Experience With Bexarotene to Treat Cutaneous T-Cell Lymphomas: A Study of the Spanish Working Group of Cutaneous Lymphomas. / [[Artículo traducido]]Experiencia con bexaroteno en linfoma cutáneo de células T: un estudio del Grupo Español de Linfomas Cutáneos (GELC).

BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combinationwith other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.

Experience With Bexarotene to Treat Cutaneous T-Cell Lymphomas: A Study of the Spanish Working Group of Cutaneous Lymphomas.

BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.

[Translated article] Cost of Treating Cutaneous T-Cell Lymphoma in Spain: Analysis of MICADOS Study Data by Disease Stage.

BACKGROUND AND OBJECTIVE: The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the costs associated with the disease. This article reports the results of the cost analysis. METHODS: We estimated the cost of treating CTCL over a period of 1year from the perspective of the Spanish National Health System. Twenty-three dermatologists and hematologists from 15 public hospitals analyzed data for adult patients with mycosis fungoides (MF) or Sézary syndrome (SS). RESULTS: A total of 141 patients (57.4% male) with a mean age of 63.6 years (95%CI: 61.4-65.7 years) were included. The mean direct annual cost of treating CTCL was €34,214 per patient. The corresponding costs by stage were €11,952.47 for stageI disease, €23,506.21 for stageII disease, €38,771.81 for stageIII disease, and €72,748.84 for stageIV disease. The total direct annual cost of treating MF/SS in public hospitals in Spain was estimated at €78,301,171; stageI disease accounted for 81% of all costs, stageII for 7%, and stagesIII andIV for 6% each. CONCLUSIONS: The MICADOS study offers an accurate picture of the direct cost of treating CTCL in patients with MF/SS in Spain and shows that costs vary significantly according to disease stage. Patient-borne and indirect costs should be analyzed in future studies.

Cost of Treating Cutaneous T-Cell Lymphoma in Spain: Analysis of MICADOS Study Data by Disease Stage. / Evaluación de los costes asociados a la enfermedad de pacientes con linfoma cutáneo de células T en España: análisis en función del estadio clínico (estudio MICADOS).

BACKGROUND AND OBJECTIVE: The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the costs associated with the disease. This article reports the results of the cost analysis. METHODS: We estimated the cost of treating CTCL over a period of 1year from the perspective of the Spanish National Health System. Twenty-three dermatologists and hematologists from 15 public hospitals analyzed data for adult patients with mycosis fungoides (MF) or Sézary syndrome (SS). RESULTS: A total of 141 patients (57.4% male) with a mean age of 63.6 years (95%CI: 61.4-65.7 years) were included. The mean direct annual cost of treating CTCL was €34,214 per patient. The corresponding costs by stage were €11,952.47 for stageI disease, €23,506.21 for stageII disease, €38,771.81 for stageIII disease, and €72,748.84 for stageIV disease. The total direct annual cost of treating MF/SS in public hospitals in Spain was estimated at €78,301,171; stageI disease accounted for 81% of all costs, stageII for 7%, and stagesIII andIV for 6% each. CONCLUSIONS: The MICADOS study offers an accurate picture of the direct cost of treating CTCL in patients with MF/SS in Spain and shows that costs vary significantly according to disease stage. Patient-borne and indirect costs should be analyzed in future studies.

Prospective Pilot study of Quality of Life in patients with severe late-radiation-toxicity treated by Low hyperbaric-oxigen-therapy.

Background/purpose: The aim of this study is to assess for the first time the immediate and long term impact on quality-of-life of HBO treatments(HBOT) at 1.45 ATA (Absolute Atmospheric Pressure) Medical Hyperbaric chamber. Methods: Patients over 18 years-old, suffering of grade 3 Common Terminology Criteria for Adverse Events (CTCAE) 4.0 radiation induced late toxicity and progressing to standard support therapy were included in this prospective study. HBOT was given daily, sixty minutes per session by a Medical Hyperbaric Chamber Biobarica System at 1.45 ATA at 100% O2. Forty sessions were prescribed for all patients given in 8 weeks. Patients reported outcomes (PROs) was assessed by the QLQ-C30 questionnaire, before starting, in the last week of the treatment, as well as during follow up. Results: Between February-2018/June-2021, 48 patients fulfilled the inclusion criteria. A total of 37 patients (77%) completed the treatment prescribed HBOT sessions. Patients with anal fibrosis (9/37) and brain necrosis (7/37) were the most frequently treated. The most common symptoms were pain (65%) and bleeding (54%). In addition, thirty out of the 37 patients who completed the pre- and post-treatment Patients Reported Outcomes (PROs) assessment also completed the follow up European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire C30 (EORTC-QLQ-C30), and were evaluated in the present study. Mean follow up was 22,10 (6-39) months.The Median score of the EORTC-QLQ-C30, at the end of HBOT and during follow-up, was improved in all assessed domains, except in the cognitive aspect (p = 0.106). Conclusions: HBOT at 1.45 ATA is a feasible and well tolerated treatment, improving long term quality of life in terms of physical function, daily activities and general health subjective state of patients suffering severe late radiation-induced toxicity.

