RESUMO
BACKGROUND: Lentigo maligna (LM) can mimic benign, flat, pigmented lesions and can be challenging to diagnose. OBJECTIVE: To describe a new dermatoscopic feature termed "perifollicular linear projections (PLP)" as a diagnostic criterion for LM on the face. METHODS: Retrospective study on reflectance confocal microscopy and dermatoscopy images of flat facial pigmented lesions originating from 2 databases. PLP were defined as short, linear, pigmented projections emanating from hair follicles. Dermatoscopy readers were blinded to the final histopathologic diagnosis. RESULTS: From 83 consecutive LMs, 21/83 (25.3%) displayed "bulging of hair follicles" on reflectance confocal microscopy and 18 of these 21 (85.7%), displayed PLP on dermatoscopy. From a database of 2873 consecutively imaged and biopsied lesions, 252 flat-pigmented facial lesions were included. PLP was seen in 47/76 melanomas (61.8%), compared with 7/176 lesions (3.9%) with other diagnosis (P < .001). The sensitivity was 61.8% (95% CI, 49.9%-72.7%), specificity 96.0% (95% CI, 92.9%-98.4%). PLP was independently associated with LM diagnosis on multivariate analysis (OR 26.1 [95% CI, 9.6%-71.0]). LIMITATIONS: Retrospective study. CONCLUSION: PLP is a newly described dermatoscopic criterion that may add specificity and sensitivity to the early diagnosis of LM located on the face. We postulate that PLP constitutes an intermediary step in the LM progression model.
Assuntos
Sarda Melanótica de Hutchinson , Melanoma , Neoplasias Cutâneas , Humanos , Sarda Melanótica de Hutchinson/diagnóstico por imagem , Sarda Melanótica de Hutchinson/patologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Estudos Retrospectivos , Diagnóstico Diferencial , Melanoma/patologia , Microscopia Confocal/métodos , Dermoscopia/métodosAssuntos
Poroma , Neoplasias das Glândulas Sudoríparas , Humanos , Poroma/diagnóstico por imagem , Poroma/cirurgia , Imageamento Tridimensional , Diagnóstico Diferencial , Neoplasias das Glândulas Sudoríparas/diagnóstico por imagem , Neoplasias das Glândulas Sudoríparas/cirurgia , Microscopia ConfocalRESUMO
BACKGROUND: Adenocarcinoma is preceded by chronic atrophic gastritis, gastric intestinal metaplasia and dysplasia. Trefoil factor 3 (TFF3) is a peptide secreted by goblet cells, which is abundantly present in intestinal metaplasia. AIM: To evaluate the utility of serum TFF3 as a non-invasive biomarker for the diagnosis of intestinal metaplasia and gastric cancer. METHODS: Single-center, cross-sectional study of 274 patients who consecutively underwent upper gastrointestinal endoscopy with gastric biopsies (updated Sydney system). TFF3 levels were measured in serum by a commercial ELISA kit. Patients with normal histology or chronic atrophic gastritis without intestinal metaplasia comprised the control group. In addition, 14 patients with invasive gastric cancer were included as a reference group. The association between TFF3 levels and intestinal metaplasia was assessed by logistic regression. RESULTS: Patients with intestinal metaplasia (n=110) had a higher median TFF3 level as compared to controls (n=164), 13.1 vs. 11.9ng/mL, respectively (p=0.024). Multivariable logistic regression showed a no significant association between TFF3 levels and intestinal metaplasia (OR=1.20; 95%CI: 0.87-1.65; p-trend=0.273). The gastric cancer group had a median TFF3 level of 20.5ng/mL, and a significant association was found (OR=3.26; 95%CI: 1.29-8.27; p-trend=0.013). CONCLUSION: Serum levels of TFF3 do not discriminate intestinal metaplasia in this high-risk Latin American population. Nevertheless, we confirmed an association between TFF3 levels and invasive gastric cancer.
