The role of neuromuscular ultrasound in diagnostics of peripheral neuropathies induced by cytostatic agents or immunotherapies.

A relevant number of cancer patients who receive potentially neurotoxic cytostatic agents develop a chemotherapy-induced peripheral neuropathy over time. Moreover, the increasing use of immunotherapies and targeted agents leads to a raising awareness of treatment-associated peripheral neurotoxicity, e.g., axonal and demyelinating neuropathies such as Guillain-Barré-like syndromes. To date, the differentiation of these phenomena from concurrent neurological co-morbidities or (para-)neoplastic nerve affection as well as their longitudinal monitoring remain challenging. Neuromuscular ultrasound (NMUS) is an established diagnostic tool for peripheral neuropathies. Performed by specialized neurologists, it completes clinical and neurophysiological diagnostics especially in differentiation of axonal and demyelinating neuropathies. No generally approved biomarkers of treatment-induced peripheral neurotoxicity have been established so far. NMUS might significantly extend the repertoire of diagnostic and neuromonitoring methods in this growing patient group in short term. In this article, we present enlargements of the dorsal roots both in cytostatic and in immunotherapy-induced neurotoxicity for the first time. We discuss related literature regarding new integrative applications of NMUS for cancer patients by reference to two representative case studies. Moreover, we demonstrate the integration of NMUS in a diagnostic algorithm for suspected peripheral neurotoxicity independently of a certain cancer treatment regimen emphasizing the emerging potential of NMUS for clinical routine in this interdisciplinary field and prospective clinical trials.

Applications of the Grading Scales for the Detection of Ototoxicity in Children after Treatment of Neuroblastoma and Extracranial Germinal Tumor.

INTRODUCTION: Advances in treatment have resulted in a significant increase in survival rates for patients cured of malignant diseases such as neuroblastoma (NBL) and extracranial germ cell tumor (GCT). NBL is one of the pediatric cancers during which potentially ototoxic cytostatic drugs (cisplatin and carboplatin) are used for treatment. Other cancers include germinal tumors, hepatoblastoma, sarcomas, and brain tumors. Often, this very aggressive treatment has a high risk of causing long-term side effects, including hearing loss. Hence, the present study aimed to evaluate the usefulness of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Brock, Chang, and International Society of Pediatric Oncology (SIOP) Boston scales in terms of detecting the high-frequency nature of hearing loss induced by ototoxic drugs and monitoring hearing status in children after completion of oncological treatment. Additionally, the frequency of hearing loss in children treated for NBL and extracranial GCT was assessed, and the principles of monitoring hearing in these patients were indicated. METHODS: The study group consisted of 78 patients diagnosed with NBL (n = 47) and GCT (n = 31). There were 23 boys and 24 girls in the NBL group, aged 0-16 years, and 21 boys and 10 girls in the GCT group, aged 0-18 years. The control group consisted of 54 patients who had never received oncological treatment, were not taking potentially ototoxic drugs, and appeared socially efficient in the subjective audiological assessment. Audiometric examinations and DP-acoustic otoemission measurements were performed. Additionally, impedance audiometry tests were done to exclude a possible conductive component of the hearing loss. RESULTS: The analysis shows that ototoxicity-induced hearing loss was observed in 13.8-65.5% of children. 75.9% of patients showed hearing loss in the 16 kHz frequency range, and at least 56.8% of patients showed hearing loss in the frequency range above 12.5 kHz. Hearing impairment, relevant to speech understanding, was displayed by more than 40% of children treated for NBL and GCT. CONCLUSIONS: The confirmation of hearing loss in nearly 65% of cases in both patients indicates the necessity to monitor the long-term side effects of anticancer treatment. Acoustic otoemission measurements, the adoption of articulatory indices based on an audiogram, or the use of arbitrary ototoxicity assessment scales such as Brock, Chang, or SIOP Boston are fully justified techniques for studying ototoxicity induced by cytostatic drugs. However, they all require continuous improvement to increase their sensitivity and specificity, especially in the pediatric group.

Evaluation of membrane-destructive processes in rats with induced carcinogenesis of the colon using the cytostatic vincristine.

