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1.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde | ID: lis-LISBR1.1-46984

RESUMO

"O câncer tem como causa uma variedade de fatores, que nós chamamos fatores de risco, cuja maioria se relaciona com o ambiente externo ou com aquilo que nós colocamos no nosso organismo”, explicou Inez Gadelha, Chefe de Gabinete da Secretaria de Atenção Especializada do Ministério da Saúde.


Assuntos
Neoplasias/prevenção & controle , Estilo de Vida Saudável
2.
Brain Res ; : 146712, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32044337

RESUMO

The present electrophysiological (EEG) study investigated the neural correlates of perceiving effortful vs. effortless movements belonging to a specific repertoire (ballet). Previous evidence has shown an increased heart and respiratory rate during the observation and imagination of human actions that require a great muscular effort. In addition, TMS (transcranial magnetic stimulation) and EEG studies have evidenced a greater muscle-specific cortical excitability and an increase in late event-related potentials during the observation of effortful actions. In this investigation, fifteen professional female ballet dancers and 15 controls with no experience whatsoever with dance, gymnastics, or martial arts were recruited. They were shown 326 short videos displaying a male dancer performing standard ballet steps that could be either effortful or relatively effortless. Participants were instructed to observe each clip and imagine themselves physically executing the same movement. Importantly, they were blinded to the stimuli properties. The observation of effortful compared with effortless movements resulted in a larger P300 over frontal sites in dancers only, likely because of their visuomotor expertise with the specific steps. Moreover, an enhanced Late Positivity was identified over posterior sites in response to effortful stimuli in both groups, possibly reflecting the processing of larger quantities of visual kinematic information. The source reconstruction swLORETA performed on the Late Positivity component showed greater engagement of frontoparietal regions in dancers, while task-related frontal and occipitotemporal visual regions were more active in controls. It, therefore, appears that, in dancers, effort information was encoded in a more refined manner during action observation and in the absence of explicit instruction. Acquired motor knowledge seems to result in visuomotor resonance processes, which, in turn, underlies enhanced action representation of the observed movements.

3.
Eur Rev Med Pharmacol Sci ; 24(1): 323-332, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31957846

RESUMO

OBJECTIVE: S100 proteins are demonstrated to exert a protective role in the gastrointestinal tract. In the present study, we investigated whether S100B protein, that is typically expressed by enteroglial cells, is detectable in feces and could be a useful noninvasive indicator of gut chronic inflammation. PATIENTS AND METHODS: This clinical prospective study included n=48 patients suffering Crohn's disease (CD) or ulcerative colitis (UC) and non IBD-controls. The clinical disease activity was evaluated using Harvey-Bradshaw or Mayo Score Index while the diagnosis of IBD was defined based on standard endoscopic and histological criteria. S100B and calprotectin were extracted and analyzed using commercial enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Unlike calprotectin, S100B was significantly decreased in both CD and UC compared to non IBD-patients. The strongest quantitative alterations of S100B were detected concomitantly with signs of active or quiescent disease, including high/normal expression of fecal calprotectin, mucosal damage/cryptitis, mucin depletion and inflammatory infiltrate, as defined by endoscopic evaluation and histological analysis. At the onset of disease and under no Infliximab-based therapy, the lowest was detected suggesting that S100B in feces could have a potential diagnostic value for IBD. CONCLUSIONS: Testing for S100B and calprotectin could be a useful screening tool to better predict IBD activity.

