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Pleiotropic variants (i.e., genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted ten years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61,052 variants reported to be associated by at least one genome wide association study (GWAS) with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16,055 pancreatic ductal adenocarcinoma (PDAC) cases and 212,149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P=6.52×10-5) and 7q36.3-rs288762 (P=3.03×10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.
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PURPOSE: Pretreatment staging is the milestone for planning either surgical or endoscopic treatment in duodenal neuroendocrine neoplasms (dNENs). Herein, a series of surgically treated dNEN patients was evaluated to assess the concordance between the pre- and postsurgical staging. METHODS: Retrospective analysis of patients with a histologically confirmed diagnosis of dNENs, who underwent surgical resection observed at eight Italian tertiary referral centers. The presurgical TNM stage, based on the radiological and functional imaging, was compared with the pathological TNM stage, after surgery. RESULTS: From 2000 to 2019, 109 patients were included. Sixty-six patients had G1, 26 a G2, 7 a G3 dNEN (Ki-67 not available in 10 patients). In 46/109 patients (42%) there was disagreement between the pre- and postsurgical staging, being it understaged in 42 patients (38%), overstaged in 4 (3%). As regards understaging, in 25 patients (22.9%), metastatic loco-regional nodes (N) resulted undetected at both radiological and functional imaging. Understaging due to the presence of distal micrometastases (M) was observed in 2 cases (1.8%). Underestimation of tumor extent (T) was observed in 12 patients (11%); in three cases the tumor was understaged both in T and N extent. CONCLUSIONS: Conventional imaging has a poor detection rate for loco-regional nodes and micrometastases in the presurgical setting of the dNENs. These results represent important advice when local conservative approaches, such as endoscopy or local surgical excision are considered and it represents a strong recommendation to include endoscopic ultrasound in the preoperative tools for a more accurate local staging.
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Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Duodenais/patologia , Metástase Linfática/diagnóstico , Estadiamento de Neoplasias/normas , Tumores Neuroendócrinos/patologia , Cuidados Pré-Operatórios , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Duodenais/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/cirurgia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (ORdom ) = 1.78, 95% confidence interval (CI) = 1.26-2.52, p = 1.19 × 10-3 and ORdom = 1.74, 95% CI = 1.15-2.63, p = 8.57 × 10-3 , respectively). Neither mutation was significantly associated with risk of developing early-onset PDAC. This retrospective study demonstrates novel risk estimates of K3326X and I157T in sporadic PDAC which suggest that upon validation and in combination with other established genetic and non-genetic risk factors, these mutations may be used to improve pancreatic cancer risk assessment in European populations. Identification of carriers of these risk alleles as high-risk groups may also facilitate screening or prevention strategies for such individuals, regardless of family history.
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Proteína BRCA2/genética , Carcinoma Ductal Pancreático/genética , Quinase do Ponto de Checagem 2/genética , Genes BRCA2 , Neoplasias Pancreáticas/genética , Idoso , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
INTRODUCTION: Medical photography is a noninvasive technique used for diagnostic, monitoring, and educational purposes. It is important to understand the patient's attitude to all or part of their body being photographed. The objective of this study was to analyze the attitudes of patients towards medical photography at a district hospital in Tarragona, Spain. METHODOLOGY: This exploratory study used a questionnaire to evaluate attitudes to medical photography among outpatients at Pius Hospital de Valls. The questionnaire explored the patients' beliefs about the usefulness of medical photography, the circumstances in which they would agree to be photographed and by whom, as well as their prior experience of medical photography. They were also asked whether they would authorize the use of photography and, if not, to explain their motives. RESULTS: The questionnaire was completed by 134 patients. The results showed that patients had a clearly positive attitude to being photographed for medical purposes (94.8%), treatment follow-up (88.1%), and consultation of their case with other physicians (86.6%). Acceptance was 88.8% if the lesion was malignant and 85.1% if it was extensive. For facial lesions, only 78.4% were willing to be photographed and in the case of genitals the percentage fell to 70.2%. Most patients (95.5%) would agree to being photographed by their doctor. The rate of acceptance was 66.4% in the case of a nurse, 64.9% for another doctor, and 21.6% for a professional photographer. CONCLUSIONS: Our study revealed that patients have a positive attitude to being photographed for medical purposes, particularly when they have a malignant lesion, when the photograph is taken by their specialist, and when they cannot be identified.
