RESUMO
The activity of dental caries, combined with its multifactorial etiology, alters salivary molecule composition. The present systematic review was developed to answer the following question: "Are salivary biomarkers reliable for diagnosis of dental caries?". Following the "Preferred Reporting Item for Systematic Reviews and Meta-analysis" (PRISMA) guidelines, the review was conducted using multiple database research (Medline, Web of Science, and Scopus). Studies performed on healthy subjects with and without dental caries and providing detailed information concerning the clinical diagnosis of caries (Decayed, Missing, Filled Teeth-DMFT and International Caries Detection and Assessment System-ICDAS criteria) were included. The quality assessment was performed following a modified version of the Joanna Briggs Institute Prevalence Critical Appraisal Checklist. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42022304505). Sixteen papers were included in the review. All studies reported statistically significant differences in the concentration of salivary molecules between subjects with and without caries (p < 0.05). Proteins were the most investigated molecules, in particular alpha-amylase and mucins. Some studies present a risk of bias, such as identifying confounding factors and clearly defining the source population. Nevertheless, the 16 papers were judged to be of moderate to high quality. There is evidence that some salivary compounds studied in this review could play an important diagnostic role for dental caries, such as salivary mucins, glycoproteins (sCD14), interleukins (IL-2RA, 4,-13), urease, carbonic anhydrase VI, and urea.
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COVID-19 , Úlceras Orais , Vacinas , Humanos , SARS-CoV-2 , Vacina BNT162 , COVID-19/prevenção & controleRESUMO
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (AHSCT) represents the only curative treatment for the majority of pediatric patients with Myelodysplastic Syndrome (MDS). We aimed to evaluate overall survival (OS), disease-free survival (DFS), non-relapse mortality (NRM) and relapse incidence in children who underwent AHSCT for MDS in six institutions from Argentina. PROCEDURE: A retrospective analysis of 54 AHSCT was carried out in 52 patients (mean age: 9 years; range: 2-19; 35 males). RESULTS: MDS subtypes were refractory cytopenia of childhood (RCC) (n: 26, 50%), refractory anemia with excess blasts (RAEB) (n: 9, 18%), RAEB in transformation (RAEB-T) (n: 8, 15%) and juvenile myelomonocytic leukemia (JMML) (n: 9, 17%). At time of transplant, seven (13%) patients transformed to acute myeloid leukemia (AML) and two patients with RCC to RAEB. Donors were related in 32 cases (59%) and the stem cells source was: bone marrow (63%), peripheral blood (26%), and umbilical cord blood (11%). Five-year DFS and OS were 50% and 55% respectively; and for patients with JMML, 57% and 67% respectively. Cumulative incidence of NRM and relapse were 27% and 21% respectively. In the multivariate analysis, umbilical cord blood (HR 4.07; P = 0.025) and age ≥ 9 years at transplantation (HR 3.28; P = 0.017) were associated with lower OS; age and graft-versus-host disease (GVHD) had a higher NRM. CONCLUSIONS: In our series, more than half of the patients achieved long term OS with AHSCT. Less toxic conditioning regimens or more intensive GVHD prophylaxis could lead to better results in some children.
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Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas/terapia , Recidiva Local de Neoplasia/epidemiologia , Adolescente , Adulto , Argentina/epidemiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Lactente , Masculino , Síndromes Mielodisplásicas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto JovemRESUMO
The treatment plan represents the final step in every diagnostic procedure and is the result of a series of assessments based on information gathered from a detailed clinical history. This clinical case reports the replacement of two central incisors that were lost because of a trauma. The advantages and disadvantages of the two treatment options (i.e. implantology or prosthetic restoration) were carefully evaluated in relation to the case in hand. Patient compliance and aesthetic requirements had been also considered. In this case, a conventional prosthetic restoration was performed using a metal-ceramic bridge, utilising full crowns between the right and left maxillary lateral incisors associated with minimal canine preparation. By this strategy, the treatment plan allows for a future implant restoration, should this become necessary.