4.
Cerebellum ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900855

RESUMO

Relative frequency of hereditary ataxias remains unknown in many regions of Latin America. We described the relative frequency in spinocerebellar ataxias (SCA) due to (CAG)n and to (ATTCT)n expansions, as well as Friedreich ataxia (FRDA), among cases series of ataxic individuals from Peru. Among ataxic index cases from 104 families (38 of them with and 66 without autosomal dominant pattern of inheritance), we identified 22 SCA10, 8 SCA2, 3 SCA6, 2 SCA3, 2 SCA7, 1 SCA1, and 9 FRDA cases (or families). SCA10 was by far the most frequent one. Findings in SCA10 and FRDA families were of note. Affected genitors were not detected in 7 out of 22 SCA10 nuclear families; then overall maximal penetrance of SCA10 was estimated as 85%; in multiplex families, penetrance was 94%. Two out of nine FRDA cases carried only one allele with a GAA expansion. SCA10 was the most frequent hereditary ataxia in Peru. Our data suggested that ATTCT expansions at ATXN10 might not be fully penetrant and/or instability between generations might frequently cross the limits between non-penetrant and penetrant lengths. A unique distribution of inherited ataxias in Peru requires specific screening panels, considering SCA10 as first line of local diagnosis guidelines.

5.
Cerebellum ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31940124

RESUMO

The original version of this article unfortunately contained some mistakes in Table 2. The additional row (just above SCA2) with the following information "SCA1, 1(1), 1, 50, 74, 24, 46 and 0/1" should be inserted.

6.
Sci Rep ; 10(1): 507, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949257

RESUMO

Inflammatory bowel diseases (IBD) are chronic relapsing disorders that have a negative impact on quality of life. They can be highly disabling and have been associated with sleep disturbance. The aim of our study was to evaluate the sleep quality of a large cohort of IBD patients to identify possible associated cofactors. We prospectively recruited consecutive patients attending the IBD Unit of "Azienda Ospedaliera" of Padua from November 2018 to May 2019 and collected demographics and clinical characteristics. The patients completed the Pittsburgh Sleep Quality Index (PSQI), the IBD questionnaire (IBDQ), the IBD-Disability Index (IBD-DI) questionnaire, and the Hospital Anxiety and Depression Scale (9-HADS). A multivariate regression model was applied to assess independent risk factors of sleep disturbance among IBD-related variables, disability, quality of life, anxiety, and depression. We investigated the sleep quality of 166 patients with IBD, finding 67.5% of them suffering from sleep disturbance. In particular, low quality of life, presence of disability and extraintestinal manifestations were identified as independent risk factors of sleep disturbance. We discovered that all depressed patients were also affected by sleep disturbance, while we found no difference in sleep disturbance between patients with or without anxiety state. However, a positive correlation was reported between both anxiety and depression scores and PSQI score (Spearman correlation: r = 0.31 and r = 0.38 respectively). Our study showed that sleep quality is not directly associated with an active or inactive IBD state or with the ongoing treatment, but it is mostly correlated with the patients' mood state, disability, and quality of life. Gastroenterologists and psychologists should join forces during clinical outpatients' visits to evaluate emotional states for a better IBD management.

7.
Medwave ; 19(10): e7734, 2019 Nov 25.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-31887108

RESUMO

School kiosks are spaces where food is provided to preschool and school-age students. Sanitary control of products can help curb and reduce obesity in this study population. We determined compliance and regularity of the evaluation of school kiosks in general and by Regular Elementary Education Institutions in an area of Peru. We performed a secondary cross-sectional analysis of the database of biannual evaluations of school kiosks conducted by the North Pacific Health Network. The main response variables were (a) level of compliance, categorized in Initial (I), In-Process (P), Healthy Kiosk (KS), and Outstanding Healthy Kiosk (KSD). We assigned values from 1 = I to 4 = KSD and assessed the regularity of assessment (schools visited in either semester 1 or 2 or visited in both semesters). The study population consisted of 31 (47.7%) schools out of a total of 65. KS level was reached by 29.1% of the preschool facilities, while 40% of kindergarten/elementary kiosks reached the KS level. Regarding regularity of assessments, 54.8% of kiosks were evaluated in both semesters. All strategic actors of the Ministry of Health and Education must become involved in promoting and facilitating the attainment of the health goals by increasing the number of healthy or featured school kiosks.

