Characteristics and prognosis of jejunoileal gastrointestinal stromal tumours (GISTs) in the era of imatinib: a comparative study with gastric GISTs

Backgroung Gastrointestinal stromal tumours (GISTs) located in the jejunum or ileum (JI-GIST) are considered worse prognosis compared to those of gastric (G-GIST) location. It has been suggested that this dogma should be revised. The aim of this study was to describe the characteristics of jejunoileal GISTs and its prognosis and to compare them with G-GISTs in the era of imatinib. Methods We retrospectively reviewed the clinical histories of all the patients diagnosed with GISTs between January 2000 and November 2016: Clinical and pathological data, as recurrence, metastatic state, disease-free survival (DFS) as well as overall survival (OS) rates of patients were reviewed. Results JI-GIST patients comprise 29 cases (37.7%). Compared to G-GIST, JI-GIST patients had undergone emergency surgery more frequently (37.9% vs. 10.4%, p = 0.007). According to the NIH-Fletcher classification, the low or very-low risk group represents 17.2% of JI-GISTs as opposed to 37.6% of G-GISTs (p < 0.005). When the AFIP-Miettinen system was used the low or very-low group represented 17.2% of JI-GISTs vs. 58.4% in the G-GISTs group (p < 0.001). Both local recurrence (24.1% vs. 12.5%, p < 0.05) and metastatic rate (34.5% vs. 22.9%, p < 0.05) were higher in the JI-GIST group than in G-GIST. 5- and 10-year DFS and 10-year OS rate were lower for JI-GIST (54.5% and 39.6% vs. 77.2% and 60.8%, and 57.9% vs. 65%, respectively, p < 0.05). Conclusions The observed differences between both groups in DFS and OS rates at long term could be attributed to the effect of imatinib (AU)

Characteristics and prognosis of jejunoileal gastrointestinal stromal tumours (GISTs) in the era of imatinib: a comparative study with gastric GISTs.

BACKGROUND: Gastrointestinal stromal tumours (GISTs) located in the jejunum or ileum (JI-GIST) are considered worse prognosis compared to those of gastric (G-GIST) location. It has been suggested that this dogma should be revised. The aim of this study was to describe the characteristics of jejunoileal GISTs and its prognosis and to compare them with G-GISTs in the era of imatinib. METHODS: We retrospectively reviewed the clinical histories of all the patients diagnosed with GISTs between January 2000 and November 2016: Clinical and pathological data, as recurrence, metastatic state, disease-free survival (DFS) as well as overall survival (OS) rates of patients were reviewed. RESULTS: JI-GIST patients comprise 29 cases (37.7%). Compared to G-GIST, JI-GIST patients had undergone emergency surgery more frequently (37.9% vs. 10.4%, p = 0.007). According to the NIH-Fletcher classification, the low or very-low risk group represents 17.2% of JI-GISTs as opposed to 37.6% of G-GISTs (p < 0.005). When the AFIP-Miettinen system was used the low or very-low group represented 17.2% of JI-GISTs vs. 58.4% in the G-GISTs group (p < 0.001). Both local recurrence (24.1% vs. 12.5%, p < 0.05) and metastatic rate (34.5% vs. 22.9%, p < 0.05) were higher in the JI-GIST group than in G-GIST. 5- and 10-year DFS and 10-year OS rate were lower for JI-GIST (54.5% and 39.6% vs. 77.2% and 60.8%, and 57.9% vs. 65%, respectively, p < 0.05). CONCLUSIONS: The observed differences between both groups in DFS and OS rates at long term could be attributed to the effect of imatinib.

Radiotherapy is safe in patients with implantable cardiac devices. Analysis of a systematic interrogation follow-up.