Assuntos
Aumento da Coroa Clínica , Prótese Parcial Fixa , Incisivo/lesões , Fraturas dos Dentes/terapia , Reimplante Dentário , Adolescente , Coroas , Feminino , Seguimentos , Humanos , Maxila , Ligas Metalo-Cerâmicas , Reabsorção da Raiz/etiologia , Fraturas dos Dentes/complicaçõesRESUMO
BACKGROUND: The aim of the present study was to evaluate the cyclic fatigue resistance of Mtwo NiTi rotary instruments after clinical use by 1 experienced and 1 novice operator. MATERIAL/METHODS: Cyclic fatigue testing of instruments was performed on tapered artiï¬cial canals with a 5 mm radius of curvature and 60° angle of curvature. Twenty Mtwo instruments for each size were selected and divided into 2 groups: group A consisted of 10 instruments of each size used for shaping 10 root canals in molar teeth of patients by an experienced operator; group B consisted of 10 instruments of each size used for shaping 10 root canals in molar teeth of patients by a novice operator. Instruments were rotated until fracture occurred and the numbers of cycles to failure (NCF) were recorded. Data obtained were subjected to an independent sample t-test to determine statistical differences. The signiï¬cance was determined at a 95% conï¬dence level. RESULTS: No statistically signiï¬cant difference (P<0.05) was noted between the instruments of groups A and B for all sizes. More instruments with visible signs of plastic deformation were identified for the novice operator. CONCLUSIONS: The clinical use of Mtwo NiTi rotary instruments by a novice operator did not signiï¬cantly affect the cyclic fatigue resistance when compared with the control group of the same instrument sizes used by an experienced operator. It can be concluded that novice operators can use these instruments safely under the recommended technical guidelines.
Assuntos
Competência Clínica , Instrumentos Odontológicos , Análise do Estresse Dentário/instrumentação , Teste de Materiais/instrumentação , Níquel/química , Titânio/química , HumanosRESUMO
BACKGROUND: As a rule, endocervical tumours with signet-ring cell are classed as metastatic extra-genital neoplasms. In a patient aged 45 years, we describe primary cervical signet-ring cell carcinoma (PCSRCC) characterized by prominent endometrial and myometrial involvement, simulating primary endometrial adenocarcinoma with cervical extension. In addition, a review was made of the literature to identify the clinical and pathological features of this rare malignancy. CASE PRESENTATION: A 45-year-old woman was referred to our Gynaecology Department due to persistent abnormal vaginal bleeding. Transvaginal ultrasonography showed slight endometrial irregularities in the whole uterine cavity suggestive of endometrial neoplasms. Pelvic magnetic resonance imaging revealed diffuse enlargement of the cervix, which had been replaced by a mass. Induration extended to the parametria and sigmoid colon fat.Histological examination of endometrial curettage and a cervical biopsy revealed a neoplasm characterized by neoplastic signet-ring cells and trabecular structures. Immunohistochemical analysis and molecular studies showed certain findings consistent with a cervical neoplasm, such as positivity to CEA, keratin 7, Ca-125 and p16 and the presence of HPV (Human Papilloma Virus) DNA 18.On examination of the hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy, the lesion replacing the cervix, endometrium and myometrium, revealed the same immunohistochemical findings observed on endometrial curettage and cervical biopsy specimens. Metastases were found in an ovarian cystic lesion and the lymph nodes. CONCLUSION: With this report the authors have demonstrated that the spread of cervical adenocarcinoma to the uterine corpus, although rare, may be observed, and that in this instance immunohistochemical and molecular studies can provide sufficient information for accurate diagnosis even on small biopsy specimens.
Assuntos
Carcinoma de Células em Anel de Sinete/patologia , Neoplasias do Endométrio/patologia , Miométrio/patologia , Neoplasias do Colo do Útero/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-IdadeRESUMO
Delayed replantation of an avulsed tooth may result in rapid root resorption or, more frequently, dental ankylosis with subsequent bone substitution. If this process develop slowly, it is possible to observe that tooth loss is characterized by a well conserved alveolus with regard to bone preservation, particularly in vertical dimension. This clinical case reports a dental trauma of a central incisor in a young boy characterized by tooth avulsion and its delayed replantation. After 10 years, dental ankylosis of the incisor was recorded and the patient underwent a prosthetic-orthodontic rehabilitation using CAD-CAM technology and no-prep veneers.
