ABSTRACT
The data presented in this article is related with the research paper entitled "Evaluation of MGP gene expression in colorectal cancer", available on Gene journal [1]. From all the transcription factors known to regulate MGP, FGF2 is the most described in colon adenocarcinoma and colon tumor cell lines, where it was shown to: i) contribute for the invasiveness potential; and ii) promote proliferation and survival of colorectal cancer cells. These in vitro studies pose the hypothesis that FGF2 associated signaling pathways could be promoting the regulation of others genes, such as MGP, that may lead to tumor progression which ultimately could result in poor prognosis in colon adenocarcinoma.
ABSTRACT
PURPOSE: Matrix Gla protein (MGP) is a vitamin K-dependent, γ-carboxylated protein that was initially found to be a physiological inhibitor of ectopic calcifications affecting mainly cartilage and the vascular system. Mutations in the MGP gene were found to be responsible for a human pathology, the Keutel syndrome, characterized by abnormal calcifications in cartilage, lungs, brain and vascular system. MGP was recently implicated in tumorigenic processes such as angiogenesis and shown to be abnormally regulated in several tumors, including cervical, ovarian, urogenital and breast. This fact has triggered our interest in analyzing the expression of MGP and of its regulator, the transcription factor runt related transcription factor 2 (RUNX2), in colorectal cancer (CRC). METHODS: MGP and RUNX2 expression were analyzed in cancer and non-tumor biopsies samples from 33 CRC patients and 9 healthy controls by RT-qPCR. Consequently, statistical analyses were performed to evaluate the clinical-pathological significance of MGP and RUNX2 in CRC. MGP protein was also detected by immunohistochemical analysis. RESULTS: Showed an overall overexpression of MGP in the tumor mucosa of patients at mRNA level when compared to adjacent normal mucosa and healthy control tissues. In addition, analysis of the expression of RUNX2 mRNA demonstrated an overexpression in CRC tissue samples and a positive correlation with MGP expression (Pearson correlation coefficient 0.636; pâ¯≤â¯0.01) in tumor mucosa. However correlations between MGP gene expression and clinical-pathological characteristics, such as gender, age and pathology classification did not provide relevant information that may shed light towards the differences of MGP expression observed between normal and malignant tissue. CONCLUSIONS: We were able to associate the high levels of MGP mRNA expression with a worse prognosis and survival rate lower than five years. These results contributed to improve our understanding of the molecular mechanism underlying MGP deregulation in cancer.
Subject(s)
Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/metabolism , Colorectal Neoplasms/pathology , Core Binding Factor Alpha 1 Subunit/genetics , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Up-Regulation , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Survival Analysis , Matrix Gla ProteinABSTRACT
Gastrostomy site metastization is considered an uncommon complication of percutaneous endoscopic gastrostomy (PEG) placement in patients with head and neck tumours, but it is important to consider this possibility when evaluating gastrostomy-related symptoms. The authors present the case of a 40-year-old male with excessive alcohol consumption and active smoking, diagnosed with a stage IV oropharyngeal squamous cell carcinoma. The patient developed a paraneoplastic demyelinating motor polyneuropathy that, associated with tumour mass effect, caused dysphagia with need for nasogastric tube feeding. Treatment with radiotherapy and then chemoradiotherapy was administered and a PEG was placed with the pull method. Cancer remission and resolution of polyneuropathy was achieved, so PEG was removed. Two weeks later, the patient presented with pain and swelling at the gastrostomy site suggesting a local abscess, with improvement after drainage and antibiotic therapy. After 1 month, there was a tumour mass at the gastrostomy site and an oropharyngeal cancer metastasis was diagnosed. The patient underwent surgical excision of abdominal wall metastasis and abdominal disease was controlled. Nevertheless, there was subsequent oropharyngeal neoplasia recurrence and the patient died 6 months later. This case raises the discussion about gastrostomy placement methods that could avoid gastrostomy site metastization, the possible differential diagnosis, and diagnostic workout. Surgical resection may allow metastatic disease control, but by primary disease evolution greatly affects prognosis.