INTRODUCTION: The number of patients who have a cardiac implantable electronic device (CIEDs) that undergo a course of radiotherapy is increasing due to the ageing population. The majority of clinical studies only evaluate any CIED malfunction at the end of a course of irradiation or in a case of there being symptoms of possible malfunction. As a result, little data has been collected on CIED status acquired during an active course of irradiation. MATERIAL AND METHODS: We aimed to evaluate the correct functioning of a CIED during a course of radiotherapy. So, a retrospective analysis was made of all patients having CIEDS in a single institution during their course of radiotherapy. All CIEDs were systematically checked before and during the course of radiotherapy according to the risk of device failure and patient dependence. RESULTS: Data was analysed from 56 patients (43 men, 13 women) with a mean age of 78.2 years, of whom 87.5% of the patients carried a pacemaker (PM), the 39% of the patients were PM dependent, and the remaining patients carried an implantable cardioverter-defibrillator (ICD). An observable dose of irradiation was evident in only 10 cases. 69.1% of the CIEDs were checked daily and the remainder were checked weekly. During the radiotherapy course, 82% of the patients did not complain of any cardiological event. The CIED of five patients experienced an increase in the threshold and, in another case, a sudden reduction in the duration of the battery was reported. Another patient with a CIED experienced a cardiac insufficiency episode triggered by a ventricular tachycardia. CONCLUSION: In conclusions, although adverse clinical events from exposure of a CIED to irradiation are rare, they can appear in any group of risk. No dose-dependency was observed on the malfunction of the CIED.

Additional malignancies in patients with gastrointestinal stromal tumors (GIST): incidence, pathology and prognosis according to a time of occurrence-based classification.

BACKGROUND: The aim of the study is to clarify if a classification based on the time of occurrence of associated malignancies in GIST patients can help in the understanding of the clinical controversies observed in these patients. METHODS: We retrospectively reviewed all the patients diagnosed with GIST tumors between January 1999 and October 2016. They were divided into GIST patients associated with other tumors (A-GIST) and those not associated (NA-GIST). A-GIST patients were also divided into four types according to the proposed classification. RESULTS: Of 104 GIST patients, 32 (30.7%) (A-GIST group) had at least one additional primary malignancy. The most frequent location of the associated malignancy was the GI tract (26%). Compared to NA-GIST, A-GIST were more often asymptomatic with a lower risk of recurrence. The main cause of death in NAGIST was GIST itself, being associated tumors the main cause of death in A-GIST group. No differences were found in DFS and OS between A-GIST and NA-GIST. CONCLUSIONS: The use of the proposed classification classifies GIST patients with associated malignancies in different subtypes that differ substantially in terms of incidence, type of neoplasms associated, cause of the association and prognosis.

Non-compaction cardiomyopathy and early respiratory failure in an adult symptomatic female carrier of centronuclear myopathy caused by a MTM1 mutation.

X-linked myotubular myopathy (XLMTM) is a rare neuromuscular condition caused by mutations in the MTM1 gene. Female carriers are believed to be usually asymptomatic; nevertheless, recent reports have displayed a wide a spectrum of clinical involvement in females suggesting that MTM1 mutations might be underestimated in this population. Here we report a 55-year-old woman manifesting with an abrupt respiratory decline, whose respiratory function tests revealed a severe restrictive ventilatory defect. The neurological examination identified mild proximal leg weakness and her cardiac evaluation showed a non-compaction cardiomyopathy with normal left ventricle function. Muscle biopsy was consistent with centronuclear myopathy. Next-generation sequencing of 49 genes related to congenital myopathies allowed the identification of a 4 bp deletion in the MTM1 gene, leading to a truncating mutation previously described in males but for the first time reported in a female patient.

From individual to collective 3D cancer dissemination: roles of collagen concentration and TGF-ß.

