bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydatid Cyst Migration in Peritoneal Cavity: A Case Report
Authors: Markov Petar , Milev Ilija , Mitevski Aleksandar
Published: February 2020

Introduction. Cystic echinococcosis is a zoonosis caused by the larval stage of Echinococcus granulosus. In most of cases hydatid cysts are found in the liver but in rare cases a migration of the hydatid cyst can occur following rupture of hepatal pericist.Case. A 38 year old female presented with abdominal pain, fatigue, weakness and fever for more than three months. Computed tomography show segment II and IV hepatic per-magna cystic formations with dimensions: No I: 80×60×74 mm and No. II: 70×60×58 mm. Per magna cystic formation in the Douglas space, with dimensions of 93×90×62 mm with clearly expressed mass effect on surrounding organ structures.Discussion. Active hydatid disease may show migration of cysts due to rupture of hepatal pericyst, pressure difference between the anatomic cavities, and by contribution of gravity. Sudden death, anaphylactic shock and dissemination of disease can be seen with cystic content spillage into the peritoneal cavity.Conclusion. Migrated hydatid cysts are very rare parasitic manifestation presenting with symptoms deriving from the neighboring organs. They are diagnosed typically by CT and managed with evacuation of cysts following abdominal exploration. Full abdominal organ ultrasonography, with accent on the liver, should be performed in any case of intraabdominal simple cyst presence.
Numerical model of mass transfer processes using fractional derivatives
Authors: Lopuh Nazariy
Published: February 2020

The article describes the scheme of construction and application of finite element method using Grunwald-Letnikov algorithm. Obtained results make it possible to estimate influence of fractional derivative order in terms of time and space on process of gas filtration in porous medium. Numerical ecperification and analysis performed
Analysis of approaches to mass-transfer modeling n non-stationary mode
Authors: Pyanylo Yaroslav , Pyanylo Galyna
Published: February 2020

A significant number of natural and physical processes are described by differential equations in partial derivatives or systems of differential equations in partial derivatives. Numerical methods have been found to find their solutions. Partial derivatives systems are solved mainly by reducing the order of the system of equations or reducing it to one differential equation. This procedure leads to an increase in the order of the differential equation. There are various restrictions and errors that can lead to additional solutions, boundary conditions for intermediate derivatives, and so on. The work is devoted to the analysis of such situations and ways of exit.
Scattering of an elastic wave by a rigid sphere in a semi-bounded domain
Authors: Selezov Ihor
Published: February 2020

The problem of scattering of plane elastic waves by a rigid sphere near a rigid boundary is considered. This leads to the appearance of multiply re-reflected dilatation and shear waves, which generate strong oscillations of the wave field. The problem for a vector operator of the shear waves is reduced to the definition of scalar functions as a consequence of symmetry. Approximate formulas for the far field and the long-wave Rayleigh approximation are presented. The construction of multiply re-reflected waves by the image method is presented and analyzed. Calculations of the scattered wave fields are plotted in the form of scattering diagrams.
Implementasi Good Governance Di Indonesia
Authors: Handayani Fitria Andalus , Nur Mohamad Ichsana
Published: February 2020

The good governance promoted by the World Bank and UNDP still has no a definitive agreement. This concept is more interpreted as a solution for the realization of effective and efficient government performance. Furthermore, the World Bank as a donor provides assistance to countries to build institutional capacity and training for public officials to improve their competence. The methodology in this study employes descriptive qualitative data collection techniques with literature review. The good governance as a concept reaps criticism in its implementation, one of the criticisms given is the lack of control in the implementation of good governance in governmental actors. Not only that the application of good governance in a country is often forced, even though the principle does not fit into the existing government system, state, culture of society. In Indonesia case in terms of Good Governance implementation, there are still many problems such as bureaucratic reform that is not good, practices of KKN, demands for the application of good governance principles which among them are not in accordance with the local characteristics of the Indonesian people, and the participation is still low.
Dampak Retribusi Jasa Umum Terhadap Pendapatan Asli Daerah Kabupaten Kuningan
Authors: Umam Khaerul , Fadila Yendri Iqbal
Published: February 2020

The target for public service levies is high every year but revenue realization is still far from the target. This shows the existence of fluctuations in revenue from general service levies on Kuningan's own-source revenue (PAD). This study aims to analyze the effect of public service levies on the original income of Kuningan Regency. The research approach used in this study is quantitative with an associative type of research. This research employed saturated sampling types. Techniques from data collection efforts were obtained through field research and library research. Based on the results of the hypothesis test, it appears that public service fees have a positive effect, amounting to 0.514 for an increase in local own-source revenue and in the quite high category. This means that between public service levies and local own-source revenue (PAD) have a fairly high (positive) relationship. If public service levies are higher, it will be followed by higher local own-source revenues.
Analisis Laporan Keuangan Pemerintah Daerah Kabupaten Subang
Authors: Farida Ai Siti , Nugraha Raden Faisal Maulana
Published: February 2020

