Genomic landscapes of ovarian clear cell carcinoma from latin countries reveal aberrations linked to survival and progression.

BACKGROUND: Ovarian clear cell carcinomas (OCCCs) are rare, aggressive and chemoresistant tumors. Geographical and ethnic differences in the incidence of OCCC have been reported with a higher incidence in Asiatic countries. There is a paucity of information regarding OCCC in Latin America (LA) and other countries. METHODS: Here, we characterized two cohorts of 33 patients with OCCC from LA (24 from Brazil and 9 from Costa Rica) and a cohort of 27 patients from Spain. Genomic analysis was performed for 26 OCCC using the OncoScan platform. Tumors were classified according to their genomic landscapes into subgroups. Clinical parameters were related to the frequency of genomic aberrations. RESULTS: The median overall survival (OS) was not significantly different between the cohorts. Genomic landscapes were characterized by different homologous recombination deficiency (HRD) levels. No difference in the distribution of genomic landscapes profiles was detected between patients from the different cohorts. OCCCs with MYC-amplified tumors harboring a concomitant loss of a region in chromosome 13q12-q13 that includes the BRCA2 gene had the longest OS. In contrast, patients carrying a high number (> 30) of total copy number (CN) aberrations with no concomitant alterations in MYC and BRCA2 genes presented the shortest OS. Furthermore, amplification of the ASH1L gene was also associated with a shorter OS. Initial-stage OCCCs with early progression were characterized by gains in the JNK1 and MKL1 genes. CONCLUSIONS: Our results provide new data from understudied OCCC populations and reveal new potential markers for OCCCs.

Two-Minute Step Test as a Complement to Six-Minute Walk Test in Subjects With Treated Coronary Artery Disease.

The 2-Minute Step Test (2MST) has been presented as an alternative to the 6-Minute Walk Test (6MWT) based on the association between the two tests in older adults; however, some authors propose that it should not be a substitute but rather a complement to the latter in the fitness evaluation. Specifically, in coronary disease, despite the potential and clinical utility of 2MST, the relationship of both tests in this population is unknown. This study aimed to determine the relationship between 6MWT and 2MST and to explore the relationship of biodemographic factors for both tests in subjects with treated coronary artery disease. For this, the 6MWT and the 2MST were applied to patients with coronary artery disease treated in 6 hospitals in Chile between May 2019 and February 2020. Additionally, lower limb strength was assessed by a chair-stand test, grip strength was assessed by a dynamometer, and physical measurements were applied. In total, 163 participants underwent both tests (average age = 58.7 ± 9.8 years; 73.6% men; 64.4% revascularized by angioplasty; 28.2% revascularized by surgery, and 7.4% treated by drugs or thrombolysis). Heart rate was higher at the end of the 6MWT, while the perception of effort was greater at the end of the 2MST. There was a weak positive correlation between the 6MWT and the 2MST in subjects with treated coronary disease (r = 0.28, p = 0.0003). While age (r = -0.27), weight (r = 0.25), height (r = 0.49), and strength of both lower limbs (r = 0.41) and grip strength (r = 0.53) correlated weakly or moderately to the covered distance in 6MWT, the number of steps by the 2MST correlated only weakly to height (r = 0.23), lower limb strength (r = 0.34), and grip strength (r = 0.34). Age, weight, height, lower limb strength, and grip strength would explain better the meters walked in the 6MWT than the steps achieved in the 2MST. With these findings, we can conclude that, in patients with treated coronary artery disease, it does not seem advisable to replace 6MWT with 2MST when it is possible to do so. Additionally, the 2MST may provide additional information in the fitness evaluation. However, the usefulness of 2MST in this population needs to be further studied.