Cancer cells have the ability to migrate from the primary (original) site to other places in the body. The extracellular matrix affects cancer cell migratory capacity and has been correlated with tissue-specific spreading patterns. However, how the matrix orchestrates these behaviors remains unclear. Here, we investigated how both higher collagen concentrations and TGF-ß regulate the formation of H1299 cell (a non-small cell lung cancer cell line) spheroids within 3D collagen-based matrices and promote cancer cell invasive capacity. We show that at low collagen concentrations, tumor cells move individually and have moderate invasive capacity, whereas when the collagen concentration is increased, the formation of cell clusters is promoted. In addition, when the concentration of TGF-ß in the microenvironment is lower, most of the clusters are aggregates of cancer cells with a spheroid-like morphology and poor migratory capacity. In contrast, higher concentrations of TGF-ß induced the formation of clusters with a notably higher invasive capacity, resulting in clear strand-like collective cell migration. Our results show that the concentration of the extracellular matrix is a key regulator of the formation of tumor clusters that affects their development and growth. In addition, chemical factors create a microenvironment that promotes the transformation of idle tumor clusters into very active, invasive tumor structures. These results collectively demonstrate the relevant regulatory role of the mechano-chemical microenvironment in leading the preferential metastasis of tumor cells to specific tissues with high collagen concentrations and TFG-ß activity.

Multicentric cutaneous keratoacanthomas in a free-living marmoset (Callithrix sp.).

Cutaneous neoplasia is common in non-human primates. We describe the gross and microscopic features of multicentric cutaneous keratoacanthomas in a free-living marmoset (Callithrix sp.). Immunohistochemistry for human papillomavirus and herpes simplex virus type I and simplex virus type II was negative. Keratoacanthomas should be included in the differential diagnosis for cutaneous masses in non-human primates.

ddradseqtools: a software package for in silico simulation and testing of double-digest RADseq experiments.

Double-digested RADseq (ddRADseq) is a NGS methodology that generates reads from thousands of loci targeted by restriction enzyme cut sites, across multiple individuals. To be statistically sound and economically optimal, a ddRADseq experiment has a preliminary design stage that needs to consider issues related to the selection of enzymes, particular features of the genome of the focal species, possible modifications to the library construction protocol, coverage needed to minimize missing data, and the potential sources of error that may impact upon the coverage. We present ddradseqtools, a software package to help ddRADseq experimental design by (i) the generation of in silico double-digested fragments; (ii) the construction of modified ddRADseq libraries using adapters with either one or two indexes and degenerate base regions (DBRs) to quantify PCR duplicates; and (iii) the initial steps of the bioinformatics preprocessing of reads. ddradseqtools generates single-end (SE) or paired-end (PE) reads that may bear SNPs and/or indels. The effect of allele dropout and PCR duplicates on coverage is also simulated. The resulting output files can be submitted to pipelines of alignment and variant calling, to allow the fine-tuning of parameters. The software was validated with specific tests for the correct operability of the program. The correspondence between in silico settings and parameters from ddRADseq in vitro experiments was assessed to provide guidelines for the reliable performance of the software. ddradseqtools is cost-efficient in terms of execution time, and can be run on computers with standard CPU and RAM configuration.

[Differential diagnosis of chest pain: a case of acute aortic syndrome]. / Diagnóstico diferencial del dolor torácico: un caso de síndrome aórtico agudo.

Chest pain is one of the most frequent reasons for consulting in any healthcare setting, however its diagnosis remains a challenge for both Primary Care and Emergency Department physicians. We report a case of an Acute Aortic Syndrome which was diagnosed late after an insidious course of chest pain, repetitive syncope, and in which the delay in diagnosis and treatment could be fatal. We also describe the definition, diagnosis, treatment, and outcome of this condition.

Diagnóstico diferencial del dolor torácico: un caso de síndrome aórtico agudo / Differential diagnosis of chest pain: a case of acute aortic syndrome

El dolor torácico es uno de los motivos de consulta más frecuentes en cualquier ámbito sanitario, no obstante sigue suponiendo un reto diagnóstico tanto en la consulta del médico de atención primaria como en el ámbito de los médicos que prestan atención en los servicios de urgencias. Describimos un caso de síndrome aórtico agudo que se presentó de forma insidiosa en forma de dolor torácico y síncope de repetición en el que el retraso en el diagnóstico y tratamiento pudo resultar fatal. Hacemos también un breve repaso en la definición, diagnóstico, tratamiento y pronóstico de esta entidad (AU)