Background: Every year the number of cases of colorectal cancer increases. Chemotherapy is one of the main methods of treating cancer. However, chemotherapeutic treatment of colorectal cancer is inextricably linked to hepatotoxic reactions. Objective: The aim of this study was to investigate the effect of the cytostatic vincristine on the background of previous enterosorption correction with the drug aut-m in adenocarcinoma of the colon. Material and methods: To simulate carcinogenesis, dimethylhydrazine (DMH) was administered subcutaneously to 77 rats for 30 weeks at a dose of 7.2 mg/kg body weight. After simulation of colon cancer, the animals were intragastricly administered entorosorbent at a dose of 1 ml of suspension (corresponding to 0.2 g of net weight of the drug) per 100 g of body weight of the animal, daily for 21 days. After detoxification therapy, rats with simulated carcinogenesis were administered the daily cytostatic vincristine at a dose of 0.23 mg/kg for 14 days. Results: It was found that prolonged administration of dimethylhydrazine is accompanied by destructive changes in plasma membranes, as evidenced by increased activity of enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and serum urea. Conclusions: The used sorbent aut-m showed an effective effect on reducing the manifestations of cytolytic processes in induced carcinogenesis, as indicated by the normalization of the studied parameters. The cytostatic vincristine, which was used in rats with induced colorectal cancer after enterosorption therapy, did not significantly affect the enhancement of cytolytic processes, which confirms the effectiveness of previous sorption measures under these conditions.

Efectos de la inhalación de vanadio sobre las espermatogonias y calidad seminal en el modelo de ratón in vivo / Effect of vanadium inhalation on spermatogonia and seminal quality in vivo mouse model

El vanadio es un metal de transición que en las últimasdécadas se convirtió en un contaminante ambiental, producto de laquema de los combustibles fósiles. La alteración de los distintosparámetros espermáticos y daño a ADN en células gaméticas se asociacon el aumento de la contaminación ambiental, la interacción con lasespermatogonias probablemente explique estos efectos, debido a queuno de los órganos blancos del vanadio, es el testículo. El objetivo delestudio fue analizar los efectos citostático y citotóxico sobre lasespermatogonias y espermatozoides de ratones tratados de forma agudapor vía aérea con pentóxido de vanadio (V2O5), en distintasconcentraciones (0.0, 0.02, 0.04 y 0.08 M). Consistió en evaluar lasproporciones de los diferentes tipos de espermatogonias A0(Indiferenciadas), en Renovación y, diferenciadas (Tipo B) en elmodelo de ratón in vivo. Y la estimación de los valores de densidad ymorfología espermáticas, para establecer la calidad seminal. Losresultados muestran que la exposición a V2O5 aumenta la proliferaciónde las espermatogonias en Renovación, y las B disminuyen, en la dosisalta; la densidad espermática y la morfología normal disminuyeronsignificativamente (p<0.05), en todos los grupos tratados. Lasmodificaciones significativas en las proporciones de lasespermatogonias, explica el efecto del vanadio y su asociación conmala calidad seminal (efectos toxico-reproductivos). Por lo tanto, seconcluye que la exposición aguda a vanadio por vía aérea de ratones,es capaz de generar efectos citostáticos y citotóxicos sobre lasespermatogonias y los espermatozoides, respectivamente. (AU)

The Vanadium is a transition metal that in the last decades has becomean environmental pollutant, product of the burning of fossil fuels. Thealteration of the different sperm parameters and damage to DNA ingametic cells has been associated with the increase of environmentcontamination, in animals reprotoxic effects have been described, thereare some reports that describe how vanadium produces these effects,the interaction with spermatogonia could be a possibility to relate theseeffects, because one of the white organs of vanadium is the testicle. Theobjective of this study was to analyze the cytostatic and cytotoxiceffects on spermatogonias and spermatozoa of mice treated acutely byair with vanadium pentoxide (V2O5) in different concentrations (0.0,0.02, 0.04 and 0.08M). It consisted in evaluating the changes in theproportions of the different types of spermatogonia A0(Undifferentiated), Renewal and Differentiated (Type B) in a mousemodel in vivo, and in the estimation of the parameters of density andsperm morphology, to establish seminal quality. The results show thatthe exposure to vanadium 5+, increases the proliferation ofspermatogonia renewal, and type B ones decrease in the high dose;sperm density and normal morphology decreased significantly (p<0.05) in all groups treated. The change in spermatogonial proportionscould explain the effect of vanadium and its association with poorseminal quality (reprotoxic effect). Acute exposure to vanadium by airof mice is capable of generating cytostatic and cytotoxic effects onspermatogonial and spermatozoa, respectively (AU)

Cytostatic drugs and risk of genotoxicity in health workers. A literature review.