The existence of regional autonomy requires each region to manage its finances independently. In its financial management, in 2014-2017 Subang District had several problems such as, the largest income was still from the balance fund which was a transfer from the Central Government, low capital expenditure, regional financial growth was at very low value, and inefficient local revenue. This study aims to find out how the financial performance of the Subang Regency Government in 2014-2017 was measured using regional financial ratios. This research is a qualitative descriptive study. In data collection researchers used the method of observation, interviews, and documentation. The type of data used is primary data from the Subang District Government Budget Realization Report 2014-2017. The results of the analysis show that the Financial Performance of the Subang Regency Government in terms of (1) The independence ratio shows that Subang Regency is very independent, because the average is 17.1% (2) The harmony ratio of the Subang Regency government is more likely to prioritize operational expenditure than capital expenditure. Large operating expenses are at an average of 73.75%. While for capital expenditures at an average of 21.75% (3) Regional financial growth ratios can be said to be still very low, because the average is 8.6% (4) The efficiency ratio of local revenue can be said to be inefficient, because the average the efficiency rate is 63.3% (5) The effectiveness ratio of Subang Regency's original income has been effective, because the average effectiveness is above 100% which is 113.8%.
Competencias profesionales en la gestión educativa de los núcleos escolares rurales del estado Táchira
Authors: Camperos-Parada Carmen Odila
Published: February 2020

La preparación académica de los docentes rurales, desde el punto de vista de las competencias, ha sido cuestionada por la pocapreparación, tal vez, o por falta de vocación hacia una gerencia educativa. En el estudio se propone como objetivo general el diseño de unmodelo gerencial de competencias profesionales para la gestión educativa en los Núcleos Escolares Rurales (NER) del Estado Táchira,Venezuela. La metodología asumida se encuentra bajo el paradigma pospositivista. respaldada en la investigación cualitativa con el método deestudio de casos, donde se describen las teorías de acuerdo con los factores que inciden en el desenvolvimiento de las competencias profesionaleseducativas en la realidad del contexto, con una descripción abundante, interpretando detalladamente el fenómeno estudiado para así desarrollarcategorías que sirvieron de soporte en el análisis de resultados. Para la recolección de la información se utilizaron fuentes de carácter teórico,la entrevista y notas de campo, aplicada a un grupo de quince (15) informantes seleccionados de manera intencional. Los datos recogidos seregistraron y sometieron al correspondiente análisis cualitativo (registro, categorización, sistematización e interpretación), pues permite laobtención de constructos teóricos conceptuales con la posibilidad de reivindicar las posibles competencias pérdidas y aportar nuevas tendenciasen cuanto a competencias profesionales de los directores de los NER.
Lineamientos gerenciales para la organización del centro de rehabilitación cardioneuromuscular de Norte de Santander, Colombia.
Authors: Amaya-Mancilla María Alexandra
Published: February 2020

La presente investigación tiene por objetivo realizar un diagnóstico sobre los procesos gerenciales y de atención de la EmpresaSocial del Estado Centro de Rehabilitación Cardioneuromuscular del Norte de Santander, Colombia y en base a ello proponer lineamientosque solventen la problemática detectada. Para ello, se condujo una investigación descriptiva, de campo y de corte transversal. La variable delestudio estuvo dada por la organización de la Empresa Social del Estado Centro de Rehabilitación Cardioneuromuscular, la misma sedimensiona en: acción gerencial, proceso de atención y resultados de la atención. El estudio constó de dos poblaciones: una de profesionalesde la salud y otra de usuarios. Se diseñaron dos cuestionarios de tipo estructurado, con respuestas cerradas y opciones de respuesta basado enuna escala de frecuencia siempre, algunas veces y nunca. La confiabilidad para el instrumento A arrojó un coeficiente de alfa no estandarizadode 0.96 y alfa estandarizado de 0.97, para el cuestionario B arrojó un alfa no estandarizado de 0.99 y estandarizado de 0.95, indicando altaconfiabilidad. Los resultados se analizaron estadísticamente calculando frecuencias y porcentajes por ítem. Los mismos evidenciaron queexisten fallas en la aplicación de la acción gerencial, en el proceso de atención, y en los resultados de la atención. Se concluye en la necesidadde la Organización de la Empresa Social en estudio desde el punto de vista gerencial, a fin de mejorar el proceso de atención y por ende losresultados de la atención. Se recomienda diseñar lineamientos gerenciales para la organización de la Empresa Social en estudio.
Diagnostic value of N-terminal pro-B-type natriuretic peptide in hemodialysis patients
Authors: Sedov D. S. , Fedotov E. A. , Rebrov A. P.
Published: February 2020

Aim. To assess the diagnostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in hemodialysis (HD) patients.

Material and methods. A total of 80 patients over the age of 18 with an end-stage renal disease (ESRD) on HD were included in this study. NT-proBNP serum levels were measured for all patients in addition to traditional clinical and biochemical studies. Transthoracic echocardiography and bioimpedance spectroscopy using the Body Composition Monitor (BCM) device (Fresenius, Germany) were performed for all patients on HD. Patients were divided into two groups depending on the hydration status determined by BCM. Patients were also divided into three groups depending on the ejection fraction (EF) of the left ventricle: HF with reduced EF (less than 40%) (HFrEF), mid-range EF (from 40% to 49%) (HFmrEF), and HF with preserved EF (50% or more) (HFpEF). Three groups of patients were identified according to quartile level of NT-proBNP (<1095 pg/ml (n=20); 1095-4016 pg/ml (n=40); >4016 pg/ml (n=20).

