Analysis of the prevalence and social security situation of pneumoconiosis in non-coal mine industry in Jiangsu Province / 中华劳动卫生职业病杂志

Objective: To understand the social security situation of current cases of pneumoconiosis in non-coal mine industries in Jiangsu Province, and to provide reference for the treatment and security work of pneumoconiosis patients. Methods: From January to October 2020, a follow-up survey was conducted on 4038 cases of pneumoconiosis in non-coal mine industries of the province from October 1949 to December 2019. The age, type of pneumoconiosis, industry type, and social security status of the patients were collected. Namely, work-related injury insurance, employer compensation, basic medical insurance for urban and rural residents, major illness insurance, etc. SPSS 19.0 was used for statistical description and analysis. Results: The cases of pneumoconiosis in non-coal mine industries in Jiangsu Province ranged in age from 36 to 105 (70.78±8.43) years old, and had been exposed to dust for 1 to 55 (19.27±9.29) years. Silicosis was the main form (3875 cases, 95.96%), and non-metallic mining and dressing industry was the main form (2618 cases, 64.83%). A total of 3991 cases (98.84%) of pneumoconiosis patients enjoyed social security, most of them were urban and rural residents with basic medical insurance (3624 cases, 89.75%), but there were still 47 patients without any social security. 15 cases (0.37%) enjoyed the subsistence allowance, with the monthly allowance amount ranging from 104 to 3960 yuan, with the average amount of 954.87 yuan/month. Conclusion: In Jiangsu Province, the proportion of pneumoconiosis patients in non-coal mine industries enjoying social security is relatively high, but there are still patients who do not enjoy any social security, and the difference in the amount of subsistence allowance is slightly larger. It is necessary to further improve the medical security of pneumoconiosis patients and improve their quality of life.

Extrato de Echinodorus grandiflorus apresenta efeito renoprotetor em ratos com nefrotoxicidade aguda induzida pela ciclofosfamida / Extract of Echinodorus grandiflorus presents renoprotetic effect on rats with acute nephrotoxicity induced by cyclophosphamid / El extracto de Echinodorus grandiflorus tiene un efecto renoprotector en ratas con nefrotoxicidad aguda inducida por ciclofosfamida

Pelas características anatômicas e fisiológicas dos rins, a lesão renal aguda tem sua origem nefrotóxica pela alta circulação local, o que favorece a alta concentração de substâncias tóxicas e seus metabólitos no tecido. A lesão renal aguda é uma complicação comum em internações hospitalares e principalmente em internações em unidades de terapia intensiva. A ciclofosfamida, um quimioterápico utilizado no tratamento de doenças autoimunes e neoplasias sólidas, pode causar nefrotoxicidade com disfunção glomerular e tubular. O uso de plantas medicinais, pelas suas potentes ações antioxidantes, tem sido usado para prevenção ou tratamento de lesões celulares induzidas pelo desequilíbrio entre enzimas antioxidantes e oxidantes. Por esse motivo, o objetivo do experimento foi avaliar o potencial efeito protetor da Echinodorus grandiflorus na prevenção da nefrotoxidade induzida pela ciclofosfamida. Para isso, foi realizado o experimento com a utilização de 35 ratos machos, Wistar, divididos em seis grupos experimentais, sendo administrado a ciclofosfamida na dose de 150mg/kg nos grupos G2 a G6 e diferentes doses da Echinodorus grandiflorus, com posterior análise de parâmetros sanguíneos e histológicos. A administração de ciclofosfamida na dose de 150mg/kg de massa corporal, em dose única, foi capaz de induzir a nefrotoxicidade aguda em todos os ratos. O extrato bruto de Echinodorus grandiflorus apresentou potencial efeito renoprotetor ao uso da ciclofosfamida, na dose de 300mg/kg de massa corporal, sendo possível observar redução dos efeitos nefrotóxicos do quimioterápico, pela redução dos danos tubulares e pela diminuição dos espaços capsulas, nitidamente encontradas alterados no grupo que recebeu apenas ciclofosfamida, denotando resultados promissores para utilização desta planta medicinal na prevenção da nefrotoxicidade induzida pelo fármaco. Contudo, novos estudos dos efeitos renoprotetor do chapéu de couro, poderão elucidar os mecanismos envolvidos na ação do extrato bruto do chapéu de couro. A utilização de extrato bruto de plantas medicinais torna-se um adjuvante aos tratamentos pelo baixo custo e pela facilidade de acesso das diferentes populações as plantas desde que devidamente orientados pelos profissionais habilitados.