Modalidad previa de diálisis y su influencia en los resultados del trasplante renal / Impact of predialysis therapy on kidney transplant outcomes

Resumen Introducción: el trasplante renal es el tratamiento de elección para los pacientes con enfermedad renal crónica terminal; sin embargo, un trasplante renal anticipado no siempre es posible y muchos pacientes requieren algún tipo de terapia de reemplazo renal previa al trasplante. Objetivo: este estudio tiene como objetivo evaluar los desenlaces a corto y largo plazo, post-trasplante renal, de acuerdo con la modalidad de diálisis previa al trasplante. Métodos: estudio de tipo cohorte retrospectiva. Se incluyeron pacientes mayores de 18 años que recibieron un trasplante renal durante 2005-2018. Inicialmente se realizó estadística descriptiva y posteriormente se realizó análisis multivariado mediante un modelo de riesgos proporcionales de Cox, con el objetivo de evaluar la relación entre la supervivencia del paciente y del injerto y la necesidad de diálisis previa al trasplante. Se evaluó, además, la tasa de filtración glomerular durante los primeros dos años del trasplante renal. Resultados: durante 2005-2018 se realizaron 925 trasplantes renales, 289 estaban en diálisis peritoneal, 439 en hemodiálisis y 197 no estaban en diálisis. La supervivencia del paciente a 6, 12, 24, 48 y 60 meses posterior al trasplante renal fue de 97,5 %, 96,7 %, 96,0 %, 93,7 % y 92,3 %, respectivamente, y del injerto fue de 94,5 %, 92,9 %, 90,5 %, 84,8 %, 81,1 %, también respectivamente, sin encontrar diferencia estadísticamente significativa entre los que tuvieron diálisis peritoneal vs. hemodiálisis (p = 0,402, p = 0,180), tampoco se encontraron diferencias significativas en el análisis multivariado. El 8,1 % de los pacientes presentó rechazo agudo en el primer año post trasplante y el 13,2 % durante todo el seguimiento, sin encontrarse diferencias significativas entre los que habían tenido diálisis peritoneal vs. hemodiálisis. No se encontraron diferencias en la TFG. Conclusiones: no se encontraron diferencias estadísticamente significativas en los desenlaces duros a corto y largo plazo, según la modalidad de diálisis pretrasplante.

Abstract Introduction: kidney transplantation is the standard treatment option for patients with end-stage chronic kidney disease. However, early kidney transplantation is not always possible, and many patients require renal replacement therapy. This study aims to evaluate the short and long-term outcomes after kidney transplantation in patients undergoing dialysis therapy before transplantation. Methods: a retrospective cohort of renal transplant patients older than 18 years of age were evaluated during the years 2005-2018. A descriptive analysis was performed. A proportional Cox-Hazard model was used to evaluate the relationship between patient and transplant survival and pre-transplant dialysis. An analysis of variance was used to compare the glomerular filtration rate during the first two years after transplantation. Results: between 2005-2018, 925 kidney transplants were performed, of which 289 required peritoneal dialysis, 439 haemodialysis and 197 did not require dialysis. Patient and transplant survival rates at 6, 12, 24, 48, 60 months after kidney transplantation were 97.5%, 96.7%, 96.0%, 93.7%, 92.3%, 94.5%, 92.9%, 90.5%, 84.8%, 81.1%. No statistically significant difference was found between peritoneal dialysis patients and hemodialysis patients (p=0.402, p=0.180). Acute rejection occurred in 8.1% of patients in the first year after transplantation and in 13.2% during the entire follow-up. Glomerular filtration rate values were similar in patients with and those without pre-transplant dialysis Conclusions: there were no significant statistical differences in short and long-term outcomes among patients undergoing pre-transplant dialysis vs. no.

Enfoque del paciente con adenopatías generalizadas. Importancia de la estrategia didáctica del estudio de casos clínicos: a propósito de un paciente con linfoma de Hodgkin asociado a una infección por el virus de Epstein-Barr

Se muestra el caso de un paciente con 56 años de edad, con un síndrome adenomegálico generalizado que presentó un linfoma de Hodgkin de celularidad mixta, asociado al virus de Epstein-Barr. El paciente previo al inicio del linfoma presentó episodios prolongados de estrés emocional, lo que posiblemente contribuyó a la disminución de la vigilancia inmunológica. El caso fue abordado por los estudiantes de quinto semestre en la asignatura Acto médico, una estrategia didáctica interdisciplinaria. Este artículo presenta los aspectos a tener en cuenta en el enfoque clínico de los pacientes con adenopatías desde una perspectiva integradora de la inmunología, la clínica y los diagnósticos diferenciales. Se resalta el valor del estudio de los casos clínicos con varios métodos diagnósticos como estrategia didáctica. Finalmente, se realiza una revisión de la literatura sobre el linfoma Hodgkin orientada al papel en el que participa la infección por el virus de Epstein-Barr, relacionada con la inmunosupresión por estrés.