Assuntos
Gastrite Atrófica , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Fator Trefoil-3 , Estudos Transversais , Biomarcadores , Metaplasia/patologia , Mucosa Gástrica , Lesões Pré-Cancerosas/patologiaRESUMO
Gallbladder cancer (GBC) is a highly fatal cancer that can be cured through cholecystectomy if identified early. The presence of gallstones is the primary risk factor for GBC, but few people with gallstones develop GBC. A key question is what drives the development of GBC among persons with gallstones. We initiated the Chile Biliary Longitudinal Study (Chile BiLS) to address this question. From 2016 to 2019, Chile BiLS enrolled 4,726 women aged 50-74 years with ultrasound-detected gallstones from southern-central Chile, accounting for an estimated 36% of eligible women with gallstones in the study area. The median age was 59 years; 25% of the women were Amerindian (Mapuche), 60% were obese, 25% had diabetes, and 6% had cardiovascular disease. Participants will be followed for gallbladder dysplasia or cancer for 6 years. As of April 30, 2020, over 91% of those eligible completed the year 2 follow-up visit. Data being collected include epidemiologic and sociodemographic information, anthropometric measurements, blood pressure, and tooth counts. Biosamples being taken include baseline plasma, buffy coat, red blood cells, serum, blood clot from serum, and PAXgene whole blood (PreAnalytiX GmbH, Hombrechtikon, Switzerland). Complete gallbladder sampling is conducted for most participants undergoing cholecystectomy. The Chile BiLS cohort study will increase our understanding of GBC etiology and could identify potential risk stratification and early detection strategies in high-risk areas.
Assuntos
Neoplasias da Vesícula Biliar/epidemiologia , Cálculos Biliares/epidemiologia , Idoso , Pressão Sanguínea , Pesos e Medidas Corporais , Doenças Cardiovasculares/epidemiologia , Chile , Diabetes Mellitus/epidemiologia , Feminino , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/etnologia , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/etnologia , Humanos , Mediadores da Inflamação/sangue , Estudos Longitudinais , Pessoa de Meia-Idade , Obesidade/epidemiologia , Projetos de Pesquisa , Fatores de Risco , Fatores Socioeconômicos , Perda de Dente/epidemiologiaRESUMO
Ectopic thyrotropin-secreting pituitary adenomas are rare, with only 10 published cases. We report the case of a 52-year-old woman who was referred for primary hypothyroidism, who showed clinical signs of hyperthyroidism and had been under treatment with levothyroxine. Her exams revealed high levels of thyroid stimulating hormone (TSH), at odds with free thyroxin (FT4) and raised triiodothyronine (T3), which remained elevated after medication suspension, suggesting possible central hyperthyroidism. Sellar MRI showed normal pituitary gland, with a mass in the sphenoid sinus of 24â¯mm. A possible ectopic TSH secreting pituitary tumor of sphenoid sinus was hypothesized. After a intramuscularly (IM) single dose of a sustained-relase of a somatostatin analog (octreotide) 20â¯mg, plasma levels of thyroid hormones were normalized and a significant tumor reduction was demonstrated in MRI control at 7-weeks' follow-up. The tumor was removed by transsphenoidal endoscopy, and the biopsy confirmed an adenoma with positive immunostaining for TSH and GH. Hyperthyroidism recurrence was observed in hormonal controls 4â¯weeks after surgery. Treatment with sustained-release octreotide was reinitiated, every 60-days for two years, with normalization of the thyroid hormone profile, but with a residual lesion with the appearance of a tumor in the MRI. A second tumor resection was performed, achieving sustained hormonal cure and no residual tumor lesion at 2-years' follow-up. To our knowledge, this is the first report of an ectopic thyrotropin-secreting pituitary adenoma of the sphenoid sinus. Clinical and laboratory aspects relevant to this entity are reviewed, emphasizing the usefulness of octreotide in the management of the reported case.