A metastização do local de gastrostomia é considerada uma complicação incomum da colocação de gastrostomia endoscópica percutânea (PEG) em pacientes com tumores da cabeça e pescoço, no entanto é importante considerar essa possibilidade ao avaliar sintomas relacionados com a gastrostomia. Os autores apresentam o caso de um homem de 40 anos com consumo excessivo de álcool e tabagismo ativo, diagnosticado com carcinoma espinocelular orofaríngeo no estádio IV. O paciente desenvolveu uma polineuropatia motora desmielinizante paraneoplásica que, associada ao efeito de massa tumoral, causou disfagia com necessidade de alimentação por sonda nasogástrica. Foi administrado tratamento com radioterapia, seguido de quimioradioterapia e foi colocada PEG com o método de pull. Foi obtida remissão tumoral e resolução da polineuropatia, sendo removida a PEG. Duas semanas depois, o paciente apresentou dor e edema no local da gastrostomia, sugerindo um abscesso local, com melhoria após drenagem e antibioterapia. Um mês depois o local da gastrostomia apresentava uma massa tumoral e foi diagnosticada uma metástase do cancro orofaríngeo. O paciente foi submetido a excisão cirúrgica da metástase da parede abdominal, com controlo da doença abdominal. Contudo, houve recorrência neoplásica orofaríngea subsequente e o paciente faleceu 6 meses depois. Este caso levanta a discussão sobre os métodos de realização de gastrostomia que poderiam evitar a metastização do local de gastrostomia, possíveis diagnósticos diferenciais e marcha diagnóstica. A ressecção cirúrgica pode permitir o controle da doença metastática, no entanto o prognóstico é muito afetado pela evolução da doença primária.
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No disponible
Subject(s)
Humans , Male , Middle Aged , Pancreatitis/complications , Pancreatitis/diagnostic imaging , Cholangitis/complications , Cholangitis/diagnostic imaging , Foreign-Body Migration/diagnostic imaging , Foreign-Body Migration/surgery , Cholecystectomy, Laparoscopic/methods , Fever/etiology , Abdominal Pain/etiology , Common Bile Duct/diagnostic imaging , Common Bile Duct/surgeryABSTRACT
BACKGROUND AND AIM: Recently, the European Association for the Study of the Liver - Chronic Liver Failure (CLIF) Consortium defined two new prognostic scores, according to the presence or absence of acute-on-chronic liver failure (ACLF): the CLIF Consortium ACLF score (CLIF-C ACLFs) and the CLIF-C Acute Decompensation score (CLIF-C ADs). We sought to compare their accuracy in predicting 30- and 90-day mortality with some of the existing models: Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD), MELD-Na, integrated MELD (iMELD), MELD to serum sodium ratio index (MESO), Refit MELD and Refit MELD-Na. METHODS: Retrospective cohort study that evaluated all admissions due to decompensated cirrhosis in 2 centers between 2011 and 2014. At admission each score was assessed, and the discrimination ability was compared by measuring the area under the ROC curve (AUROC). RESULTS: A total of 779 hospitalizations were evaluated. Two hundred and twenty-two patients met criteria for ACLF (25.9%). The 30- and 90-day mortality were respectively 17.7 and 37.3%. CLIF-C ACLFs presented an AUROC for predicting 30- and 90-day mortality of 0.684 (95% CI: 0.599-0.770) and 0.666 (95% CI: 0.588-0.744) respectively. No statistically significant differences were found when compared to traditional models. For patients without ACLF, CLIF-C ADs had an AUROC for predicting 30- and 90-day mortality of 0.689 (95% CI: 0.614-0.763) and 0.672 (95% CI: 0.624-0.720) respectively. When compared to other scores, it was only statistically superior to MELD for predicting 30-day mortality (p = 0.0296). CONCLUSIONS: The new CLIF-C scores were not statistically superior to the traditional models, with the exception of CLIF-C ADs for predicting 30-day mortality
ANTECEDENTES Y OBJETIVOS: Recientemente The European Association for the Study of the Liver-Chronic Liver Failure Consortium estableció 2 nuevos sistemas pronósticos considerando la existencia o no de Acute-on-chronic liver failure (ACLF): el score CLIF Consortium ACLF (CLIF-C ACLF) y el CLIF-C Acute Descompensation score (CLIF-C ADs). Pretendimos comparar su fiabilidad para predecir la mortalidad a los 30 y 90 días con la de algunos de los sistemas de puntuación existentes: Child-Turcotte-Pugh, Model for End-Stage Liver Disease (MELD), MELD-Na, integrated MELD, MELD to serum sodium ratio index, Refit MELD y Refit MELD-Na. MÉTODOS: Estudio retrospectivo de cohortes incluyendo todos los pacientes con cirrosis ingresados en 2 centros entre 2011 y 2014 por descompensación de su enfermedad. En el momento de la admisión cada puntación fue calculada y fueron comparadas las áreas bajo la curva ROC (AUROC) para