Chest pain is one of the most frequent reasons for consulting in any healthcare setting, however its diagnosis remains a challenge for both Primary Care and Emergency Department physicians. We report a case of an Acute Aortic Syndrome which was diagnosed late after an insidious course of chest pain, repetitive syncope, and in which the delay in diagnosis and treatment could be fatal. We also describe the definition, diagnosis, treatment, and outcome of this condition (AU)

Prolonged bisphosphonate release after treatment in women with osteoporosis. Relationship with bone turnover.

Bisphosphonates (BP), especially alendronate and risedronate, are the drugs most commonly used for osteoporosis treatment, being incorporated into the skeleton where they inhibit bone resorption and are thereafter slowly released during bone turnover. However, there are few data on the release of BP in patients who have received treatment with these drugs for osteoporosis. This information is essential for evaluating the possibility of BP cyclic therapy in these patients and for controlling their long-term presence in bone tissue. This study evaluated the urinary excretion of alendronate and risedronate in patients treated with these drugs for osteoporosis and analysed its relationship with bone turnover, time of previous drug exposure and time of treatment discontinuation. We included 43 women (aged 65±9.4 years) previously treated with alendronate (36) or risedronate (7) during a mean of 51±3 and 53±3 months, respectively, who had not been treated with other antiosteoporotic treatment and with a median time of discontinuation of 13.5 and 14 months, respectively. Both BP were detected in 24-hour urine by HPLC. In addition, bone formation (PINP) and resorption (NTx) markers were analysed. Both BP were also determined in a control group of women during treatment. Alendronate was detected in 41% of women previously treated with this drug whereas no patient previously treated with risedronate showed detectable urinary values. All control patients showed detectable values of both BP. In patients with detectable alendronate levels, the time of drug cessation was shorter than in patients with undetectable values (12 [6-19] versus 31 [7-72] months, p<0.001). Alendronate was not detected in any patient 19 months after treatment cessation. Alendronate levels were inversely related to time of treatment discontinuation (r=-0.403, p=0.01) and the latter was directly related to NTx (r=0.394, p=0.02). No relationship was observed with age, length of drug exposure, renal function or weight. In conclusion, contrary to risedronate, which was not detected in patients after cessation of treatment, alendronate was frequently detected in women previously treated with this agent up to 19 months after discontinuation of therapy. The relationship between alendronate levels and both bone resorption and time of treatment cessation further indicates a residual effect of this drug in bone, despite treatment discontinuation.

Quiste broncogénico fetal: diagnóstico antenatal y revisión de la literatura / Fetal bronchogenic cyst: prenatal diagnosis and review of literature

Las patologías torácicas son poco frecuentes. Dentro de éstas se encuentran los quistes broncopulmonares, que por lo general son de carácter benigno. Se presentan dos casos de diagnóstico antenatal, de evolución benigna y resolución espontánea.

Megavejiga fetal en el segundo trimestre: síndrome de Berdon- un signo fácil, un diagnóstico difícil / Fetal megabladder in the second trimester: Berdon syndrome a simple sign, a difficult diagnosis

El diagnóstico de megavejiga en el embarazo es infrecuente más aun si se trata de un feto femenino. Este hecho nos permite delimitar bastante las alternativas diagnósticas, dentro de un espectro bastante heterogénico. El síndrome Megavejiga-Microcolon Hipoperistalsis Intestinal(MMIHS) es una patología de muy mal pronóstico que asocia megavejiga y alteraciones intestinales severas. Es por esto que es importante tenerla presente, para poder dar a los padres una información fidedigna y certera en cuanto al pronóstico. Presentamos 2 casos de nuestro servicio en el período 1998-2003. Se comentan los aspectos diagnósticos, terapéuticos y la evolución.