Assuntos
Octreotida/metabolismo , Hipófise/metabolismo , Neoplasias Hipofisárias/metabolismo , Seio Esfenoidal/metabolismo , Tireotropina/metabolismo , Feminino , Humanos , Hipertireoidismo/diagnóstico por imagem , Hipertireoidismo/metabolismo , Hipertireoidismo/terapia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Octreotida/administração & dosagem , Hipófise/diagnóstico por imagem , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/terapia , Seio Esfenoidal/diagnóstico por imagemRESUMO
There is no systematic histopathologic analysis of non-neoplastic polyps in the gallbladder. In this study, in addition to a computer search for cases designated as "polyp," a systematic review of 2533 consecutive routinely sampled archival and 203 totally submitted prospective cholecystectomies were analyzed for >2 mm polyps (cut-off was based on radiologic sensitivity). A total of 447 non-neoplastic polyps were identified. The frequency was 3% in archival cases and 5% in totally submitted cases. Only 21 (5%) were ≥1 cm. The average age was 52 years, and the female to male ratio was 3.1. Two distinct categories were delineated: (1) injury-related polyps (n=273): (a) Fibro(myo)glandular polyps (n=214) were small (mean=0.4 cm), broad-based, often multiple (45%), almost always (98%) gallstone-associated, and were composed of a mixture of (myo)fibroblastic tissue/lobular glandular units with chronic cholecystitis. Dysplasia seen in 9% seemed to be secondary involvement. (b) Metaplastic pyloric glands forming polypoid collections (n=42). (c) Inflammatory-type polyps associated with acute/subacute injury (11 granulation tissue, 3 xanthogranulomatous, 3 lymphoid). (2) Cholesterol polyps (n=174) occurred in uninjured gallbladders, revealing a very thin stalk, edematous cores devoid of glands but with cholesterol-laden macrophages in 85%, and cholesterolosis in the uninvolved mucosa in 60%. Focal low-grade dysplasia was seen in 3%, always confined to the polyp, unaccompanied by carcinoma. In conclusion, non-neoplastic polyps are seen in 3% of cholecystectomies and are often small. Injury-related fibromyoglandular polyps are the most common. Cholesterol polyps have distinctive cauliflower architecture, often in a background of uninjured gallbladders with cholesterolosis and may lack the cholesterol-laden macrophages in the polyp itself. Although dysplastic changes can involve non-neoplastic polyps, they do not seem to be the cause of invasive carcinoma by themselves.
Assuntos
Doenças da Vesícula Biliar/patologia , Pólipos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Chile/epidemiologia , Colecistectomia , Colesterol/análise , Feminino , Doenças da Vesícula Biliar/epidemiologia , Doenças da Vesícula Biliar/metabolismo , Doenças da Vesícula Biliar/cirurgia , Humanos , Masculino , Metaplasia , Pessoa de Meia-Idade , Pólipos/química , Pólipos/epidemiologia , Pólipos/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Turquia/epidemiologia , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Background Chile has one of the highest mortality rates by gastric cancer (GC) worldwide. Primary prevention of GC and detection of pre-neoplastic and early neoplastic lesions should be a national priority. Aim To assess the impact of the protocolization of endoscopy referral and the use of H. pylori stool antigen test (HPSA) in the management of dyspepsia to decrease the waiting list for endoscopy and increase the detection of gastric pre-neoplastic and early neoplastic lesions. Material and Methods We included all patients referred to the Endoscopy Unit of a regional hospital, from January 2015 to December 2017. We also included patients with known pre-neoplastic lesions and all those with first degree relatives with GC. We implemented protocols for referral of patients with dyspepsia considering the use of HPSA test, prioritizing to endoscopy those with a higher risk of GC. Results A total of 4,641 endoscopies and 2,631 HPSA tests were carried out. After the adoption of these protocols, we observed a 52% decrease in the waiting time for endoscopy. The GC detection rate in this period was 1.8 to 3.1 cases per 100 endoscopies. After the adoption of the protocols, we observed a significant increase in early GC detection rate (from none in 2015 to 13% in 2017, p = 0.03). Conclusions The protocolization of the referral for endoscopy associated with widespread use of HPSA test in the management of patients with dyspepsia, are successful strategies to decrease waiting lists for endoscopy and optimize the detection rate of pre-neoplastic lesions and early GC.
Assuntos
Humanos , Lesões Pré-Cancerosas/diagnóstico , Listas de Espera , Helicobacter pylori/isolamento & purificação , Infecções por Helicobacter/diagnóstico , Dispepsia/diagnóstico , Fezes/microbiologia , Antígenos de Bactérias/análise , Lesões Pré-Cancerosas/microbiologia , Atenção Primária à Saúde , Encaminhamento e Consulta , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Sensibilidade e Especificidade , Diagnóstico Precoce , Dispepsia/microbiologia , Endoscopia/estatística & dados numéricosRESUMO
Gastric cancer (GC) is the first cancer-related cause of death in Chile; however, no plan for GC early detection has been implemented in this country. The OLGA system characterizes gastritis from stages 0 to IV according to the risk of developing GC based on H. pylori infection, atrophy, metaplasia and GC. In this study, the performance of the OLGA system was evaluated in 485 Chilean patients receiving routine endoscopy to improve the detection of early GC or preneoplastic lesions. The results showed that OLGA scores, atrophy, metaplasia and GC increased significantly with age (p < 0.001). Conversely, H. pylori infection was higher in younger groups (p < 0.05). All gastric lesions were more frequent in men than women. The majority of patients with atrophy also had metaplasia (99%, p < 0.0001). Patients with H. pylori infection had more gastric atrophy and metaplasia than those without infection (p < 0.05). Of the 485 patients, 21 (4.3%) had GC, being 2.3 times more frequent among men than women and about 2/3 (14) were in OLGA stage ≥2. In addition, 19 (90%) GC patients had atrophy and 18 (85%) had metaplasia (p < 0.001). In conclusion, the OLGA system facilitated the evaluation of GC precursor lesions particularly in patients with an OLGA score > 2 between 45 and 56 years old, because this group showed atrophy and intestinal metaplasia more frequently. Therefore, biennial endoscopic surveillance of patients with an OLGA >2 can be an important health policy in Chile for diagnosing GC in its early stages and reducing mortality over the next two decades.