Due to the anatomical and physiological characteristics of the kidneys, acute kidney injury has its nephrotoxic origin due to the high local circulation, which favors the high concentration of toxic substances and their metabolites in the tissue. Acute kidney injury is a common complication in hospital admissions and especially in intensive care unit admissions. Cyclophosphamide, a chemotherapy drug used in the treatment of autoimmune diseases and solid neoplasms, can cause nephrotoxicity with glomerular and tubular dysfunction. The use of medicinal plants, due to their potent antioxidant actions, has been used for the prevention or treatment of cellular injuries induced by the imbalance between antioxidant and oxidant enzymes. For this reason, the aim of the experiment was to evaluate the potential protective effect of Echinodorus grandiflorus in preventing cyclophosphamide-induced nephrotoxicity. For this, the experiment was carried out with the use of 35 male Wistar rats, divided into six experimental groups, being administered cyclophosphamide at a dose of 150mg/kg in groups G2 to G6 and different doses of Echinodorus grandiflorus, with subsequent analysis of parameters blood and histology. The administration of cyclophosphamide at a dose of 150mg/kg of body weight, in a single dose, was able to induce acute nephrotoxicity in all rats. The crude extract of Echinodorus grandiflorus showed a potential renoprotective effect with the use of cyclophosphamide, at a dose of 300mg/kg of body mass, and it was possible to observe a reduction in the nephrotoxic effects of the chemotherapy, due to the reduction of tubular damage and the reduction of capsule spaces, clearly found altered in the group that received only cyclophosphamide, showing promising results for the use of this medicinal plant in the prevention of drug-induced nephrotoxicity. However, further studies of the renoprotective effects of the leather hat may elucidate the mechanisms involved in the action of the crude extract of the leather hat. The use of raw extract of medicinal plants becomes an adjuvant to treatments due to the low cost and ease of access of different populations to plants, provided that they are properly guided by qualified professionals.

Debido a las características anatómicas y fisiológicas de los riñones, la lesión renal aguda tiene su origen nefrotóxico por la elevada circulación local, que favorece la alta concentración de sustancias tóxicas y sus metabolitos en el tejido. La lesión renal aguda es una complicación frecuente en los ingresos hospitalarios y principalmente en las unidades de cuidados intensivos. La ciclofosfamida, un quimioterápico utilizado en el tratamiento de enfermedades autoinmunes y neoplasias sólidas, puede causar nefrotoxicidad con disfunción glomerular y tubular. El uso de plantas medicinales, debido a sus potentes acciones antioxidantes, se ha utilizado para la prevención o el tratamiento de lesiones celulares inducidas por el desequilibrio entre enzimas antioxidantes y oxidantes. Por este motivo, el objetivo del experimento era evaluar el posible efecto protector del Echinodorus grandiflorus en la prevención de la nefrotoxicidad inducida por la ciclofosfamida. Para ello, se realizó el experimento utilizando 35 ratas Wistar macho, divididas en seis grupos experimentales, administrándoseles ciclofosfamida a una dosis de 150mg/kg en los grupos G2 a G6 y diferentes dosis de Echinodorus grandiflorus, con posterior análisis de sangre y parámetros histológicos. La administración de ciclofosfamida a una dosis de 150mg/kg de masa corporal, en dosis única, fue capaz de inducir nefrotoxicidad aguda en todas las ratas. El extracto crudo de Echinodorus grandiflorus presentó un potencial efecto renoprotector al uso de ciclofosfamida, a una dosis de 300mg/kg de masa corporal, siendo posible observar una reducción de los efectos nefrotóxicos de la quimioterapia, por la reducción del daño tubular y por la disminución de los espacios capsulares, encontrándose claramente alterados en el grupo que recibió solamente ciclofosfamida, denotando resultados promisorios para el uso de esta planta medicinal en la prevención de la nefrotoxicidad inducida por el fármaco. Sin embargo, nuevos estudios sobre los efectos renoprotectores del sombrero de cuero podrían dilucidar los mecanismos implicados en la acción del extracto crudo de sombrero de cuero. El uso de extractos crudos de plantas medicinales se convierte en un coadyuvante de los tratamientos por su bajo coste y la facilidad de acceso de las diferentes poblaciones a las plantas desde que son guiadas adecuadamente por profesionales cualificados.

