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1.
Lancet ; 395(10221): 350-360, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-32007170

RESUMEN

BACKGROUND: Improved markers of prognosis are needed to stratify patients with early-stage colorectal cancer to refine selection of adjuvant therapy. The aim of the present study was to develop a biomarker of patient outcome after primary colorectal cancer resection by directly analysing scanned conventional haematoxylin and eosin stained sections using deep learning. METHODS: More than 12 000 000 image tiles from patients with a distinctly good or poor disease outcome from four cohorts were used to train a total of ten convolutional neural networks, purpose-built for classifying supersized heterogeneous images. A prognostic biomarker integrating the ten networks was determined using patients with a non-distinct outcome. The marker was tested on 920 patients with slides prepared in the UK, and then independently validated according to a predefined protocol in 1122 patients treated with single-agent capecitabine using slides prepared in Norway. All cohorts included only patients with resectable tumours, and a formalin-fixed, paraffin-embedded tumour tissue block available for analysis. The primary outcome was cancer-specific survival. FINDINGS: 828 patients from four cohorts had a distinct outcome and were used as a training cohort to obtain clear ground truth. 1645 patients had a non-distinct outcome and were used for tuning. The biomarker provided a hazard ratio for poor versus good prognosis of 3·84 (95% CI 2·72-5·43; p<0·0001) in the primary analysis of the validation cohort, and 3·04 (2·07-4·47; p<0·0001) after adjusting for established prognostic markers significant in univariable analyses of the same cohort, which were pN stage, pT stage, lymphatic invasion, and venous vascular invasion. INTERPRETATION: A clinically useful prognostic marker was developed using deep learning allied to digital scanning of conventional haematoxylin and eosin stained tumour tissue sections. The assay has been extensively evaluated in large, independent patient populations, correlates with and outperforms established molecular and morphological prognostic markers, and gives consistent results across tumour and nodal stage. The biomarker stratified stage II and III patients into sufficiently distinct prognostic groups that potentially could be used to guide selection of adjuvant treatment by avoiding therapy in very low risk groups and identifying patients who would benefit from more intensive treatment regimes. FUNDING: The Research Council of Norway.


Asunto(s)
Neoplasias Colorrectales/diagnóstico , Aprendizaje Profundo , Anciano , Biomarcadores de Tumor/metabolismo , Estudios de Cohortes , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/terapia , Detección Precóz del Cáncer/métodos , Eosina Amarillenta-(YS)/metabolismo , Femenino , Hematoxilina/metabolismo , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos
2.
Anticancer Res ; 40(1): 35-52, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892551

RESUMEN

BACKGROUND/AIM: Co-expression of c-Met and ALDH1A3 indicates a poor prognosis in stage III-IV breast cancers and contributes to cell proliferation and tumor formation by ALDH1-positive breast CSCs. PKCλ is overexpressed and contributes to a poor prognosis in several cancers. MATERIALS AND METHODS: A breast cancer genomics data set (METABRIC, n=2509) was downloaded and analyzed, as was the effect c-Met and PKCλ inhibitors on ALDH1high cell viability and tumor-sphere formation. RESULTS: c-Met expression correlates with expression of PKCλ in breast cancer. Stage III-IV breast cancer patients with c-Methigh PKCλhigh ALDH1A3high have a poorer prognosis than patients with c-Metlow PKCλlow ALDH1A3low Foretinib and auranofin suppressed cell viability and tumor-sphere formation by ALDH1high cells. These results suggest that c-Met and PKCλ are cooperatively involved in cancer progression and contribute to poor prognoses in breast cancer. CONCLUSION: c-Met and PKCλ are potentially useful prognostic markers and therapeutic targets in late-stage breast cancer.


Asunto(s)
Aldehído Oxidorreductasas/genética , Biomarcadores de Tumor , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Proteína Quinasa C/genética , Proteínas Proto-Oncogénicas c-met/genética , Aldehído Oxidorreductasas/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Supervivencia Celular/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Proteína Quinasa C/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo
3.
Anticancer Res ; 40(1): 81-86, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892555

RESUMEN

BACKGROUND/AIM: Zinc finger protein ZKSCAN3 (ZNF306) is a promising oncogene candidate in colon, bladder, breast, uterine cervical, and prostate cancers. The present study aimed to investigate ZKSCAN3 protein expression in gastric carcinoma patient tissues and to evaluate oncological outcomes in these patients. MATERIALS AND METHODS: ZKSCAN3 was detected using the anti-ZKSCAN3 rabbit polyclonal antibody. For immunohistochemical examination, we used paraffin-embedded specimens from 87 consecutive patients with gastric cancer who underwent gastrectomy. We investigated ZKSCAN3 expression in relation with patient prognosis and clinicopathological factors. RESULTS: ZKSCAN3 was detected in 28 (32.2%) tumour specimens, with significant association with lymphatic system invasion and distant metastasis. Patients with ZKSCAN3-positive tumours had worse overall survival (OS) than those with ZKSCAN3-negative tumours based on log-rank testing. Furthermore, multivariate analysis revealed that ZKSCAN3 was an independent prognostic parameter for OS (hazard ratio: 2.6379, p=0.0164). CONCLUSION: ZKSCAN3 is a potential novel prognostic factor in gastric cancer patients.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidad , Factores de Transcripción/genética , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Recurrencia , Factores de Riesgo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo
4.
Anticancer Res ; 40(1): 261-269, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892575