Results. The median of the NT-proBNP serum level was 2114,6 [1095; 4016] pg/ml. A significant increase in the NT-proBNP levels was found in HD patients with hyperhydration (p<0,05). Statistically significant differences were generally found between the concentration of NT-proBNP depending on the LVEF (n=80). However, in pairwise comparisons, significant differences were found only between the groups of patients with HFpEF and HFmrEF (p=0,02); a tendency to differences was revealed when comparing the groups of HFpEF and HFrEF (p=0,07). A proportional increase in the concentration of prohormone to the increase in systolic dysfunction was found while analyzing the median NT-proBNP, both among all patients and after separation into groups depending on the hydration status. A tendency to increase the frequency of new cardiovascular events, systolic and diastolic myocardial dysfunction in group of patients with prohormone increase was revealed.

Conclusion. NT-proBNP serum levels in HD patients are significantly higher than the average population levels. A significant increase in the NT-proBNP levels was found in hemodialysis patients with hyperhydration. NT-proBNP should be used as an additional method for the diagnosis of heart failure on HD, including clarifying of the phenotype of heart failure depending on left ventricle EF. NT-proBNP high levels in patients on HD may be associated with a risk of developing cardiovascular events, systolic and diastolic myocardial dysfunction. It is necessary to use an examination algorithm for the differential diagnosis of heart failure and hyperhydration syndrome during dialysis: clinical examination, bioimpedansometry, transthoracic echocardiography, determination of serum NT-proBNP level.
Validity and reliability of the Russian-language version of the Self-Care of Heart Failure Index in patients with heart failure
Authors: Kartamyscheva E. D. , Lopatin Yu. M.
Published: February 2020

Aim. To assess the validity and reliability of the Russian-language version of The SelfCare of Heart Failure Index (SCHFI, version 6.2) in patients with heart failure (HF).

Material and methods. The translation of the SCHFI (version 6.2) into Russian was performed according to the Brislin’s model. The Russian version of the SCHFI was tested in 128 patients with NYHA class II-IV HF (mean age 63,6Ѓ}8,8 years, 70,3% men). The Cronbach’s alpha, test-retest reliability, construct (confirmatory factor analysis) and concurrent (comparison of the SCHFI and European Heart Failure Self-Care Behavior Scale (EHFScBS_9) results) validities were determined.

Results. The Cronbach’s alpha for the SCHFI scale was 0,74 and characterized sufficient level of test reliability. The test-retest reliability (estimated after 3 months of observation) was 0,81 (p<0,01), which also indicates a sufficient level of reliability. The baseline level of selfcare ability in HF patients according to SCHFI was 136,8Ѓ}40,6 points. The factor analysis confirmed the expediency of dividing the SCHFI into 3 sections: A — self-care maintenance, B — self-care management, C — self-care confidence. Analysis of the concurrent validity of the SCHFI and EHFScBS_9 revealed an inverse correlation between both scales.

Conclusion. The Russian-language version of The Self-Care of Heart Failure Index (version 6.2) is a simple and effective tool for assessing self-care ability in HF patients, and can be used both in clinical trials and in actual clinical practice.
Rationale and design of multicenter prospective observational study of types, GRAde, VariabilITY, associations and prognosis of orthostatic responses in Heart Failure (GRAVITY-HF)
Authors: Shlyakhto E. V. , Villevalde S. V. , Soloveva A. E. , Zvartau N. E. , Sitnikova M. Yu. , Fedorova D. N. , Vinogradova N. G. , Fomin I. V.
Published: February 2020

Heart failure (HF) is one of the leading causes of adult mortality. Increased risk of death determines need for better understanding of the pathophysiological mechanisms, predictive risk stratification models and applicable methods to improve prognosis. One of the unfavorable prognostic factors may be an inadequate hemodynamic response to orthostatic stress. Orthostatic hypotension (OH) is known to be an independent predictor of many cardiovascular diseases, particularly HF, and death. Singlecenter study of HF population revealed that systolic blood pressure within 3-5 minutes after standing up may be a predictor of long-term unfavorable outcomes. Nevertheless, data about OH in patients with HF are limited and inconsistent due to heterogeneity of populations and different methodology in published studies. In this regard, a population-based study of the orthostatic response in patients with HF (stable and decompensated) is needed. The article describes the rationale and design of a multicenter prospective observational study aimed to assess the clinical and prognostic significance of orthostatic responses in HF patients.
What does Multidrug Resistance (MDR) Expression Mean in the Clinic?
Authors: Duhem C. , Ries F. , Dicato M.
Published: February 2020

For 15 years, an overflowing literature has been published about MDR-1 gene expression in tumor cell lines and in cancerous tissues at various stages of disease and treatment (chemotherapy-naive, during treatment and at relapse). However, the clinical significance of this particular feature, if it seemed obvious in the 1980s as a factor responsible for the development of chemoresistance, is currently reconsidered. MDR-1 gene expression seems to be, at least in some instances, a hallmark of tumor cell aggressiveness and of chemoresistance rather than its cause, the mechanisms of which are probably far more complex. The failure of MDR reversal trials might result from the misunderstood or overvalued role of MDR expression in cancer cells rather than from a lack of control of pharmacological parameters.