Assuntos
Incisivo/lesões , Reabsorção da Raiz/etiologia , Avulsão Dentária/cirurgia , Perda de Dente/etiologia , Reimplante Dentário/efeitos adversos , Adolescente , Implantação Dentária Endóssea , Prótese Dentária Fixada por Implante , Facetas Dentárias , Humanos , Masculino , Maxila , Fechamento de Espaço Ortodôntico , Fatores de Tempo , Perda de Dente/cirurgiaRESUMO
Obstructive sleep apnoea syndrome (OSA) in paediatrics is a rather frequent pathology caused by pathophysiological alterations leading to partial and prolonged obstruction (hypoventilation) and/or intermittent partial (hypopnoea) or complete (apnoea) obstruction of the upper airways. Paediatric OSA is characterised by daytime and night-time symptoms. Unfortunately, there are few data on shared diagnostic-therapeutic pathways that address OSA with a multidisciplinary approach in paediatric age. This document summarizes recommendations from the Emilia-Romagna Region, Italy, developed in order to provide the most appropriate tools for a multidisciplinary approach in the diagnosis, treatment and care of paediatric patients with OSA. The multidisciplinary group of experts distinguished two different 'step' pathways, depending on the age group considered (i.e., under or over two years). In most cases, these pathways can be carried out by the primary care paediatrician, who represents the first filter for approaching the problem. For this reason, it is essential that the primary care paediatrician receives adequate training on how to formulate the diagnostic suspicion of OSA and on what criteria to use to select patients to be sent to the hospital centre. The relationship between the paediatrician of the patient and her/his parents must see a synergy of behaviour between the various players in order to avoid uncertainty about the diagnostic and therapeutic decisions as well as the follow-up phase. The definition and evaluation of the organizational process and outcome indicators of the developed flow-chart, and the impact of its implementation will remain fundamental.
RESUMO
Among healthcare workers, oral and maxillofacial surgeons are some of the most exposed to coronavirus disease (COVID-19). The aim of this retrospective study was to develop suggestions for continuing the work of oral and maxillofacial surgeons using a safe protocol for elective and urgent aerosol-generating procedures that could prevent the onset of new clusters. Based on the results obtained and a guidelines review of those Asian countries that had promptly managed the current pandemic, the following safety protocol was developed.
Assuntos
COVID-19 , Procedimentos Cirúrgicos Bucais , Aerossóis , COVID-19/prevenção & controle , Humanos , Pandemias/prevenção & controle , Estudos Retrospectivos , SARS-CoV-2RESUMO
Metaplastic papillary tumor (MPT) of the salpinx is a rare lesion found in the lumen of fallopian tubes during the postpartum period. This lesion is very small and is composed microscopically of papillae lined by stratified epithelium. Similar to serous borderline ovarian tumors (BOTs), epithelial elements of MPT show a budding, abundant, dense, and eosinophilic cytoplasm, bland nuclei or with mild atypia. It is not clear whether this lesion is a papillary metaplastic proliferation or a small atypical proliferative (borderline) serous tumor associated with pregnancy. Owing to its rarity, MPT has never been investigated in molecular studies and compared with ovarian serous neoplasms. In this study, a case of tubal MPT was molecularly examined and compared with 4 BOTs and with 2 low-grade ovarian carcinomas, using microsatellite analysis with 13 markers at 8 chromosomal regions involved in ovarian carcinogenesis. The tubal MPT and one of the BOTs showed no alterations in the investigated chromosomal regions. The remaining 3 BOTs showed only single allelic imbalances. Instead, low-grade serous carcinomas showed a higher frequency of alterations, including allelic imbalance at chr10q23, 1p36, 9p22, and 17. In conclusion, this study provides, for the first time, molecular data on an MPT of the fallopian tube, indicating that this entity might share both morphologic and molecular similarities with a subset of minimally altered BOTs, termed atypical proliferative serous tumors, which behave in a benign manner. However, in our opinion, further molecular studies should be conducted on other cases of MPTs to confirm this hypothesis.