RESUMEN

BACKGROUND: Pulmonary pleomorphic carcinoma (PPC) is a rare aggressive neoplasm, with dismal prognosis. Whether tumor immunity is associated with the progressive biological behavior of PPC remains unclear. The purpose of this study was to examine the prognostic significance of tumor immunity-related markers such as programmed death-1 ligand (PD-L1) and CD4+ or CD8+ tumor-infiltrating lymphocytes (TILs) in patients with surgically resected PPC. PATIENTS AND METHODS: Ninety-nine patients with surgically resected PPC were assessed by immunohistochemistry. The expression of PD-L1, CD4, and CD8 was examined in specimens of the resected tumors. RESULTS: PD-L1 was highly expressed in 61% (60/99) of lesions and high expression of CD4 and CD8 was identified in 42% (42/99) and 51% (51/99) of lesions, respectively. There was no relationship between the expression PD-L1 and the numbers of CD4+ or CD8+ TILs. The expression of PD-L1 was not identified as a significant prognostic marker; however, a low number of CD4+ TILs was identified as an independent marker for predicting a worse outcome after surgical resection of PPC, especially in patients with an epithelial component of adenocarcinoma or early stage of disease. By univariate analysis, a low number of CD8+ TILs was found to be a significant prognostic marker linked to poor overall survival in patients with non-adenocarcinoma components. CONCLUSION: A low number of CD4+ TILs is an independent marker for predicting a favorable prognosis after surgical resection in patients with PPC, especially in patients with adenocarcinoma components or early stage of disease.


Asunto(s)
Adenoma Pleomórfico/inmunología , Inmunidad , Neoplasias Pulmonares/inmunología , Adenoma Pleomórfico/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico
5.
Anticancer Res ; 40(1): 287-291, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892578

RESUMEN

BACKGROUND/AIM: Estimating survival is important for treatment personalization in patients with metastatic cancer. In this study, we aimed to develop a survival score for patients irradiated for bone metastases from colorectal cancer. PATIENTS AND METHODS: Eleven factors were retrospectively analyzed in 25 patients, including age, gender, Eastern Cooperative Oncology Group performance score, tumor site, time between diagnosis of colorectal cancer and irradiation, visceral or other bone metastases, type and number of irradiated sites, upfront surgery and previous systemic treatment. RESULTS: On multivariate analysis, performance score (p=0.005) and previous systemic treatment (p=0.007) were significantly associated with survival and used for the score. One point (performance score 0-1 or no previous systemic treatment) or 0 points (performance score ≥2 or previous systemic treatment) were assigned resulting in 0, 1 or 2 points. Six-month survival rates of these groups were 0%, 64% and 100%, respectively. CONCLUSION: This new survival score can support physicians during personalization of treatment for patients with bone metastases from colorectal cancer.


Asunto(s)
Neoplasias Óseas/secundario , Neoplasias Colorrectales/patología , Anciano , Humanos , Estimación de Kaplan-Meier , Pronóstico
6.
Bone Joint J ; 102-B(1): 108-116, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31888356

RESUMEN

AIMS: Limited evidence is available on mid-term outcomes of robotic-arm assisted (RA) partial knee arthroplasty (PKA). Therefore, the purpose of this study was to evaluate mid-term survivorship, modes of failure, and patient-reported outcomes of RA PKA. METHODS: A retrospective review of patients who underwent RA PKA between June 2007 and August 2016 was performed. Patients received a fixed-bearing medial or lateral unicompartmental knee arthroplasty (UKA), patellofemoral arthroplasty (PFA), or bicompartmental knee arthroplasty (BiKA; PFA plus medial UKA). All patients completed a questionnaire regarding revision surgery, reoperations, and level of satisfaction. Knee Injury and Osteoarthritis Outcome Scores (KOOS) were assessed using the KOOS for Joint Replacement Junior survey. RESULTS: Mean follow-up was 4.7 years (2.0 to 10.8). Five-year survivorship of medial UKA (n = 802), lateral UKA (n = 171), and PFA/BiKA (n = 35/10) was 97.8%, 97.7%, and 93.3%, respectively. Component loosening and progression of osteoarthritis (OA) were the most common reasons for revision. Mean KOOS scores after medial UKA, lateral UKA, and PFA/BiKA were 84.3 (SD 15.9), 85.6 (SD 14.3), and 78.2 (SD 14.2), respectively. The vast majority of the patients reported high satisfaction levels after RA PKA. Subgroup analyses suggested tibial component design, body mass index (BMI), and age affects RA PKA outcomes. Five-year survivorship was 98.4% (95% confidence interval (CI) 97.2 to 99.5) for onlay medial UKA (n = 742) and 99.1% (95% CI 97.9 to 100) for onlay medial UKA in patients with a BMI < 30 kg/m2 (n = 479). CONCLUSION: This large single-surgeon study showed high mid-term survivorship, satisfaction levels, and functional outcomes in RA UKA using metal-backed tibial onlay components. In addition, favourable results were reported in RA PFA and BiKA. Cite this article: Bone Joint J 2020;102-B(1):108-116.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/estadística & datos numéricos , Prótesis de la Rodilla/estadística & datos numéricos , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla/métodos , Índice de Masa Corporal , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/cirugía , Medición de Resultados Informados por el Paciente , Falla de Prótesis , Reoperación/estadística & datos numéricos , Estudios Retrospectivos
7.
Bone Joint J ; 102-B(1): 55-63, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31888375