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Atitude , Fotografação , Dermatopatias/psicologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , EspanhaRESUMO
PURPOSE: Ampullary neuroendocrine neoplasms (NENs) account for < 0.3% of gastrointestinal NENs. Surgical options include transduodenal ampullectomy/tumour excision or pancreaticoduodenectomy (PD). We report the experience of two high-volume pancreatic surgical centres of ampullary NENs. METHODS: Clinical records of patients who underwent surgery for ampullary NENs (January 2007-November 2017) in the study centres were retrieved retrospectively. We evaluated clinical-pathological features, post-operative outcome and follow-up (FU). RESULTS: Eighteen patients (9 M/9 F, averaging 62 years) were enrolled. All but one were non-functioning NENs; four (22%) patients presented with jaundice. Seven (39%) of the patients underwent ampullectomy/excision (median tumour size 1.5 cm), and 11 (61%) patients underwent PD (median tumour size 2.4 cm). The median operation time of ampullectomy/excision was 221 min with operative blood loss of 75 ml (vs. 506 min and 425 ml in PD). The median hospital stay was 10 days in both groups. Overall surgical morbidity was 33%, due to four biochemical leaks, one pancreatic fistula and one abdominal haemorrhage. No reoperations were needed. The median tumour size was 1.8 (range 0.5-6.7) cm. All G2-G3 NENs were N1 (vs. 1/7 in G1 NENs). Three (17%) cases were mixed exocrine/G3 NECs. After a median FU of 45 (up to 124) months, recurrence occurred in four G3 NEC (31%) patients (median disease-free survival 14 months) after an R0 PD. Disease-related survival was 93, 77 and 66% at 1, 3 and 5 years, respectively. CONCLUSION: Ampullary NENs are mostly G1-G2 neoplasms. Lymph node metastases rarely occur in G1 NENs < 2 cm in size, which may be treated with ampullectomy/excision. Survival is 66% 5 years after surgery.
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Ampola Hepatopancreática , Neoplasias do Ducto Colédoco/cirurgia , Tumores Neuroendócrinos/cirurgia , Adulto , Idoso , Neoplasias do Ducto Colédoco/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/mortalidade , Duração da Cirurgia , Pancreaticoduodenectomia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Santiago del Estero is a province located in northwestern Argentina. The Dulce River is used for irrigation through a vast network of channels and ditches, including the San Martin Canal (SMC), which crosses the capital city of Santiago del Estero. This canal's water is used for drinking, as well as recreational use for the general population. However, this river has been seriously polluted for several decades. The present study focuses on the identification and the quantification of the water pollution levels of total phenols in the SMC according to the seasonal periods. Water samples from various areas of the canal in different months of the year, extending from December to September, were collected for analysis. Additionally, the concentration of total dissolved solids (TDS), chlorides, sulphates, nitrites and organic matter, as well as water hardness and alkalinity, were analysed in order to conduct a more complete study of the contamination of this area. The results showed a worrying total phenol concentration that exceeded the limit set by Argentine legislation for drinking water, as well as water for recreational use (5⯵g/L). The total phenol (TP) concentration was directly determined by a molecular absorption spectroscopy method based on a new flow injection analysis system (FIA). Under the selected experimental conditions, the detection and quantification limits were 0.0490 and 0.1633⯵g/mL, respectively. The developed method provides a number of improvements related to the speed of analysis, the restricted consumption of the reagents and sample volumes and the unnecessary sample treatment that contribute to environmentally friendly analytical chemistry. The results showed that TP make a significant contribution in the SMC pollution, especially during the months of April (400⯱â¯110⯵g/L) and September (240⯱â¯20⯵g/L). A high sulphate concentration that was higher than the limit allowed by the legislation was also found.
