial pathological response (pPR), pathological complete response (pCR) and progressive/stable disease (PD/SD). It was shown that multifractal analysis of breast tumour tissue prior to chemotherapy indeed has the capacity to distinguish between histological images of the different chemotherapy responder groups with accuracies of 91.4% for pPR, 82.9% for pCR and 82.1% for PD/SD. F(α)max was identified as the most important predictive parameter. It represents the maximum of multifractal spectrum f(α), where α is the Hölder's exponent. This is the first study investigating the predictive value of multifractal analysis as a simple and cost-effective tool to predict the chemotherapy response. Improvements in chemotherapy prediction provide clinical benefit by enabling more optimal chemotherapy decisions, thus directly affecting the quality of life and survival.

Primary Ewing’s Sarcoma of Jejunum Presenting as a Small Bowel Obstruction: A Case Report

Introduction: Primary Ewing’s sarcoma/ PNET of the jejunum is a very rare presentation of Ewing sarcoma family of tumors (EFT) of extra-osseous origin. Case reports of duodenal, rectal, and abdominal Ewing’s sarcoma can be found in the literature, but to our knowledge, this is the first case of primary jejunal Ewing’s sarcoma. Case Report: A 48-year-old male with no past medical history presented to an urgent care facility with a 3-day history of constipation, not relieved by laxatives with associated abdominal pain. On physical examination, vital signs were stable, but the patient appeared uncomfortable with mild distention of the abdomen and hypoactive bowel sounds. The patient was prescribed laxatives and referred to a gastroenterologist. Over the course of the week, the patient’s symptoms worsened. An outpatient CT-scan of the abdomen with IV and PO contrast revealed a jejunal intussusception. The patient underwent an exploratory laparotomy revealing a 10-cm jejunal intussusception 12 inches from the ligament of Trietz with a large polyp as a lead point. Gross inspection of the resected specimen showed a fungating, ulcerative, obstructing tumor of the jejunum. Pathology revealed a tumor invading through the muscularis propria into the subserosa. A histological diagnosis was grade 4 PNET/Ewing sarcoma. FISH showed a EWSR1 (22q12) gene rearrangement and CD45 (-) /CD56 (+) cells ruling out hematolymphoid origin. Immunoperoxidase stains revealed CD99 positive marker for Ewing’s sarcoma. Subsequent bone scan and PET-studies failed to demonstrate any osseous primary sources or other sites of metastasis. The patient was referred to oncology for chemotherapy with vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC/IE). Discussion: The majority of Ewing’s sarcoma are predominantly cancers of children and rarely seen after the age of 30. Molecularly, they have variable translocations of EWSR1 gene. Immunohistochemical staining is essential in differentiating amongst the various subtypes. Treatment of localized disease is surgical resection, preferably before chemotherapy with (VDC/IE) based on the IESS-III study. We believe this case is the first described primary jejunal Ewing’s sarcoma, presenting in the gastro-intestinal tract masked by common symptoms in a patient with no family history of malignancy. These tumors carry a poor prognosis regardless of surgical or chemotherapeutic management. It is always beneficial to identify the cause and ascertain the pathological diagnoses for prompt treatment to prevent metastases and improve prognosis of individuals affected by Ewing’s sarcoma.