8.
J Dig Dis ; 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31859432

RESUMO

OBJECTIVES: Ulcerative colitis (UC) can give rise to several restrictions of patients' working and social activities. We aimed to determine the association between disease chronicity and the state of disability in a large population with UC. METHODS: We recruited consecutive patients with UC attending the inflammatory bowel disease (IBD) unit of the Azienda Ospedaliera of Padua between July and December 2017. We collected patients' characteristics and clinical information, and all participants completed the IBD questionnaire (IBDQ) for quality of life assessment and the IBD disability index (IBD-DI) questionnaire. Using univariate logistic regression models we assessed whether the patients' characteristics and IBD-related variables were associated with an IBD-DI score ≤3.5. Statistically significant variables in the univariate analyses were then included in a multivariate regression model. Correlations between IBD-DI and all the above mentioned characteristics were investigated using the Spearman's rank correlation coefficient. RESULTS: We included 201 patients. A positive correlation was observed between IBD-DI and IBDQ (r = 0.82, P < 0.001). Multivariate regression modelling identified the following as independent factors related to disability: active disease (partial Mayo score ≥2) (odds ratio [OR] 6.54, 95% CI 3.21-13.22), the presence of extraintestinal manifestations (EIM) (OR 2.48, 95%, CI 1.11-5.54) and occasional alcohol consumption (OR 0.39, 95% CI 0.20-0.76). CONCLUSIONS: Impaired disability is mainly correlated with disease activity, the presence of EIM and no alcohol consumption. Moreover, there is a strong correlation with patients' quality of life. Therefore, in clinical practice, greater awareness of IBD-related disability is needed to better manage patients' outcomes.

9.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde, LIS-bvsms | ID: lis-LISBR1.1-46880

RESUMO

O câncer de pâncreas mais comum é do tipo adenocarcinoma (que se origina no tecido glandular), correspondendo a 90% dos casos diagnosticados. A maioria dos casos afeta o lado direito do órgão (a cabeça). As outras partes do pâncreas são corpo (centro) e cauda (lado esquerdo).


Assuntos
Neoplasias , Neoplasias Pancreáticas
10.
J Immunother Cancer ; 7(1): 316, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752994

RESUMO

BACKGROUND: Bone metastases (BoM) are a negative prognostic factor in non-small-cell lung cancer (NSCLC). Beyond its supportive role, bone is a hematopoietic organ actively regulating immune system. We hypothesized that BoM may influence sensitivity to immunotherapy. METHODS: Pretreated non-squamous (cohort A) and squamous (cohort B) NSCLCs included in the Italian Expanded Access Program were evaluated for nivolumab efficacy according to BoM. RESULTS: Cohort A accounted for 1588 patients with non-squamous NSCLC, including 626 (39%) with (BoM+) and 962 (61%) without BoM (BoM-). Cohort B accounted for 371 patients with squamous histology including 120 BoM+ (32%) and 251 (68%) BoM- cases. BoM+ had lower overall response rate (ORR; Cohort A: 12% versus 23%, p <  0.0001; Cohort B: 13% versus 22%, p = 0.04), shorter progression free survival (PFS; Cohort A: 3.0 versus 4.0 months, p <  0.0001; Cohort B: 2.7 versus 5.2 months, p <  0.0001) and overall survival (OS; Cohort A: 7.4 versus 15.3 months, p <  0.0001; Cohort B: 5.0 versus 10.9 months, p < 0.0001). Moreover, BoM negatively affected outcome irrespective of performance status (PS; OS in both cohorts: p < 0.0001) and liver metastases (OS cohort A: p < 0.0001; OS Cohort B: p = 0.48). At multivariate analysis, BoM independently associated with higher risk of death (cohort A: HR 1.50; cohort B: HR 1.78). CONCLUSIONS: BoM impairs immunotherapy efficacy. Accurate bone staging should be included in clinical trials with immunotherapy.