OBJECTIVE: To analyse the genotoxic risk of cytostatic drugs in health professionals after occupational exposure. METHOD: Literature was searched for the databases PubMed, Lilacs, The Cochrane Library and Scopus with free and controlled language (MeSH terms) using boolean operators AND and OR. The research was limited to articles published between 2005-2016. RESULTS: 11 articles were selected depending on their relevancy to this review's aim. Nine of the 11 articles proved the existence of damage to genetic material (DNA) of health workers, who were exposed to cytostatics. Furthermore, current security practices do not eliminate the chance of exposure completely. Therefore, the creation of new clinical trials is required. CONCLUSIONS: Handling cytostatic drugs can cause a genotoxic risk to health workers who are exposed to these substances. This exposure may cause damage on the workers' DNA. There are not enough data to prove a cause-effect relationship between the genotoxic risk and adverse reactions on individuals. Health education will be the main way to raise the awareness and prevention this problem.

The Angiotensin II Receptor Blocker Losartan Sensitizes Human Liver Cancer Cells to Lenvatinib-Mediated Cytostatic and Angiostatic Effects.

Molecular targeted therapy with lenvatinib is commonly offered to advanced hepatocellular carcinoma (HCC) patients, although it is often interrupted by adverse effects which require a reduction in the initial dose. Thus, an alternative lenvatinib-based therapy to compensate for dose reduction is anticipated. This study aimed to assess the effect of combination of low-dose of lenvatinib and the angiotensin-II (AT-II) receptor blocker losartan on human HCC cell growth. In vitro studies found that losartan suppressed the proliferation by inducing G1 arrest and caused apoptosis as indicated by the cleavage of caspase-3 in AT-II-stimulated HCC cell lines (Huh-7, HLE, and JHH-6). Losartan attenuated the AT-II-stimulated production of vascular endothelial growth factor-A (VEGF-A) and interleukin-8 and suppressed lenvatinib-mediated autocrine VEGF-A production in HCC cells. Moreover, it directly inhibited VEGF-mediated endothelial cell growth. Notably, the combination of lenvatinib and losartan augmented the cytostatic and angiostatic effects of the former at a low-dose, reaching those achieved with a conventional dose. Correspondingly, a HCC tumor xenograft assay showed that the oral administration of losartan combined with lenvatinib reduced the subcutaneous tumor burden and intratumor vascularization in BALB/c nude mice. These findings support that this regimen could be a viable option for patients intolerant to standard lenvatinib dosage.

Current Possibilities of Early Detection of Cardiotoxicity of Cytostatic Treatment.

BACKGROUND: Due to growing long-term survival rate of oncologic patients, there is increased interest in cardiotoxicity of oncologic treatment among medical professionals. It is concerning both paediatric and adult patients. When prescribing oncologic treatment, there should be focus on the efficacy and safety of the used drugs. Nowadays, the main problem is early dia-gnosis of cardiotoxicity. PURPOSE: In our work we wanted to investigate whether the increase in bio-markers after the cytostatic therapy with anthracyclines can predict further increase in the left ventricular volume and decrease of the left ventricular ejection fraction. MATERIALS AND METHODS: We were monitoring 36 patients with the dia-gnosis of non-Hodgkins lymphoma who received therapy with anthracyclines. After the therapy we were measuring the cardiac bio-markers NT-proBNP and high-sensitivity troponin I and performed echocardiography. RESULTS: In our group of patients there is a statistically significant correlation between increased levels of troponin I, NT-proBNP and increment of the left ventricular volume measured before the treatment and 3 months after the treatment. There is also a significant inverse correlation between the left ventricular volume and left ventricular ejection fraction. There was no relationship between higher cumulative doses of anthracyclines and the increment of the left ventricular volume. There is a significant correlation between higher cumulative doses of anthracyclines and higher levels of troponin I. CONCLUSION: The measurement of bio-markers troponin I and NT-proBNP should be considered for an early dia-gnosis of cardiotoxicity in oncologic patients. Echocardiography is also beneficial for the dia-gnosis in these patients. All efforts after the dia-gnosis should be focused on the therapy with cardioprotective drugs, which can prevent the development of severe heart failure.