evaluar su capacidad de discriminación respecto a la mortalidad a los 30 y 90 días. RESULTADOS: Fueron analizadas un total de 779 hospitalizaciones. Doscientos y veintidós pacientes cumplían criterios para ACLF (25,9%). La mortalidad a los 30 y 90 días fue de 17,7% y 37,3% respectivamente. En los pacientes con ACLF el AUROC del CLIF-C ACLF para predecir la mortalidad a los 30 y 90 días fue 0,684 (IC 95%: 0,599-0,770) y 0,666 (IC 95%: 0,588-0,744) respectivamente. No se encontraron diferencias significativas con los modelos tradicionales. En los pacientes sin ACLF, el AUROC del CLIF-C ADs para predecir la mortalidad a los 30 y 90 días fue 0,689 (IC 95%: 0,614-0,763) y 0,672 (IC 95%: 0,624-0,720) respectivamente. Únicamente fue estadísticamente superior al MELD para predecir la mortalidad a los 30 días (p = 0,0296). CONCLUSIONES: Los nuevos modelos CLIF-C no fueron superiores estadísticamente a los modelos tradicionales, con la excepción del CLIF-C ADs en la predicción de la mortalidad a los 30 días
Subject(s)
Humans , Liver Cirrhosis/mortality , Hepatic Insufficiency/mortality , Predictive Value of Tests , Liver Function Tests/statistics & numerical data , Risk Factors , Retrospective Studies , Survival AnalysisABSTRACT
BACKGROUND AND AIM: Recently, the European Association for the Study of the Liver - Chronic Liver Failure (CLIF) Consortium defined two new prognostic scores, according to the presence or absence of acute-on-chronic liver failure (ACLF): the CLIF Consortium ACLF score (CLIF-C ACLFs) and the CLIF-C Acute Decompensation score (CLIF-C ADs). We sought to compare their accuracy in predicting 30- and 90-day mortality with some of the existing models: Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD), MELD-Na, integrated MELD (iMELD), MELD to serum sodium ratio index (MESO), Refit MELD and Refit MELD-Na. METHODS: Retrospective cohort study that evaluated all admissions due to decompensated cirrhosis in 2 centers between 2011 and 2014. At admission each score was assessed, and the discrimination ability was compared by measuring the area under the ROC curve (AUROC). RESULTS: A total of 779 hospitalizations were evaluated. Two hundred and twenty-two patients met criteria for ACLF (25.9%). The 30- and 90-day mortality were respectively 17.7 and 37.3%. CLIF-C ACLFs presented an AUROC for predicting 30- and 90-day mortality of 0.684 (95% CI: 0.599-0.770) and 0.666 (95% CI: 0.588-0.744) respectively. No statistically significant differences were found when compared to traditional models. For patients without ACLF, CLIF-C ADs had an AUROC for predicting 30- and 90-day mortality of 0.689 (95% CI: 0.614-0.763) and 0.672 (95% CI: 0.624-0.720) respectively. When compared to other scores, it was only statistically superior to MELD for predicting 30-day mortality (p=0.0296). CONCLUSIONS: The new CLIF-C scores were not statistically superior to the traditional models, with the exception of CLIF-C ADs for predicting 30-day mortality.
Subject(s)
End Stage Liver Disease/complications , End Stage Liver Disease/mortality , Liver Cirrhosis/complications , Models, Statistical , Cohort Studies , Female , Humans , Male , Middle Aged , Prognosis , Retrospective StudiesABSTRACT
BACKGROUND AND AIMS: The definition of early therapeutic strategies to control Crohn's disease aggressiveness and prevent recurrence is key to improve clinical practice. This study explores the impact of early surgery and immunosuppression onset in the occurrence of disabling outcomes. METHODS: This was a multicentric and retrospective study with 754 patients with Crohn's disease, who were stratified according to the need for an early surgery (group S) or not (group I) and further divided according to the time elapsed from the beginning of the follow-up to the start of immunosuppression therapy. RESULTS: The rate of disabling events was similar in both groups (S: 77% versus I: 76%, P = 0.700). The percentage of patients who needed surgery after or during immunosuppression therapy was higher among group S, both for first surgeries after the index event (38% of groups S versus 21% of group I, P < 0.001) and for reoperations (38% of groups S versus 12% of group I, P < 0.001). The time elapsed to reoperation was shorter in group I (HR = 2.340 [1.367-4.005]), stratified for the onset of immunosuppression. Moreover, reoperation was far more common among patients who had a late start of immunosuppression (S36: 50% versus S0-6: 27% and S6-36: 25%, P < 0.001) and (I36: 16% versus I0-6: 5% and I6-36: 7%, P < 0.001). CONCLUSIONS: Although neither early surgery nor immunosuppression seem to be able to prevent global disabling disease, an early start of immunosuppression by itself is associated with fewer surgeries and should be considered in daily practice as a preventive strategy.