Assuntos
Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/patologia , Complicações Neoplásicas na Gravidez/genética , Complicações Neoplásicas na Gravidez/patologia , Adulto , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Cistadenoma Seroso/genética , Cistadenoma Seroso/patologia , Tubas Uterinas/patologia , Feminino , Humanos , Repetições de Microssatélites , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , GravidezRESUMO
Merkel cell polyomavirus (MCPyV) has been found in patients with Merkel cell carcinoma and respiratory tract infections. Merkel cell carcinoma is a primary aggressive neuroendocrine carcinoma of the skin. It has been demonstrated that MCPyV can be transmitted during sexual activity and may be present in the oral and anogenital mucosa. The aim of the present study was to evaluate whether MCPyV coexisted with HPV in three cases of neuroendocrine small cell carcinoma of the cervix using PCR and immunohistochemical analysis Three cases of NSC of the cervix were identified in the pathology archives of Parma University (Italy). Of these, two cases were associated with an adenocarcinomatous component. A set of general primers from the L1 region (forward, L1C1 and reverse, L1C2 or L1C2M) was PCR amplified to detect the broad-spectrum DNA of genital HPV. The presence of MCPyV was investigated via immunohistochemistry using a mouse monoclonal antibody against the MCPyV LT antigen and through PCR analysis to separate viral DNA. HPV DNA was present in all three neuroendocrine carcinomas and in the adenocarcinoma component of the two mixed cases. None of the cases were immunoreactive to CM2B4 and did not contain viral DNA in either their neuroendocrine or adenocarcinomatous component. Whilst it is difficult to draw definitive conclusions from such a small sample size, these data suggested that MCPyV does not coexist with HPV in the cervix. However, in the present study, the absence of detectable MCPyV may have been due to the presence of a genotype that was not detected by the primers used in the PCR analysis or by the antibody used for the immunohistochemical study. MCPyV microRNA may also have been present, inhibiting LT expression. Additional studies with larger cohorts and more advanced molecular biology techniques are required to confirm the hypothesis of the current study.
RESUMO
Dental trauma is a frequent occurrence in children and adolescent and a correct diagnosis and treatment are essential for a favourable long-term prognosis. The present Guidelines aim to formulate evidence-based recommendations to assist dentists, paediatricians, surgeons, teachers, school and sport staff, parents in the prevention and first aid of dental trauma in children and to provide a careful assessment of the medico-legal implications, reviewing the first draft of the guidelines published in 2012. A multidisciplinary panel on the behalf of the Italian Ministry of Health and in collaboration with the WHO Collaborating Centre for Epidemiology and Community Dentistry of Milan, developed this document. The following four queries were postulated: 1) Which kind of precautions the health personnel, parents, sports and educational personnel must activate in order to prevent the dental trauma damage? 2) How an orofacial trauma in paediatric patients should be managed either in the Emergency Care Unit and/or in private dental office? 3) What criteria should be adopted by a dentist private practitioner to fill in a certificate in cases of dental and/or tempomandibular joint trauma occurring in children and adolescents? 4) What are the elements that should lead clinicians to suspect a non-accidental dental trauma? A systematic review and analysis of the scientific literature published in English, Italian and French from 2007 to 2017 regarding dental trauma in children and adolescents aged 0-18 years was performed, and about 100 papers were analysed and included. The following four domains were analysed and discussed: Dental Trauma Prevention Strategies and Health Education, First aid in orofacial and dental trauma, Certificate of the dental trauma, Oral and dental signs of child abuse and neglect. Twenty-eight recommendations were draw up and codified by the panel according to the Methodological handbook, produced by the Istituto Superiore di Sanità, in order to guide physicians in the prevention and first aid of dental trauma in children and adolescents. In addition, a careful assessment of the medico-legal implications is reported in this document.