Medidas para prevenir los riesgos asociados con la exposición a citostáticos en cirugía filtrante de glaucoma / Measures to prevent the risks associated with exposure to cytostatic drugs in glaucoma filtering surgery

INTRODUCCIÓN: El uso de medicamentos citostáticos como la mitomicina C y el 5-fluorouracilo es bien conocido en cirugía filtrante de glaucoma y en el manejo de sus complicaciones, no obstante, existe una falta de información en cuanto a las medidas preventivas a tomar por parte del profesional que maneja este tipo de sustancias. OBJETIVO: Concienciar al profesional sobre los riesgos asociados con el uso de medicamentos citostáticos sin la adecuada prevención. RESULTADOS: Revisión de la bibliografía y legislación disponible sobre medidas preventivas en el manejo de citostáticos en el ámbito médico y oftalmológico. CONCLUSIONES: La prevención y concienciación del profesional cualificado que maneja estas sustancias es la medida más importante para prevenir los posibles riesgos derivados. Es necesaria la coordinación con los equipos de Salud Laboral del Hospital y los profesionales y personal implicados en las distintas fases del proceso, desde la preparación en Farmacia Hospitalaria hasta su eliminación

INTRODUCTION: The use of cytostatic drugs such as Mitomycin C and 5-Fluorouracil is well-known in glaucoma filtering surgery, as well as the management of its complications. However, there is a lack of information regarding the preventive measures to be taken by the professional that handles these types of substances. OBJECTIVE: Raise awareness among professionals of the risks associated with the use of cytostatic drugs without adequate prevention measures. RESULTS: Review of the available literature and legislation on preventive measures in the management of cytostatic drugs in the medical and ophthalmological field. CONCLUSIONS: The prevention and awareness of the risks of the qualified professionals that handle these substances is the most important measure to prevent the possible risks. Coordination is necessary with the Occupational Health teams of the Hospital, as well as the professionals and staff involved in the different phases of the process, from the preparation in Hospital Pharmacy to its elimination

Measures to prevent the risks associated with exposure to cytostatic drugs in glaucoma filtering surgery. / Medidas para prevenir los riesgos asociados con la exposición a citostáticos en cirugía filtrante de glaucoma.

INTRODUCTION: The use of cytostatic drugs such as Mitomycin C and 5-Fluorouracil is well-known in glaucoma filtering surgery, as well as the management of its complications. However, there is a lack of information regarding the preventive measures to be taken by the professional that handles these types of substances. OBJECTIVE: Raise awareness among professionals of the risks associated with the use of cytostatic drugs without adequate prevention measures. RESULTS: Review of the available literature and legislation on preventive measures in the management of cytostatic drugs in the medical and ophthalmological field. CONCLUSIONS: The prevention and awareness of the risks of the qualified professionals that handle these substances is the most important measure to prevent the possible risks. Coordination is necessary with the Occupational Health teams of the Hospital, as well as the professionals and staff involved in the different phases of the process, from the preparation in Hospital Pharmacy to its elimination.

Occupational exposure to cytostatic fumes during hyperthermic intraperitoneal chemotherapy.

Hyperthermic intraperitoneal chemotherapy (HIPEC)-heated, intra-abdominal chemotherapy-has become the treatment of choice for treating peritoneal metastases from ovarian, stomach or colorectal cancers. HIPEC has several advantages and disadvantages. The major benefit is minimal systemic toxicity for the patient, but there is a risk of occupational exposure for operating room staff. We have not found any reports of workers with chronic aplastic anaemia as a result of exposure to cytostatic fumes during HIPEC. The aim of this case report is to raise the awareness of potential negative health effects of inhalation exposure to cytostatic drugs. We present a rare case of a 43-year-old woman, suffering from aplastic anaemia as a long-term consequence of exposure to cytostatics. During the HIPEC procedure, surgical revision of the peritoneal cavity was undertaken which resulted in release of cytostatic fumes. Despite awareness of the health effects of occupational exposure to cytostatic drugs and well-developed procedures for safely handling them, unexpected exposure may occur causing serious medical conditions. These may develop in sensitive subjects although accidental high-level exposure may lead to unexpected long-term consequences in all workers. Medical staff need to be informed of the risks of HIPEC and safety guidelines to reduce the risk of exposure.

Cytostatics as hazardous chemicals in healthcare workers' environment.