SUMMARY We present the case of a 56-year-old patient with a generalized adenomegalic syndrome who presented a mixed cellular Hodgkin's lymphoma associated with Epstein Barr Virus. The patient had had great emotional stress prior to the onset of lymphoma, which possibly contributed to the decrease in immunological surveillance. The case was addressed by the students of the fifth semester in the subject "Medical Act", an interdisciplinary didactic strategy. We present the aspects to be taken into account in the approach of the clinician of patients with adenopathies from an integrative perspective of immunology, clinical and differential diagnoses; and the value of the study of clinical cases with several diagnostic approaches as a didactic strategy is highlighted. Finally, we present a literature review about Hodgkin lymphoma and the role which plays stress related Epstein Barr Virus infection.

Angioplastía con balón para el tratamiento de la hipertensión arterial pulmonar por enfermedad tromboembólica crónica. Resultados hemodinámicos y clínicos inmediatos / Balloon pulmonary angioplasty for the treatment of chronic thromboembolic pulmonary hypertension

Background: Balloon pulmonary angioplasty (BPA) is a therapeutic alternative for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Aim: To report the initial experience with the "refined BPA technique" with the use of intravascular images. Patients and Methods: Between June 2015 and June 2016 we selected fourteen patients with CTEPH who were considered candidates for BPA. Lesions targeted for treatment were further analyzed using intravascular imaging with optical frequency domain imaging (OFDI). We report the immediate hemodynamic results and four weeks of follow-up of the first eight patients of this series. Results: We performed 16 BPA in eight patients aged 61 ± 14 years (88% women). Mean pulmonary artery pressure (PAPm) was 48.6 ± 5.8 mmHg. Success was achieved in seven patients (88%). A mean of 2.3 segments per patient were intervened in 11 sessions (1.6 sessions/ patient). Only one patient developed lung reperfusion injury. No mortality was associated with the procedure. After the last BPA session, PAPm decreased to 37.4 ± 8.6 mmHg (p=0.02). Pulmonary vascular resistance (RVP) decreased from 858,6 ± 377,0 at baseline to 516,6 ± 323,3 Dynes/sec/cm−5 (p<0.01) and the cardiac index increased from 2.4±0.6 at baseline to 2.8±0.3 L/min/m2 (p=0.01). At 4 weeks after the last BPA, WHO functional class improved from 3.3±0.5 to 2.5±0.5 (p<0,01) and six minutes walking distance from 331±92 to 451±149 m (p=0.01). Conclusions: BPA guided by OFDI for the treatment of inoperable CTEPH patients is a safe alternative with excellent immediate hemodynamic and clinical results.

Results of endoscopic nasal surgery in the treatment of invasive fungal sinusitis in children with cancer and immunosuppression. / Resultados de cirugía endoscópica nasal en el tratamiento de sinusitis fúngica invasiva en niños con cáncer e inmunosupresión.