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Monitoramento Ambiental/métodos , Água Doce/química , Fenol/análise , Poluentes Químicos da Água/análise , Argentina , Cidades , Estações do Ano , Urbanização , Qualidade da ÁguaRESUMO
The inflammasome-IL-1 axis and type I interferons (IFNs) have been shown to exert protective effects upon respiratory tract infections. Conversely, IL-1 has also been implicated in inflammatory airway pathologies such as asthma and chronic obstructive pulmonary disease (COPD). OM-85 is a bacterial extract with proved efficacy against COPD and recurrent respiratory tract infections, a cause of co-morbidity in asthmatic patients. We therefore asked whether OM-85 affects the above-mentioned innate immune pathways. Here we show that OM-85 induced interferon-ß through the Toll-like receptor adaptors Trif and MyD88 in bone marrow-derived dendritic cells. Moreover, it exerted a dual role on IL-1 production; on the one hand, it upregulated proIL-1ß and proIL-1α levels in a MyD88-dependent manner without activating the inflammasome. On the other hand, it repressed IL-1ß secretion induced by alum, a well-known NLRP3 activator. In vivo, OM-85 diminished the recruitment of inflammatory cells in response to peritoneal alum challenge. Our findings therefore suggest that OM-85 favors a protective primed state, while dampening inflammasome activation in specific conditions. Taken together, these data bring new insights into the mechanisms of OM-85 action on innate immune pathways and suggest potential explanations for its efficacy in the treatment of virus-induced airway diseases.
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Adjuvantes Imunológicos/farmacologia , Extratos Celulares/farmacologia , Células Dendríticas/efeitos dos fármacos , Inflamassomos/efeitos dos fármacos , Interferon beta/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Células Cultivadas , Células Dendríticas/metabolismo , Inflamassomos/metabolismo , Interleucina-1/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Peritonite/genética , Peritonite/metabolismo , Peritonite/prevenção & controleRESUMO
Infection-associated inflammatory stress during pregnancy is the most common cause of fetal growth restriction and/or miscarriage. Treatment strategies for protection of at-risk mothers are limited to a narrow range of vaccines, which do not cover the bulk of the common pathogens most frequently encountered. Using mouse models, we demonstrate that oral treatment during pregnancy with a microbial-derived immunomodulator (OM85), currently used clinically for attenuation of infection-associated airway inflammatory symptoms in infants-adults, markedly reduces risk for fetal loss/growth restriction resulting from maternal challenge with bacterial lipopolysaccharide or influenza. Focusing on LPS exposure, we demonstrate that the key molecular indices of maternal inflammatory stress, notably high levels of RANTES, MIP-1α, CCL2, KC, and G-CSF (granulocyte colony-stimulating factor) in gestational tissues/serum, are abrogated by OM85 pretreatment. Systems-level analyses conducted in parallel using RNASeq revealed that OM85 pretreatment selectively tunes LPS-induced activation in maternal gestational tissues for attenuated expression of TNF, IL1, and IFNG-driven proinflammatory networks, without constraining Type1-IFN-associated networks central to first-line antimicrobial defense. This study suggests that broad-spectrum protection-of-pregnancy against infection-associated inflammatory stress, without compromising capacity for efficient pathogen eradication, represents an achievable therapeutic goal.
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Aborto Espontâneo/imunologia , Antígenos de Bactérias/imunologia , Infecções Bacterianas/imunologia , Fatores Imunológicos/imunologia , Vírus da Influenza A/imunologia , Infecções por Orthomyxoviridae/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Aborto Espontâneo/etiologia , Aborto Espontâneo/prevenção & controle , Animais , Infecções Bacterianas/complicações , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Desenvolvimento Fetal , Humanos , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/complicações , Gravidez , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Estudo de Prova de ConceitoRESUMO
Prosthetic mesh rolled up and fixed with stitches like a slim cigarette ("slim-mesh") for laparoscopic ventral hernia (VH) repair is an new technique which allows an easy intraperitoneally introduction, distension and circumferential fixation of a prosthetic mesh without transabdominal fixation sutures even for meshes larger than 16 cm up to 30 cm for the "slim-mesh" repair of wide ventral hernias. We report the technique of laparoscopic repair of VH with "slim-mesh". This technique enables an easy intra-peritoneally introduction of the mesh through the trocar because it reduces consistently its size, it allows a rapid intra-abdominal handling of the mesh and a fast and easy fixation for VH repair. The average time of surgery with "slim-mesh" for treatment of all 28 VH was 97 min ranging from 57 to 160 min. The average time for the repair of the 24 VH smaller than 10 cm was 91 and 135 min for the four VH larger than 10-22 cm. This new surgical technique leads to a reduction of surgical risks avoiding the use of transfascial sutures with the associated complications. This new surgical procedure in our experience is fast, safe, simple and also easily reproducible by surgeons in laparoscopic training. This technique may be used in wide VH (larger than 10-22 cm) that generally require open surgery.