RESUMEN

AIMS: The aim of this study was to describe implant and patient-reported outcome in patients with a unilateral transfemoral amputation (TFA) treated with a bone-anchored, transcutaneous prosthesis. METHODS: In this cohort study, all patients with a unilateral TFA treated with the Osseointegrated Prostheses for the Rehabilitation of Amputees (OPRA) implant system in Sahlgrenska University Hospital, Gothenburg, Sweden, between January 1999 and December 2017 were included. The cohort comprised 111 patients (78 male (70%)), with a mean age 45 years (17 to 70). The main reason for amputation was trauma in 75 (68%) and tumours in 23 (21%). Patients answered the Questionnaire for Persons with Transfemoral Amputation (Q-TFA) before treatment and at two, five, seven, ten, and 15 years' follow-up. A prosthetic activity grade was assigned to each patient at each timepoint. All mechanical complications, defined as fracture, bending, or wear to any part of the implant system resulting in removal or change, were recorded. RESULTS: The Q-TFA scores at two, five, seven, and ten years showed significantly more prosthetic use, better mobility, fewer problems, and an improved global situation, compared with baseline. The survival rate of the osseointegrated implant part (the fixture) was 89% and 72% after seven and 15 years, respectively. A total of 61 patients (55%) had mechanical complications (mean 3.3 (SD 5.76)), resulting in exchange of the percutaneous implant parts. There was a positive relationship between a higher activity grade and the number of mechanical complications. CONCLUSION: Compared with before treatment, the patient-reported outcome was significantly better and remained so over time. Although osseointegration and the ability to transfer loads over a 15-year period have been demonstrated, a large number of mechanical failures in the external implant parts were found. Since these were related to higher activity, restrictions in activity and improvements to the mechanical properties of the implant system are required. Cite this article: Bone Joint J 2020;102-B(1):55-63.


Asunto(s)
Amputación/métodos , Prótesis Anclada al Hueso , Fémur/cirugía , Adolescente , Adulto , Anciano , Amputación/instrumentación , Amputados/psicología , Miembros Artificiales , Femenino , Neoplasias Femorales/cirugía , Fémur/lesiones , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Oseointegración/fisiología , Medición de Resultados Informados por el Paciente , Estudios Prospectivos , Falla de Prótesis , Adulto Joven
8.
Lancet ; 395(10217): 33-41, 2020 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-31908284

RESUMEN

BACKGROUND: Adhesions are the most common driver of long-term morbidity after abdominal surgery. Although laparoscopy can reduce adhesion formation, the effect of minimally invasive surgery on long-term adhesion-related morbidity remains unknown. We aimed to assess the impact of laparoscopy on adhesion-related readmissions in a population-based cohort. METHODS: We did a retrospective cohort study of patients of any age who had abdominal or pelvic surgery done using laparoscopic or open approaches between June 1, 2009, and June 30, 2011, using validated population data from the Scottish National Health Service. All patients who had surgery were followed up until Dec 31, 2017. The primary outcome measure was the incidence of hospital readmissions directly related to adhesions in the laparoscopic and open surgery cohorts at 5 years. Readmissions were categorised as directly related to adhesions, possibly related to adhesions, and readmissions for an operation that was potentially complicated by adhesions. We did subgroup analyses of readmissions by anatomical site of surgery and used Kaplan-Meier analyses to assess differences in survival across subgroups. We used multivariable Cox-regression analysis to determine whether surgical approach was an independent and significant risk factor for adhesion-related readmissions. FINDINGS: Between June 1, 2009, and June 30, 2011, 72 270 patients had an index abdominal or pelvic surgery, of whom 21 519 (29·8%) had laparoscopic index surgery and 50 751 (70·2%) had open surgery. Of the 72 270 patients who had surgery, 2527 patients (3·5%) were readmitted within 5 years of surgery for disorders directly related to adhesions, 12 687 (17·6%) for disorders possibly related to adhesions, and 9436 (13·1%) for operations potentially complicated by adhesions. Of the 21 519 patients who had laparoscopic surgery, 359 (1·7% [95% CI 1·5-1·9]) were readmitted for disorders directly related to adhesions compared with 2168 (4·3% [4·1-4·5]) of 50 751 patients in the open surgery cohort (p<0·0001). 3443 (16·0% [15·6-16·4]) of 21 519 patients in the laparoscopic surgery cohort were readmitted for disorders possibly related to adhesions compared with 9244 (18·2% [17·8-18·6]) of 50 751 patients in the open surgery cohort (p<0·005). In multivariate analyses, laparoscopy reduced the risk of directly related readmissions by 32% (hazard ratio [HR] 0·68, 95% CI 0·60-0·77), and of possibly related readmissions by 11% (HR 0·89, 0·85-0·94) compared with open surgery. Procedure type, malignancy, sex, and age were also independently associated with risk of adhesion-related readmissions. INTERPRETATION: Laparoscopic surgery reduces the incidence of adhesion-related readmissions. However, the overall burden of readmissions associated with adhesions remains high. With further increases in the use of laparoscopic surgery expected in the future, the effect at the population level might become larger. Further steps remain necessary to reduce the incidence of adhesion-related postsurgical complications. FUNDING: Dutch Adhesion Group and Nordic Pharma.