Tumor miofibroblástico inflamatorio de laringe: a propósito de un caso / Inflammatory myofibroblastic tumor of the larynx: a case report

Resumen El tumor miofibroblástico inflamatorio (TMI) es una patología muy poco frecuente. Los TMI localizados en laringe pueden ocasionar disfonía o sensación de cuerpo extraño. El diagnóstico se realiza a través de pruebas de imagen y visualización directa con obtención de muestras para estudio histopatológico. Presentamos el caso de una mujer de 43 años, con antecedentes personales de carcinoma indiferenciado de nasofaringe, tratado con radioterapia y quimioterapia, que acude a revisiones periódicas en consulta de otorrinolaringología. Se objetiva por nasofibroscopia una lesión rugosa en cuerda vocal izquierda. Se realiza biopsia con fibroscopio de canal, compatible con tumoración fusocelular atípica, con áreas celulares y mixoides, sospechosa de malignidad, con necesidad de completar estudio inmunohistoquímico. En comité de tumores de cabeza y cuello se decide cirugía programada (laringectomía supracricoidea con cricohioidoepiglotopexia) y posterior tratamiento adyuvante con quimioterapia y/o radioterapia, según resultados del estudio histopatológico. Como conclusión, el TMI es una patología que se encuentra predominantemente en el pulmón, siendo rara la afectación laríngea. Su pronóstico es favorable y el diagnóstico histopatológico es de vital importancia. El diagnóstico correcto va seguido de una escisión local amplia para prevenir la recurrencia, sin embargo, el tratamiento debe adaptarse a la ubicación del tumor y al estado del paciente.

Abstract Inflammatory myofibroblastic tumor (IMT) is a very rare pathology. IMTs located in the larynx can cause dysphonia or foreign body sensation. The diagnosis is made through imaging tests and direct visualization and confirmation with samples for histopathological study. We present the case of a 43-year-old woman with a personal history of undifferentiated carcinoma of the nasopharynx treated with radiotherapy and chemotherapy, who attended periodic check-ups in an otolaryngology clinic. A rough granulomatous lesion was observed by nasofibrolaryngoscopy in the left vocal cord. A canal fibroscope biopsy is performed, compatible with an atypical spindle cell tumor, with cellular and myxoid areas, suspicious of malignancy, requiring an immunohistochemical study to be completed. The head and neck tumor committee decides on scheduled surgery (supracricoid laryngectomy with cricohyoidoepiglottopexy) and subsequent adjuvant treatment with chemotherapy and/or radiotherapy, according to the results of the histopathological study. As a conclusion finally, the IMT is a pathology found predominantly in the lung, laryngeal involvement being rare. Its prognosis is favorable and the histopathological diagnosis is of vital importance to be able to be differentiated from other malignant neoplasms. The correct diagnosis is followed by a wide local excision to prevent recurrence, however, treatment must be tailored to the location of the tumor and the condition of the patient.

Melanoma nasofaríngeo: caso clínico

Resumen El melanoma mucoso primario (MM) de la cavidad nasal y los senos paranasales sigue siendo un tumor maligno poco frecuente. El pico de incidencia se sitúa entre 50 y 60 años, siendo la epistaxis y la obstrucción nasal unilateral los síntomas más frecuentes. La resección quirúrgica es el tratamiento primario con radioterapia y quimioterapia adyuvante si es necesario, el pronóstico depende de la extensión. Presentamos el caso de una paciente mujer de 81 años con hemoptisis y halitosis de un año de evolución. La nasofibrolaringoscopia mostró una lesión parduzca, excrecente, irregular y friable, en el borde derecho del rodete tubárico derecho. El resultado histopatológico fue MM nasofaríngeo. Perfil inmunohistoquímico: S100 +, MelanA +, HMB45 +, SOX10 +, AE1AE3 negativo. El PET-CT mostró una hipercaptación a nivel del rodete tubárico derecho, sin evidencia de adenopatías o metástasis a distancia. Se realizó la resección tumoral completa mediante abordaje endoscópico. El Comité de Oncología del Melanoma decidió que no era necesario un tratamiento adyuvante debido a la resección completa de la lesión y considerando la edad y el deterioro cognitivo de la paciente.