This review summarizes recent data and hypothesis about the expression of P-170 and its clinical significance in some important human tumor types, suggesting that it should rather be considered in the future as an adverse prognostic factor.
Bone Marrow Transplantation for Cancer—An Update
Authors: Pavletic Z. Steven , Armitage James O.
Published: February 2020

The number of allogeneic and autologous bone marrow transplants continues to grow worldwide. Bone marrow transplantation (BMT) has become standard therapy for many patients with leukemia, lymphoma, multiple myeloma and testicular cancer. Encouraging results of autologous BMT in treating patients with poor-risk breast cancer have led to this approach being tested in nationwide randomized trials. In order to increase availability and efficacy of BMT, other sources of hematopoietic cells are explored for transplantation, such as from HLA-matched unrelated volunteer donors, partially matched related donors, placental/umbilical cord blood and allogeneic peripheral blood. Relapse of original malignancy remains the main obstacle for the success of BMT. Recent clinical investigations have demonstrated that donor-derived peripheral blood leukocytes are effective in inducing remissions in patients with hematological malignancies who relapse after allogeneic BMT. BMT procedures are associated with significant complexity and should be carried out only in transplant units that meet adequate standards. In order to better define the role of BMT in treating cancer, more phase III clinical trials are needed. The future of BMT will depend on further improvements in its efficacy and economic constraints.
The Clinical Development of Paclitaxel: A Successful Collaboration of Academia, Industry and the National Cancer Institute
Authors: Donehower Ross C.
Published: February 2020

The successful development of paclitaxel as an important new antineoplastic agent with the potential to have an impact on a number of human cancers was possible as a result of significant contributions from individuals and groups with diverse areas of interest and expertise.

The advancement of paclitaxel through the preclinical and clinical evaluation which ultimately led to its approval, as well as surmounting the regulatory hurdles which were faced required the close collaboration of individual investigators at academic institutions, the pharmaceutical industry (Bristol-Myers Squibb) and the National Cancer Institute. The latter stages of this developmental effort can be viewed as a prime example of the potential of the Cooperative Research and Development Agreement mechanism to bring novel therapies to patients with serious illnesses in a timely fashion. It is also tangible evidence of the vision and perseverance of a number of members of the Division of Cancer Treatment under the direction of Dr. Bruce Chabner, in whose honor this symposium is given.
All-Trans-Retinoic Acid Pharmacology and Its Impact on the Treatment of Acute Promyelocytic Leukemia
Authors: Adamson Peter C.
Published: February 2020

The approach to the treatment of acute promyelocytic leukemia (APL) has changed dramatically over the past decade and, as a result, the long-term event-free survival for patients has improved significantly. The addition of the vitamin A derivative, all-trans-retinoic acid (ATRA), to treatment regimens has been responsible for this improvement in survival. Although ATRA is a potent remission induction agent in APL, continuous administration of ATRA as a single agent does not maintain patients in remission. Although lower plasma concentrations were initially noted at the time of relapse in patients with APL, subsequent studies have demonstrated that the decline in plasma drug concentrations occurs within one to two weeks of initiation of treatment, and possibly as early as three days. The inability to maintain adequate plasma concentrations of ATRA because of rapid upregulation of its catabolism is an attractive hypothesis to explain the inevitable recurrences in patients with initially responsive disease, but more recent data suggest that this mechanism alone is unlikely to be responsible for drug resistance. Cellular retinoic acid binding proteins (CRABPs) play a critical role in regulating the amount of free retinoic acid capable of reaching and activating nuclear receptors. Recent studies using leukemic blasts obtained at the time of relapse have demonstrated a shift in the ATRA dose-response curve in vitro. In addition, there is an upregulation in the expression of CRABP in leukemic blasts obtained at relapse. These observations suggest that ATRA resistance is not simply an inability to maintain therapeutic plasma concentrations of drug, but rather may be linked to the intracellular regulation of drug. The intricate nature of the homeostatic mechanisms that maintain tight control over retinoids, combined with the multiplicity of retinoid receptors and signaling pathways, leave open the possibility of a yet-to-be-defined mechanism of resistance that is independent of the clinical pharmacology of ATRA.
Difficulties with Fungal Infections in Acute Myelogenous Leukemia Patients: Immune Enhancement Strategies
Authors: Safdar Amar
Published: February 2020

Invasive fungal infection in severely immunosuppressed patients with acute myelogenous leukemia (AML) remains a serious challenge because (a) of the higher rates of non–drug susceptible fungal sinopulmonary disease; (b) despite advances in diagnostic fungal assays, the correct identification of causative organism(s) is difficult, and antifungal drug susceptibility data are seldom available during clinical decision making; and (c) the increasing frequencies of zygomycosis, scedosporiosis, and highly virulent Candida tropicalis infection have undermined the gains attributed to effective anti-Aspergillus drug therapy. Recombinant cytokines, such as recombinant human (rh)GM-CSF and interferon (IFN)-γ, have been explored to augment host antifungal immune responses. These cytokines promote activation and recruitment of granulocyte and mononuclear phagocytic effector cells. Prophylaxis with rhGM-CSF was associated with significantly fewer life-threatening and serious (grade ≥3) infections, especially in older patients undergoing treatment for AML. The limited experience with rhGM-CSF for the treatment of invasive fungal infections in combination with antifungal drug(s) was associated with a favorable outcome, and in contrast to Escherichia coli–derived rhGM-CSF, the new preparation (sargramostim) was well tolerated and rarely associated with serious systemic toxicities. Similarly, IFN-γ has been successfully used in patients with antimicrobial drug–refractory and/or disseminated fungal infection. Most patients tolerate the T-helper type 1 protagonist cytokine without serious adverse events. In difficult-to-treat fungal infections, the addition of cytokines appears to improve outcome and may be considered early in severely immunosuppressed patients with AML.
The Role of Sargramostim (rhGM-CSF) as Immunotherapy
Authors: Waller Edmund K.
Published: February 2020