Assuntos
Odontologia/normas , Guias de Prática Clínica como Assunto , Traumatismos Dentários/prevenção & controle , Traumatismos Dentários/terapia , Adolescente , Criança , Pré-Escolar , Medicina Baseada em Evidências , Feminino , Humanos , Escala de Gravidade do Ferimento , Itália , Masculino , Pediatria/normas , Prevenção Primária/normas , Prevenção Secundária/normas , Índices de Gravidade do Trauma , Resultado do TratamentoRESUMO
The role of Wnt pathway in digestive endocrine tumours is debated. The aim of this work is to investigate key players in Wnt pathway by a multimodal approach. Sixty cases (49 well-differentiated and 11 poorly differentiated) were investigated for methylation of adenomatous polyposis coli (APC) and E-cadherin promoters, the loss of heterozygosity (LOH) at APC locus and beta-catenin and E-cadherin expression by immunohistochemistry. Tumours showing altered beta-catenin localization were tested for beta-catenin and APC mutations. APC promoter methylation was restricted to gastroduodenal tumours (21 out of 59, 36%), prevalent in poorly differentiated carcinomas (P=0.042) and correlating with aggressive features (high histology grade, P<0.02; tumour death, P=0.026; high fractional allelic loss, P=0.002, in turn correlating with short survival, P=0.017). LOH at APC locus was found in 14 out of 53 cases (26%, 10 gastroduodenal and 4 colorectal), prevalent in poorly differentiated carcinomas (P=0.002) and correlating with histology grade (P=0.012). beta-catenin abnormal expression was found in 41 out of 54 cases (76%), with nuclear staining correlating with APC alteration (P=0.047) and short survival (P=0.006). APC, but not beta-catenin, gene mutations were found (7 out of 35 tumours), 4 of which in the midgut. E-cadherin promoter methylation was rarely detected (2 out of 52 cases), with cytoplasmic expression in 18 out of 43 cases (42%), not correlating with any clinico-pathological feature. In conclusion, Wnt pathway alterations, as represented by abnormal beta-catenin localization, are common events in digestive endocrine tumours, but only nuclear expression correlates with tumour aggressiveness. Though with different alteration mechanisms according to anatomical site, APC plays a major role in Wnt pathway activation and in determining the high chromosomal instability observed in aggressive endocrine carcinomas.
Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Núcleo Celular/metabolismo , Instabilidade Cromossômica , Neoplasias das Glândulas Endócrinas/genética , Neoplasias Gastrointestinais/genética , beta Catenina/genética , Proteína da Polipose Adenomatosa do Colo/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Núcleo Celular/patologia , Citoplasma/metabolismo , Citoplasma/patologia , Metilação de DNA , Neoplasias das Glândulas Endócrinas/metabolismo , Neoplasias das Glândulas Endócrinas/patologia , Feminino , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/patologia , Humanos , Técnicas Imunoenzimáticas , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Mutação/genética , Regiões Promotoras Genéticas , Proteínas Wnt , Adulto Jovem , beta Catenina/metabolismoRESUMO
PURPOSE: The X and Y chromosomes have been associated with malignancy in different types of human tumors. This study attempts to determine the involvement of X chromosome and pseudoautosomal regions (PAR) in sporadic colorectal carcinogenesis. EXPERIMENTAL DESIGN: An allelotyping of X chromosome in 20 premalignant and 22 malignant sporadic colorectal tumors (CRC) from female patients and an analysis of losses [loss of heterozygosity (LOH)] on PARs from 44 CRCs and 12 adenomas of male patients were carried out. In male tumors, a fluorescence in situ hybridization analysis was done to identify which sex chromosome was possibly lost. RESULTS: The LOH frequency in female CRCs was 46% with higher incidence in patients with tumor recurrence than in those who were disease-free (P < 0.01) and with a significant difference from adenomas (11%; P < 0.0001). The LOH rate of PARs in male CRCs was 37% with a frequency significantly higher in patients with recurrence (P < 0.03). These results were maintained also when data from PARs of all 66 male and female patients were cumulated (P < 0.05). LOH in PARs was significantly correlated with LOH at 5q (P < 0.01) and 18q (P < 0.01), early and late events, respectively, in colorectal carcinogenesis. Fluorescence in situ hybridization analysis in male patients with extensive PAR LOH revealed a preferential loss of the Y chromosome. CONCLUSIONS: Our data suggest a role for sex chromosome deletions in the malignant progression of sporadic CRCs and support the presence in the PARs of putative tumor suppressor genes involved in the progression of human sporadic CRCs.