Evaluación de efectividad y seguridad comparativas del mesna para la prevención de cistitis hemorrágica, en pacientes con cáncer sometidos a quimioterapia con oxazofosfamidas / Evaluation of comparative effectiveness and safety of mesna for the prevention of hemorrhagic cystitis in patients with cancer undergoing oxazophosphamide chemotherapy

Introducción: la cistitis hemorrágica es una complicación frecuente en pacientes con cáncer sometidos a quimioterapia con ciclofosfamida o isofosfamida. Entre las opciones para prevenir esta complicación está el mesna. Esta evaluación de tecnología se desarrolló para informar la toma de decisiones en el marco de la actualización integral del Plan Obligatorio de Salud para Colombia. Objetivo: examinar la efectividad y seguridad comparativas del mesna para la prevención de cistitis hemorrágica, en pacientes con cáncer sometidos a quimioterapia con oxazofosfamidas. Metodología: se realizó una búsqueda sistemática en MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects y LILACS. La tamización de referencias se realizó por dos revisores de forma independiente y la selección de estudios fue hecha por un revisor, aplicando los criterios de elegibilidad predefinidos en el protocolo de la evaluación. La calidad de las revisiones sistemáticas se valoró con la herramienta AMSTAR. Se realizó una síntesis narrativa de las estimaciones del efecto para las comparaciones y desenlaces de interés. Resultados: los hallazgos de efectividad y seguridad de la presente evaluación se basan en una revisión narrativa y diez ensayos clínicos cabeza a cabeza, nueve de ellos aleatorizados, para un total aproximado de 787 pacientes. Se identificó evidencia de los efectos del mesna comparado con diuresis forzada, irrigación vesical continua, N-acetilcisteína, placebo y no mesna para una variedad de desenlaces incluyendo, cistitis hemorrágica, microhematuria, macrohematuria, hematuria de diferentes grados y eventos adversos específicos. La evidencia disponible corresponde principalmente a adultos con cáncer de pulmón, leucemias, linfoma no Hodgkin, enfermedad de Hodgkin, cáncer de mama y sarcomas, tratados con ifosfamida o ciclofosfamida y sometidos a trasplante de médula ósea. También se presentan los eventos adversos reportados en la etapa post-clínica con el uso del mesna. Conclusiones: la evidencia identificada en esta evaluación de tecnología, muestra efectos mixtos en la efectividad y seguridad del mesna para la prevención de cistitis hemorrágica, en pacientes con cáncer sometidos a quimioterapia con oxazofosfamidas: algunos resultados de efectividad demuestran que este medicamento es superior a sus comparadores y para otros desenlaces resulta similar. Respecto a su seguridad, algunos datos indican que esta tecnología no representa diferencias frente a sus alternativas y en otros efectos muestra ser inferior. A juicio de los expertos clínicos y representantes de los pacientes, el mesna tiene una relación favorable entre los beneficios y riesgos, esto sugiere que los efectos deseables con el uso de esta tecnología superan a los efectos indeseables.(AU)

Treatment outcomes of IMEP as a front-line chemotherapy for patients with peripheral T-cell lymphomas

BACKGROUND: This study aimed to assess the treatment outcomes of ifosphamide, mesna, etoposide, and prednisolone (IMEP) combination regimen as a front-line chemotherapy in patients with peripheral T-cell lymphomas (PTCLs). METHODS: Clinical data of 38 newly diagnosed PTCLs patients who underwent IMEP at Busan Paik Hospital from January 2002 to December 2013 were retrospectively analyzed. RESULTS: The overall response rate was 68.5%, with 21 (55.3%) complete response/complete response unconfirmed and 6 (15.8%) partial response (PR). The median follow-up duration was 25.5 months (range, 0.2-87.3). The median overall survival was not reached and 2-year survival rate was 67%. The median progression free survival was 23 months. The most frequently reported adverse effects higher than grade 3 were hematologic toxicities including neutropenia (68.4%), thrombocytopenia (42.1%). There was no treatment-related mortality. CONCLUSION: IMEP regimen is effective and safe as a front-line chemotherapy in patients with PTCLs.

Review of Mesna (Mistabron) as a Mucolytic for Preventing Plumonary complications in Intensive Care Setting.

Impaired mucus clearance or mucus hypersecretion are important feature of many pathological respiratory conditions and in ICU patients. Mesna is a potent mucolytic available as 200 mg/ml solution for neublization and endotracheopulmonary instillation. As effective “mucus clearance” is critical in managing post-operative and other ICU conditions to prevent complications like atelectasis and hypoxia, there is a need to review the clinical results of mucolytic agent Mesna, and its role in mucociliary clearance in critical care patients and in other respiratory conditions.

BK virus-associated hemorrhagic cystitis after pediatric stem cell transplantation / 소아과

Hemorrhagic cystitis is a common stem cell transplantation-related complication. The incidence of early-onset hemorrhagic cystitis, which is related to the pretransplant conditioning regimen, has decreased with the concomitant use of mesna and hyperhydration. However, late-onset hemorrhagic cystitis, which is usually caused by the BK virus, continues to develop. Although the BK virus is the most common pathogenic microorganism of poststem cell transplantation late-onset hemorrhagic cystitis, pediatricians outside the hemato-oncology and nephrology specialties tend to be unfamiliar with hemorrhagic cystitis and the BK virus. Moreover, no standard guidelines for the early diagnosis and treatment of BK virus-associated hemorrhagic cystitis after stem cell transplantation have been established. Here, we briefly introduce poststem cell transplantation BK virus-associated hemorrhagic cystitis.