11.
Eur J Gastroenterol Hepatol ; 31(11): 1361-1369, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31567640

RESUMO

BACKGROUND: Disease phenotype and outcome of late-onset Crohn's disease are still poorly defined. METHODS: In this Italian nationwide multicentre retrospective study, patients diagnosed ≥65 years (late-onset) were compared with young adult-onset with 16-39 years and adult-onset Crohn's disease 40-64 years. Data were collected for 3 years following diagnosis. RESULTS: A total of 631 patients (late-onset 153, adult-onset 161, young adult-onset 317) were included. Colonic disease was more frequent in late-onset (P < 0005), stenosing behaviour was more frequent than in adult-onset (P < 0003), but fistulising disease was uncommon. Surgery rates were not different between the three age groups. Systemic steroids were prescribed more frequently in young adult-onset in the first year, but low bioavailability steroids were used more frequently in late-onset in the first 2 years after diagnosis (P < 0.036, P < 0.041, respectively). The use of immunomodulators and anti-TNF's even in patients with more complicated disease, that is, B2 or B3 behaviour (Montreal classification), remained significantly inferior (P < 0.0001) in late-onset compared to young adult-onset. Age at diagnosis, Charlson comorbidity index, and steroid used in the first year were negatively associated with the use of immunomodulators and biologics. Comorbidities, related medications and hospitalizations were more frequent in late-onset. Polypharmacy was present in 56% of elderly Crohn's disease patients. CONCLUSION: Thirty-two percent of late-onset Crohn's disease presented with complicated disease behaviour. Despite a comparable use of steroids and surgery, immunomodulators and biologics were used in a small number of patients.

12.
Clin Med Insights Circ Respir Pulm Med ; 13: 1179548419871527, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31516312

RESUMO

Small-bore pleural drainage device insertion has become a first-line therapy for the treatment of pleural effusions (PLEFF) in the intensive care unit; however, no data are available regarding the performance of resident doctors in the execution of this procedure. Our aim was to assess the prevalence of complications related to ultrasound-guided percutaneous small-bore pleural drain insertion by resident doctors. In this single-center observational study, the primary outcome was the occurrence of complications. Secondary outcomes studied were as follows: estimation of PLEFF size by ultrasound and postprocedure changes in PaO2/FiO2 ratio. In all, 87 pleural drains were inserted in 88 attempts. Of these, 16 were positioned by the senior intensivist following a failed attempt by the resident, giving a total of 71 successful placements performed by residents. In 13 cases (14.8%), difficulties were encountered in advancing the catheter over the guidewire. In 16 cases (18.4%), the drain was positioned by a senior intensivist after a failed attempt by a resident. In 8 cases (9.2%), the final chest X-ray revealed a kink in the catheter. A pneumothorax was identified in 21.8% of cases with a mean size (±SD) of just 10 mm (±6; maximum size: 20 mm). The mean size of PLEFF was 57.4 mm (±19.9), corresponding to 1148 mL (±430) according to Balik's formula. Ultrasound-guided placement of a small-bore pleural drain by resident doctors is a safe procedure, although it is associated with a rather high incidence of irrelevant pneumothoraces.

13.
Inflamm Bowel Dis ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31504536

RESUMO

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBDs) are treated with anti-TNF agents. Strategies to monitor response to therapy may improve clinical control of the disease and reduce economical costs. Previous evidence suggests cleavage of infliximab (IFX) by Matrix Metalloproteinase 3 (MMP3) as a mechanism leading to loss of response. Our study aimed to evaluate if MMP3 serum levels could be considered an early marker of anti-TNF nonresponse and to analyze the correlation with other biochemical markers of treatment failure such as IFX trough levels and anti-IFX antibodies, inflammatory markers, and albumin levels. METHODS: Retrospectively, 73 IBD patients who had received IFX for at least 1 year were enrolled: 35 patients were responders and 38 were nonresponders at 52 weeks. Clinical and biochemical data (Harvey-Bradshaw index [HBI], Mayo score, body mass index [BMI], C-reactive protein [CRP], fecal calprotectin and albumin levels), MMP3 serum levels, and drug monitoring were assessed at baseline, postinduction, and 52 weeks. RESULTS: The MMP3 levels were similar at baseline (19.83 vs 17.92 ng/mL), but at postinduction, patients who failed to respond at 1 year had significantly higher levels than patients who responded (26.09 vs 8.68 ng/mL, P < 0.001); the difference was confirmed at week 52 (29.56 vs 11.48 ng/mL, P < 0.001). The MMP3 levels tended to be higher in patients without antidrug antibodies than in patients with antidrug antibodies at postinduction and 52 weeks. CONCLUSIONS: The MMP3 serum determination may represent an early marker of response to infliximab.