Asunto(s)
Laparoscopía/efectos adversos , Readmisión del Paciente/estadística & datos numéricos , Procedimientos Quirúrgicos Operativos/efectos adversos , Adherencias Tisulares/etiología , Abdomen/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pelvis/cirugía , Complicaciones Posoperatorias/epidemiología , Reoperación/efectos adversos , Estudios Retrospectivos , Adherencias Tisulares/cirugía , Adulto Joven
9.
J Surg Oncol ; 121(3): 503-510, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31907941

RESUMEN

BACKGROUND: The survival benefit of lymphadenectomy among patients with gallbladder cancer (GBC) remains poorly understood. METHODS: Patients who underwent resection for GBC between 2000 and 2015 were identified from a US multi-institutional database. The therapeutic index (LNM rate multiplied by 3-year overall survival [OS]) was determined to assess the survival benefit of lymphadenectomy. RESULTS: Among 449 patients, less than half had LNM (N = 183, 40.8%). The median number of evaluated and metastatic lymph nodes (LNs) was 3 (interquartile range [IQR]: 1-6) and 1 (IQR: 0-1), respectively. 3-year OS among patients with LNM in the entire cohort was 26.8%. The therapeutic index was lower among patients with T4 (5.9) or T1 (6.0) tumors as well as carbohydrate antigen (CA19-9) ≥200 UI/mL (6.0). Of note, a therapeutic index difference ≥10 was noted relative to CA19-9 (<200: 18.7 vs ≥200: 6.0), American Joint Committee on Cancer T Stage (T1: 6.0 vs T2: 17.8 vs T4: 5.9) and number of LNs examined (1-2: 6.9 vs ≥6: 16.9). Concomitant common bile duct resection was not associated with a higher therapeutic index among patients with either T2 or T3 disease. CONCLUSION: Certain clinicopathological factors including T1 or T4 tumor and CA19-9 ≥200 UI/mL were associated with a low therapeutic index. Resection of six or more LNs was associated with a meaningful therapeutic index benefit among patients with LNM.


Asunto(s)
Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/cirugía , Ganglios Linfáticos/cirugía , Anciano , Estudios de Cohortes , Conducto Colédoco/cirugía , Bases de Datos Factuales , Femenino , Neoplasias de la Vesícula Biliar/patología , Humanos , Estimación de Kaplan-Meier , Escisión del Ganglio Linfático/métodos , Escisión del Ganglio Linfático/mortalidad , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tasa de Supervivencia , Índice Terapéutico , Estados Unidos/epidemiología
10.
N Engl J Med ; 382(5): 427-436, 2020 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-31995688

RESUMEN

BACKGROUND: Helicobacter pylori infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate H. pylori can reduce the risk of gastric cancer in persons with a family history of gastric cancer in first-degree relatives is unknown. METHODS: In this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives of patients with gastric cancer. We randomly assigned 1838 participants with H. pylori infection to receive either eradication therapy (lansoprazole [30 mg], amoxicillin [1000 mg], and clarithromycin [500 mg], each taken twice daily for 7 days) or placebo. The primary outcome was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to H. pylori eradication status, assessed during the follow-up period. RESULTS: A total of 1676 participants were included in the modified intention-to-treat population for the analysis of the primary outcome (832 in the treatment group and 844 in the placebo group). During a median follow-up of 9.2 years, gastric cancer developed in 10 participants (1.2%) in the treatment group and in 23 (2.7%) in the placebo group (hazard ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.94; P = 0.03 by log-rank test). Among the 10 participants in the treatment group in whom gastric cancer developed, 5 (50.0%) had persistent H. pylori infection. Gastric cancer developed in 0.8% of participants (5 of 608) in whom H. pylori infection was eradicated and in 2.9% of participants (28 of 979) who had persistent infection (hazard ratio, 0.27; 95% CI, 0.10 to 0.70). Adverse events were mild and were more common in the treatment group than in the placebo group (53.0% vs. 19.1%; P<0.001). CONCLUSIONS: Among persons with H. pylori infection who had a family history of gastric cancer in first-degree relatives, H. pylori eradication treatment reduced the risk of gastric cancer. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT01678027.).


