Treatment of cutaneous leishmaniasis with thermotherapy in Brazil: an efficacy and safety study

Abstract: BACKGROUND: Pentavalent antimonials remain as the standard drugs in the treatment of cutaneous leishmaniosis. The high cost, difficult administration, long treatment time, toxicity and increasing morbidity are factors that limit the use of these drugs. OBJECTIVES: To describe the response to radiofrequency thermotherapy in the treatment of localized cutaneous leishmaniasis in Brazil, and to evaluate its safety and tolerability. METHODS: We conducted a non-comparative open trial with a total of 15 patients confirmed to have cutaneous leishmaniasis on parasitological examination. A single radiofrequency thermotherapy session at 50ºC for 30 seconds was applied to the lesion and its edges. In patients with more than one lesion, only the largest one was treated initially. If after 30 days there was no evidence of healing, the smaller lesion was also treated with thermotherapy. Clinical cure was defined as visible healing for three months after treatment. The patients were followed-up for six months and there was no follow-up loss. RESULTS: Of all 23 lesions, only two evolved to complete healing without the need of treatment. Of 21 lesions, 18 (85.7%) achieved full healing. The main observed side effects were itching, burning sensation, pain and blisters. STUDY LIMITATIONS: Sample with a small number of patients and short follow-up. CONCLUSION: Thermotherapy can be considered a therapeutic alternative in localized cutaneous leishmaniasis, especially in cases of single cutaneous lesions and with formal contraindications to conventional treatment with pentavalent antimonials.

Quimioterapia hipertérmica intraperitoneal transoperatória: o que a enfermagem precisa saber / Intraoperative hyperthermic intraperitoneal chemotherapy: what nurses should know / Quimioterapia intraperitoneal hipertérmica transoperatória: qué necesita saber la enfermería

Objetivo: apresentar o estado do conhecimento científico sobre quimioterapia hipertérmica intraperitoneal transoperatória no tratamento da carcinomatose peritoneal e os cuidados de enfermagem pós-operatórios para pacientes submetidos a essa terapia. Métodos: apresentam-se aspectos técnicos da quimioterapia hipertérmica intraperitoneal transoperatória, suas complicações potenciais e cuidados de enfermagem pós-operatórios envolvidos. Resultados: destaca-se a importância dos cuidados de enfermagem, quais sejam: monitorar sinais vitais, perfusão periférica, débito cardíaco e pressão venosa central; avaliar dor; encorajar tosse e realização de exercícios de respiração profunda; registrar drenagem de ferida operatória e drenos; investigar ruídos intestinais; medir volume residual gástrico; promover mudanças de decúbito; avaliar resultados laboratoriais de exames sanguíneos; instituir balanço hídrico e; aferir peso corporal. Conclusão: a quimioterapia hipertérmica intraperitoneal transoperatória é terapia promissora no tratamento de pacientes com carcinomatose peritoneal. Entretanto, para ser bem-sucedida, a prestação de cuidados de enfermagem é fundamental.

Objective: to present the current state of scientific knowledge about intraoperative hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis, and postoperative nursing care for patients undergoing this therapy. Methods: the study describes technical aspects of intraoperative hyperthermic intraperitoneal chemotherapy, the potential complications and post-operative nursing care involved. Results: emphasis was placed on the importance of nursing care, viz.: monitoring of vital signs, peripheral perfusion, cardiac output, and central venous pressure; pain assessment; encouraging coughing and deep breathing exercises; recording drainage of surgical wound and drains; investigating bowel sounds; measuring gastric residual volume; ensuring change of decubitus; evaluating laboratory blood test results; establishing water balance; and measuring body weight. Conclusion: intraoperative hyperthermic intraperitoneal chemotherapy has been shown to be a promising therapy in treatment of patients with peritoneal carcinomatosis. However, to be successful, the nursing care provided is fundamental.

Objetivo: presentar el estado del conocimiento científico sobre quimioterapia intraperitoneal hipertérmica transoperatoria en el tratamiento de la carcinomatosis peritoneal y los cuidados de enfermería posoperatorios para pacientes sometidos a ella. Métodos: se presentan aspectos técnicos de la quimioterapia intraperitoneal hipertérmica transoperatoria, sus complicaciones potenciales y cuidados de enfermería posoperatorios involucrados. Resultados: se destaca la importancia de los cuidados de enfermería: monitorear señales vitales, perfusión periférica, débito cardíaco, presión venosa central; evaluar dolor; estimular la tos y realización de ejercicios de respiración profunda; registrar drenaje de herida operatoria y drenes; investigar ruidos intestinales; medir volumen residual gástrico; promover cambios de decúbito; evaluar resultados de análisis de sangre en laboratorio; establecer balance hídrico; verificar peso corporal. Conclusión: la quimioterapia intraperitoneal hipertérmica transoperatoria es terapia prometedora en el tratamiento de pacientes con carcinomatosis peritoneal. Sin embargo, para ser exitosa, la prestación de cuidados de enfermería es fundamental.

Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study / 부인종양

OBJECTIVE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been recently reported with favorable oncological outcomes as treatment of advanced epithelial ovarian cancer (EOC). The aim of this study was to demonstrate the feasibility of CRS+HIPEC with cisplatin and paclitaxel for the treatment of advanced EOC. METHODS: This is a prospective observational study of 54 patients, from April 2007 to October 2013, with primary or recurrent peritoneal carcinomatosis due to EOC. The mean age was 54.51+/-9.34. Thirty patients (59%) had primary EOC, and 24 patients (41%) had recurrent disease. RESULTS: Mean peritoneal cancer index was 10.11 (range, 0 to 28), complete cytoreduction (CC0) was achieved for 47 patients (87%), CC1 for seven patients (13%). Patients with suboptimal cytoreduction (CC2 and CC3) were not included in the study. The mean stay in intensive care unit was 4.73+/-5.51 days and the mean hospitalization time was 24.0+/-10.03 days. We did not observe any intraoperative death. Seven patients (13%) required additional operations. Three patients (5.6%) died within 30 days from the procedure. Severe complications were seen in 19 patients (35.2%). During the follow-up period, disease recurred in 33 patients (61.1%); the median disease-free survival time was 12.46 months and the median overall survival time was 32.91 months. CONCLUSION: CRS+HIPEC with cisplatin and paclitaxel for advanced EOC is feasible with acceptable morbidity and mortality. Additional follow-up and further studies are needed to determine the effects of HIPEC on long term survival.

Thermoterapy effective and safer than miltefosine in the treatment of cutaneous leishmaniasis in Colombia / Termoterapia efectiva y más segura que la miltefosina en el tratamiento de la leishmaniasis cutánea en Colombia

In Colombia, pentavalent antimonials and miltefosine are the drugs of choice for the treatment of cutaneous leishmaniasis; however, their toxicity, treatment duration, (treatment adherence problems), cost, and decreased parasite sensitivity make the search for alternative treatments of American cutaneous leishmaniasis necessary. Based on the results found in a controlled, open, randomized, phase III clinical trial, the efficacy and safety of miltefosine was compared to that of thermotherapy for the treatment of cutaneous leishmaniasis in Colombia. Adult patients from the Colombian army participated in the study; they received either 50 mg of miltefosine three times per day for 28 days by the oral route (n = 145) or a thermotherapy (Thermomed®) application of 50 °C for 30 seconds over the lesion and surrounding area (n = 149). Both groups were comparable with respect to their sociodemographic, clinical, and parasitological characteristics. The efficacy of miltefosine by protocol and by intention to treat was 70% (85/122 patients) and 69% (85/145 patients), respectively. The adverse effects were primarily gastrointestinal for miltefosine and pain at the lesion site after treatment for thermotherapy. No statistically significant difference was found in the efficacy analysis (intention to treat and protocol) between the two treatments. ClinicalTrials.gov: NCT00471705.

En Colombia antimoniales pentavalentes y miltefosina son los medicamentos de primera elección para el tratamiento de la leishmaniosis cutánea; sin embargo, su toxicidad, duración (que lleva a problemas de adherencia), costo y la disminución de la sensibilidad de los parásitos a los mismos, hacen necesaria la búsqueda de nuevas alternativas de tratamiento para la leishmaniosis cutánea americana. A partir de resultados derivados de un ensayo clínico controlado abierto, aleatorizado, fase III, se comparó la eficacia y seguridad de la miltefosina con la de la termoterapia, para el tratamiento de la leishmaniosis cutánea en Colombia. Adultos pertenecientes al Ejército de Colombia participaron el estudio. Miltefosina, una cápsula de 50 mg tres veces día durante 28 días, vía oral (n = 145). Termoterapia (Thermomed®) aplicación de 50 °C/30" sobre la lesión y el área circundante (n = 149). Ambos grupos fueron comparables en características sociodemográficas, clínicas y parasitológicas. Eficacia de la miltefosina por protocolo 70% (85/122 pacientes) y 69% (85/145 pacientes) por intención a tratar. Termoterapia eficacia por protocolo 64% (86/134 pacientes) y 58% (86/149 pacientes) por intención a tratar. En miltefosina los eventos adversos fueron principalmente de tipo gastrointestinal y en termoterapia se encontró dolor en el sitio de la lesión luego del tratamiento. En el análisis de eficacia (intención a tratar y protocolo) no se encontró diferencia estadísticamente significativa entre los tratamientos evaluados. ClinicalTrials.gov: NCT00471705.

