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1.
Int J Mol Sci ; 25(7)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38612698

RESUMO

Helicobacter pylori (H. pylori) infection induces DNA Double-Strand Breaks (DSBs) and consequently activates the DNA Damage Response pathway (DDR) and senescence in gastric epithelium. We studied DDR activation and senescence before and after the eradication of the pathogen. Gastric antral and corpus biopsies of 61 patients with H. pylori infection, prior to and after eradication treatment, were analyzed by means of immunohistochemistry/immunofluorescence for DDR marker (γH2AΧ, phosporylated ataxia telangiectasia-mutated (pATM), p53-binding protein (53BP1) and p53) expression. Samples were also evaluated for Ki67 (proliferation index), cleaved caspase-3 (apoptotic index) and GL13 staining (cellular senescence). Ten H. pylori (-) dyspeptic patients served as controls. All patients were re-endoscoped in 72-1361 days (mean value 434 days), and tissue samples were processed in the same manner. The eradication of the microorganism, in human gastric mucosa, downregulates γH2AΧ expression in both the antrum and corpus (p = 0.00019 and p = 0.00081 respectively). The expression of pATM, p53 and 53BP1 is also reduced after eradication. Proliferation and apoptotic indices were reduced, albeit not significantly, after pathogen clearance. Moreover, cellular senescence is increased in H. pylori-infected mucosa and remains unaffected after eradication. Interestingly, senescence was statistically increased in areas of intestinal metaplasia (IM) compared with adjacent non-metaplastic mucosa (p < 0.001). In conclusion, H. pylori infection triggers DSBs, DDR and senescence in the gastric epithelium. Pathogen eradication reverses the DDR activation but not senescence. Increased senescent cells may favor IM persistence, thus potentially contributing to gastric carcinogenesis.


Assuntos
Helicobacter pylori , Humanos , Proteína Supressora de Tumor p53/genética , Mucosa Gástrica , Reparo do DNA , Epitélio
2.
Int J Mol Sci ; 25(1)2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38203269

RESUMO

Esophageal adenocarcinoma (EAC) is a malignant tumor with poorly understood molecular mechanisms. This study endeavors to elucidate how the long non-coding RNAs (lncRNAs) MALAT1, MANCR and PSMA3-AS1, as well as the microRNA miR-101, exhibit specific expression patterns in the pathogenesis and prognosis of EAC. A total of 50 EAC tissue samples (tumors and lymph nodes) and a control group comprising 26 healthy individuals were recruited. The samples underwent quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses. The relative expression levels of MALAT1, MANCR, PSMA3-AS1, and miR-101 were ascertained and correlated with various clinicopathological parameters including TNM staging, tumor characteristics (size and grade of the tumor) lymphatic invasion, disease-free (DFS) and overall survival (OS) of EAC patients. Quantitative analyses revealed that MALAT1 and MANCR were significantly upregulated in EAC tumors and positive lymph nodes when compared to control tissues (p < 0.05). Such dysregulations correlated positively with advanced lymphatic metastases and a higher N stage. DFS in the subgroup of patients with negative lymph nodes was higher in the setting of low-MANCR-expression patients compared to patients with high MANCR expression (p = 0.02). Conversely, miR-101 displayed a significant downregulation in EAC tumors and positive lymph nodes (p < 0.05), and correlated negatively with advanced tumor stage, lymphatic invasion and the grade of the tumor (p = 0.006). Also, patients with low miR-101 expression showed a tendency towards inferior overall survival. PSMA3-AS1 did not demonstrate statistically significant alterations (p > 0.05). This study reveals MALAT1, MANCR, and miR-101 as putative molecular markers for prognostic evaluation in EAC and suggests their involvement in EAC progression.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Adenocarcinoma/genética , Neoplasias Esofágicas/genética , MicroRNAs/genética , Complexo de Endopeptidases do Proteassoma
3.
Clin Endocrinol (Oxf) ; 91(4): 534-543, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31254407