Abstract Primary mucous melanoma (MM) of the nasal cavity and paranasal sinuses remains a rare malignancy. The peak of incidence is between 50 and 60 years old, being epistaxis and unilateral nasal obstruction the most frequent symptoms. Surgical resection is the primary treatment with radiotherapy and adjuvant chemotherapy if necessary, the prognosis depends on the spreading. We present the case of an 81-year-old female patient attending for hemoptysis and halitosis of a year of evolution. The nasofibrolaryngoscopy showed a brownish, excrescent, irregular and friable lesion, outgrowth of the right tube rim. Histopathology result was nasopharyngeal MM. Immunohistochemical profile: S100 +, MelanA +, HMB45 +, SOX10 +, AE1AE3 negative. PET-CT showed a hypercaptation at the level of the right tube rim, without evidence of adenopathies or distant metastases. Complete tumor resection was performed by endoscopic surgery. Melanoma Oncology Committee decided no need of adjuvant therapy due to the complete resection of the lesion and considering the age and cognitive deterioration of the patient.

Evaluación de la efectividad del Triclabendazol como fasciolicida en caprinos de la provincia de Neuquén, Argentina / Evaluation of the efficacy of Triclabendazol to treat liver worm in goats in Nequen province, Argentina

Resumen Debido al uso frecuente del triclabendazol (TCBZ) por parte de los productores, sumado al reporte reciente de resistencia de Fasciolahepatica al fármaco detectada en rodeos y majadas de Neuquén, se llevó a cabo el presente trabajo con el objetivo de evaluar la eficacia del TCBZ como fasciolicida en caprinos bajo un sistema de producción trashumante del norte de la provincia de Neuquén, Argentina. La eficacia se evaluó mediante un test de reducción de conteo de huevos de F. hepatica en caprinos Criollo Neuquino parasitados naturalmente. Se utilizaron dos grupos de animales: un Grupo Control (n: 10) que no recibió tratamiento y un Grupo Tratado (n: 10) al que se le administró TCBZ al 10% (Biofasiolex T10-Biogénesis Bagó ®) vía oral a dosis de 10 mg/kg PV. Al día 0 y 21 post tratamiento, se tomaron muestras de materia fecal para análisis coproparasitológicos. Se evidenció una reducción del conteo de huevos de F. hepatica del 100%, indicando el mantenimiento de la eficacia del fasciolicida en los caprinos evaluados. Se discuten los alcances del uso del test de reducción de conteo de huevos en zonas con producción trashumante del ganado.

Abstract Because of the frequent use of triclabendazole TCBZ by farmers and the recent reports of Fasciola hepatica resistance to this drug in herds and flocks from Neuquén, we carried out this study with the aim to evaluate the efficacy of TCBZ as fasciolicide in goats under a transhumance system from northern of Neuquén, Argentina. A fecal egg count reduction test (FECRT) was performed on Creale Neuquino goats naturally parasitized with F. hepatica. Twenty goats were divided into two groups: A control group (n: 10) which was left untreated, and a treatment group (n: 10) that was dosed orally with TCBZ 10% (Biofasiolex T10-Biogénesis Bagó ®). On Day 0 and Day 21 post-treatment, fecal samples were taken and analyzed by coproscopical examination. According to the FECRT, drug efficacy was 100 % and confirms that TCBZ maintains its efficacy against F. hepatica on goats. The usefulness of the FECRT in these zones under transhumance livestock production is discussed.

Correlation of molecular data with histopathological and clinical features in a series of 66 patients with medullary thyroid carcinoma.

PURPOSE: Medullary thyroid carcinoma (MTC) displays a wide variety of histopathological features, and several histological variants have been described. In follicular cell-derived thyroid carcinomas, there is a good correlation between genotype and phenotype. In this study, we investigated whether such a correlation is also present in MTC. METHODS: The histopathological features were evaluated in a series of 66 molecularly characterised tumours and correlated with the clinical characteristics. RESULTS: Most MTC exhibited the classical variant (83.3%). Other variants included spindle cell (6.1%), pseudopapillary (4.5%), paraganglioma-like (3.0%), angiosarcoma-like (1.5%), and oncocytic follicular (1.5%). Tumours were classified into four groups: group 1, with somatic p.Met918Thr and p.Ala883Phe RET mutations; group 2, with other RET mutations; group 3, with RAS mutations; and group 4, without RET or RAS mutations. Tumours from groups 1 and 4 were typically associated with the classical variant, with abundant fibrosis, lymphovascular invasion, extrathyroidal extension, and more advanced stages of disease, whereas group 2 included histological variants other than the classical variant (namely, pseudopapillary and paraganglioma-like), with tumours that were highly cellular, less invasive, and with a better overall prognosis. In tumours from group 4, amyloid deposition was characteristically absent or low. The spindle cell variant appeared only in tumours from group 3, which had high cellularity and a degree of invasion and prognosis intermediate between groups 1 and 2, but better than group 4. The grade of fibrosis correlated directly with the clinical outcome. CONCLUSION: Our results support the idea that a genotype-phenotype correlation does, indeed, exist in MTC. However, further studies are warranted to confirm these findings in a larger sample size.