Assuntos
Detecção Precoce de Câncer/métodos , Gastrite/diagnóstico , Infecções por Helicobacter/complicações , Metaplasia/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Índice de Gravidade de Doença , Neoplasias Gástricas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Seguimentos , Gastrite/etiologia , Gastrite/patologia , Infecções por Helicobacter/virologia , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Metaplasia/etiologia , Metaplasia/patologia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/patologia , Prognóstico , Fatores de Risco , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologia , Adulto JovemRESUMO
Background Chile has one of the highest mortality rates by gastric cancer (GC) worldwide. Primary prevention of GC and detection of pre-neoplastic and early neoplastic lesions should be a national priority. Aim To assess the impact of the protocolization of endoscopy referral and the use of H. pylori stool antigen test (HPSA) in the management of dyspepsia to decrease the waiting list for endoscopy and increase the detection of gastric pre-neoplastic and early neoplastic lesions. Material and Methods We included all patients referred to the Endoscopy Unit of a regional hospital, from January 2015 to December 2017. We also included patients with known pre-neoplastic lesions and all those with first degree relatives with GC. We implemented protocols for referral of patients with dyspepsia considering the use of HPSA test, prioritizing to endoscopy those with a higher risk of GC. Results A total of 4,641 endoscopies and 2,631 HPSA tests were carried out. After the adoption of these protocols, we observed a 52% decrease in the waiting time for endoscopy. The GC detection rate in this period was 1.8 to 3.1 cases per 100 endoscopies. After the adoption of the protocols, we observed a significant increase in early GC detection rate (from none in 2015 to 13% in 2017, p = 0.03). Conclusions The protocolization of the referral for endoscopy associated with widespread use of HPSA test in the management of patients with dyspepsia, are successful strategies to decrease waiting lists for endoscopy and optimize the detection rate of pre-neoplastic lesions and early GC.
Assuntos
Antígenos de Bactérias/análise , Dispepsia/diagnóstico , Fezes/microbiologia , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Lesões Pré-Cancerosas/diagnóstico , Listas de Espera , Dispepsia/microbiologia , Diagnóstico Precoce , Endoscopia/estatística & dados numéricos , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Humanos , Lesões Pré-Cancerosas/microbiologia , Atenção Primária à Saúde , Encaminhamento e Consulta , Sensibilidade e EspecificidadeRESUMO
Gallbladder dysplasia can progress to cancer and may be associated with increased cancer risk at other biliary tract sites. Thus, its accurate identification is relevant both for etiologic understanding and for clinical purposes. Data on the frequency and distribution of gallbladder dysplasia are lacking owing to limited gallbladder sampling and inability to visualize dysplasia grossly. An expert pathology group used consensus criteria to review 140 totally sampled consecutive cholecystectomy specimens from Chilean women. Three cases (2%) revealed incidental invasive carcinoma, all T2, along with high-grade dysplasia (HGD). The surface areas covered by dysplasia or cancer in these cases were 9%, 37%, and 87%. Although the first longitudinal ("diagnostic") section of the whole gallbladder captured HGD or cancer in all 3 cases, the deepest focus of invasive carcinoma was not present in this section. Fourteen additional cases (10%) had low-grade dysplasia (LGD), which was typically very focal (covering <5% of the surface) and most often occurred in the fundus. LGD was not present in the diagnostic section of 5 cases (38%) and would have been missed without additional sampling. None of the cancers or dysplasias were grossly visible. Although HGD and carcinoma are likely to be identified in "diagnostic" sections, accurate staging requires total sampling. LGD is typically very focal and would often be missed in routine practice. To identify cancer precursors, additional sampling, particularly of the fundus, may be warranted. The predominance of LGD in the fundus also provides etiologic insight, supporting the contribution of gallstones and chronic inflammation.