The mechanism of mesna in protection from cisplatin-induced ovarian damage in female rats / 부인종양

OBJECTIVE: Cisplatin is a widely used chemotherapeutic agent in the treatment of cancers in clinic; but it often induces adverse effects on ovarian functions such as reduced fertility and premature menopause. Mesna could attenuate the cisplatin-induced ovarian damages; however, the underlying mechanism is still unknown. This study aimed to figure out the underlying mechanism of the protection of mesna for ovaries against cisplatin therapy in cancers. METHODS: We performed female adult Sprague-Dawley rats into normal saline control (NS), low-dose cisplatin (CL), high-dose cisplatin (CH), CL plus mesna (CL+M), and CH plus mesna (CH+M) groups and detected anti-Mullerian hormone (AMH)-positive follicle, oxidative stress status and anti-oxidative capability in ovaries. RESULTS: AMH-positive follicles were significantly decreased after cisplatin administration, which was significantly reversed when mesna was co-administered with cisplatin. The end product of lipid peroxidation, malondialdehyde (MDA), was significantly increased, but the anti-oxidative enzymatic activity of superoxide dismutase (SOD) and glutathione (GSH) were significantly decreased in cisplatin groups when compared with NS group. In contrast, after co-administration of cisplatin with mesna, MDA was significantly decreased whereas the activity of SOD and the concentration of GSH were increased. Moreover, mesna did not decrease the anti-tumor property of cisplatin in HePG2 cell lines. CONCLUSION: Cisplatin damages the granulosa cells by oxidative stress to deplete the ovarian reserve and mesna could protect ovarian reserve through anti-oxidation. These results might highlight the mechanism of the protection of mesna for ovarian reserve and open an avenue for the application of mesna as a protective additive in cisplatin chemotherapy in clinical practise.

Treatment and prognosis of stage IV alveolar soft part sarcoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the clinical features, treatment and prognosis of Stage IV alveolar soft part sarcoma.</p><p><b>METHODS</b>To analyze the clinical and pathological features, therapeutic methods and follow-up results in 21 patients with stage IV alveolar soft part sarcoma. There were 11 males and 10 females, in the age of 26-57 years (average 37.0 years old). All the 21 patients had metastasis: nine cases had multiple pulmonary metastasis, three cases had multiple pulmonary and brain metastasis, two cases had multiple brain metastasis, two cases had multiple pulmonary and bone metastasis, two cases had single pulmonary metastasis, one case had single bone metastasis, one case had single brain metastasis and one case had single soft tissue metastasis. Eight patients were treated by surgical operation, including five cases of complete resection for the primary and (or) metastatic tumor and 3 cases of palliative operation for the primary tumor. All patients received chemotherapy, including seven cases of CAVD regimen and 14 cases of MAID regimen treatment. One patient with single bone metastasis and five patients with multiple brain metastasis received post-operative whole brain radiation therapy.</p><p><b>RESULTS</b>All the eight patients with surgical operation had healing by first intention, and pathological examination showed that seven patients achieved R0 surgical margin and one case with R2 status. One patient with single brain metastasis had recurrence after operation. The toxic and adverse reactions of all patients treated with chemotherapy were tolerable. Among them, 17 cases had stable disease and 4 cases had disease progression after chemotherapy. The disease control rate (DCR) was 81.0%. The DCR of patients with CAVD regimen chemotherapy was 85.7% and that of patients treated with MAID regimen was 78.6% (P = 0.862). All patients were followed up for 8 - 86 months (average 32.4 months). The median survival time of all patients was 32.6 months. The 2-year survival rate was 55.1% and the 5-year survival rate was 21.8%. The median survival time in the patients with complete resection was 60.0 months, and that in patients with palliative operation was 27.0, showing a significant difference between them (P = 0.048). The median progression-free survival in patients with complete excision was 57.2 months and that in patients with palliative operation or without operation was 19.6 months, with a significant difference (P = 0.029). The median survival time in patients who received CAVD regimen chemotherapy was 30.0 months, and that in patients with MAID regimen was 51.0 months, with a non-significant difference (P = 0.511). The median progression-free time in patients with CAVD regimen chemotherapy was 13.0 months, and that in patients with MAID regimen was 38.0 months, also with a non-significant difference (P = 0.066).</p><p><b>CONCLUSIONS</b>Alveolar soft part sarcomas are rarely seen and highly malignant tumors, and the prognosis of stage IV ASPS is poor. Complete resection of all tumors is the key of successful treatment of Stage IV ASPS, and the site and number of tumor metastasis are important factors affecting prognosis. The curative effects of radiotherapy and chemotherapy for ASPS need to be further investigated.</p>