Indirect and atypical imaging signals of endometriosis: A wide range of manifestations.

BACKGROUND: Whilst some imaging signs of endometriosis are common and widely accepted as 'typical', a range of 'subtle' signs could be present in imaging studies, presenting an opportunity to the radiologist and the surgeon to aid the diagnosis and facilitate preoperative surgical planning. OBJECTIVE: To summarise and analyse the current information related to indirect and atypical signs of endometriosis by ultrasound (US) and magnetic resonance imaging (MRI). METHODS: Through the use of PubMed and Google scholar, we conducted a comprehensive review of available articles related to the diagnosis of indirect signs in transvaginal US and MRI. All abstracts were assessed and the studies were finally selected by two authors. RESULTS: Transvaginal US is a real time dynamic exploration, that can reach a sensitivity of 79-94% and specificity of 94%. It allows evaluation of normal sliding between structures in different compartments, searching for adhesions or fibrosis. MRI is an excellent tool that can reach a sensitivity of 94% and specificity of 77% and allows visualisation of the uterus, bowel loop deviation and peritoneal inclusion cysts. It also allows the categorisation and classification of ovarian cysts, rectovaginal and vesicovaginal septum obliteration, and small bowel endometriotic implants. CONCLUSION: The use of an adequate mapping protocol with systematic evaluation and the reporting of direct and indirect signs of endometriosis is crucial for detailed and safe surgical planning.

Bowel anastomosis leakage following endometriosis surgery: an evidence based analysis of risk factors and prevention techniques.

BACKGROUND: Deep endometriosis most commonly involves the rectosigmoid junction and its management often requires a colorectal resection. Anastomotic leakage is a severe complication after resection and affects 1-6% of the cases. OBJECTIVE: To evaluate the risk factors related to anastomotic leakage following endometriosis sur-gery, its prevention techniques and the role of protective stomas. METHODS: A comprehensive literature review was carried out for English-language publications in Pubmed and Google Scholar. We included all studies including the following MeSH terms and key words: Anastomotic leakage AND bowel surgery OR Endometriosis OR Colorectal surgery OR Bowel endometriosis. Two authors independently made a selection and analysed relevant abstracts according to the aim of this review. RESULTS: Risk factors and preventive measures were categorised considering the patient condition, the intra- operative setting and the surgical procedure itself. Level I and II recommendations include modifiable risk factors such as the use of stapled or handsewn anastomosis; intra-operative air leak test to check the integrity of the anastomosis; systematic use of pelvic and trans-anal drainage; application of protective or ghost ileostomy in low rectal resections; vaginal closure before the bowel resection; use of oral antibiotics the day before surgery and performing partial mesorectal resection near the bowel wall. Diverting stomas may decrease the morbidity and the clinical consequences of leakage over 65% of low rectal resections but may cause significant adverse effects. CONCLUSION: Evidence-based protective actions are crucial to reduce clinical consequences of anastomotic leakage and to minimise the use of protective stomas in endometriosis surgery.

Doramectin efficacy against Psoroptes ovis in sheep: Evaluation of pharmacological strategies.

The aims of this study were to evaluate the efficacy of two injectable formulations of doramectin (DRM) against Psoroptes ovis in sheep infested under controlled experimental conditions and to characterize the DRM plasma disposition kinetics in the infested animals. To this end, sheep were experimentally infested with a P. ovis strain from a farm with a history of treatment failure, and then treated either with DRM 1% (traditional preparation) on days 0 and 7 or with DRM 3.15% (long-acting formulation) on day 0. The efficacy of each treatment was calculated by counting live mites in skin scrapings. Plasma samples were obtained from each animal and DRM concentrations were measured by HPLC. After the two doses of DRM 1%, the maximum efficacy (98.8%) was reached on day 28, whereas after the single dose of DRM 3.15%, the maximum efficacy (100%) was reached on day 35 and ratified on day 42. The long-acting formulation allowed obtaining higher exposure and more sustained concentrations of DRM than the traditional preparation. Although both DRM formulations studied were effective according to international protocols, they did not reach 100% effectiveness in the time required for approved pharmaceutical products against sheep scab, according to Argentine regulations.