BACKGROUND AND OBJECTIVE: to describe the results of the treatment of invasive fungal sinusitis with nasal endoscopic surgery in an immunocompromised paediatric oncological population. METHODS: retrospective study of all patients diagnosed with invasive fungal sinusitis operated in the National Paediatric Oncology Unit between 2012 and 2016. Data taken from their medical history included: epidemiological characteristics, oncological diagnosis, haematological data, symptoms, tomographic studies, surgical interventions, results of pathology and cultures, medications received, complications, evolution and survival. RESULTS: 18 patients were identified, 7 male and 11 female. The average age was 12 years, 13 had a diagnosis of acute lymphocytic leukemia and 5 of acute myeloid leukemia. Seventeen patients presented severe neutropenia at the time of diagnosis. The most frequently identified aetiological agent was Aspergillus in 13 patients. In 16 patients (89%) the disease was controlled with nasal endoscopic surgery. Ten patients died due to unrelated causes throughout the study. DISCUSSION AND CONCLUSIONS: Invasive fungal sinusitis should be considered a medical emergency due to its high mortality. The diagnosis is based on a high index of suspicion in patients with predisposing factors (leukaemia, neutropenia, persistent fever, nasogastric tube) and endoscopic nasal evaluation. Antifungal medical treatment and aggressive nasal endoscopic surgery is indicated regardless of the patient's condition to reduce the fungal burden and associated high mortality. The treatment must be provided by a multidisciplinary team that includes paediatrics, haemato-oncology, infectology and otorhinolaryngology.

Laryngeal Epstein-Barr Virus-Associated Smooth Muscle Tumor in an Undernourished Child.

Smooth muscle tumors associated with Epstein-Barr virus infections (EBV-SMT) of laryngeal origin are exceedingly rare and have been reported in few adult patients, but not in children. This reported case describes a lesion found in the larynx of an 8-year-old Guatemalan undernourished girl. Microscopically, the lesion showed a highly cellular mesenchymal spindle cell tumor, containing frequent lymphocytes. The immunohistochemical analysis revealed positivity for α-smooth muscle actin and h-caldesmon. In addition, most of the tumor cells were positive for EBV by in situ hybridization. To the best of the author's knowledge, this is the first literature-reported case of laryngeal EBV-SMT occurring in an undernourished child.

Nasopharyngeal Angiofibroma: A Clinical, Histopathological and Immunohistochemical Study of 42 Cases with Emphasis on Stromal Features.

Nasopharyngeal angiofibroma is a benign but aggressive tumor of unknown etiology, typically occurring in adolescent males. It is described as a rare neoplasm; however, the prevalence seems to have geographic differences. All cases referred to our head and neck clinical and pathology service were reviewed. Most of the patients presented at an advanced stage. The clinical and radiographic features are presented and discussed. Histologically, the tumor shows a highly vascular fibrous proliferation with characteristic plump, angulated and stellate cells, categorized as fibroblasts. Immunohistochemistry was performed on 42 cases to further elucidate the nature of these cells. The stromal cells expressed vimentin and factor XIIIa, the latter expressed most commonly in the giant stellate cells. Inflammation was almost exclusively present in peripheral subepithelial areas. Mast cells were abundant, even in the absence of other inflammatory cells. Lymphatics were observed principally in peripheral regions. Proliferating cells (Ki-67 reactive) were restricted to endothelial cells.

Pseudotumor inflamatorio o miofibroblástico del bazo: manejo laparoscópico / Inflammatory pseudotumor or myofibroblastic tumor of the spleen: laparoscopic management

El pseudotumor inflamatorio o tumor miofibroblástico del bazo es una neoplasia primaria esplénica benigna, inusual, descrita también en otros órganos linfoides, tracto gastrointestinal, meninges y tejidos blandos. No se conoce con claridad la causa, pero se han propuesto teorías relacionadas con déficit inmunológico, infección por virus Epstein Barr y trastornos vasculares. El caso que se describe en un paciente joven corresponde a esta patología que hasta donde investigamos no se ha descrito en nuestro país y son pocos los reportados en la literatura...

Inflammatory pseudotumor or myofibroblastic tumor of the spleen is an uncommon primary benign neoplasm, described in other lymphoid organs such as, gastrointestinal tract, meninges and soft tissues. Its cause is not clearly known, but some theories such as immunologic deficiency related causes, Epstein Barr virus infection and vascular disorder, have been proposed. The described case in a young patient corresponds to this condition. To the best of our knowledge, this condition has not been described in our country and few cases have been reported in the literature...