Concentrações hormonais e desenvolvimento folicular de vacas leiteiras em hipertermia sazonal e aguda / Hormone concentration and follicular development in dairy cows under seasonal and acute hyperthermia

Avaliaram-se as concentrações hormonais e os parâmetros de desenvolvimento folicular de vacas leiteiras expostas ao calor sazonal e agudo. Dividiram-se os animais em quatro grupos: verão (n=5), outono (n=5), inverno com hipertermia aguda (grupo câmara climática, (CC), n=5) e inverno (n=9). Os animais foram abatidos no sétimo dia após a ovulação, e os parâmetros de desenvolvimento folicular avaliados. O líquido folicular do maior folículo foi aspirado e armazenado para posterior análise de hormônios esteróides e inibina. O número de células da granulosa vivas no verão e no outono foi 40 e 45 por cento respectivamente, menor que no inverno (P<0,05). A concentração de estradiol (E2) no inverno foi 62 por cento maior que no outono (P<0,05) e 34 por cento superior ao grupo verão (P<0,06). Houve um aumento na quantidade de androstenediona no verão em relação aos grupos inverno (P<0,08) e outono (P<0,05). A concentração de inibina foi maior no inverno do que no verão e CC (P<0,05). A exposição ao calor sazonal e agudo modificou os parâmetros de desenvolvimento do folículo e as concentrações hormonais no líquido folicular, podendo explicar em parte a queda nas taxas de concepção no verão.

The present study evaluated the seasonal and acute heat stress on follicular development and steroid and inhibin concentrations in follicular fluid, in bovine dominant follicle. Cows were distributed into four treatments: summer (n=5), autumn (n=5), animals heat stressed during the winter (n=5) and winter (n=9). On day 7 of the estrous cycle, animals were slaughtered and parameters related to follicle development were evaluated. The follicular fluid (FF) was aspirated and stored for further hormonal analysis. During the summer, the number of viable granulosa cells was 40 percent lower than during the winter, and there was a 45 percent decrease in this parameter during the autumn (P<0.05). In the winter, estradiol concentration was 62 percent higher than during the autumn (P<0.05) and 42 percent higher than during the summer (P<0.06). There was an increase in androstenedione concentration in summer group, when compared to winter (P<0.08) and autumn (P<0.05) groups. Inhibin concentration was higher in winter groups than summer and winter heat stressed groups (P<0.05). Seasonal and acute heat stress altered developmental parameters in dominant follicle and hormonal concentration in follicular fluid, those effects can partially explain the decrease in conception rates during summer.

Hyperthermia induced brain oedema: current status and future perspectives.

Recent years have witnessed a large number of deaths due to hyperthermia and heat-related illnesses across the globe in human population resulting in great social and medical problems. The detailed mechanisms and probable therapeutic measures have still not been worked out. Sporadic autopsy reports show profound brain swelling leading to compression of vital centers that could be responsible for instant death. Increased permeability of the blood-brain barrier (BBB) and brain swelling is also seen in experimental models of heat stress. It appears that hyperthermia is instrumental in opening of the BBB either directly or indirectly leading to vasogenic oedema formation, a feature crucial to molecular and cellular alteration in the brain inducing cell and tissue injury. The probable mechanisms and functional significance of heat induced brain oedema and BBB damage in relation to neurodegenerative changes are discussed.

Síndrome neuroléptico maligno / Neuroleptic malignant syndrome

El Síndrome Neuroléptico Maligno es una enfermedad rara pero con alta mortalidad, por lo cual es conveniente tenerla presente ante la aparición de un cuadro de hipertermia inducido por drogas. En ocasiones la presentación clínica suele ser indistinguible de una Hipertermia Maligna, si bien su mecanismo fisiopatológico es completamente diferente. Sus características clínicas comprenden hipertermia, rigidez muscular, elevación de la creatininfosfoquinasa (C.P.K.) además de mioglobinemia y mioglobinuria, como consecuencia de la rabdomiólisis. En esta recopilación mencionaremos su fisiopatología, etiología, criterios clínicos, su relación con Hipertermia maligna y los detalles de su tratamiento.