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Inhibidores de la Bomba de Protones/uso terapéutico , Neoplasias Gástricas/prevención & control , Adenoma/epidemiología , Adenoma/etiología , Adenoma/prevención & control , Adulto , Anciano , Amoxicilina/uso terapéutico , Claritromicina/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Femenino , Infecciones por Helicobacter/complicaciones , Humanos , Incidencia , Estimación de Kaplan-Meier , Lansoprazol/uso terapéutico , Masculino , Persona de Mediana Edad , República de Corea , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/etiología , Neoplasias Gástricas/genética
12.
Medicine (Baltimore) ; 99(1): e18494, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31895783

RESUMEN

INTRODUCTION: Peripherally inserted central catheters (PICC-line) are devices inserted through peripheral venous access. In our institution, this technology has been rapidly adopted by physicians in their routine practice. Bacteremia on catheters remains an important public health issue in France. However, the mortality attributable to bacteremia on PICC-line remains poorly evaluated in France and in the literature in general. We report in our study an exhaustive inventory of bacteremia on PICC-line and their 30 days mortality, over a 7 years period. MATERIAL AND METHODS: From January 2010 to December 2016, we retrospectively matched PICC-line registers of the radiology department, blood culture records of the microbiology laboratory and medical records from the Hospital Information Systems. RESULTS: The 11,334 hospital stays during which a PICC-line was inserted were included over a period of 7 years. Among them, 258 episodes of PICC-line-associated bacteremia were recorded, resulting in a prevalence of 2.27%. Hematology units: 20/324 (6.17%), oncology units: 55/1375 (4%) and hepato-gastro-enterology units: 42/1142 (3.66%) had the highest prevalence of PICC-line related bacteremia. The correlation analysis, when adjusted by exposure and year, shows that the unit profile explains 72% of the variability in the rate of bacteremia with a P = .023. Early bacteremia, occurring within 21 days of insertion, represented 75% of cases. The crude death ratio at 30 days, among patients PICC-line associated bacteremia was 57/11 334 (0.50%). The overall 30-day mortality of patients with PICC-line with and without bacteremia was 1369/11334 (12.07%). On day 30, mortality of patients with bacteremia associated PICC-line was 57/258 or 22.09% of cases, compared to a mortality rate of 1311/11076, or 11.83% in the control group (P < .05, RR 2.066 [1.54-2.75]). Kaplan-Meier survival analysis revealed a statistically significant excess mortality between patients with PICC-line associated bacteremia and PICC-line carriers without bacteremia (P < .0007, hazard ratio 1.89 [1307-2709]). CONCLUSION: Patients with PICC-line associated bacteremia have a significant excess mortality. The implementation of a PICC-line should remain the last resort after a careful assessment of the benefit/risk ratio by a senior doctor.


Asunto(s)
Infecciones Relacionadas con Catéteres/mortalidad , Cateterismo Venoso Central/efectos adversos , Cateterismo Periférico/efectos adversos , Catéteres de Permanencia/efectos adversos , Anciano , Bacteriemia/microbiología , Bacteriemia/mortalidad , Estudios de Casos y Controles , Francia/epidemiología , Hospitales Públicos/estadística & datos numéricos , Humanos , Estimación de Kaplan-Meier , Tiempo de Internación/estadística & datos numéricos , Persona de Mediana Edad , Estudios Retrospectivos
13.
Medicine (Baltimore) ; 99(2): e18591, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31914038

RESUMEN

This analysis aimed to investigate whether the long-term administration of temozolomide (TMZ) claimed a survival advantage for patients with glioblastoma in China.A total of 75 patients with newly diagnosed glioblastoma at the Department of Radiation Oncology, Shenzhen People's Hospital between August 2008 and August 2016 were retrospectively evaluated during analysis. A propensity-matched analysis was performed to balance the basic characteristics of patients between compared groups. Kaplan-Meier method and Cox proportional hazards model were used to assess progression-free survival (PFS) and overall survival (OS) of patients receiving 6 adjuvant TMZ cycles compared with patients treated with more than 6 cycles.Twenty of 75 patients received more than 6 cycles of TMZ, and the other 55 patients were treated with a median of 6 cycles ranging from 1 to 6. The patients with long-term administration of TMZ had better OS (47.0 months, 95% CI 20.0-73.9 vs 20.6 months, 95% CI 17.9-23.2, P = .014) but not PFS (17.0 months, 95% CI 10.1-24.5 vs 14.2 months, 95% CI 11.8-16.6, P = .133). Balancing the clinical factors with a propensity-matched analysis also showed the significant advantage of prolonged TMZ application in terms of OS but not PFS.Prolonged administration of TMZ beyond 6 cycles did demonstrate survival benefits for patients with initially diagnosed glioblastoma.


Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/mortalidad , Glioblastoma/tratamiento farmacológico , Glioblastoma/mortalidad , Temozolomida/uso terapéutico , Adolescente , Adulto , Anciano , Antineoplásicos Alquilantes/administración & dosificación , Neoplasias Encefálicas/terapia , Quimioterapia Adyuvante , Esquema de Medicación , Femenino , Glioblastoma/terapia , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Puntaje de Propensión , Estudios Retrospectivos , Temozolomida/administración & dosificación , Adulto Joven
14.
Medicine (Baltimore) ; 99(2): e18725, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31914088

RESUMEN

The NOTCH signaling pathway plays a crucial role in cell phenotype and transformation. Single nucleotide polymorphisms (SNPs) may regulate gene expression to trigger bladder cancer susceptibility. Here, we aimed to explore the relationships between genetic variants in the NOTCH pathway and bladder cancer progression.We screened SNPs located in NOTCH pathway genes using the 1000 Genomes Project dataset (CHB). A case-control cohort study including 580 bladder cancer cases and 1101 controls was conducted to genotype the candidate SNPs. The expression quantitative trait locus (eQTL) and bioinformatics analyses were performed to explore the biological function of the SNPs' host gene and their relationship. Kaplan-Meier analysis was performed to assess the association between host gene expression and bladder cancer patient prognosis.The rs7944701 in the intron of mastermind-like 2 (MAML2) had the strongest signal and was related to bladder cancer risk (OR = 1.329, 95% CI = 1.115-1.583, P = .001). eQTL analysis showed that rs7944701 with a C allele was negatively associated with mastermind-like 2 (MAML2) expression (TT versus TC/CC). Bioinformatics analysis indicated that MAML2expression was lower in bladder cancer tissues than in non-tumor tissues (P = 5.46 × 10). Additionally, bladder cancer patients with high MAML2 expression had a significantly poorer prognosis (HR = 1.53, 95% CI = 1.29-1.82, P = .010).The rs7944701 in MAML2 was strongly associated with bladder cancer susceptibility in a Chinese population. This genetic variant and its host gene could be a potential novel biomarker for individuals suffering from bladder cancer.


Asunto(s)
Transactivadores/genética , Neoplasias de la Vejiga Urinaria/genética , China , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Intrones , Estimación de Kaplan-Meier , Masculino , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Transducción de Señal
15.
Lancet Haematol ; 7(2): e100-e111, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31958417

RESUMEN

BACKGROUND: Previous trials testing prevention strategies for chronic graft versus host disease (GVHD) have measured its cumulative incidence. In this trial of anti-thymocyte globulin, we measured treatment-independence at a long-term timepoint as the primary endpoint. METHODS: This was a randomised, open-label, multicentre, phase 3 trial done at ten centres in Canada and one in Australia. Eligible patients had a haematological malignancy (leukaemia, myelodysplastic syndrome, or lymphoma), were between 16 and 70 years of age, eligible for transplantation with a Karnofsky score of at least 60, and received an unrelated donor (fully matched or one-locus mismatched at HLA-A, HLA-B, HLA-C, or DRB1 loci) graft following myeloablative or non-myeloablative-reduced intensity conditioning. Patients were randomly assigned to receive anti-thymocyte globulin 4·5 mg/kg plus standard GVHD prophylaxis (cyclosporine or tacrolimus plus methotrexate or mycophenolate) or standard GVHD prophylaxis alone. The primary endpoint, freedom from immunosuppressive therapy without resumption at 12 months, was previously reported. Here we report on the prespecified 24-month analysis. Analyses were per-protocol, excluding those patients who did not proceed to transplantation. This trial is registered as ISRCTN 29899028 and NCT01217723, status completed. FINDINGS: Between June 9, 2010, and July 8, 2013, we recruited and randomly assigned 203 eligible patients to receive anti-thymocyte globulin (n=101) or no additional treatment (n=102) along with standard GVHD prophylaxis. 7 (3%) patients did not receive a transplant and were excluded from the analysis. 38 (38%) of 99 evaluable patients in the anti-thymocyte globulin plus GVHD prophylaxis group were free from immunosuppressive therapy at 24 months compared with 18 (19%) of 97 patients in the standard GVHD prophylaxis group (adjusted odds ratio [OR] 3·49 [95% CI 1·60-7·60]; p=0·0016. At 24 months, the cumulative incidence of relapse was 16·3% (95% CI 8·9-23·7) in the anti-thymocyte globulin plus GVHD prophylaxis group compared with 17·5 (9·9-25·1) in the standard GVHD prophylaxis group (p=0·73) and non-relapse mortality was 21·2% (95% CI 13·2-29·2) versus 31·3% (21·9-40·7; p=0·15). The cumulative incidence of chronic GVHD at 24 months was 26·3% (95% CI 17·5-35·1) in the anti-thymocyte globulin group and 41·3% (31·3-51·3) in the standard GVHD prophylaxis group (p=0·032). Overall survival at 24 months was 53·3% (95% CI 42·8-62·7) in the anti-thymocyte globulin plus GVHD prophylaxis group compared with 70.6% (95% CI 60·6-78·6) in the standard GVHD prophylaxis group (adjusted hazard ratio [HR] 0·56, 95% CI [0·35-0·90]; p=0·017. Symptoms of chronic GVHD by the Lee Scale were more prevalent in the standard GVHD prophylaxis group, with scores of 13·27 (SD 10·94) in the anti-thymocyte globulin plus GVHD prophylaxis group and 20·38 (SD 14·68) in the standard GVHD prophylaxis group (p=0·040). Depressive symptoms were more prominent in the standard GVHD prophylaxis group, the mean Center for Epidemiological Studies Depression scale (CES-D) scores were 10·40 (SD 9·88) in the anti-thymocyte globulin group and 14·62 (SD 12·26) in the standard GVHD prophylaxis group (p=0·034). Serious adverse events (CTCAE grade 4 or 5) occurred in 38 (38%) patients in the anti-thymocyte globulin group and in 49 (51%) in the standard GVHD prophylaxis group, the most common being infection and GVHD. One patient died of Epstein-Barr virus hepatitis. INTERPRETATION: The results of this prespecified 24-month analysis suggest that pretreatment with anti-thymocyte globulin provides clinically meaningful benefits when added to standard GVHD prophylaxis in patients undergoing unrelated donor transplantation, including a decrease in use of immunosuppressive therapy, chronic GVHD and its symptoms, depressive symptoms, and improved overall survival. Anti-thymocyte globulin could be included in the preparative regimens of patients with haematological malignancies selected for unrelated donor transplantation. FUNDING: Canadian Institutes of Health Research and Sanofi.