GM-CSF stimulates the differentiation of hematopoietic progenitors to monocytes and neutrophils, and reduces the risk for febrile neutropenia in cancer patients. GM-CSF also has been shown to induce the differentiation of myeloid dendritic cells (DCs) that promote the development of T-helper type 1 (cellular) immune responses in cognate T cells. This review summarizes some of the immunological effects of GM-CSF relevant to antitumor immunity in cancer patients. GM-CSF has been used to augment the activity of rituximab in patients with follicular lymphoma and to induce autologous antitumor immunity in patients with hormone-refractory prostate cancer. GM-CSF causes upregulation of costimulatory molecule expression on leukemia blasts in vitro, enhancing their ability to present antigen to allogeneic T cells, and, in combination with interferon-α, can induce antitumor immune responses in patients whose acute leukemia has relapsed following allogeneic hematopoietic progenitor cell transplant. Tumor cells engineered to secrete GM-CSF are particularly effective as antitumor vaccines, and the addition of GM-CSF to standard vaccines may increase their effectiveness by recruiting DCs to the site of vaccination. However, a significant limitation in the use of GM-CSF as an immunostimulatory agent is that objective antitumor responses are infrequent, and are often not durable. Effective and durable antitumor immunity will likely require novel methods to eliminate counterregulatory immune responses that limit activation and expansion of cytotoxic T cells with antitumor activity.
Peripheral Blood Stem Cells: A Novel Source for Allogeneic Transplantation
Authors: Körbling Martin
Published: February 2020

Cytokine-mobilized peripheral blood stem cells (PBSCs) are increasingly viewed as a promising alternative to bone marrow (BM)-derived stem cells for allografting in patients with hematologic malignancies. Preliminary results seem to indicate several potential advantages of this approach, such as: A) a more “donor-friendly” and possibly safer stem cell collection procedure; B) the procurement of a significantly larger number of progenitor cells (allowing for graft engineering opportunities); C) a faster hematopoietic engraftment including immunologic reconstitution, and D) comparable rates of acute graft-versus-host disease. Although the superiority of this approach over the traditional BM allografting has not been clearly demonstrated thus far in a randomized trial and many open issues remain, experience is accumulating rapidly, and major transplant centers worldwide seem to have endorsed this procedure. The acceptance of the peripheral blood as the primary source of stem cells for hematopoietic reconstitution in the allogeneic setting is likely to have a profound impact in areas such as graft-versus-leukemia/tumor effect, unrelated donor registries, and transplants. In the following, currently available information on blood stem cell harvesting and allografting is reviewed with the particular focus on donor safety.
Indications and Role of Liver Transplantation for Malignant Tumors
Authors: Pichlmayr Rudolf , Weimann Arved , Tusch Günter , Schlitt Hans J.
Published: February 2020

Purpose. The indication for liver transplantation in malignant liver tumors has been controversial due to disappointing results and shortage of donor organs. The authors evaluated the experience and results of a single center in order to define present indications and selection criteria in hepatobiliary malignancy.

Patients and Methods. Retrospective analysis of 212 patients who underwent liver transplantation for malignant tumors between 1972 and 1995: Primary hepatobiliary tumors: hepatocellular carcinoma, n = 124 (with underlying cirrhosis, n = 86; fibrolamellar subtype, n = 8); intrahepatic bile duct (cholangiocellular) carcinoma, n = 24; proximal bile duct carcinoma, n = 29; other uncommon entities (n = 15); secondary liver tumors: neuroendocrine, n = 11, and nonendocrine, n = 9.

Results. Survival rates in primary liver cancer were correlated to International Union Against Cancer (UICC) tumor stage. For hepatocellular and proximal bile duct carcinoma significantly better outcome was found in UICC-tumor stage I and II versus III and IV. No long-term survival was found after transplantation for intrahepatic bile duct carcinoma, hemangiosarcoma and nonendocrine liver metastases. Comparison of transplant and resected patients with hepatocellular carcinoma stage I and II with underlying cirrhosis showed better survival after transplantation: 1-, 3-, 5-year survival rate of 83.3% versus 76.9%, 75.8% versus 44.0%, 60.6% versus 44.0%, and median survival 96.5 versus 23.2 months. Although this difference was not significant, no patient died from tumor recurrence in the transplant group versus three in the resection group.