Effect of antiepileptic drugs and calcium channel blocker on hyperthermic seizures in rats: animal model for hot water epilepsy.

Hyperthermic seizures were elicited in groups of freely ambulant rats with jets of hot water of 55 degrees C on the head for about 10 mins. Bipolar depth EEG from the hippocampus and the behavioural seizures following the stimulation were recorded. The rectal temperature (threshold) for seizure initiation was 41.5 degrees C. The seizures were predominantly clonic jerks accompanied by large spikes and slow waves lasting for 30-60s. After 3 stimulations (once a day), Phenobarbitone (Pb) 0.02 mg/g daily, Diphenylhydantoin (DPH) 0.001 mg/g, 0.005 mg/g and 0.04 mg/g. daily and Nifedipine (Nif) 0.005 mg/g twice daily were administered intraperitoneally in different rats. During the 10-days injection trials, Pb completely suppressed seizures whereas DPH and Nif did not have any effect. One of the rats with DPH showed increased epileptic activity. After a 10 day 'washout' period' Pb and DPH were interchanged and again the rats were tested for seizures on 10 days. On changing over to Pb from DPH there was complete suppression of seizures and electrical seizure discharges. Whereas those rats which earlier had no seizure activity with Pb started showing the same on changing over to DPH.

Perfusao antiblástica hipertérmica regional no melanoma de membros em adultos / Regional hyperthermic antiblastic perfusion in extremities melanoma in adults

The first antiblastic regional perfusion was performed in 1957, in New Orleans, to treat a patient with locally advanced melanoma. This technique allows to use high doses of antiblastic drugs and was improved about 10 years later by additional hyperthermia, an idea suggested by Cavaliere et al and by Stehlin. Three types of isolated perfusion are possible: normothermic antiblastic perfusion. The use of adjuvant hyperthermic antiblastic perfusion offers to patients with extremity melanomas an excellent chance of cure. To patients with ® in transit ¼ metastases, hyperthermic antiblastic perfusion offers the most effective treatment with limb salvage. The main complication in isolated perfusion is the escape of the perfusate to the systemic circulation, but methods for escape evaluation are improving with the utilization of radiolabelled serum albumin and gamma-detecting probes. The hyperthermia is one of the most promising means of cancer therapy and it can be a local, regional or systemic treatment. Several retrospective and a few prospective and randomized studies have demonstrated the superiority of using hyperthermic antiblastic perfusion in extremity melanoma as compared to other forms of treatment. The World Health Organization and the European Organization for Research and Treatment of Cancer are performing randomized and controlled studies to evaluate the role of hyperthermic antiblastic perfusion in melanoma

Cooperative clinical studies of hyperthermia using a capacitive type heating device GHT-RF8(Greenytherm)

Yonsei Cancer Center developed an RF(Radiofrequency) capacitive type heating device, GHT-RF8(Greenytherm) in cooperation with Green Cross Medical Corp., Korea in 1986 for the first time in Korea. Cooperative clinical studies of hyperthermia for the treatment of cancer using GHT-RF8 were conducted by Yonsei Cancer Center in collaboration with the Presbyterian Medical Center, Chonju, Korea. A total of forty patients with various histologically proven malignant tumors, including superficial (N = 13) and deep-seated tumors (N = 27), were treated with this newly developed heating device in conjunction with radiotherapy (N = 38) or chemotherapy (N = 2) at two different institutes between October 1986 and September 1987. These patients were locally far advanced or recurrent cases and considered to be refractory to conventional cancer treatment modalities. Radiotherapy was given in 200cGy per day, five times a week fractionations with a total tumor dose of 50-60Gy in 5-6 weeks. Within an hour after radiotherapy, the RF capacitive type of hyperthermia was given two times a week for a total of 4-10 treatment sessions and an attempt was made to maintain the tumor temperature at 41-45 degrees C for 30-60 minutes. Of forty patients treated, 14 patients with deep-seated tumors showed complete response and 20 patients showed partial response. The overall response rate was 85% (34 out of 40 patients) and only 6 patients showed no response. Complications from this treatment were mainly burns, superficial first degree burn in 2 cases, second degree in 4 cases and subcutaneous fat necrosis was observed in 2 cases.