Assuntos
Adenocarcinoma/genética , Transformação Celular Neoplásica , Aberrações Cromossômicas , Cromossomos Humanos X/genética , Neoplasias Colorretais/genética , Idoso , Idoso de 80 Anos ou mais , Mapeamento Cromossômico , DNA de Neoplasias/genética , Progressão da Doença , Feminino , Humanos , Técnicas Imunoenzimáticas , Perda de Heterozigosidade , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
The introduction of fiber posts has improved the treatment of endodontically treated teeth, increasing retention, and distributing the stress along the root in order to reduce the risk of fracture. This clinical case describes the use of posts during the prosthetic rehabilitation of severely compromised teeth in the anterior segment.
Assuntos
Planejamento de Prótese Dentária , Técnica para Retentor Intrarradicular/instrumentação , Adulto , Bis-Fenol A-Glicidil Metacrilato , Cimentação , Resinas Compostas , Coroas , Porcelana Dentária , Retenção em Prótese Dentária , Facetas Dentárias , Feminino , Humanos , Incisivo/lesões , Polietilenoglicóis , Ácidos Polimetacrílicos , Cimentos de Resina , Retratamento , Tratamento do Canal Radicular , Estresse Mecânico , Clareamento Dental , Descoloração de Dente/terapia , Fraturas dos Dentes/terapiaRESUMO
BACKGROUND AND AIM OF THE WORK: Among hospital facilities the dental unit is an environment that is at major risk of Legionella due to equipment such as the air/water syringe, the turbine, the micromotor and the scaler which generate potentially harmful aerosols that may to be a source of exposure to Legionella spp. particularly in immunodeficient patients, and those affected by chronic diseases, and also in dental personnel. Therefore, an examination of the extent of Legionella spp. contamination in the dental chairs waterlines and the incoming water supply of some public dental units is the subject of the present study. METHODS: From February 2002 to March 2004, a total of 208 water samples were collected: 160 samples from the water supply of 4 dental chair and 48 samples from the cold incoming tap water of 2 units. RESULTS: Legionella spp. was detected in 46 samples (22.1% ): 19 of them (41.3% of Legionella spp.; 9.1% of the total) were Legionella pneumophila; Pseudomonas aeruginosa was detected in 86 samples (41.4%) and both microorganisms were detected in 2 samples (0.96%). CONCLUSIONS: Our results show a microbiological condition in dental settings, that is not at all satisfactory due to the presence of Legionella in concentrations that are considered to be a health hazard (> or = 10(3)) in certain cases. Given the extent of the health risk in these surroundings, the difficulty in its assessment, and also considering the wide diffusion of general dental care, our investigation has confirmed the need to regularly monitor the microbiological condition of water in dental units.
Assuntos
Equipamentos Odontológicos/microbiologia , Unidade Hospitalar de Odontologia , Legionella/isolamento & purificação , Legionelose/transmissão , Microbiologia da Água , Humanos , Legionella pneumophila/isolamento & purificação , Legionelose/prevenção & controle , Doença dos Legionários/prevenção & controle , Doença dos Legionários/transmissão , Pseudomonas aeruginosa/isolamento & purificação , Fatores de Risco , Abastecimento de ÁguaRESUMO
Loss of heterozygosity (LOH) for markers on X chromosome are associated with malignancy in endocrine tumors of the stomach and pancreas. The aim of this work is to investigate low-grade, well-differentiated endocrine carcinomas (WDEC) vs high-grade, poorly differentiated endocrine carcinomas (PDEC) of the gastroenteropancreatic (GEP) tract for common deletion regions on X chromosome. We performed a comparative allelotyping analysis with 24 highly polymorphic markers for the X chromosome in 12 WDECs and 5 PDECs. Overall, the LOH frequency in all informative loci investigated was 59% in primary and 61% in metastasis, with a significantly higher rate in PDECs than in WDECs (p<0.015 for primary and p<0.00005 for metastasis). In both WDECs and PDECs, the small Xq25 region as defined by DXS8059, DXS8098, and DXS8009 markers showed higher LOH rate as compared to the rest of the chromosome markers (p<0.04). In addition, LOH was very frequently elevated also in DXS294 and in DXS102 loci mapping the chromosomal region Xq26. In no instances differences were found between primary tumors and metastases. Methylation analysis revealed that Xq25 loss preferentially occurred on the inactive X chromosome, a feature in agreement with findings from other human cancers suggesting escape of tumor suppressor genes to X chromosome inactivation at this region. Overall, our data indicate that the two chromosomal regions, Xq25 and Xq26, may participate to the malignant progression of GEP endocrine carcinomas.