RESUMO

BACKGROUND: The aim of our study was to assess clinico-pathological and biochemical parameters of Type 1 Gastric Neuroendocrine Neoplasms (GNEN1) with respect to tumours propensity for recurrence and metastasis. METHODS: Hospital charts of GNEN1 patients were reviewed at a single tertiary referral centre. RESULTS: We included 114 consecutive patients (74 women; age at baseline 54.5 ± 12.7 years [mean ± SD]) with GNEN1. All tumours (n = 114) were well differentiated; Grade 1 (G1) accounted for 56 patients (49%), whereas 46 (40%) were Grade 2 (G2) and 12 (11%) of unknown Grade. Overall follow-up encompassed 45.3 ± 46 (mean ± SD) months in 84 patients who were subjected to annual surveillance; 44 (52%) developed recurrence in the stomach during follow-up with 22 experiencing multiple recurrences; three (2.6%) presented with metastases in locoregional lymph nodes (n = 3) and/or the liver (n = 2); No metastasis or death was reported during follow-up. Median recurrence-free survival (RFS) was 31 months (95% CI: 7.6-54.4). Among clinico-pathological and biochemical parameters investigated, endoscopic intervention compared with surgery (P-value = .009) and higher serum-gastrin levels (s-gastrin) at baseline and first-year follow-up were associated with recurrence (P-value = .022 and .003 respectively) and also shorter RFS (log-rank P = .009 for type of intervention and .014 for s-gastrin, respectively). Receiver Operator Curve analysis of s-gastrin levels at first-year follow-up for recurrence demonstrated an area under the curve of 0.702. CONCLUSION: Despite the relatively high prevalence of G2 tumours, endoscopically and/or surgically treated GNEN1 remains an indolent disease with a low metastatic propensity and no disease-specific mortality reported in our series. Many patients though will experience local recurrence, warranting long-term endoscopic surveillance with s-gastrin biomarker being a complementary tool in recurrence prediction.


Assuntos
Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/patologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Gastrinas/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/mortalidade , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/mortalidade , Curva ROC , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade
4.
BMC Cancer ; 16: 174, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26931562

RESUMO

BACKGROUND: Advanced glycation end products (AGEs) and their receptor RAGE emerge as important pathogenic contributors in colorectal carcinogenesis. However, their relationship to the detoxification enzyme Glyoxalase (GLO)-I and Adiponectin receptors (AdipoR1, AdipoR2) in colorectal carcinoma (CRC) is currently understudied. In the present study, we investigated the expression levels of the above molecules in CRC compared to adjacent non-tumoral tissue and their potential correlation with clinicopathological characteristics and patients' survival. METHODS: We analyzed the immunohistochemical expression of AGE, RAGE, GLO-1, AdipoR1 and AdipoR2 in 133 primary CRC cases, focusing on GLO-I. The tumour MSI status was further assessed in mucinous carcinomas. Western immunoblotting was employed for validation of immunohistochemical data in normal and tumoral tissues as well in three CRC cell lines. An independent set of 55 patients was also used to validate the results of univariate survival analysis regarding GLO-I. RESULTS: CRC tissue showed higher intensity of both AGE and RAGE expression compared with normal colonic mucosa which was negative for GLO-I in most cases (78 %). Western immunoblotting confirmed AGE, RAGE and GLO-I overexpression in tumoral tissue. GLO-I expression was directly related to RAGE and inversely related to AGE immunolabeling. There was a trend towards higher expression of all markers (except for RAGE) in the subgroup of mucinous carcinomas which, although of borderline significance, seemed to be more prominent for AdipoR1 and AGE. Additionally, AGE, AdipoR1 and Adipo R2 expression was related to tumor grade, whereas GLO-1 and AdipoR1 to T-category. In survival analysis, AdipoR2 and GLO-I overexpression predicted shortened survival in the entire cohort and in early stage cases, an effect which for GLO-I was reproduced in the validation cohort. Moreover, GLO-I emerged as an independent prognosticator of adverse significance in the patients' cohort. CONCLUSIONS: We herein provide novel evidence regarding the possible interactions between the components of AGE-RAGE axis, GLO-I and adiponectin receptors in CRC. AGE and AdipoR1 are possibly involved in colorectal carcinogenesis, whereas AdipoR2 and GLO-I emerged as novel independent prognostic biomarkers of adverse significance for patients with early disease stage. Further studies are warranted to extend our observations and investigate their potential therapeutic significance.


Assuntos
Neoplasias Colorretais/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Linhagem Celular Tumoral , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Lactoilglutationa Liase/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Reprodutibilidade dos Testes , Estudos Retrospectivos
5.
Clin Endocrinol (Oxf) ; 80(5): 685-90, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24118101