14.
Gastroenterol Res Pract ; 2019: 5354320, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531015

RESUMO

Background/Aim: Inflammatory bowel disease (IBD) is a chronic disorder affecting patients' quality of life and increasing their disability. The aim of our study was to evaluate clinical and pharmacological factors associated with impaired quality of life and disability in a large cohort of IBD patients during IBD treatment. Methods: We consecutively and prospectively recruited all IBD patients referred to the IBD Unit of the "Azienda Ospedaliera" of Padua. Demographics and clinical information were collected, and all patients completed the IBD questionnaire (IBDQ) and the IBD-Disability Index (IBD-DI) questionnaire. A multivariate regression model and Spearman's rank correlation coefficient were applied for detecting IBD-related variables relevant to disability and quality of life. Results: We included 435 IBD patients. Multivariate regression modelling identified active disease, anaemia, presence of extraintestinal manifestations, and Crohn subtype as independent predictors for both disability and poor quality of life. We observed a strong positive correlation between IBD-DI and IBDQ (r = 0.84, p < 0.001), while there was no association with ongoing therapy or other clinical features disease-related. Conclusions: Our study showed that disability and quality of life are both associated with active disease, anaemia, presence of extraintestinal manifestations, and Crohn phenotype while ongoing therapy seems not to be associated with disability and QoL during disease management.

15.
Inflamm Bowel Dis ; 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31498388

RESUMO

BACKGROUND: In a 6-year, multicenter, prospective nested case-control study, we aimed to evaluate risk factors for incident cancer in inflammatory bowel disease (IBD), when considering clinical characteristics of IBD and immunomodulator use. The secondary end point was to provide characterization of incident cancer types. METHODS: All incident cases of cancer occurring in IBD patients from December 2011-2017 were prospectively recorded in 16 Italian Group for the Study of Inflammatory Bowel Disease units. Each of the IBD patients with a new diagnosis of cancer was matched with 2 IBD patients without cancer, according to IBD phenotype (ulcerative colitis [UC] vs Crohn's disease [CD]), age (±5 years), sex. Risk factors were assessed by multivariate logistic regression analysis. RESULTS: Cancer occurred in 403 IBD patients: 204 CD (CD cases), 199 UC (UC cases). The study population included 1209 patients (403 IBD cases, 806 IBD controls). Cancer (n = 403) more frequently involved the digestive system (DS; 32%), followed by skin (14.9%), urinary tract (9.7%), lung (6.9%), genital tract (6.5%), breast (5.5%), thyroid (1.9%), lymphoma (2.7%, only in CD), adenocarcinoma of the small bowel (SBA; 3.9%, 15 CD, 1 pouch in UC), other cancers (15.9%). Among cancers of the DS, colorectal cancer (CRC) more frequently occurred in UC (29% vs 17%; P < 0.005), whereas SBA more frequently occurred in CD (13% vs 6.3% P = 0.039). In CD, perforating (B3) vs non-stricturing non-perforating (B1) behavior represented the only risk factor for any cancer (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.33-4.11). In CD, risk factors for extracolonic cancer (ECC) were a B3 vs B1 and a stricturing (B2) vs B1 behavior (OR, 2.95; 95% CI, 1.62-5.43; OR, 1.79; 95% CI, 1.09-2.98). In UC, risk factors for ECC and for overall cancer were abdominal surgery for UC (OR, 4.63; 95% CI, 2.62-8.42; OR, 3.34; 95% CI, 1.88-5.92) and extensive vs distal UC (OR, 1.73; 95% CI, 1.10-2.75; OR, 1.99; 95% CI, 1.16-3.47). Another risk factor for ECC was left-sided vs distal UC (OR, 1.68; 95% CI, 1.00-2.86). Inflammatory bowel disease duration was a risk factor for skin and urinary tract cancers. CONCLUSIONS: Perforating CD, extensive UC, and abdominal surgery for UC were identified as risk factors for overall incident cancer and for ECC. The clinical characteristics associated with severe IBD may increase cancer risk.