Assuntos
Deleção Cromossômica , Cromossomos Humanos X/genética , Neoplasias Gastrointestinais/patologia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Ilhas de CpG/genética , Metilação de DNA , Neoplasias Duodenais/genética , Neoplasias Duodenais/metabolismo , Neoplasias Duodenais/patologia , Feminino , Neoplasias Gastrointestinais/enzimologia , Neoplasias Gastrointestinais/genética , Genoma Humano , Humanos , Imuno-Histoquímica , Perda de Heterozigosidade , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 9 da Matriz/análise , Repetições de Microssatélites , Pessoa de Meia-Idade , Metástase Neoplásica , Hibridização de Ácido Nucleico/métodos , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/genética , Reação em Cadeia da Polimerase/métodos , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologiaRESUMO
In contrast with the large amount of data generated from endocrine tumors of the pancreas, sparse and mostly unconfirmed data are available on the criteria for the assessment of malignancy risk and patient outcome in endocrine tumors of the gastrointestinal tract. In these conditions the 2000 WHO classification with its standardized scheme of pathologic report constitutes a framework facilitating the assessment of tumor malignancy and has been regarded as useful for clinical purposes, providing the basis for proper management of the patients and for the design of treatment protocols. The classification is based on a combination of pathological and clinical features with parameters specific for each organ in which the endocrine tumors originate. Three main categories, one further subdivided into two subgroups, are considered: (1) well-differentiated endocrine tumors, further subdivided into tumors with benign and with uncertain behavior; (2) well-differentiated endocrine carcinomas, low grade; and (3) poorly differentiated endocrine carcinomas, high grade. In this review the differential tumor characteristics between the different categories are summarized. Moreover, the relevance of additional features with respect to tumor prognostication, chiefly the Ki-67 proliferation index and malignancy-associated genetic changes, is discussed with emphasis on the discrepancies emerging between tumors of foregut and of midgut origin.
Assuntos
Neoplasias das Glândulas Endócrinas/classificação , Neoplasias das Glândulas Endócrinas/diagnóstico , Neoplasias Gastrointestinais/classificação , Neoplasias Gastrointestinais/diagnóstico , Invasividade Neoplásica/diagnóstico , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Neoplasias das Glândulas Endócrinas/patologia , Neoplasias Gastrointestinais/patologia , Humanos , Antígeno Ki-67 , Índice Mitótico , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Prognóstico , Organização Mundial da SaúdeRESUMO
INTRODUCTION: Hematopoietic cell transplantationis a therapy with a risk of transplant-related mortality (TRM), which may vary depending on prior comorbidities. The Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) is an instrument developed to measure this risk. There are very few reports on its use in pediatrics. The objective of this study was to validate the HCT-CI in a pediatric cohort of allogeneic hematopoietic-cell transplantation recipients in Argentina. POPULATION AND METHODS: Retrospective cohort made up of 140 transplant patients a, Hospital J. P. Garrahan between 2008 and 2012. Medical records were reviewed to identify patient history and course. The HCT-CI was estimated for each patient, who was classified as having a low (score: 0), intermediate (score: 1-2) or high (score: >3) risk. Survival was estimated for each group using the Kaplan-Meier method and compared with the log-rank test. For malignancies, relapse was considered an event consistent with TRM. A p value ã 0.05 was considered significant. RESULTS: The median score in the HCT-CI was 1 (r: 0-6). A score of 0 was observed in 45.7% of patients, 1-2 in 40.7%, and >3 in 13.6%. The most common comorbidities included obesity, infection, pulmonary and liver involvement. TRM was 14.1% among patients with a score of 0; 43.7% with a score of 1-2, and 52.6% with a score >3. Differences were observed among the survival curves of the three groups (p = 0.01). CONCLUSIONS: The HCT-CI demonstrated to be an effective tool to predict the risk of TRM in our setting. KEY WORDS: comorbidity, hematopoietic stem cell transplantation, non-relapse mortality, pediatrics.