Assuntos
Carcinoma/patologia , Neoplasias da Vesícula Biliar/patologia , Vesícula Biliar/patologia , Lesões Pré-Cancerosas/patologia , Adulto , Idoso , Biópsia , Carcinoma/epidemiologia , Carcinoma/cirurgia , Chile/epidemiologia , Colecistectomia , Feminino , Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/cirurgia , Valor Preditivo dos Testes , Prevalência , Medição de Risco , Fatores de RiscoRESUMO
Epstein-Barr virus-associated gastric carcinoma shows a higher prevalence in the Americas than Asia. We summarize all studies of Epstein Barr virus-associated gastric carcinoma in the Americas, focusing on host characteristics, environmental associations and phylogeographic diversity of Epstein-Barr virus strains. In the Americas, the prevalence of Epstein Barr virus-associated gastric carcinoma is 11.4%, more frequent in males and portray predominantly diffuse-type histology. EBERs, EBNAs, BARTs and LMP are the highest expressed genes; their variations in healthy individuals may explain the phylogeographic diversity of Epstein-Barr virus across the region. Gastric cancer cases harbor exclusively the western genotype (subtype D and kept Xho I site), suggesting a disrupted co-evolution between the pathogen and its host. Epstein-Barr virus-associated gastric carcinoma molecular subtype cases from The Cancer Genome Atlas display PIK3CA gene mutations, amplification of JAK2, PD-L1 and PD-L2 and CpG island methylator phenotype, leading to more extensive methylation of host and viral genomes than any other subtypes from the study. Environmental conditions include negative- and positive- associations with being firstborn child and smoking, respectively. A marginal association with H. pylori has also been reported. Lymphoepithelioma-like carcinoma is associated with Epstein Barr virus in 80%-86% of cases, most of which have been included as part of Epstein Barr virus-associated gastric carcinoma series (prevalence 1.1%-7.6%). Whether these cases represent a variant of Epstein-Barr virus-associated gastric carcinoma is discussed. We propose novel research strategies to solve the conundrum of the high prevalence of Epstein-Barr virus-associated gastric carcinoma in the Americas.
RESUMO
Background: To validate the BIRADS in mammography, the calculation of its predictive value in each center is required, as recommended by the American College of Radiology. Aim: To determine the predictive value of the BIRADS system in our center. Material and Methods: All ultrasound guided needle percutaneous biopsies, performed at our center between 2006 and 2010 were reviewed. Predictive value, sensitivity, specificity and diagnostic accuracy of BIRADS were calculated, with a confidence interval of 95%. Results: Of 1,313 biopsies available, 1,058 met the inclusion criteria. Fifty eight percent of biopsies were performed to women with mammographies classified as BIRADS 4 or 5. The presence of cancer in mammographies classified as BIRADS 0 was 4%. The prevalence of cancer for mammographies BIRADS 1, 2, 3, 4 and 5 were 0, 3, 2.7, 17.7 and 72.4% respectively. The positive and negative predictive values of BIRADS classification were 55 and 92 % respectively. Conclusions: In our institution BIRADS classification 4 and 5 has a high positive predictive value for detecting cancer as in developed countries.