16.
Nat Commun ; 10(1): 3929, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477734

RESUMO

AT-1/SLC33A1 is a key member of the endoplasmic reticulum (ER) acetylation machinery, transporting acetyl-CoA from the cytosol into the ER lumen where acetyl-CoA serves as the acetyl-group donor for Nε-lysine acetylation. Dysfunctional ER acetylation, as caused by heterozygous or homozygous mutations as well as gene duplication events of AT-1/SLC33A1, has been linked to both developmental and degenerative diseases. Here, we investigate two models of AT-1 dysregulation and altered acetyl-CoA flux: AT-1S113R/+ mice, a model of AT-1 haploinsufficiency, and AT-1 sTg mice, a model of AT-1 overexpression. The animals display distinct metabolic adaptation across intracellular compartments, including reprogramming of lipid metabolism and mitochondria bioenergetics. Mechanistically, the perturbations to AT-1-dependent acetyl-CoA flux result in global and specific changes in both the proteome and the acetyl-proteome (protein acetylation). Collectively, our results suggest that AT-1 acts as an important metabolic regulator that maintains acetyl-CoA homeostasis by promoting functional crosstalk between different intracellular organelles.


Assuntos
Acetilcoenzima A/metabolismo , Citosol/metabolismo , Metabolismo dos Lipídeos , Proteínas de Membrana Transportadoras/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Acetilação , Animais , Retículo Endoplasmático/metabolismo , Haploinsuficiência , Fígado/citologia , Fígado/metabolismo , Lisina/metabolismo , Proteínas de Membrana Transportadoras/genética , Camundongos Knockout , Camundongos Transgênicos
17.
Genes (Basel) ; 10(8)2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370293

RESUMO

: Hearing loss (HL) is a common sensory disorder affecting over 5% of the global population. The etiology underlying HL includes congenital and acquired causes; genetic factors are the main cause in over 50% of congenital cases. Pathogenic variants in the GJB2 gene are a major cause of congenital non-syndromic hearing loss (NSHL), while their distribution is highly heterogeneous in different populations. To the best of our knowledge, there is no data regarding the genetic etiologies of HL in Peru. In this study, we screened 133 Peruvian families with NSHL living in Lima. We sequenced both exons of the GJB2 gene for all probands. Seven probands with familial NSHL that remained negative for GJB2 variants underwent whole genome sequencing (WGS). We identified biallelic pathogenic variants in GJB2 in 43 probands; seven were heterozygous for only one allele. The c.427C>T variant was the most common pathogenic variant followed by the c.35delG variant. WGS revealed three novel variants in MYO15A in two probands, one of them was predicted to affect splicing and the others produce a premature stop codon. The Peruvian population showed a complex profile for genetic variants in the GJB2 gene, this particular profile might be a consequence of the admixture history in Peru.


Assuntos
Surdez/genética , Polimorfismo de Nucleotídeo Único , Conexinas/genética , Humanos , Taxa de Mutação , Miosinas/genética , Linhagem , Peru
18.
Clin Cancer Res ; 25(24): 7312-7319, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31416808

RESUMO

PURPOSE: MET-deregulated NSCLC represents an urgent clinical need because of unfavorable prognosis and lack of specific therapies. Although recent studies have suggested a potential role for crizotinib in patients harboring MET amplification or exon 14 mutations, no conclusive data are currently available. This study aimed at investigating activity of crizotinib in patients harboring MET or ROS1 alterations. PATIENTS AND METHODS: Patients with pretreated advanced NSCLC and evidence of ROS1 rearrangements (cohort A) or MET deregulation (amplification, ratio MET/CEP7 >2.2 or MET exon 14 mutations, cohort B) were treated with crizotinib 250 mg twice daily orally. The coprimary endpoint was objective response rate in the two cohorts. RESULTS: From December 2014 to March 2017, 505 patients were screened and a total of 52 patients (26 patients per cohort) were enrolled onto the study. At data cutoff of September 2017, in cohort A, objective response rate was 65%, and median progression-free survival and overall survival were 22.8 months [95% confidence interval (CI) 15.2-30.3] and not reached, respectively. In cohort B, objective response rate was 27%, median progression-free survival was 4.4 months (95% CI 3.0-5.8), and overall survival was 5.4 months (95% CI, 4.2-6.5). No difference in any clinical endpoint was observed between MET-amplified and exon 14-mutated patients. No response was observed among the 5 patients with cooccurrence of a second gene alteration. No unexpected toxicity was observed in both cohorts. CONCLUSIONS: Crizotinib induces response in a fraction of MET-deregulated NSCLC. Additional studies and innovative therapies are urgently needed.