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Hérnia Ventral/cirurgia , Herniorrafia/métodos , Laparoscopia/métodos , Telas Cirúrgicas , Humanos , Desenho de Prótese , Técnicas de SuturaRESUMO
The authors report their experience about the use of P.R.L. PLATELET RICH LIPOTRANSFERT method (platelet rich plasma mixed fat grafting) in 223 patients affected by soft tissue defects (ulcers, Romberg syndrome, Hemifacial atrophy, loss of substance, and signs of aging). This paper introduces the reader to PRP therapy and reviews the current literature on this emerging treatment modality, showing at the current clinical use of PRP in plastic and reconstructive surgery, with description of innovative methods and future prospects. This technique provides a promising alternative to surgery by promoting safe and natural healing. Here recent studies concerning the use of PRP in the treatment of chronic ulcers and soft tissue defect are reviewed.
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Tecido Adiposo , Plasma Rico em Plaquetas , Cirurgia Plástica/métodos , Úlcera/terapia , Plaquetas/patologia , Humanos , Úlcera/patologia , CicatrizaçãoRESUMO
There are a large number of publications describing the use of platelet-rich plasma (PRP) in multiple fields of application. These illustrate a large number of therapeutic elements with different and specific actions within 'platelet gel' (this term is used in the current regulations to define this product). This term, however, lacks specificity and, depending on the method used in its production is variable both in its blood composition and in platelet concentration, and several publications consider better and easier methods of platelet gel production, which may or may not lead to greater standardization in the product. The authors illustrate the general aspects of PRP and other blood components for non-transfusion use, briefly touching on the history and different fields of application and the rational of for its use. Given the increased use of such preparations, the authors describe critically the regulations in force in Europe and propose a new regulatory framework aimed to simplify and facilitate the use of such material as a therapeutic agent within medicine.
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Legislação Médica , Plasma Rico em Plaquetas , Transfusão de Componentes Sanguíneos/legislação & jurisprudência , Géis , Humanos , Itália , Plasma Rico em Plaquetas/citologia , Plasma Rico em Plaquetas/metabolismoRESUMO
PURPOSE: The aim of this study was to assess the performance measurements of the new PET/CT system Discovery-600 (D-600, GEMS, Milwaukee, WI). METHODS: Performance measures were obtained with the National Electrical Manufacturers Association (NEMA) NU 2-2007 procedures. RESULTS: The transverse (axial) spatial resolution FWHMs were 4.9 (5.6) mm and 5.6 (6.4) mm at 1 and 10 cm off axis, respectively. The sensitivity (average at 0 and 10 cm) was 9.6 cps/kBq. The scatter fraction was 36.6% (low energy threshold: 425 keV). The NEC peak rate (k=1) was 75.2 kcps at 12.9 kBq/cc. The hot contrasts for 10, 13, 17, and 22 mm spheres were 41%, 51%, 62%, and 73% and the cold contrasts for 28 and 37 mm spheres were 68% and 72%. CONCLUSIONS: The Discovery-600 has good performance for the NEMA NU 2-2007 parameters, particularly in improved sensitivity compared to the scanners of the same Discovery family, D-ST and D-STE.