Cytostatics not only induce significant side-effects in patients treated oncologically but also pose a threat to the health of occupationally exposed healthcare workers: pharmacists, physicians, nurses and other personnel. Since the 1970s numerous reports from various countries have documented the contamination of working areas with cytostatics and the presence of drugs/metabolites in the urine or blood of healthcare employees, which directly indicates the occurrence of occupational exposure to these drugs. In Poland the significant scale of occupational exposure to cytostatics is also confirmed by the data collected in the central register of occupational carcinogens/mutagens kept by the Nofer Institute of Occupational Medicine. The assessment of occupational exposure to cytostatics and health risks constitutes employers' obligation. Unfortunately, the assessment of occupational risk resulting from exposure to cytostatics raises a number of concerns. Provisions governing the problem of workers' health protection are not unequivocal because they derive from a variety of law areas, especially in a matter of hazard classification and safety data sheets for cytostatics. Moreover, no legally binding occupational exposure limits have been set for cytostatics or their active compounds, and analytical methods for these substances airborne and biological concentrations are lacking. Consequently, the correct assessment of occupational exposure to cytostatics, the evaluation of health hazards and the development of the proper preventive strategy appear difficult. The authors of this article described and discussed the amendments to the European provisions concerning chemicals in the light of employers' obligations in the field of employees' heath protection against the consequences of exposure to cytostatics. Some modifications aimed at a more effective health protection of workers occupationally exposed to cytostatics were also proposed. Int J Occup Med Environ Health. 2019;32(2):141-59.

Neutropenia inducida por citostáticos en oncología / Neutropenia induced by cytostatics in oncology

Se realizó un estudio descriptivo y transversal de 330 pacientes con cáncer, atendidos en el Hospital Oncológico Conrado Benítez de Santiago de Cuba, desde junio hasta diciembre del 2014, para determinar la presencia de neutropenias inducidas por quimioterapia. Presentaron esa afección 145 pacientes (44,0 por ciento). Predominaron el grupo etario de 41-60 años (51,0 por ciento), el sexo femenino (87,5 por ciento), el cáncer de mama (64,8 por ciento), el estadio clínico II (50,3 por ciento), los afectados con 2 episodios de neutropenia (62,1 por ciento), así como los grados leve (51,7 por ciento) y moderado (37,9 por ciento). Respondieron al tratamiento con ior® LeukoCIM 118 pacientes (81,4 por ciento). No se estableció asociación entre las diferentes combinaciones de citostáticos, el número de episodios y los grados de esa enfermedad. La disponibilidad del ior® LeukoCIM para tratar dicha afección facilitará su uso profiláctico y mejorará la calidad de vida de estos pacientes

A descriptive and cross-sectional study of 330 patients with cancer, assisted in Conrado Benítez Oncological Hospital in Santiago de Cuba, was carried out from June to December, 2014, to determine the presence of neutropenias induced by chemotherapy. This disorder was present in 145 patients (44.0 percent). There was a prevalence of the 41-60 age group (51.0 percent), female sex (87.5 percent), breast cancer (64.8 percent), clinical stage II (50.3 percent), those affected patients with 2 neutropenia episodes (62.1 percent), as well as light (51.7 percent) and moderate grades (37.9 percent). One hundred eighteen patients responded to the treatment with ior® LeukoCIM (81.4 percent). There was no association between the different combinations of cytostatics, number of episodes and grades of that disease. The availability of the ior® LeukoCIM to treat this disorder will facilitate its prophylactic use and will improve these patients life quality

Neutropenia inducida por citostáticos en oncología / Neutropenia induced by cytostatics in oncology

Se realizó un estudio descriptivo y transversal de 330 pacientes con cáncer, atendidos en el Hospital Oncológico Conrado Benítez de Santiago de Cuba, desde junio hasta diciembre del 2014, para determinar la presencia de neutropenias inducidas por quimioterapia. Presentaron esa afección 145 pacientes (44,0 por ciento). Predominaron el grupo etario de 41-60 años (51,0 por ciento), el sexo femenino (87,5 por ciento), el cáncer de mama (64,8 por ciento), el estadio clínico II (50,3 por ciento), los afectados con 2 episodios de neutropenia (62,1 por ciento), así como los grados leve (51,7 por ciento) y moderado (37,9 por ciento). Respondieron al tratamiento con ior® LeukoCIM 118 pacientes (81,4 por ciento). No se estableció asociación entre las diferentes combinaciones de citostáticos, el número de episodios y los grados de esa enfermedad. La disponibilidad del ior® LeukoCIM para tratar dicha afección facilitará su uso profiláctico y mejorará la calidad de vida de estos pacientes(AU)

A descriptive and cross-sectional study of 330 patients with cancer, assisted in Conrado Benítez Oncological Hospital in Santiago de Cuba, was carried out from June to December, 2014, to determine the presence of neutropenias induced by chemotherapy. This disorder was present in 145 patients (44.0 percent). There was a prevalence of the 41-60 age group (51.0 percent), female sex (87.5 percent), breast cancer (64.8 percent), clinical stage II (50.3 percent), those affected patients with 2 neutropenia episodes (62.1 percent), as well as light (51.7 percent) and moderate grades (37.9 percent). One hundred eighteen patients responded to the treatment with ior® LeukoCIM (81.4 percent). There was no association between the different combinations of cytostatics, number of episodes and grades of that disease. The availability of the ior® LeukoCIM to treat this disorder will facilitate its prophylactic use and will improve these patients life quality(AU)

Reactions to cytostatic agents in children.