INTRODUCCIÓN: El trasplante hematopoyético es una terapia con riesgo de mortalidad relacionada con el trasplante (MRT), que puede variar según la comorbilidad previa. El índice de comorbilidad para trasplante hematopoyético (ICTH) es un instrumento desarrollado para medir este riesgo. Los reportes sobre su uso en pediatría son escasos. El objetivo de este estudio fue validar el ICTH en una cohorte pediátrica de receptores de trasplante hematopoyético alogénico en Argentina. POBLACIÓN Y MÉTODOS: Cohorte retrospectiva de 140 pacientes trasplantados en e, Hospital J. P. Garrahan entre 2008 y 2012. Se revisaron, de las historias clínicas, sus antecedentes y evolución. Se calculó el ICTH de cada paciente y se clasificaron como de riesgo bajo (puntaje 0), intermedio (puntaje 1-2) o alto (puntaje ã 3). Se estimó la supervivencia para cada grupo por el método de Kaplan-Meier y se comparó con la prueba de logaritmos de rangos. En el caso de las enfermedades malignas, la recaída fue considerada un evento competitivo con la MRT. Se consideró significativa una p ã 0,05. RESULTADOS: La mediana del ICTH fue 1 (r: 0-6). El 45,7% de los pacientes tuvieron puntaje 0; el 40,7%, 1-2; y el 13,6%, ã 3. Las comorbilidades más frecuentes fueron obesidad, infección y compromiso pulmonar y hepático. La MRT de los pacientes con puntaje 0 fue 14,1%; con puntaje 1-2, 43,7%; y con puntaje ã 3, 52,6%. Las curvas de supervivencia manifestaron diferencias entre los tres grupos (p 0,01). CONCLUSIONES: El ICTH mostró ser una herramienta efectiva para predecir el riesgo de MRT en nuestro medio.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Complicações Pós-Operatórias/epidemiologia , Adolescente , Argentina , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Transplante HomólogoRESUMO
The role of Fhit protein in the oncogenesis of colorectal cancer is still in debate. Recent studies have revealed that reduced Fhit protein expression is associated with a deficiency of the mismatch repair protein. One hundred and twenty unselected patients who underwent curative resection for sporadic colorectal cancer in a three-year period were evaluated for microsatellite instability (MSI) using six microsatellite markers, and for the presence of Fhit and mismatch repair (MMR) proteins (Mlh1 and Msh2) by means of immunostaining. The relations between these markers were analysed. Reduced or absent Fhit expression was noted in 18 out of 118 patients. This altered expression was significantly higher in right-sided cancer (P = 0.005), mucinous tumours (P = 0.005) and in poorly differentiated histological types (P = 0.0001). MSI was found in 22 out of 109 patients, more so in right-sided cancer (P = 0.0001), poorly differentiated histology (P = 0.0001), and mucinous tumours (P = 0.0001). No association was found with TNM stage. MSI was present in 66.7% of tumours with altered Fhit expression and in only 10% of tumours with preserved or intermediate Fhit expression (P = 0.0001). Of the tumours with reduced or absent Fhit expression, 72.2% had loss of nuclear Mlh1 or Msh2 expression compared with only 14% of the preserved or intermediate Fhit expression tumours (P = 0.0001). These results support the hypothesis that deficiency in a MMR gene could be a cause of the high frequency of alterations in Fhit expression, and they permit the suggestion that FHIT gene alteration may be part of the genetic pathway involving MSI through which some colorectal cancers arise.