Discussion and Conclusions. Patients with malignant tumors can be selected for transplantation with predictable likelihood for long-term survival. According to the present data, liver transplantation can be considered in unresectable UICC-stage II hepatocellular and proximal bile duct carcinoma, the uncommon entities fibrolamellar carcinoma, epithelioid hemangioendothelioma and hepatoblastoma as well as liver metastases from neuroendocrine tumors. UICC-stage III and IV hepatocellular carcinoma as well as intrahepatic bile duct carcinoma, hemangiosarcoma and metastases from nonendocrine tumors should be excluded from transplantation alone. For hepatocellular carcinoma, multimodality treatment protocols have had a proven impact on the prevention of early recurrence and prolongation of survival. There is evidence that liver transplantation in still resectable hepatocellular carcinoma with underlying cirrhosis might be more appropriate in order to cure the cancer-bearing disease.
Fertility and Pregnancy Outcome after Treatment for Cancer in Childhood or Adolescence
Authors: Green Daniel M.
Published: February 2020

Successful therapy for children and adolescents with cancer includes the use of ionizing irradiation and/or chemotherapeutic agents. These may produce DNA damage, resulting in cell death, or the damage may be sublethal. These effects may be expressed in the gonads as sterilization or germ cell DNA damage. Sterilization may be acute, or identified by the occurrence of premature menopause. DNA damage may be identified by an increased risk for chromosomal syndromes, single gene defects or major congenital malformations in the offspring. Management of pediatric and adolescent cancer patients must include recognition of the potential for germ cell injury, counseling of patients regarding strategies for germ cell preservation, and long-term follow-up of the offspring of pediatric and adolescent cancer survivors to determine their increased risk, if any, for adverse pregnancy outcome, genetic disease and cancer.
Screening Childhood Cancer Survivors for Breast Cancer
Authors: Joseph Emmanuella , Clark Robert , Berman Claudia , Miller Marcia , Cox Charles , Greenberg Harvey , Reintgen Douglas S.
Published: February 2020

The development of second primary solid tumors, especially breast neoplasms, is increased among patients who have survived childhood or adolescent malignancies. With the increased long-term survival of patients with pediatric cancer, questions regarding breast cancer screening in this group have been raised. At this time, there are no established guidelines for breast cancer surveillance in this high-risk population. The objective of this review is to summarize the incidence, list additional risk factors for the development of breast cancer, and discuss the benefits of early detection of second primary breast cancers in pediatric cancer survivors. We have devised an algorithm for breast cancer screening in survivors of childhood malignancy. Implications of treatment with radiation and chemotherapy and the influence on prognosis of genetic abnormalities such as p53 mutations are debated.
High-Dose Therapy for Ovarian Carcinoma
Authors: Makatsoris Thomas , Seiden Michael V.
Published: February 2020

Epithelial ovarian carcinomas are successfully treated but seldom cured with standard platinum-based chemotherapy regimens. Investigation continues on the role of high-dose chemotherapy as part of salvage, consolidation and primary induction treatment strategies. Currently, the majority of available clinical studies suggest that modest increases in the dose of platinum in primary induction therapy does not translate into increased survival and comes at the cost of increased toxicity. Interest continues in the use of very high-dose chemotherapy regimens typically with peripheral blood stem cell or bone marrow transplantation. Several series have demonstrated that this approach can provide prolonged disease-free survival in a subset of carefully selected patients with low-volume chemotherapy-sensitive disease. The appropriate application of this expensive and potentially toxic treatment to women with ovarian cancer requires further clinical investigation.
Topoisomerase I Inhibitors
Authors: Ewesuedo Reginald B. , Ratain Mark J.
Published: February 2020

Topoisomerase I inhibitors are a new class of anticancer agents with a mechanism of action aimed at interrupting DNA replication in cancer cells, the result of which is cell death. Most if not all Topoisomerase I inhibitors are derivatives of the plant extract camptothecin. Irinotecan (CPT-11), a semi-synthetic derivative of camptothecin, is approved in the United States for the treatment of colorectal cancer. Ongoing clinical trials with CPT-11 show a 13% to 32% response rate when it is used singly or in combination with other chemotherapeutic agents such as 5-fluorouracil. The major dose-limiting toxicities of CPT-11 are myelosuppression and a dual phase diarrhea. Topotecan is another semi-synthetic analogue of camptothecin. It is approved for use in the United States for the treatment of cisplatin refractory ovarian carcinoma. Current clinical trials suggest antitumor activity against a variety of human tumor types. There is significant interindividual variability in the plasma disposition of this drug. The main dose-limiting toxicity is myelosuppression. There are other derivatives of camptothecin, as well as new formulations of the parent plant extract, that are in various stages of clinical trials. Some of these clinical trials are aimed at increasing the therapeutic benefits of the agents when used singly or in combination with other chemotherapeutic agent(s) or treatment modalities. The dose-limiting toxicity observed in most of these clinical trials is myelosuppression.
Childhood Acute Lymphoblastic Leukemia
Authors: Rubnitz Jeffrey E. , Pui Ching-Hon
Published: February 2020

The cure rate for childhood acute lymphoblastic leukemia (ALL) now exceeds 70%. This success has been achieved in part by improvements in the biologic characterization of newly diagnosed patients. Modern treatment protocols rely on this information to tailor therapy to a patient's risk of relapse. Patients with favorable genetic features, such as hyperdiploidy or the TEL-AML1 fusion, can be treated with conventional antimetabolite-based therapy to minimize long-term side effects. By contrast, extremely high-risk patients, such as infants with MLL gene rearrangements and cases with BCR-ABL fusion and poor early response, are candidates for allogeneic hematopoietic stem cell transplantation in first remission. Future areas of research include the identification of new genetic subgroups of ALL and the development of novel therapies.
Intracranial Germ Cell Tumors
Authors: Packer Roger J. , Cohen Bruce H. , Cooney Kathleen
Published: February 2020

Intracranial germ cell tumors are a heterogeneous group of lesions which occur in children and adults. Within the classification of intracranial germ cell tumors, there are a variety of different tumor types which carry different prognoses. The diagnosis of an intracranial germ cell tumor usually requires histological information, but a subgroup of tumors will secrete specific tumor markers, including α-fetoprotein and β-human chorionic gonadotropin, which may obviate the need for surgical intervention.