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Eletricidade , Tomografia por Emissão de Pósitrons/normas , Tomografia Computadorizada por Raios X/normas , Padrões de Referência , Estados UnidosRESUMO
AIM: To evaluate evolution for bone (EfB), one of the recent corrective collimator detector response (CDR) image reconstruction packages, resolution recovery and iterative reconstruction protocols were compared to the standard Filtered Back Projection (FBP) protocol and the possibility of time reduced acquisition (15 instead of 30 seconds/projection) was evaluated. METHODS: Tomographic spatial resolution, contrast, noise and signal-to-noise ratio (SNR) were analyzed in phantom studies. Patient studies were conducted on sixteen [99mTc]HMPAO labeled leukocyte patients with suspected local inflammation, submitted to SPECT/CT and conventional leukocyte scintigraphy. Target background ratio (TBR) and boundary of each lesion were calculated. Images were also analyzed by visual inspection by two blinded expert physicians. RESULTS: a) Phantom: resolution in phantom improves with the use of EfB mainly due to iterative reconstruction methods vs FBP. EfB shows a reduction in noise. No differences were found in contrast data, while SNR changes were mainly due to changes in noise. Time reduction, while increasing image noise, does not modify resolution; nevertheless, half-time EfB noise is the same as full-time FBP noise. b) PATIENTS: lesion boundary is better defined in patient studies using iterative reconstruction vs FBP; no changes were observed for CDR vs iterative OSEM, or for full-time vs half-time acquisition. TBR is comparable in iterative and FBP protocols, while it is improved by EfB. At visual inspection, a higher score is always associated with EfB. CONCLUSION: Resolution, noise, SNR and TBR improve when applying the resolution recovery. EfB permits reduction of acquisition time without compromising image quality.
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Algoritmos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Leucócitos/diagnóstico por imagem , Osteomielite/diagnóstico , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Idoso , Células Cultivadas , Feminino , Humanos , Marcação por Isótopo , Masculino , Pessoa de Meia-Idade , Imagens de Fantasmas , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Razão Sinal-Ruído , Técnica de Subtração , Tomografia Computadorizada de Emissão de Fóton Único/instrumentação , Tomografia Computadorizada por Raios X/métodos , Adulto JovemRESUMO
A new rapid flow injection procedure for the simultaneous determination of nitrate, nitrite and ammonium in single flow injection analysis system is proposed. The procedure combines on-line reduction of nitrate to nitrite and oxidation of ammonium to nitrite with spectrophotometric detection of nitrite by using the Griess-Ilosvay reaction. The formed azo dye was measured at 543 nm. The influence of reagent concentration and manifold parameters were studied. Nitrite, nitrate and ammonium can be determined within the range of 0.02-1.60 microgmL(-1), 0.02-1.60 microgmL(-1) and 0.05-1.40 microgmL(-1), respectively. R.S.D. values (n=10) were 2.66; 1.41 and 3.58 for nitrate, nitrite and ammonium, respectively. This procedure allows the determination and speciation of inorganic nitrogen species in soils with a single injection in a simple way, and high sampling rate (18 h(-1)). Detection limits of 0.013, 0.046 and 0.047 microgmL(-1)were achieved for nitrate, nitrite and ammonium, respectively. In comparison with others methods, the proposed one is more simple, it uses as single chromogenic reagent less injection volume (250 mL in stead of 350 mL) and it has a higher sampling rate.
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Análise de Injeção de Fluxo/instrumentação , Análise de Injeção de Fluxo/métodos , Nitratos/análise , Nitritos/análise , Compostos de Amônio Quaternário/análise , Solo/análise , Espectrofotometria/métodos , Soluções , Espectrofotometria/instrumentaçãoRESUMO
Pancreaticoduodenectomy is considered the standard procedure for the surgical treatment of the pancreatic head cancer. However, the extent of lymph node clearance associated to the procedure is still largely debated. Arguments in favour of an extended lymphadenectomy are the regular progression of lymph node invasion, without skip metastases, and the removal of the extrapancreatic neural plexus that is invaded in 52-72% of patients. Arguments against the extended lymphadenectomy are the failure of extended lymphadenectomy to improve survival in other cancers, and the severe diarrhoea that follows the skeletonisation of the superior mesenteric artery. After Ishikawa's paper, several retrospective studies supported a longer survival after an extended than after a standard lymphadenectomy, but as much retrospective studies failed to demonstrate any difference. Only three prospective randomised controlled trials have been performed so far. Unfortunately all are underpowered, and the substantial differences in the surgical procedures, in the adjuvant treatment, and in the length of follow-up make the comparison impossible. Only one study reports a significantly longer survival for lymph node positive patients who underwent an extended lymphadenectomy, but adjuvant treatment was not performed. Furthermore, the difference was of minimal clinical impact. At least two adequately powered prospective Randomised Controlled Trials including a true extended lymphadenectomy, and a standardised adjuvant treatment, would be required to answer the question. Unfortunately, we have not yet a standardised adjuvant (or neoadjuvant) treatment, and we do not know the impact of such treatment on the expected statistical difference in the survival after a standard or extended lymphadenectomy. The lot of work required to perform such trials probably doesn't worth the expected results.