Functional and oncological results of non-surgical vs surgical treatment in squamous cell carcinomas of the oropharynx.

INTRODUCTION AND OBJECTIVES: Squamous cell carcinomas of the oropharynx are aggressive tumours usually diagnosed at advanced stage. Their optimal treatment has not been established. The aim of this study was to compare the oncological and functional outcomes in patients with carcinomas of the oropharynx treated by radiotherapy (with chemotherapy in advanced stages) vs surgery (with radiotherapy in advanced stages). METHODS: A retrospective study on 50 patients with squamous cell cancer of the oropharynx treated by radiotherapy (with or without chemotherapy) at our institution between 1998 and 2008 was carried out. The oncological and functional results were compared with patients with same cancer location and stage treated by surgery (with or without radiotherapy). In both groups, the patients were classified as follows: 10% Stage I, 12% Stage II, 16% Stage III, 48% Stage IVa and 14% Stage IVb. RESULTS: The 5-year disease-specific survival was 33% in the radiotherapy group and 52% in the surgical group (P=.17). Five-year disease-specific survival for Stage I and II patients was 82% in the radiotherapy group and 70% in the surgical group. In Stage III and IV disease, 5-year disease-specific survival was higher in the surgical group (47% vs 17%). The functional results were similar; anatomical and functional preservation of the larynx was higher in the radiotherapy group but the successful return to oral food intake was higher in the surgical group. CONCLUSIONS: The prognosis of squamous cell carcinoma of the oropharynx is poor. Oncological results in Stages I and II were similar for radiotherapy and surgical treatments. In advanced stages, the prognosis was better in patients treated by surgery with or without radiotherapy. Functional results were similar in both treatment modalities.

[Neurolaryngology]. / Neurolaringología.

The neuroanatomy of voice and speech is complex. An intricate neural network is responsible for ensuring the main functions of the larynx: airway protection, cough and Valsalva production, and providing voice. Coordination of these roles is very susceptible to disruption by neurological disorders. Neurological disorders that affect laryngeal function include Parkinson's disease, stroke, amyotrophic lateral sclerosis, multiple sclerosis, dystonia and essential tremor. A thorough neurological evaluation should be routine for any patient presenting with voice complaints suggestive of neurogenic cause. Endoscopic visualisation of the larynx using a dynamic voice assessment with a flexible laryngoscope is a crucial part of the evaluation and ancillary tests are sometimes performed. Otolaryngologic evaluation is important in the diagnosis and treatment of neurological disorders that affect laryngeal function.

Wnt-pathway activation in intestinal-type sinonasal adenocarcinoma.

BACKGROUND: Intestinal-type sinonasal adenocarcinoma (ITAC) is an epithelial cancer of the sinonasal sinuses that shows histological similarity to colorectal cancer (CRC) and share chronic inflammation as a possible etiological factor. The Wnt-pathway is one of the most important tumourigenic pathways in CRC. The aim of this study was to investigate if the Wnt-pathway is activated in ITAC. METHODOLOGY: Protein expression profiles of E-cadherin, ß-catenin, c-myc and cyclin D1 were analysed by immunohistochemistry in 83 samples of ITAC, organized into tissue microarray blocks. RESULTS: Nuclear ß-catenin expression was observed in 31% of the cases and was twice as frequent in papillary/colonic ITAC compared to solid/mucinous subtypes. Loss of membranous ß-catenin staining occurred in 24% and loss of membranous E-cadherin in 6% of the cases and this was more prominent in mucinous types. Strong c-myc and cyclin D1 expression was observed in 30% and 4% of the cases, respectively. Nuclear ß-catenin expression was significantly related to poor clinical outcome, independent from established factors as tumour stage and histological type. CONCLUSION: The presence of nuclear ß-catenin in 31% of patients with ITACs indicated that in a subset of patients, the Wnt-pathway is active and conveys a worse prognosis.

Oncologic and functional results after transhyoid surgical approach for cancer of the base of tongue.