The management of intracranial germ cell tumors in both children and adults remains unsettled. Germinomas have a good prognosis, as over 90% of patients can be effectively treated with radiation therapy. The dose and volume of radiation therapy needed for disease control is not well established, and controversy exists concerning the need for whole brain or craniospinal radiation therapy for localized tumors. Germinomas are also chemosensitive and recent reports suggest that the dose and volume of radiation therapy required for disease control can be lessened with the addition of adjuvant chemotherapy.

The outcome for patients with nongerminomatous germ cell tumors is less favorable. Radiation therapy alone will result in disease control in 40%-60% of patients. The addition of chemotherapy to radiation therapy may improve the rate of survival.
Best Practices in the Management of Nonmedical Opioid Use in Patients with Cancer-Related Pain
Authors: Ulker Esad , Del Fabbro Egidio
Published: February 2020

Introduction

Nonmedical opioid use (NMOU) in patients with cancer is a term covering a spectrum of nonprescribed opioid use. The extent to which an individual uses opioids in a nonprescribed manner will influence propensity for adverse effects such as neurotoxicity, substance use disorder, overdose, and death.

Objectives

The objectives of this study were to (A) evaluate current literature regarding management of NMOU in patients with cancer-related pain; (B) provide best practice recommendations based on evidence; and (C) integrate practices derived from the management of noncancer pain, where clinically appropriate or when the oncology literature is limited.

Methods

This study is a narrative review.

Implications

Although harm from NMOU was thought to be rare among oncology patients, about one in five patients with cancer is at risk of adverse outcomes including prolonged opioid use, high opioid doses, and increased health care utilization. The management of NMOU can be challenging because pain is a multidimensional experience encompassing physical, psychological, and spiritual domains. An interdisciplinary team approach is most effective, and management strategies may include (A) education of patients and families; (B) harm reduction, including opioid switching, decreasing the overall daily dose, avoiding concurrent sedative use, and using adjuvant medications for their opioid-sparing potential; (C) managing psychological and spiritual distress with an interdisciplinary team and techniques such as brief motivational interviewing; and (D) risk mitigation by pill counts, frequent clinic visits, and accessing statewide prescription drug monitoring plans.

Conclusion

Although many of the management strategies for NMOU in patients with cancer-related pain are modeled on those for chronic non–cancer-related pain, there is emerging evidence that education and harm-reduction initiatives specifically for cancer-related pain are effective.
A Phase II Study of Pazopanib in Patients with Malignant Pleural Mesothelioma: NCCTG N0623 (Alliance)
Authors: Parikh Kaushal , Mandrekar Sumithra J. , Allen-Ziegler Katie , Esplin Brandt , Tan Angelina D. , Marchello Benjamin , Adjei Alex A. , Molina Julian R.
Published: February 2020

Purpose

Preclinical and clinical data have shown promise in using antiangiogenic agents to treat malignant pleural mesothelioma (MPM). We conducted this phase II study to evaluate the efficacy and toxicity of single-agent pazopanib in patients with MPM.

Materials and Methods

Patients with MPM who had received 0–1 prior chemotherapy regimens were eligible to receive pazopanib at a dose of 800 mg daily. The primary endpoint was progression-free survival rate at 6 months (PFS6), with a preplanned interim analysis for futility. Secondary endpoints included overall survival (OS), PFS, adverse events assessment and clinical benefit (complete response, partial response [PR], and stable disease [SD]).

Results

Thirty-four evaluable patients were enrolled, with a median age of 73 years (49–84). The trial was closed early because of lack of efficacy at the preplanned interim analysis. Only 8 patients (28.6%; 95% confidence interval [CI], 13.2–48.7%) in the first 28 evaluable were progression-free at 6 months. PFS6 was 32.4% (95% CI, 17.4–50.5). There were 2 PR (5.9%) and 16 SD (47.1%). The overall median PFS and OS were 4.2 months (95% CI, 2.0–6.0) and 11.5 months (95% CI: 5.3–18.2), respectively. The median PFS and OS for the previously untreated patients was 5.4 months (95% CI, 2.7–8.5) and 16.6 months (95% CI, 6.6–30.6), respectively; and 2.0 months (95% CI, 1.3–4.2) and 5.0 months (95% CI: 3.0–11.9), respectively, for the previously treated patients. Grade 3 or higher adverse events were observed in 23 patients (67.6%).

Conclusion

Single-agent pazopanib was poorly tolerated in patients with MPM. The primary endpoint of PFS6 was not achieved in the current study. ClinicalTrials.gov  identification number. NCT00459862.