PURPOSE OF REVIEW: The current review will focus on drug hypersensitivity reactions to chemotherapy specifically to those drugs most used in children. We know that potentially all chemotherapeutic agents can cause infusion reactions, generally defined as adverse drug reactions. Of these, some are Type A, defined as expected and described in the characteristics of the drug and others, and Type B, defined as unexpected reactions which cannot be explained by the known toxicity profile of the drug. When an unexpected reaction occurs, drugs we can refer as hypersensitivity reactions (HSRs). Some of these (HSRs) are allergic reactions as they have an underlying immunologic mechanism. In general, the cytotoxic agents most commonly associated with HSRs are the platinum salts derivatives, taxanes, pegylated liposomal doxorubicin, L-asparaginase, procarbazine, etoposide, bleomycin, and cytarabin. RECENT FINDINGS: HSRs may also occur in children with cancer, during the treatment with chemotherapeutic drugs. The most used drugs of this group in children to cause HSRs are: carboplatin, L-asparaginase, and methothrexate. The aim of this review is to summarize the incidence and the clinical features of HSRs occurring with these drugs in children. SUMMARY: The aim of this review is to summarize the incidence and the clinical features of HSRs occurring with these drugs in children. The current review will focus on the most involved drugs in children, the type of reactions, the mechanisms involved, and the best way to manage them.

Extravasación de citostáticos por vía periférica. tratamiento quirúrgico: ¿cuándo y cómo? / Extravasation of peripheral cytostatic. surgical treatment: when and how?

Se analiza el tratamiento quirúrgico en las extravasaciones de citostáticos por vía periférica. Se discute cuándo y cómo realizarlo. Se lo ubica dentro del contexto de los otros dos tratamientos: el de urgencia y el clínico. Se señala que el tipo de citostático utilizado y el estado clínico de paciente influyen en esta decisión.

Surgical treatment in peripheral cytostatic extravasations is analysed. It discusses when and how to perform it. It is placed within the context of the other two treatments: the emergency and the clinical. It is pointed out that the type of cytostatic used and the clinical status of the patient influence this decision.

Magnetic field therapy in patients with cytostatics-induced polyneuropathy: A prospective randomized placebo-controlled phase-III study.

No causal treatment for chemotherapy-induced peripheral neuropathy (CIPN) is known. Therefore, there is an urgent need to develop a therapy for CIPN. Only scarce clinical data are available concerning magnetic field therapy (MFT) in this context. We conducted a unicentric, randomized, double-blind, placebo-controlled phase-III trial of an MFT device versus placebo. In this study, we randomized 44 patients with CIPN to two treatment groups, where 21 patients were treated with MFT (Group 1) and 23 patients received placebo (Group 2). We evaluated the efficacy of MFT at baseline (T1 ), after 3 weeks of study treatment (T2 ), and after 3 months of study treatment (T3 ). The primary endpoint was nerve conduction velocity (NCV), while secondary endpoints were the Common Toxicity Criteria (CTCAE) score and the Pain Detect End Score at T3 . Seventeen of the patients in Group 1 and 14 patients in Group 2 completed the respective study treatment. The primary endpoint, significant improvement of NCV at T3 , was achieved by MFT (P = 0.015), particularly for sensory neurotoxicity of the peroneal nerve. Also, in respect to the secondary endpoints, significant improvement (P = 0.04) was achieved in terms of the patients' subjectively perceived neurotoxicity (CTCAE score), but not of neuropathic pain (P = 0.11). From data in the randomized study presented here, a positive effect on the reduction of neurotoxicity can be assumed for the MFT device. Patients with sensory neurotoxicity in the lower limbs, especially, should therefore be offered this therapy. Bioelectromagnetics. 38:85-94, 2017. © 2016 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc.