BACKGROUND: The optimal treatment for base of tongue cancer remains unclear, especially in advanced stages. METHODS: We retrospectively review 84 previously untreated patients that underwent a transhyoid resection of a base of tongue carcinoma. Sixty-four patients (76%) underwent postoperative radiotherapy. RESULTS: Five patients had stage II disease, 6 had stage III, 58 had stage IVA, and 15 had stage IVB. The overall recurrence rate was 68%. Five-year disease-specific survival rates by stage were 100%, 67%, 27%, and 8% for stage II to IVB, respectively (p = .0007). Multivariate analysis showed that the presence of lymph node metastases was an independent predictor of reduced disease-specific survival rates (p = .02). All patients maintained an intelligible voice, and oral alimentation was successfully recovered in 97.5% of them. CONCLUSIONS: The transhyoid approach allowed adequate resection of base of tongue cancers with low morbidity and acceptable functional results, but the oncologic outcomes in advanced stages are poor. Head Neck, 2011.

[Oncologic and functional results of surgical treatment for base of tongue carcinomas]. / Resultados oncológicos y funcionales del tratamiento quirúrgico de los carcinomas de base de lengua.

INTRODUCTION AND OBJECTIVES: Squamous cell carcinomas at the base of the tongue are usually diagnosed at advanced stages, and their optimal treatment has not been established. The aim of this study was to describe the functional and oncological outcomes of patients with base of tongue carcinomas treated with surgery. MATERIALS AND METHODS: A retrospective study on 132 patients with base of tongue carcinoma surgically treated in our hospital between 1990 and 2007 was carried out. One patient (0.75%) was in stage I, 8 (6%) were in stage II, 15 (11%) in stage III, 91 (69%) in stage IVA, and 17 (13%) with stage IVB. A total of 92 (70%) patients received postoperative radiotherapy. RESULTS: Eighty-seven patients (66%) had recurrence: 23 patients (17%) had local recurrence, 15 (11%) regional, 20 (15%) locoregional, 16 (12%) locoregional and distant, and 9 (7%) distant metastases. The disease-specific survival was 34% at 5 years (100% for stages I and II, 44% for stage III, 28% for stage IVA and 12% for IVB; p=0.0004). Multivariate analysis showed two variables independently associated with worse survival: lymph node metastases classified as N2-3 (p=0.016) and primary tumours classified as T3-4 (p=0.040). Adequate oral intake was achieved by 96% of the patients and 79% could be decannulated. CONCLUSIONS: The prognosis of squamous cell carcinomas of the base of the tongue is poor, especially in advanced stages. Surgical treatment provides oncological and functional results similar to other therapeutic modalities.

[Surgical treatment of head and neck chondrosarcomas]. / Tratamiento quirúrgico de los condrosarcomas de cabeza y cuello.

INTRODUCTION: Head and neck chondrosarcomas may adopt different locations and biological behaviour. MATERIAL AND METHOD: We present a retrospective clinical series of 17 chondrosarcomas surgically treated in our Department from 1977 until 2006. RESULTS: Chondrosarcomas were located in the nasosinusal area (n=6), larynx (n=5), petrous bone (n=3), atlas (n=1), parapharyngeal space (n=1) and trachea (n=1). All patients except for one underwent surgery with radical intention. The mean follow-up period was 84 months (median, 71 months). Six patients developed recurrent disease with a mean latency of 10 months. Two patients died due to the disease and two remained alive with evidence of tumour. Patients with grade I chondrosarcomas presented less recurrent disease than those with grade II or III chondrosarcomas (17% versus 80%, P=0.029). The estimated 5-year survival was 88% with the better survival of patients with grade I chondrosarcomas reaching statistical significance (P=0.023). In 2 patients with cricoid chondrosarcomas, the reconstruction was carried out using the Rethi-Ward technique, and they were without evidence of disease at 71 months (with no cannula) and 145 months (with cannula). Chondrosarcomas of the jugular foramen were treated using a modified infratemporal type A approach. CONCLUSION: Low grade head and neck chondrosarcomas have a good prognosis while high grade chondrosarcomas tend to recur, despite radical surgical treatment.