Asociación entre el diagnóstico clínico e histopatológico de las pulpopatías / Association between clinical and histopathologic diagnosis of pulp diseases

Se realizó un estudio experimental, con el objeto de determinar la asociación del diagnóstico clínico de las pulpopatías con los hallazgos histopatológicos que se producen en el órgano dentinopulpar. Esta investigación analizó, bajo determinados criterios clínicos e histopatológicos, 51 piezas dentarias humanas, incluyendo dientes sanos y dientes con diferentes grados de compromiso del órgano pulpar. Las piezas dentarias fueron fijadas y descalcificadas, para posteriormente ser procesadas, obteniéndose diferentes cortes histológicos, los que fueron teñidos y observados al microscopio óptico. Como resultados, se obtuvo un alto porcentaje de asociación (84.4 por ciento) entre los hallazgos histopatológicos y los criterios clínicos utilizados para el diagnóstico. Fue interesante observar el compromiso parcial, en estados pulpares diagnosticados clínicamente como irreversibles y la falta evidente de relación entre la sintomatología dolorosa y la extensión del compromiso pulpar. Además, alrededor de un 21.6 por ciento de las muestras presentaron trastornos regresivos que corresponden a una respuesta del tejido conjuntivo vascular de la pulpa frente a un estímulo de larga data

Planning for the Mercy Center for Breast Health.

During the last months of 2000, administrators at the Mercy San Juan Medical Center in Carmichael, Calif., convened a steering committee to plan the Mercy Center for Breast Health. The Steering Committee was composed of the director of ancillary and support services, the oncology clinical nurse specialist, the RN manager of the oncology nursing unit, the RN surgery center manager, and me, the manager of imaging services. The committee was responsible for creating a new business with five specific objectives: to position the Center as a comprehensive diagnostic and resource center for women; to generate physician referrals to the Breast Center through various vehicles; to create awareness of the Breast Center's capabilities among area radiologists; to create awareness of the Breast Center among employees of six sister facilities; to create "brand awareness" for the Mercy Center for Breast Health among referring physicians and patients who could use competing centers in the area. The Steering Committee's charter was to design a center with a feminine touch and ambience and to provide a "one-stop shopping" experience for patients. A major component of the Breast Center is the Dianne Haselwood Resource Center, which provides patients with educational support and information. The Steering Committee brought its diverse experience and interests to bear on arranging for equipment acquisition, information and clerical systems, staffing, clinic office design, patient care and marketing. Planning the Mercy Center for Breast Health has been a positive challenge that brought together many elements of the organization and people from different departments and specialties to create a new business venture. Our charge now is to grow and to live up to our vision of offering complete breast diagnostic, education and support services in one location.

Contaminación intradomiciliaria en un sector de extrema pobreza de la comuna de La Pintana / Indoor air pollution in a zone of extreme poverty at La Pintana community, Santiago

Background: Indoor pollution can be an important risk factor for human health, considering that people spend more than 60 percent of their time in their houses. Aim: To investigate indoor pollution in a zone of extreme poverty in Metropolitan Santiago. Material and methods: During 24h, carbon monoxide (CO), sulfur dioxide (SO2), respirable particulate matter (PM10), polycyclic aromatic hydrocarbons absorbed in PM5, temperature and humidity, were measured in the interior of 24 houses in La Pintana, Santiago. Results: The higher pollutant concentrations were observed during hours when heating was used, in houses that used coal (mean PM10 250 µg/m3, CO 42 ppm, SO2 192 ppb) or firewood (mean PM10 489 µg/m3, CO 57 ppm, SO2 295 ppb). In all houses, polycyclic aromatic hydrocarbons were detected and they came from the interior of the house and not from external filtered air. Coal, firewood and cigarette smoke were important sources of carcinogenic and kerosene and gas were sources of non carcinogenic polycyclic aromatic hydrocarbons. Conclusions: In the houses studied, the population was exposed to an accumulation of highly toxic pollutants, caused by a lack of ventilation. A high relative humidity also contributed to the growth of biological pollutants