Asunto(s)
Suero Antilinfocítico/uso terapéutico , Trasplante de Médula Ósea/efectos adversos , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/terapia , Inmunosupresores/uso terapéutico , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Adolescente , Adulto , Anciano , Ciclosporina/administración & dosificación , Ciclosporina/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/etiología , Humanos , Inmunosupresores/administración & dosificación , Estimación de Kaplan-Meier , Masculino , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/uso terapéutico , Medición de Resultados Informados por el Paciente , Linfocitos T/inmunología , Tacrolimus/administración & dosificación , Tacrolimus/uso terapéutico , Trasplante Homólogo/efectos adversos , Resultado del Tratamiento , Donante no Emparentado , Adulto Joven
16.
J Craniomaxillofac Surg ; 48(1): 75-82, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31902716

RESUMEN

OBJECTIVES: Rhabdomyosarcoma (RMS) involving the parameningeal-nonparameningeal region (PNP) is relatively rare in pediatric patients (PPs). The current study aimed to report the outcomes of RMS-PNP-PPs who received surgical resection combined with concurrent flap reconstruction. METHODS: A retrospective study was conducted concerning RMS-PNP-PPs who received combined skull-maxillofacial resection with flap reconstruction during the period from 2012 to 2016. Predictive factors for recurrence-free survival (RFS), metastasis-free survival (MFS), and overall survival (OS) were preliminarily identified by Kaplan-Meier analysis. RESULTS: A total of 16 RMS-PNP-PPs were finally enrolled; recurrence, metastasis and death were found in 7, 7 and 5 patients, respectively. Following surgical ablation involving the skull base and maxillofacial region, reconstruction was performed with a local flap in 9 patients, a latissimus dorsi flap in 3 patients, and an anterolateral thigh flap in 4 patients. Through univariate analysis, we demonstrated that the primary site + surgical margins, postoperative RT/CT + Ki-67/Bcl-2 IHC, and surgical margins + Ki-67/Bcl-2 IHC could be used as the preliminarily prognostic factors for RFS, MFS and OS, respectively. CONCLUSIONS: RMS-PNP-PPs showed poor prognosis even when surgical resection combined with flap reconstructions was performed. Achieving a clear surgical margin and good conduction of postoperative RT/CT should be taken into consideration to acquiring a better surgical outcome.


Asunto(s)
Recurrencia Local de Neoplasia , Rabdomiosarcoma/cirugía , Niño , Humanos , Estimación de Kaplan-Meier , Estudios Retrospectivos , Colgajos Quirúrgicos , Resultado del Tratamiento
17.
Clin Sci (Lond) ; 134(2): 261-271, 2020 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-31922199

RESUMEN

Acute myeloid leukemia (AML) is a malignant disorder of hemopoietic stem cells. AML can escape immunosurveillance of natural killer (NK) by gene mutation, fusions and epigenetic modification. The mechanism of AML immune evasion is not clearly understood. Here we show that CD48 high expression is a favorable prognosis factor that is down-regulated in AML patients, which can help AML evade from NK cell recognition and killing. Furthermore, we demonstrate that CD48 expression is regulated by methylation and that a hypomethylating agent can increase the CD48 expression, which increases the NK cells killing in vitro. Finally, we show that CD48 high expression can reverse the AML immune evasion and activate NK cells function in vivo. The present study suggests that a combination the hypomethylating agent and NK cell infusion could be a new strategy to cure AML.