Implications for Practice

Single-agent pazopanib did not meet its endpoint in this phase II trial in malignant mesothelioma. Pazopanib is well tolerated in mesothelioma patients with a manageable toxicity profile. There is a need to better identify signals of angiogenesis that can be targeted in mesothelioma. Encouraging findings in frontline treatment warrant further investigations in combination with chemotherapy or immunotherapy.
Real-World Assessment of Clinical Outcomes Among First-Line Sunitinib Patients with Clear Cell Metastatic Renal Cell Carcinoma (mRCC) by the International mRCC Database Consortium Risk Group
Authors: Savard Marie-France , Wells J. Connor , Graham Jeffrey , Dudani Shaan , Steinharter John A. , McGregor Bradley A. , Donskov Frede , Bjarnason Georg A. , Vaishampayan Ulka N. , Hansen Aaron R. , Iafolla Marco A.J. , Zanotti Giovanni , Huynh Lynn , Chang Rose , Duh Mei S. , Heng Daniel Y.C.
Published: February 2020

Background

International Metastatic Renal Cell Carcinoma (mRCC) Database Consortium (IMDC) risk groups are important when considering therapeutic options for first-line treatment.

Materials and Methods

Adult patients with clear cell mRCC initiating first-line sunitinib between 2010 and 2018 were included in this retrospective database study. Median time to treatment discontinuation (TTD) and overall survival (OS) were estimated using Kaplan-Meier analysis. Outcomes were stratified by IMDC risk groups and evaluated for those in the combined intermediate and poor risk group and separately for those in the intermediate risk group with one versus two risk factors.

Results

Among 1,769 patients treated with first-line sunitinib, 318 (18%) had favorable, 1,031 (58%) had intermediate, and 420 (24%) had poor IMDC risk. Across the three risk groups, patients had similar age, gender, and sunitinib initiation year. Median TTD was 15.0, 8.5, and 4.2 months in the favorable, intermediate, and poor risk groups, respectively, and 7.1 months in the combined intermediate and poor risk group. Median OS was 52.1, 31.5, and 9.8 months in the favorable, intermediate, and poor risk groups, respectively, and 23.2 months in the combined intermediate and poor risk group. Median OS (35.1 vs. 21.9 months) and TTD (10.3 vs. 6.6 months) were significantly different between intermediate risk patients with one versus two risk factors.

Conclusion

This real-world study found a median OS of 52 months for patients with favorable IMDC risk treated with first-line sunitinib, setting a new benchmark on clinical outcomes of clear cell mRCC. Analysis of intermediate risk group by one or two risk factors demonstrated distinct clinical outcomes.

Implications for Practice

This analysis offers a contemporary benchmark for overall survival (median, 52.1 months; 95% confidence interval, 43.4–61.2) among patients with clear cell metastatic renal cell carcinoma who were treated with sunitinib as first-line therapy in a real-world setting and classified as favorable risk according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group classification. This study demonstrates that clinical outcomes differ between IMDC risk groups as well as within the intermediate risk group based on the number of risk factors, thus warranting further consideration of risk group when counseling patients about therapeutic options and designing clinical trials.
Combined Expression of Plasma Thrombospondin-2 and CA19-9 for Diagnosis of Pancreatic Cancer and Distal Cholangiocarcinoma: A Proteome Approach
Authors: Le Large Tessa Y.S. , Meijer Laura L. , Paleckyte Rosita , Boyd Lenka N.C. , Kok Bart , Wurdinger Thomas , Schelfhorst Tim , Piersma Sander R. , Pham Thang V. , van Grieken Nicole C.T. , Zonderhuis Barbara M. , Daams Freek , van Laarhoven Hanneke W.M. , Bijlsma Maarten F. , Jimenez Connie R. , Giovannetti Elisa , Kazemier Geert
Published: February 2020

Background

Minimally invasive diagnostic biomarkers for patients with pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are warranted to facilitate accurate diagnosis. This study identified diagnostic plasma proteins based on proteomics of tumor secretome.

Materials and Methods

Secretome of tumor and normal tissue was collected after resection of PDAC and dCCA. Differentially expressed proteins were measured by mass spectrometry. Selected candidate biomarkers and carbohydrate antigen 19-9 (CA19-9) were validated by enzyme-linked immunosorbent assay in plasma from patients with PDAC (n = 82), dCCA (n = 29), benign disease (BD; n = 30), and healthy donors (HDs; n = 50). Areas under the curve (AUCs) of receiver operator characteristic curves were calculated to determine the discriminative power.

Results

In tumor secretome, 696 discriminatory proteins were identified, including 21 candidate biomarkers. Thrombospondin-2 (THBS2) emerged as promising biomarker. Abundance of THBS2 in plasma from patients with cancer was significantly higher compared to HDs (p < .001, AUC = 0.844). Combined expression of THBS2 and CA19-9 yielded the optimal discriminatory capacity (AUC = 0.952), similarly for early- and late-stage disease (AUC = 0.971 and AUC = 0.911). Remarkably, this combination demonstrated a power similar to CA19-9 to discriminate cancer from BD (AUC = 0.764), and THBS2 provided an additive value in patients with high expression levels of bilirubin.

Conclusion

Our proteome approach identified a promising set of candidate biomarkers. The combined plasma expression of THBS2/CA19-9 is able to accurately distinguish patients with PDAC or dCCA from HD and BD.

Implications for Practice

The combined plasma expression of thrombospondin-2 and carbohydrate antigen 19-9 is able to accurately diagnose patients with pancreatic cancer and distal cholangiocarcinoma. This will facilitate minimally invasive diagnosis for these patients by distinguishing them from healthy individuals and benign diseases.