Fixed Drug Eruption Caused by Mesna / 대한피부과학회지

A fixed drug eruption (FDE) is a cutaneous reaction caused by various drugs. Mesna is used to decrease urotoxic side effect of cyclophosphamide and there have been no previously reported cases in Korea for any adverse reactions to this drug. Herein, we report a case of a FDE caused by mesna. A 34-year-old woman presented with asymptomatic, brownish macules and patches on the face and back for the past 4 months. She had been treated for SLE with monthly pulses of intravenous cyclophosphamide and mesna for 6 months. She had experienced similar episodes after injection of mesna. The skin biopsy specimen taken from her showed vacuolar degeneration of the basal cell layer and perivascular lymphohistiocyte infiltration in the papillary dermis. We performed prick test, scratch patch test, and intradermal test with mesna and confirmed that a FDE was caused by this drug.

Fatal Ifosfamide-Induced Metabolic Encephalopathy in Patients with Recurrent Epithelial Ovarian Cancer: Report of Two Cases / Journal of the Korean Cancer Association, 대한암학회지

Central nervous system (CNS) toxicity has been reported in approximately 10-30% of patients receiving intravenous infusions of ifosfamide. Encephalopathy is a rare but serious CNS adverse reaction in these patients, and although usually transient and reversible, may cause persistent neurological dysfunction or death. Clinical features range from fatigue and confusion to coma and death. Although methylene blue can be used to treat ifosfamide-induced neurotoxicity, including encephalopathy, its mechanism of action remains poorly defined. We describe here two patients with recurrent epithelial ovarian cancer who experienced fatal encephalopathy following ifosfamide/mesna treatment.

Neuroblastoma in an adult: Case report / Neuroblastoma en un adulto: Informe de un caso

El neuroblastoma es el tumor maligno sólido extracraneal más común en niños. Sólo el 10 por ciento de los casos se diagnostican después de la primera década de vida. Presentamos una paciente afroamericana de 23 años, con una masa paravertebral en T3-T5, múltiples lesiones en los cuerpos vertebrales y una lesión expansiva en la región parietal derecha. El estudio inmmunohistoquímico (negativo para CD99, CD20, CD3 y desmina y positivo para cromogranina, sinaptofisina y NB84), confirmó el diagnóstico de neuroblastoma. La paciente fue sometida a 12 ciclos de quimioterapia recibiendo VAC (vincristina / doxorubicina/ cyclofosfamida) intercalada con ICE (ifosfamida/ mesna/ etoposido). La doxorubicina fue reemplazada por actinomicina en el séptimo ciclo. La paciente toleró bien la quimioterapia y está clínicamente estable.

Neuroblastoma is the most common extracranial solid malignancy in children but rarely described in adults, being 10 percent of all cases diagnosed after the first decade of life. We report a 23 year-old black woman with a mass at paravertebral region of T3-T5, multiple lesions in vertebral bodies and expanding skull-brain lesion at the right parietal region. Immunohistochemical analysis (negative for CD99, CD20, CD3 and desmin; and positive chromogranin, synaptophysin and NB84) confi rmed the diagnosis of neuroblastoma. The patient was submitted to 12 cycles of chemotherapy receiving VAC (vincristine/doxorubicin/cyclophosphamide) interspersed with ICE (ifosfamide/mesna/etoposide) and doxorubicin was replaced by actinomycin in the 7th cycle. She had good tolerance to this therapy, and has been clinically stable.

Reversible Proximal Renal Tubular Dysfunction after One-Time Ifosfamide Exposure / Journal of the Korean Cancer Association, 대한암학회지

The alkylating agent ifosfamide is an anti-neoplastic used to treat various pediatric and adult malignancies. Its potential urologic toxicities include glomerulopathy, tubulopathy and hemorrhagic cystitis. This report describes a case of proximal renal tubular dysfunction and hemorrhagic cystitis in a 67-year-old male given ifosfamide for epitheloid sarcoma. He was also receiving an oral hypoglycemic agent for type 2 diabetes mellitus and had a baseline glomerular filtration rate of 51.5 mL/min/1.73 m2. Despite mesna prophylaxis, the patient experienced dysuria and gross hematuria after a single course of ifosfamide plus adriamycin. The abrupt renal impairment and serum/urine electrolyte imbalances that ensued were consistent with Fanconi's syndrome. However, normal renal function and electrolyte status were restored within 14 days, simply through supportive measures. A score of 8 by Naranjo adverse drug reaction probability scale indicated these complications were most likely treatment-related, although they developed without known predisposing factors. The currently undefined role of diabetic nephropathy in adult ifosfamide nephrotoxicity merits future investigation.