Subject(s)
Crohn Disease/drug therapy , Crohn Disease/surgery , Immunosuppression Therapy/statistics & numerical data , Immunosuppressive Agents/administration & dosage , Time-to-Treatment , Aged , Female , Humans , Immunosuppression Therapy/methods , Male , Middle Aged , Recurrence , Retrospective Studies , Risk Factors , Treatment OutcomeABSTRACT
Background: Colonic diverticular bleeding is the most common cause of lower gastrointestinal bleeding. Risk factors related to severity and repeated bleeding episodes are not completely clearly defined. Objective: To characterize a Portuguese population hospitalized due to colonic diverticular bleeding and to identify the clinical predictors related to bleeding severity and rebleeding. Methods: Retrospective analysis of all hospitalized patients diagnosed with colonic diverticular bleeding from January 2008 to December 2013 at our institution. The main outcomes evaluated were bleeding severity, defined as any transfusion support requirements and/or signs of hemodynamic shock, and 1-year recurrence rate. Results: Seventy-four patients were included, with a mean age of 75.7 ± 9.5 years; the majority were male (62.2%). Thirty-six patients (48.6%) met the criteria for severe bleeding; four independent risk factors for severe diverticular bleeding were identified: low hemoglobin level at admission (≤ 11 g/dL; OR 18.8), older age (≥ 75 years; OR 4.7), bilateral diverticular location (OR 14.2) and chronic kidney disease (OR 5.6). The 1-year recurrence rate was 12.9%. We did not identify any independent risk factor for bleeding recurrence in this population. Conclusion: In this series, nearly half of the patients hospitalized with diverticular bleeding presented with severe bleeding. Patients with low hemoglobin levels, older age, bilateral diverticular location and chronic kidney disease had a significantly increased risk for severe diverticular bleeding. In addition, a small number of patients rebled within the first year after the index episode, although we could not identify independent risk factors associated with the recurrence of diverticular bleeding (AU)
No disponible
Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Diverticulosis, Colonic/complications , Diverticulosis, Colonic/diagnosis , Diverticulosis, Colonic/physiopathology , Risk Factors , Recurrence , Gastrointestinal Hemorrhage/complications , Gastrointestinal Hemorrhage/physiopathology , Severity of Illness Index , Retrospective Studies , Data Analysis/methods , Logistic Models , Odds Ratio , Helsinki DeclarationABSTRACT
BACKGROUND: Colonic diverticular bleeding is the most common cause of lower gastrointestinal bleeding. Risk factors related to severity and repeated bleeding episodes are not completely clearly defined. OBJECTIVE: To characterize a Portuguese population hospitalized due to colonic diverticular bleeding and to identify the clinical predictors related to bleeding severity and rebleeding. METHODS: Retrospective analysis of all hospitalized patients diagnosed with colonic diverticular bleeding from January 2008 to December 2013 at our institution. The main outcomes evaluated were bleeding severity, defined as any transfusion support requirements and/or signs of hemodynamic shock, and 1-year recurrence rate. RESULTS: Seventy-four patients were included, with a mean age of 75.7 ± 9.5 years; the majority were male (62.2%). Thirty-six patients (48.6%) met the criteria for severe bleeding; four independent risk factors for severe diverticular bleeding were identified: low hemoglobin level at admission (≤ 11 g/dL; OR 18.8), older age (≥ 75 years; OR 4.7), bilateral diverticular location (OR 14.2) and chronic kidney disease (OR 5.6). The 1-year recurrence rate was 12.9%. We did not identify any independent risk factor for bleeding recurrence in this population. CONCLUSION: In this series, nearly half of the patients hospitalized with diverticular bleeding presented with severe bleeding. Patients with low hemoglobin levels, older age, bilateral diverticular location and chronic kidney disease had a significantly increased risk for severe diverticular bleeding. In addition, a small number of patients rebled within the first year after the index episode, although we could not identify independent risk factors associated with the recurrence of diverticular bleeding.