19.
J Crohns Colitis ; 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31418007

RESUMO

BACKGROUND AND AIMS: Crohn's disease-associated small bowel carcinoma is a rare event, usually reported to have a severe prognosis. However, in previous investigations we have found a minority of cases displaying a relatively favorable behavior, thus outlining the need to improve the histopathologic prediction of Crohn's disease-associated small bowel carcinoma prognosis. METHODS: As in recent studies on colorectal cancer a substantial improvement in prognostic evaluations has been provided by the histologic analysis of the tumor invasive front, we therefore systematically analyzed the tumor budding and poorly differentiated clusters in the invasive front of 47 Crohn's disease-associated small bowel carcinomas collected through the Small Bowel Cancer Italian Consortium. RESULTS: Both tumor budding and poorly differentiated cluster analyses proved highly effective in prognostic evaluation of Crohn's disease-associated small bowel carcinomas. In addition, they retained prognostic value when combined with two other parameters, i.e. glandular histology and stage I/II, both known to predict a relatively favorable small bowel carcinoma behavior. In particular, association of tumor budding and poorly differentiated clusters in a combined invasive front score allowed to identify a minor subset of cancers (12/47, 25%), characterized by combined invasive front-low grade coupled with a glandular histology and a low stage (I or II) and showing no cancer-related death during a median follow-up of 73.5 months. CONCLUSIONS: The improved distinction of lower from higher grade Crohn's disease-associated small bowel carcinomas provided by invasive front analysis should be of potential help in choosing appropriate therapy for these rare and frequently ominous neoplasms.

20.
United European Gastroenterol J ; 7(7): 974-981, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31428422

RESUMO

Background and aims: Ileo-colonoscopy is the procedure of choice for chronic nonbloody diarrhea (CNBD) of unknown origin. Histological evaluation at different colonic sites is mandatory to assess the presence of microscopic colitis. However, the value of routine ileal biopsy on normal-appearing mucosa as assessed by means of standard-resolution white-light ileoscopy is controversial given its reported low diagnostic yield. Hence, we have assessed for the first time the accuracy of retrograde ileoscopy using high-definition and dyeless chromoendoscopy (HD + DLC), thereby calculating the impact and cost of routine ileal biopsy in CNBD. Methods: Patients with CNBD of unknown origin were prospectively enrolled for ileo-colonoscopy with HD + DLC at five referral centers. Multiple biopsies were systematically performed on each colorectal segment and in the terminal ileum for histopathological analysis. Results: Between 2014 and 2017, 546 consecutive patients were recruited. Retrograde ileoscopy success rate was 97.6%. A total of 492 patients (mean age: 53 ± 18 years) fulfilled all the inclusion criteria: Following endoscopic and histopathological work-up, 7% had lymphoid nodular hyperplasia and 3% had isolated ileitis. Compared to the histopathology as the gold standard, retrograde ileoscopy with HD + DLC showed 93% sensitivity, 98% specificity and 99.8% negative predictive value. In patients with normal ileo-colonoscopy, ileum histology had no diagnostic gain and resulted in a cost of US $26.5 per patient. Conclusions: Retrograde ileoscopy with HD + DLC predicts the presence of ileitis in CNBD with excellent performance. The histopathological evaluation of the terminal ileum is the gold standard for the diagnostic assessment of visible lesions but has no added diagnostic value in CNBD patients with negative ileo-colonoscopy inspection using modern endoscopic imaging techniques.

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