Effect of lycopene on cyclophosphamide-induced hemorrhagic cystitis in rats

Cylophosphamide is used alone or in combination with other drugs for treatment of neoplastic diseases. Hemorrhagic cystitis is a major potential toxicity and dose limiting side effect of cyclophosphamide. The aim of this study was to evaluate the effects of lycopene compared with some antioxidants for the prevention of cyclophosphamide induced hemorrhagic cystitis in rats. In this study, male Sparague-Dawley rats divided into 17 groups of six animals. Group 1 received saline [10 ml/kg, i.p] as normal control, group 2 received cyclophosphamide [200 mg/kg, i.p] as a single dose, groups 3-10 received Mesna [40 mg/kg, i.p], N-acetylcysteine [100 mg/kg i.p], dithiotheritol [50 mg/kg, i.p], L-carnitine [200 and 400 mg/kg, i.p], grape seed extract [500 mg/kg i.p] and lycopene [0.1 and 0.5 mg/kg, i.p] alone. Groups 11-17 received Mesna [40 mg/kg, i.p], N-acetylcysteine [100 mg/kg, i.p], dithiotheritol [50 mg/kg, i.p], L-carnitine [400 mg/kg, i.p], grape seed extract [500 mg/kg, i.p] and lycopene [0.1 and 0.5 mg/kg, i.p], 5 minutes before, and 2 and 6 hours after administration of 200 mg/kg cyclophosphamide. Pathological and biochemical analysis was evaluated 24 hours after cyclophosphamide administration Mesna and N-acetylcysteine resulted in some but not full protection against cyclophosphamide toxicity compared to the controls. Lycopene [0.1 and 0.5 mg/kg] was efficient in protecting the bladder from cyclophosphamide induced hemorrhagic cystitis. However, dithiotheritol, L- carnitine and grape seed extract did not prevent hemorrhagic cystitis. Our results suggest that pre and co- treatment of lycopene [0.1 and 0.5 mg/kg] with cyclophosphamide may have therapeutic potential to inhibit the hemorrhagic cystitis by cyclophosphamide

comparison study of the effects of Echinacea purpurea ethanolic extract and Mesna on cyclophosphamide indueed macroscopic fetal defects in rats

There are some reports that the teratogenic effects of cyclophosphamide [CPA] can be prevented by application of antioxidant drugs and stimulation of the maternal immune system. Echinacea purpurea extract is antioxidative and immunomodulator drug. Mesna [Sodium 2-mercaptoethane sulfonate] is used for decreasing side effects of CPA, especially hemorrhagic cystitis. In this study, we compared the prophylactic effects of mesna and Echinacea extract on teratogenic effects of CPA. This study was performed on 32 pregnant rats that were divided into 4 groups. The first group [control group] received normal saline and the other groups received CPA [15 mg/kg intraperitoneally] on 13th day of gestation. Mesna and E. purpurea extracts were administrated at doses of 100 and 400 mg/kg by IP injection, respectively, along with it and 12 hr later, after CPA injection. Rats were dissected on day 20 of gestation, embryos harvested and after determination of gross malformations they were stained by Alizarin red-Alcian blue method. Cleft palate incidence was 38.46, 30.77 and 14.28% in fetuses of rats that received only CPA, CPA with mesna and CPA with Echinacea extract, respectively. In addition, skeletal anomalies incidence including limbs, vertebra, sternum, and scapula defects were decreased by Echinacea extract. E. purpurea has significant effect on preventing CPA-induced malformations and better prophylactic effect than mesna on cases like CPA-induced cleft palate

Endometrial stromal sarcoma associated with extrauterine endometriosis: a case report and literature review / 부인종양

Endometrial stromal sarcoma (ESS) that arises from extrauterine endometriosis is a rare form of malignancy. We report the case of a 37-year-old ESS patient with extrauterine endometriosis who was treated with ifosfamide/cisplatin chemotherapy. A woman presented with epigastric pain and abdominal distension. Computed tomography imaging revealed a profuse amount of ascites, including a 12.4x12.3 cm sized posterior cul-de-sac mass composed of solid and cystic components. Cytoreductive surgery was performed to remove the mass and the histopathologic findings indicated ESS associated with extrauterine endometriosis. Six cycles of combination chemotherapy [ifosfamide (5 g/m(2)) with mesna (1 g/m(2)) and cisplatin (50 mg/m(2)) (IP)] were administered. After a six-month of disease-free interval, recurrent ESS developed in the pelvic cavity and in both lung fields. Megace medication decreased tumor marker CA-125 for six weeks. However, the patient expired sixteen months after the cytoreductive surgery. ESS associated with extrauterine endometriosis showed response to IP chemotherapy and megace.