Evidence of exposure to cytostatic drugs in healthcare staff: a review of recent literature.

OBJECTIVE: Provide updated evidence and learn about the actions that must be implemented in order to prevent the occupational exposure to cytostatic drugs. METHOD: A bibliographic search was carried out on the MEDLINE, COCHRANE PLUS and WEB OF SCIENCE databases, with the terms "surface contamination", "cytostatic drug", "drug preparation", "occupational exposure", "safe handling" and "closed-system transfer device", within the 2010-2015 period. RESULTS: Thirteen articles were selected for review. These articles are from hospitals in U.S.A., Canada, Japan, Australia, Spain, Portugal and Germany. In all of them, surface contamination by cytostatic agents was found in over 15 different surfaces, with concentrations ranging from 1.69 ng/cm2 to 4-784 µg/cm2. The specific drugs were cyclophosphamide, ifosfamide, 5-fluorouracil, methotrexate, paclitaxel, cisplatin, gemcitabine, and docetaxel. Closed-system transfer devices can reduce the contamination in work surfaces significantly, but do not eliminate it. CONCLUSIONS: Presence of contamination by cytostatic drugs was confirmed in many hospitals across all 5 continents. In all cases, contamination was found in the cabinet, on the floor in front of the cabinet, and in other places of the Hospital Pharmacy. The drug most frequently found was cyclophosphamide. The most effective action used to reduce contamination was the closed-system transfer devices (CSTDs).

Objetivo: Disponer de la evidencia mas actual y conocer las medidas a aplicar para evitar la exposicion laboral a citostaticos. Método: Se realizo una busqueda bibliografica en las bases de datos MEDLINE, COCHRANE PLUS y WEB OF SCIENCE con los terminos "surface contamination", "antineoplastic drug", "drug preparation", "occupational exposure", "safe handling" y "closed-system transfer device" para el periodo 2010- 2015. Resultados: Se seleccionaron 13 articulos para la revision. Estos articulos corresponden a hospitales de USA, Canada, Japon, Australia, Espana, Portugal y Alemania. En todos ellos se ha encontrado contaminacion por farmacos citostaticos en mas de 15 superficies distintas con concentraciones que van desde los 1,69 ng/cm2 hasta 4,784 µg/cm2. Los farmacos determinados han sido ciclofosfamida, ifosfamida, 5-fluorouracilo, metotrexato, paclitaxel, cisplatino, gemcitabina y docetaxel. El sistema cerrado reduce la contaminacion de las superficies de trabajo significativamente, pero no la elimina. Conclusiones: Se verifica la presencia de contaminacion por farmacos citostaticos en numerosos hospitales de los 5 continentes. En todos los casos se ha encontrado contaminacion en la cabina, en el suelo frente a la cabina y en otros lugares de la farmacia. El farmaco mas frecuentemente encontrado es la ciclofosfamida. El sistema empleado mas eficaz para reducir la contaminacion es el uso de dispositivos cerrados de transferencia (CSTD-closed system transfer device).

Instability Due to Drug-Induced Vestibulotoxicity.

OBJECTIVE: The therapeutic use of ototoxic drugs is relatively common, particularly in patients with severe diseases. It is likely that disturbances of balance in these patients are underestimated by clinicians. MATERIALS AND METHODS: The purpose of this study was to identify drugs involved in the vestibulotoxic origin of instability in a group of 18 patients. RESULTS: Six patients showed both cochlear and vestibular damage, while 12 were affected only by posterior labyrinthine damage. Four groups of drugs were identified: antibiotics (nine patients), cytostatics (four), anti-tuberculosis medicinal products (three), and other drugs (two). Cytostatics were involved in many cases studied, a fact scarcely reported before. CONCLUSION: It is important to ensure an early diagnosis to prevent ototoxic effects induced by drugs. We propose that patients receiving potential ototoxic drugs undergo cochlear and vestibular assessments. Further, we recommend that patients with instability undergo vestibular rehabilitation.

Bilberry extract, its major polyphenolic compounds, and the soy isoflavone genistein antagonize the cytostatic drug erlotinib in human epithelial cells.