Asunto(s)
Antígeno CD48/inmunología , Epigénesis Genética/inmunología , Silenciador del Gen/inmunología , Leucemia Mieloide/inmunología , Escape del Tumor/inmunología , Enfermedad Aguda , Animales , Antimetabolitos Antineoplásicos/farmacología , Antígeno CD48/genética , Línea Celular Tumoral , Células Cultivadas , Metilación de ADN/efectos de los fármacos , Metilación de ADN/genética , Metilación de ADN/inmunología , Decitabina/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/inmunología , Humanos , Estimación de Kaplan-Meier , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Leucemia Mieloide/tratamiento farmacológico , Leucemia Mieloide/genética , Masculino , Ratones Endogámicos BALB C , Escape del Tumor/genética , Ensayos Antitumor por Modelo de Xenoinjerto
18.
N Engl J Med ; 382(9)2020 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-31995682

RESUMEN

BACKGROUND: There are scant data on long-term clinical outcomes and bioprosthetic-valve function after transcatheter aortic-valve replacement (TAVR) as compared with surgical aortic-valve replacement in patients with severe aortic stenosis and intermediate surgical risk. METHODS: We enrolled 2032 intermediate-risk patients with severe, symptomatic aortic stenosis at 57 centers. Patients were stratified according to intended transfemoral or transthoracic access (76.3% and 23.7%, respectively) and were randomly assigned to undergo either TAVR or surgical replacement. Clinical, echocardiographic, and health-status outcomes were followed for 5 years. The primary end point was death from any cause or disabling stroke. RESULTS: At 5 years, there was no significant difference in the incidence of death from any cause or disabling stroke between the TAVR group and the surgery group (47.9% and 43.4%, respectively; hazard ratio, 1.09; 95% confidence interval [CI], 0.95 to 1.25; P = 0.21). Results were similar for the transfemoral-access cohort (44.5% and 42.0%, respectively; hazard ratio, 1.02; 95% CI, 0.87 to 1.20), but the incidence of death or disabling stroke was higher after TAVR than after surgery in the transthoracic-access cohort (59.3% vs. 48.3%; hazard ratio, 1.32; 95% CI, 1.02 to 1.71). At 5 years, more patients in the TAVR group than in the surgery group had at least mild paravalvular aortic regurgitation (33.3% vs. 6.3%). Repeat hospitalizations were more frequent after TAVR than after surgery (33.3% vs. 25.2%), as were aortic-valve reinterventions (3.2% vs. 0.8%). Improvement in health status at 5 years was similar for TAVR and surgery. CONCLUSIONS: Among patients with aortic stenosis who were at intermediate surgical risk, there was no significant difference in the incidence of death or disabling stroke at 5 years after TAVR as compared with surgical aortic-valve replacement. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).


Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/etiología , Insuficiencia de la Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/mortalidad , Estudios de Cohortes , Ecocardiografía , Femenino , Estado de Salud , Humanos , Incidencia , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Análisis Multivariante , Complicaciones Posoperatorias/mortalidad , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Resultado del Tratamiento
19.
Anticancer Res ; 40(1): 367-371, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892588

RESUMEN

BACKGROUND/AIM: Individualization of treatment may improve the outcome of patients with bone metastases from breast cancer. To support physicians when selecting individualized programs for these patients, a simple instrument for predicting survival was created. PATIENTS AND METHODS: In 126 female patients with breast cancer irradiated for bone metastases, 11 characteristics were evaluated with respect to survival. RESULTS: On Cox regression analysis, Eastern Cooperative Oncology Group performance score (0-1 vs. ≥2; p=0.032) and visceral metastases (absence vs. presence; p=0.017) were independently associated with survival and incorporated into the scoring instrument. Three prognostic groups (0, 1 or 2 points) were designated with 12-month survival rates of 38%, 57% and 91%, and 24-month survival rates of 32%, 36% and 80%, respectively (p<0.001). CONCLUSION: This easy-to-use scoring instrument allows physicians to estimate the lifespan of patients irradiated for bone metastases from breast cancer and can facilitate individualization of their treatment.


Asunto(s)
Neoplasias Óseas/radioterapia , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Estimación de Kaplan-Meier , Probabilidad , Anciano , Femenino , Humanos , Persona de Mediana Edad , Pronóstico
20.
Anticancer Res ; 40(1): 393-399, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892592

RESUMEN

AIM: This study was performed to confirm the superior overall survival (OS) after pulmonary oligo-recurrence compared to pulmonary sync-oligometastases in a large nationwide study. PATIENTS AND METHODS: Patients that met the following criteria were included: 1 to 5 lung-only metastases at the beginning of stereotactic body radiation therapy (SBRT) was performed between January 2004 and June 2015, and the biological effective dose (BED) of SBRT was 75 Gy or more. The parameters included in the analyses were age, gender, ECOG PS, primary lesion, pathology, oligoetastatic state, SBRT date, chemotherapy before SBRT, chemotherapy concurrent SBRT, chemotherapy after SBRT, maximum tumor diameter, number of metastases, field coplanarity, dose prescription, BED10, OTT of SBRT. RESULTS: In total, 1,378 patients with 1,547 tumors were enrolled. Oligo-recurrence occurred in 1,016 patients, sync-oligometastases in 118, and unclassified oligometastases in 121. The three-year OS was 64.0% for oligo-recurrence and 47.5% for sync-oligometastasis (p<0.001). In the multivariate analysis, the hazard ratio (HR) for sync-oligometastases versus oligo-recurrence was 1.601 (p=0.014). Adverse events of Grade 5 were occurred in 3 patients. CONCLUSION: This is the first nationwide to indicate that the OS of patients with pulmonary oligo-recurrence is better than that of patients with sync-oligometastases.


Asunto(s)
Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundario , Radiocirugia , Encuestas y Cuestionarios , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Adulto Joven
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