A model of hemorrhagic cystitis induced with acrolein in mice

Acrolein is a urinary metabolite of cyclophosphamide and ifosfamide, which has been reported to be the causative agent of hemorrhagic cystitis induced by these compounds. A direct cytotoxic effect of acrolein, however, has not yet been demonstrated. In the present study, the effects of intravesical injection of acrolein and mesna, the classical acrolein chemical inhibitor, were evaluated. Male Swiss mice weighing 25 to 35 g (N = 6 per group) received saline or acrolein (25, 75, 225 æg) intravesically 3, 6, 12, and 24 h before sacrifice for evaluation of bladder wet weight, macroscopic and histopathological changes by Gray's criteria, and 3 and 24 h for assessment of increase in vascular permeability. In other animals, mesna was administered intravesically (2 mg) or systemically (80 mg/kg) 1 h before acrolein. Intravesical administration of acrolein induced a dose- and time-dependent increase in vascular permeability and bladder wet weight (within 3 h: 2.2- and 21-fold increases in bladder wet weight and Evans blue dye exuded, respectively, at doses of 75 æg/bladder), as confirmed by Gray's criteria. Pretreatment with mesna (2-mercaptoethanesulfonic acid), which interacts with acrolein resulting in an inactive compound, inhibited all changes induced by acrolein. Our results are the first demonstration that intravesical administration of acrolein induces hemorrhagic cystitis. This model of acrolein-induced hemorrhagic cystitis in mice may be an important tool for the evaluation of the mechanism by which acrolein induces bladder lesion, as well as for investigation of new uroprotective drugs.

Comparison of uroprotective efficacy of mesna and amifostine in Cyclophosphamide- induced hemorrhagic cystitis in rats.

BACKGROUND: Hemorrhagic cystitis (HC) is a dose limiting side effect of cyclophosphamide (CYP). AIM: In this study, we aimed to investigate the role of amifostine in the protection of CYP-induced HC and compare its efficacy with mesna. SETTING AND DESIGN: This animal study was conducted in the Experimental Animals Breeding and Research Center of the Medical Faculty of Uludag University. MATERIALS AND METHODS: Male Wistar rats (150-200 g; 10 rats per group) were randomly assigned to four groups. Group I (control group) received no drugs, group II received CYP (200 mg/kg, i.p.) alone, group III received amifostine (200 mg/kg, i.p.) and CYP, and group IV received CYP and mesna (40 mg/kg, i.p.) immediately and 4 and 8 h after administration of CYP. Bladders of animals were assessed macroscopically and histologically 24 h later. Gross assessment for presence of edema and hemorrhage and histological evaluation of damage to the bladder were scored according to Gray's criteria. STATISTICAL ANALYSIS USED: For macroscopic and microscopic data, we used statistical evaluation by Kruskal-Wallis nonparametric analysis of variance followed by the Mann-Whitney U-test. RESULTS: All the animals in group II had evidence of HC. Significant histological damage and macroscopic changes were present in this group compared to control group (P<0.001). The median scores for bladder damage in group III and IV were significantly lower compared to group II (P<0.001). When the median scores for bladder damage of group I, III, and IV were compared, there was no significant difference among these groups. CONCLUSION: This study demonstrated the efficacy of amifostine in prevention of cyclophosphamide-induced hemorrhagic cystitis.

Risk factors and treatment of hemorrhagic cystitis in children after hematopoietic stem cell transplantation / 中华儿科杂志