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Neoplasias da Mama/patologia , Neoplasias da Mama , Biópsia por Agulha , Estudos Transversais , Biópsia Guiada por Imagem , Mamografia , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: To validate the BIRADS in mammography, the calculation of its predictive value in each center is required, as recommended by the American College of Radiology. AIM: To determine the predictive value of the BIRADS system in our center. MATERIAL AND METHODS: All ultrasound guided needle percutaneous biopsies, performed at our center between 2006 and 2010 were reviewed. Predictive value, sensitivity, specificity and diagnostic accuracy of BIRADS were calculated, with a confidence interval of 95%. RESULTS: Of 1,313 biopsies available, 1,058 met the inclusion criteria. Fifty eight percent of biopsies were performed to women with mammographies classified as BIRADS 4 or 5. The presence of cancer in mammographies classified as BIRADS 0 was 4%. The prevalence of cancer for mammographies BIRADS 1, 2, 3, 4 and 5 were 0, 3, 2.7, 17.7 and 72.4% respectively. The positive and negative predictive values of BIRADS classification were 55 and 92 % respectively. CONCLUSIONS: In our institution BIRADS classification 4 and 5 has a high positive predictive value for detecting cancer as in developed countries.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Estudos Transversais , Feminino , Humanos , Biópsia Guiada por Imagem , Mamografia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
Signaling pathway alterations are important in the development of gastric cancer (GC). Deregulation of the PI3K/AKT/mTOR pathway plays a crucial role in the regulation of multiple cellular functions including cell growth, proliferation, metabolism, and angiogenesis. Our goal was to assess expression of proteins involved in the PI3K/AKT/mTOR pathway by immunohistochemistry (IHC) in tumor and nontumor gastric mucosa from patients with advanced GC. We evaluated 71 tumor and 71 nontumor gastric mucosa samples from advanced GC patients, selected from Hernán Henríquez Aravena Hospital (Temuco, Chile). The targets studied were PI3K, AKT, p-AKT, PTEN, mTOR, p-mTOR, P70S6K1, p-P70S6K1, 4E-BP1, p-4E-BP1, eIF4E, and p-eIF4E. Expression data were correlated with clinicomorphological data. Descriptive and analytical statistics were used (95 % confidence interval, p < 0.05). For survival analyses, the Kaplan-Meier method and the log-rank test were used. PI3K, AKT, p-AKT, p-mTOR, p-4E-BP1, P70S6K1, p-P70S6K1, eIF-4E, and p-eIF-4E proteins were significantly overexpressed in tumor tissue. Conversely, PTEN was underexpressed in tumor tissue, notably in pT3-pT4 tumors (p = 0.02) and tumors with lymph node metastases (p < 0.001). P70S6K1 expression was associated with pT3-pT4 tumors (p = 0.03). Moreover, PI3K (p = 0.004), AKT (p = 0.01), p-AKT (p = 0.01), P70S6K1 (p = 0.04), p-P70S6K1 (p = 0.001), and eIF-4E (p = 0.004) were overexpressed in tumors with lymph node metastases. Low expression of 4E-BP1 was associated with poor overall survival (p = 0.03). Our results suggest that the PI3K/AKT/mTOR pathway is activated in GC, with overexpression in tumor tissue of most of the studied proteins (total and phosphorylated). These might be considered as target for specific targeted therapy in GC.
Assuntos
Metástase Linfática/fisiopatologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Neoplasias Gástricas/fisiopatologia , Serina-Treonina Quinases TOR/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Idoso , Estudos de Casos e Controles , Proteínas de Ciclo Celular , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/biossíntese , Prognóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologiaRESUMO
The general impression about gallbladder carcinomas is that they are uniformly fatal; however, for the early forms, an entirely different picture indicating a very good prognosis is evolving from the high-incidence regions. We subjected 190 early gallbladder carcinomas (EGBC), defined as carcinomas confined to and above the tunica muscularis (AJCC's Tis, T1a, and T1b), and identified in cholecystectomy specimens sampled entirely according to an established protocol, to detailed analysis. Average patient age was 57.9 years (29-95). In more than half of the cases (114/190; 60%), the tumor was inapparent by gross examination. In 81 cases (42.6%), carcinomatous epithelium abutted the muscularis, whereas 57.4 % (n = 109) were qualified as intramucosal with no overt contiguity with muscularis.Intraepithelial extension into RokitanskyAschoff sinuses (RAS) was found in 34 cases (17.8 %). At the time of data analysis, 171 patients (90 %) [corrected] were alive. Overall actuarial survival was 92.3 % at 5 years and 90.4 % at 10 years. The 5- and 10-year actuarial survival rates of the intramucosal group (93.2 and 92.1%, respectively) were not statistically different from that of the muscle-abutting group (89.7% and 88.2% ; p = 0.334). Patients with RAS involvement had a significantly shorter survival than those without (p < 0.001). Of the 33 patients with RAS involvement, 13 (39%) died of disease, whereas only 6 of the 154 patients (4%) without RAS involvement died of disease. Disease-related mortality in these cases occurred relatively late (median 48 months). EGBC has a very good prognosis with a 90% 10-year survival rate. It is seen on average in patients almost a decade younger than those with advanced cancers. RAS involvement is an independent prognostic factor, and additional surgery may have to be considered for such cases. Occasional recurrences are encountered several years later, which suggests a field-effect phenomenon and warrants long-term follow-up.