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Excisão de Linfonodo , Neoplasias Pancreáticas/cirurgia , Humanos , Qualidade de Vida , Fatores de RiscoRESUMO
The Ras-association domain family 1A (RASSF1A) tumour suppressor gene is inactivated in a variety of solid tumours, usually by epigenetic silencing of the promoter and/or allelic loss of its locus at 3p21.3. RASSF1A induces cell cycle arrest through inhibition of cyclin D1 accumulation. In this work, 62 endocrine tumours from different sites in the gut were investigated for methylation of the RASSF1A promoter using the polymerase chain reaction, the presence of 3p21.3 deletions by loss of heterozygosity analysis, and cyclin D1 expression by immunohistochemistry. Methylation was found in 20/62 (32%) cases and was restricted to foregut tumours; deletion at 3p21.3 was found in 15/58 (26%) informative cases and restricted to malignant foregut tumours; cyclin D1 hyper-expression was found in 31/58 (53%) cases and correlated with RASSF1A methylation. Our data suggest that RASSF1A is involved in the development of endocrine tumours derived from the foregut only, and that the presence of both RASSF1A methylation and 3p21.3 deletion is associated with malignancy. These results may provide a rationale for foregut-targeted therapy for aggressive endocrine carcinomas entailing the use of demethylating agents.
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Carcinoma Neuroendócrino/genética , Neoplasias Gastrointestinais/genética , Perda de Heterozigosidade/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Apêndice/genética , Neoplasias do Apêndice/metabolismo , Carcinoma Neuroendócrino/metabolismo , Ciclina D1/análise , Ciclina D1/genética , Neoplasias Duodenais/genética , Neoplasias Duodenais/metabolismo , Feminino , Neoplasias Gastrointestinais/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias do Íleo/genética , Neoplasias do Íleo/metabolismo , Neoplasias Intestinais/genética , Neoplasias Intestinais/metabolismo , Masculino , Metilação , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Regiões Promotoras Genéticas/genética , Neoplasias Retais/genética , Neoplasias Retais/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Proteínas Supressoras de Tumor/metabolismoRESUMO
From 1980 to 2004, out of 109 patients who underwent surgery for neuroendocrine pancreatic tumor, 33 had a simple tumor excision. Seventy-two percent of cases were insulinomas. Age, sex, site and size of the tumor, associated diseases, hospital stay and complications were retrospectively reviewed by the clinical records. Patients (12 males and 21 females) averaged 56.8 years, range 20-86. Mean size of the tumor was 1.7 cm and 54.5% were in the pancreatic head; 78.8% of cases had medical associated diseases. Hospital stay was 12 days (median; range, 6-81 days) and mean period of gastric suction was 4 days. Forty-eight percent had a uneventful postoperative course. Complications were divided in early (related to pancreatic surgery, related to general open surgery and medical) and late events. Complication related to pancreatic surgery were 6/33 (18%); 5 pancreatic fistulas (4 low output) and 1 acute pancreatitis, while 5/33 had a general surgery complication (2 leacking due to gastric and duodenal associated operations). Medical complications were recorded in 13 cases. Late complications occurred in 4 cases (2 incisional hernias, 1 pseudocyst and 1 keloid). No patient was re-operated for pancreatic complications; 1 was reoperated for evisceration and 1 for hyper-parathyroidism in the early post-operative period. No mortality occurred. Re-evaluation of the clinical records in order to be submitted to laparoscopic surgery excluded 17/33 cases (51%) as candidate to laparoscopic approach.
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Tumores Neuroendócrinos/cirurgia , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Fatores de TempoRESUMO
From November 1994 to November 2004, seventy-seven patients with neuroendocrine gastro-entero-pancreatic tumor (71% pancreatic) were investigated with 18-fluorine-deoxi-glucose positron emission tomography (FDG-PET). PET results were compared with CT-scan, MRI and octreoscan scintigraphy and clinico-pathologic features of patients and survival. Overall PET sensitivity was 57%; 78% of malignant tumors, 67% of borderline and 17% of benign tumors were detected by FDG-PET. No duodenal tumor was detected by PET scan. Only 16% of primary less than 2 cm in size was localized. In 16% of cases PET scan provided new information able to change therapeutic management. In PET positive patients the addictive information obtained by PET scan when compared with octreoscan, MRI and CT scan were respectively 50% more, 26% more and 30% more. In malignant neuroendocrine tumors PET positivity was related to short survival. No patient with malignant tumor died for disease progression in the follow-up when PET was negative, while 13/35 PET positive patients died (p <0.003). FDG-PET proved to be a second line technique in neuroendocrine digestive tumors. PET results improve clinical staging of disease and is related to survival in malignant cases; in 16% of cases may change the therapeutic option.