<p><b>OBJECTIVE</b>Hemorrhagic cystitis (HC) is one of the common complications of hematopoietic stem cell transplantation (HSCT), which causes significant pain, prolongs hospitalization, and occasionally results in renal failure and death. This study aimed at investigating the incidence, risk factors, and outcome of HC in children post umbilical cord blood transplantation (UCBT) and peripheral blood stem cell transplantation (PBSCT).</p><p><b>METHODS</b>From October 1998 to June the clinical records of 53 pediatric patients (aged 2-18 years with median age of 7.5 years) in our HCST center who underwent UCBT (n = 37) and PBSCT (n = 16) were retrospectively analyzed. Thirty out of 53 patients were diagnosed as hereditary hemolytic anemia (56.6%), and the others as haematological malignancies (43.4%): of whom 8 had acute lymphoblastic leukemia, 12 acute myeloid leukemia, 2 chronic myeloid leukemia and 1 non-hodgkin lymphoma. Conditioning regimen varied according to disease and clinical status, however based on cyclophosphamide (CTX, 120-200 mg/kg) and busulphan (BU, 12-16 mg/kg) in the cohort. Total body irradiation (TBI) or total lymphoid irradiation was added in 7 patients respectively. The patients were divided into regular treatment group (RTG) with 15 cases who received hyperhydration, alkalinizing, diuresis and Mesna during CTX infusion and prostaglandin E1 (PGE1) group (PEG) with 38 cases who received hyperhydration, alkalinizing, diuresis and Mesna plus prostaglandin E1 (0.03 microg/kg.h). The risk factors of HC were examined by univariate and multivariate analysis.</p><p><b>RESULTS</b>In all, 11 of the 53 transplanted patients developed HC (21%) with a median onset time of day +15 (rage day +2 - +25). HC was classified as early in 4 (36%) and late in 7 (64%), and scored as grade Iin 2 cases (18%), grade II in 4 (36%) and grade III in 5 (46%). There was no significant difference between RTG and PEG in the incidence of HC, however, the incidence was much higher in the group of patients who were > or = 6 years old, positive group of graft-versus-host disease (GVHD) and group of cytomegalovirus (CMV) infection than that in the group of patients who were < 6 years of age (32% vs. 8%, P < 0.05), negative group of GVHD (35% vs. 7%, P < 0.05) and CMV non-infected group (62% vs. 13%, P < 0.05), respectively. Furthermore, by multivariate analysis, > or = 6 years old (OR = 3.53, P < 0.05) and CMV infection (OR = 4.31, P < 0.05) were significant risk factors for HC. Three of 11 patients were treated with bladder irrigation. All patients recovered from HC in a median 12.8 days (range 2-53 days).</p><p><b>CONCLUSION</b>Older age (> or = 6 years) as well as CMV infection were the risk factors of HC. Both hyperhydration and Mesna were effective in preventing HC, while addition of PGE1 could not reduce the incidence of HC. The prognosis of HC in children post HSCT was satisfactory.</p>

A phase II study of etoposide (VP-16), ifosfamide, and carboplatin combination chemotherapy plus concurrent thoracic irradiation for limited stage small cell lung cancer / 대한내과학회지

BACKGROUND: Small cell lung cancer (SCLC) is very sensitive to both chemotherapy and radiation therapy. In limited disease of SCLC, the addition of radiation therapy to chemotherapy improves survival and decrease local relapse over chemotherapy alone. This study evaluated the response rate, duration of response, overall survival and toxicity for the combination of etoposide, ifosfamide, carboplatin given concurrently with thoracic irradiation in limited SCLC. METHODS: Twenty eight patients with histologically proven SCLC who have a measurable disease and previously untreated, were enrolled in this study. Each cycle consisted of VP-16 100 mg/m2 IV days 1~3, ifosfamide 1,200 mg/m2 IV days 1~3 with mesna, carboplatin AUC 6 IV day 1. Cycles were repeated every 21days. Patients received a total of median 6,000 cGy thoracic radiation therapy (180~200 cGy/day) starting on the first day of chemotherapy. Prophylactic cranial irradiation was given to complete remission after chemoradiotherapy. RESULTS: The overall response rate in 27 evaluable patients was 93% (41% of complete response, 52% of partial response). The median time to progression was 10.3 months. The median disease free survival was 18.4 months in patients with complete response. The median overall survival was 16.7 months in all evaluable patients. Hematologic toxicities (> or = Grade3) of 129 cycles of chemotherapy were leukopenia in 38% and fever with infection in 26%. Nonhematologic toxicities (> or = Grade2) of evaluable 27 patients included alopecia in 11%, post-irradiation esophagitis in 44% and pneumonitis in 11%. CONCLUSIONS: VIC combination chemotherapy with concurrent thoracic irradiation is effective in limited SCLC. It's maior toxicity is myelosuppression.

Chronic Cyclophosphamide Induced Cystitis that is Improved by Mesna / 대한비뇨기과학회지

Cyclophosphamide is alkylating agent used in the treatment of various solid tumors. Mucosal irritation by acrolein, the metabolite of cyclophosphamide, is believed to cause various symptoms of cystitis. The thiol compound, sodium 2-mercaptoethane sulfonate (Mesna), has been found to inactivate acrolein. We present an unusual case of a 64-year-old woman, who was treated as chronic cystitis. Her symptoms did not improve, so she was treated with Mesna under the assumption of cyclophosphamide induced cystitis; her symptoms then improved.