Erlotinib (Tarceva®) is a chemotherapeutic drug approved for the treatment of pancreatic cancer and non-small cell lung cancer. Its primary mode of action is the inhibition of the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (RTK). Recently, RTK-inhibiting polyphenols have been reported to interact synergistically with erlotinib. Furthermore some anthocyanidins and anthocyanin-rich berry extracts have been reported to inhibit tyrosine kinases, including the EGFR, which raises the question of potential interactions with erlotinib. Polyphenol-rich preparations such as berry- or soy-based products are commercially available as food supplements. In the present study we tested a bilberry extract, its major anthocyanin and potential intestinal degradation products, as well as genistein, with respect to possible interactions with erlotinib. Cell growth inhibition was assessed using the sulforhodamine B assay, while interactions with EGFR phosphorylation were analyzed by SDS-PAGE/western blotting with subsequent immunodetection. Genistein, bilberry extract, delphinidin-3-O-glucoside and delphinidin were found to antagonize erlotinib whereas phloroglucinol aldehyde was found to enhance cytostatic effects of the drug on human epithelial A431 cells. Genistein also antagonized the EGFR inhibitory effects of erlotinib, whereas bilberry anthocyanins showed no significant interactions in this regard. Our data indicate that different polyphenols are potentially able to impair the cytostatic effect of erlotinib in vitro. Genistein interacts via the modulation of erlotinib-mediated EGFR inhibition whereas bilberry anthocyanins modulated the growth-inhibitory effect of erlotinib without affecting EGFR phosphorylation, thus indicating a different mechanism of interference.

Pautas de protección frente al riesgo de exposición a citostáticos en quimioterapia intraperitoneal hipertérmica / Protection guidelines against exposure to cytostatic drugs in hypertermic intraperitoneal chemotherapy

OBJETIVO: El objetivo del trabajo realizado es identificar las tareas de riesgo asociadas a la manipulación de citostáticos, detectadas en la aplicación de Quimioterapia Intraperitoneal con Hipertermia (HIPEC) aplicada según la técnica de Sugarbaker y las diferentes soluciones llevadas a cabo para su control. MÉTODO: La detección y evaluación de los riesgos existentes, así como la propuesta y selección de las diferentes medidas de prevención implantadas se realizaron siguiendo las pautas de: entrevista y estudio de la actividad con el personal especialista implicado, estudio bibliográfico, identificación de requerimientos legales y normativos aplicables, para finalizar estableciendo las medidas de control. Por último se comprobó mediante consulta a las partes involucradas el grado de satisfacción con las medidas adoptadas (adherencia a las medidas) y la eficacia de las medidas adoptadas (número de accidentes e incidentes). RESULTADOS: Se identificaron las tareas de mayor riesgo y las principales vías de exposición. Se determinaron medidas de control de la exposición por vía inhalatoria y dérmica, acordes a los requisitos establecidos para la protección de los trabajadores y para uso en campo quirúrgico, minimizando el disconfor que pudieran provocar al personal. CONCLUSIONES: Se pone de manifiesto la posibilidad de conjugar protección del personal, cumplimiento normativo, preservación del campo quirúrgico y confort del personal. A través de acciones formativas e informativas y el trabajo cooperativo de los diferentes servicios participantes, se consiguió un elevado grado de aceptación por parte del personal involucrado de las medidas de prevención establecidas. Se minimizó la inquietud del personal frente a los riesgos laborales afrontados en HIPEC. Como cierre de la acción preventiva, se considera recomendable la comprobación de la eficacia de las medidas adoptadas a través de evaluación cuantitativa

OBJECTIVE: The objective of the performed work is to identify risks associated with the handling of cytostatics drugs in the implementation of intraperitoneal chemotherapy with hyperthermia (HIPEC) applied according to Sugarbaker technique and different solutions applied to their control. METHOD: The detection and assessment of the risks as well as the proposal and selection of the various control implemented, were conducted to the following guidelines: interview and study of the activity with the involved personnel specialist, bibliographic study, identification of legal and regulatory requirements, and establishing control measures. Due to the measures taken (adherence to measures) and the effectiveness of the measures taken (number of accidents and incidents) the satisfaction level was found by consulting the parts concerned. RESULTS: Risk tasks and major routes of exposure were identified. Control measures were determined for inhalation and dermal exposures, in line with the requirements for the protection of workers and for use in surgical field, minimizing the disconformity that could lead to staff. CONCLUSIONS: It reveals the possibility of combining protection of personnel, compliance with regulatory requirements, preservation of the surgical field and staff comfort. Through training and information activities and cooperative work of the different services involved, a high degree of acceptance was achieved by staff involved in prevention measures in place. The concern of staff downplayed against occupational risks involved in HIPEC was minimized. As closing of preventive actions, checking the effectiveness of the measures taken is recommended through quantitative evaluation