Subject(s)
Diverticulosis, Colonic/complications , Diverticulosis, Colonic/epidemiology , Gastrointestinal Hemorrhage/epidemiology , Gastrointestinal Hemorrhage/etiology , Aged , Aged, 80 and over , Cohort Studies , Diverticulum, Colon , Female , Humans , Male , Middle Aged , Portugal , Recurrence , Retrospective Studies , Risk FactorsABSTRACT
INTRODUCTION: The establishment of prognostic models for Crohn's disease [CD] is highly desirable, as they have the potential to guide physicians in the decision-making process concerning therapeutic choices, thus improving patients' health and quality of life. Our aim was to derive models for disabling CD and reoperation based solely on clinical/demographic data. METHODS: A multicentric and retrospectively enrolled cohort of CD patients, subject to early surgery or immunosuppression, was analysed in order to build Bayesian network models and risk matrices. The final results were validated internally and with a multicentric and prospectively enrolled cohort. RESULTS: The derivation cohort included a total of 489 CD patients [64% with disabling disease and 18% who needed reoperation], while the validation cohort included 129 CD patients with similar outcome proportions. The Bayesian models achieved an area under the curve of 78% for disabling disease and 86% for reoperation. Age at diagnosis, perianal disease, disease aggressiveness and early therapeutic decisions were found to be significant factors, and were used to construct user-friendly matrices depicting the probability of each outcome in patients with various combinations of these factors. The matrices exhibit good performance for the most important criteria: disabling disease positive post-test odds = 8.00 [2.72-23.44] and reoperation negative post-test odds = 0.02 [0.00-0.11]. CONCLUSIONS: Clinical and demographical risk factors for disabling CD and reoperation were determined and their impact was quantified by means of risk matrices, which are applicable as bedside clinical tools that can help physicians during therapeutic decisions in early disease management.
Subject(s)
Crohn Disease/diagnosis , Adult , Bayes Theorem , Crohn Disease/drug therapy , Crohn Disease/surgery , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Prognosis , Prospective Studies , Retrospective Studies , Risk Factors , Treatment OutcomeABSTRACT
HIGHLIGHTS: A decade after patellofemoral ligament reconstruction results remains satisfactory.It is a good option for patellar instability treatment in children.Patients with trochlear dysplasia benefit from trochleoplasty after physeal closure. BACKGROUND: Patellofemoral instability is a common cause of knee disability. Acute patellofemoral dislocation is the most common acute knee disorder in skeletally immature patients. In this group, the incidence of patellofemoral dislocation is approximately 43 per 100,000 individuals. THE PRECISE OBJECTIVE ADDRESSED IN THE PAPER: Medial patellofemoral ligament (MPFL) reconstruction has a significant role in the treatment of patellofemoral instability in skeletally immature patients. We evaluated the medium and long-term results results of MPFL reconstruction as the sole method of patellofemoral instability treatment and their relationship with the presence of other potentially associated factors. METHODS: We conducted a prospective study with 35 young patients who underwent the same surgical technique between 2002 and 2009. Age, gender, patellar tilt, patella height, TT-TG, trochlear dysplasia, the Kujala score and the Tegner activity score were evaluated. Statistical analysis used SPSS® 20. RESULTS: The mean age of the patients was 15.9 years. High patella was observed in 10% of patients. All patients had TT-TG within a normal range. Trochlear dysplasia was found in 80% of the patients: 40% had Dejour's type A; 34% type B; 20% type C and 6% type D. The medium-term Kujala score (84 ± 9) significantly improved compared to the pre-operative score (54 ± 11). However, a decline in the long-term (78 ± 3) score was observed. The Tegner activity score showed a significant decrease. The long-term results were significantly lower when patients had trochlear dysplasia type B to D. CONCLUSIONS: A decade after isolated MPFL reconstruction, results remained satisfactory. Patients with trochlear dysplasia types B to D may benefit from associated trochleoplasty in a second intervention.