Assuntos
Fluordesoxiglucose F18 , Neoplasias Intestinais/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Neoplasias Gástricas/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Intestinais/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Prognóstico , Reprodutibilidade dos Testes , Neoplasias Gástricas/mortalidadeRESUMO
BACKGROUND: The incidence of pancreatic cancer and relative hospital stay and costs are not well known. AIMS: To define the incidence, hospital stay and cost of pancreatic cancer in a well-defined area of Italy. PATIENTS AND METHODS: Each new case of pancreatic cancer diagnosed between 1990 and 1992 among 669,703 inhabitants in the Veneto Region of Northern Italy was recorded and followed until death or for 5 years after diagnosis. Four types of hospital stay were defined. Type 1: undiagnosed pancreatic cancer; type 2: first diagnosis of pancreatic cancer, treatment excluded; type 3: main treatment; and type 4: follow-up and disease-related complications. Data were analysed for hospital stay-related procedures, costs and survival. RESULTS: Pancreatic cancer was diagnosed in 253 patients (12.6/100,000 per year), 43 patients (17.7%) underwent surgical resection, and 93 (36.8%) palliative surgery. The mean duration of type 3 hospital stay was similar for resection, palliative and exploratory surgery. The estimated hospital cost was significantly higher for surgical resection, almost the same for palliative and exploratory surgery, and only slightly lower for medical treatment. Each patient spent a mean of 57.7 days in the hospital. The hospital mortality rate was 4.6% for surgical resection, 22.1% for palliative surgery, and 18.7% for exploratory laparotomy. Overall, the 1-, 2-, 3- and 5-year survival rates were 20.9%, 5.1%, 2.9% and 1.2%, respectively. CONCLUSIONS: Pancreatic cancer is an expensive, almost incurable disease. Integrated treatments in specialized Centres should reduce the mortality rate and costs.
Assuntos
Neoplasias Pancreáticas/epidemiologia , Custos e Análise de Custo , Feminino , Custos Hospitalares/estatística & dados numéricos , Humanos , Incidência , Itália/epidemiologia , Tempo de Internação/estatística & dados numéricos , Masculino , Neoplasias Pancreáticas/economia , Neoplasias Pancreáticas/cirurgia , Taxa de SobrevidaRESUMO
We evaluated the role of acetyl-L-carnitine (ALCAR) in protecting primary motoneuron cultures exposed to excitotoxic agents or serum-brain derived neurotrophic factor (BDNF) deprived. To exclude that ALCAR works as a metabolic source, we compared its effects with those of L-carnitine (L-CAR), that seems to have no neurotrophic effect. A concentration of 10 mM ALCAR, but not L-CAR, significantly reduced the toxic effect of 50 microM N-methyl-D-aspartate (NMDA, % viability: NMDA 45.4+/-2.80, NMDA+ALCAR 90.8+/-11.8; P<0.01) and of 5 microM kainate in cultured motoneurons (% viability: kainate 40.66+/-10.73; kainate+ALCAR 63.80+/-13.88; P<0.05). The effect was due to a shift to the right of the dose-response curve for kainate (EC50 for kainate 5.99+/-1.012 microM; kainate+ALCAR 8.62+/-1.13 microM; P<0.05). ALCAR, but not L-CAR, significantly protected against BDNF and serum-deprivation reducing the apoptotic cell death (% viability respect to control: without BDNF/serum 61.8+/-13.3: without BDNF/serum+ALCAR 111.8+/-13.9; P<0.01). Immunocytochemistry showed an increase in choline acethyltransferase and tyrosine kinaseB receptors in motoneurons treated with ALCAR but not with L-CAR. These results suggest that ALCAR treatment improves the motoneurons activity, acting as a neurotrophic factor.