RESUMO

OBJECTIVE: The aim of this study was to investigate the prevalence of autoimmune gastritis, enterochromaffin-like cell (ECL-cell) hyperplasia and gastric neuroendocrine neoplasms type 1 (GNEN1) in patients with autoimmune thyroid disease. DESIGN: Prospective observational study in a single institutional study. PATIENTS AND MEASUREMENTS: One hundred and twenty patients with autoimmune thyroid disease were consecutively recruited from the Endocrine Unit. Upper gastrointestinal tract endoscopy (UGE) and biochemical parameters for autoimmune thyroid disease and autoimmune gastritis were assessed at recruitment and annually thereafter in patients with a mean follow-up of 37·5 ± 14·4 months. Autoimmune gastritis was defined by the presence of antiparietal cell antibodies (APCA) and histological confirmation after UGE. Serum gastrin and chromogranin Α were also measured. RESULTS: One hundred and eleven patients had Hashimoto's thyroiditis and nine Graves' disease. Autoimmune gastritis was identified in 40 (38 with Hashimoto's thyroiditis and two with Graves' disease) patients all of whom had increased levels of gastrin and chromogranin Α; Helicobacter pylori infection was histologically identified in 15 of 40 (37·5%) patients. Six patients had isolated nodular ECL-cell hyperplasia and one mixed nodular and linear ECL-cell hyperplasia [7 of 40 (17·5%)]. Only increased gastrin (P = 0·03) levels predicted the presence ECL-cell hyperplasia. A GNEN1 developed in one patient with nodular ECL-cell hyperplasia after 39 months of follow-up. CONCLUSIONS: Concomitant autoimmune gastritis was found in 33·3% of patients with autoimmune thyroid disease, 17·5% of whom had ECL-cell hyperplasia that evolved to GNEN1 in one (2·5%). Larger studies with longer follow-up are needed to define the incidence of GNEN1 in patients with autoimmune thyroid disease and ECL-cell hyperplasia and potential implications.


Assuntos
Doenças Autoimunes/diagnóstico , Gastrite/diagnóstico , Doença de Hashimoto/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Neoplasias Gástricas/genética , Doenças da Glândula Tireoide/diagnóstico , Idoso , Doenças Autoimunes/complicações , Cromogranina A/sangue , Endoscopia , Celulas Tipo Enterocromafim/citologia , Feminino , Gastrinas/sangue , Gastrite/complicações , Doença de Hashimoto/complicações , Infecções por Helicobacter/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/complicações , Fenótipo , Prevalência , Estudos Prospectivos , Risco , Doenças da Glândula Tireoide/complicações
6.
Neuroendocrinology ; 99(2): 118-22, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24776735

RESUMO

AIM: Gastrin and chromogranin A (CgA) levels have been tested for the diagnosis of enterochromaffin-like cell hyperplasia (ECLH) in patients with type 1 diabetes and autoimmune atrophic gastritis but not for patients with Hashimoto's thyroiditis (HT). The aim of the study was to develop receiver operating characteristic (ROC) curves for gastrin and CgA levels and other clinical and biochemical parameters, as means for pretest probability of gastric ECLH in patients with HT. METHODS: A total of 115 patients with HT were prospectively studied for a median period of 4 (2-7) years. Gastrin, CgA, vitamin B12, anti-parietal cell antibodies, free thyroxine, thyrotropin, and neuron-specific enolase levels were measured. Their predictive values were calculated according to the histological findings for ECLH diagnosis from esophagogastroduodenoscopy-obtained biopsies. RESULTS: Thirteen patients (11.3%) had ECLH. The areas under the curve for gastrin and CgA level were 0.898 (p < 0.001) and 0.853 (p < 0.001), respectively. The product sensitivity × specificity was 0.803 and 0.653 for gastrin and CgA levels >89.5 and >89.1 ng/ml, respectively. Two and 4 patients with ECLH had normal gastrin and CgA levels, respectively. The most specific combined parameters predicting ECLH were gastrin >89.5 ng/ml with concomitant low B12 levels (96.1% specificity). CONCLUSION: Gastrin levels have high diagnostic accuracy for ECLH identification in patients with HT, and are highly specific when combined with low B12 levels. However, they should be interpreted with caution, as some patients may harbor gastric ECLH even if gastrin levels are not increased, necessitating further follow-up.


Assuntos
Cromogranina A/sangue , Celulas Tipo Enterocromafim/patologia , Gastrinas/sangue , Doença de Hashimoto/complicações , Gastropatias/diagnóstico , Gastropatias/patologia , Estômago/patologia , Adulto , Idoso , Biomarcadores/sangue , Diabetes Mellitus Tipo 1/complicações , Feminino , Humanos , Hiperplasia/sangue , Hiperplasia/diagnóstico , Hiperplasia/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Fatores de Risco , Sensibilidade e Especificidade , Gastropatias/epidemiologia
7.
Ann Gastroenterol ; 37(4): 466-475, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974083

RESUMO

Background: The wide range of R0 resection rates (R0RR) and incomplete resection rates (IRR) observed with conventional cold snare polypectomy (CCSP) emphasizes the necessity for technique enhancement. The COLDWATER study aimed to compare underwater cold snare polypectomy (UCSP) to CCSP for 5-10-mm colorectal polyps, focusing on comprehensive histopathological evaluation, efficacy, and safety. Methods: This was a randomized, single-blind, controlled trial comparing UCSP to CCSP for non-pedunculated colorectal polyps of size 5-10 mm. The primary outcome was to report differences in the muscularis mucosa resection ratio. The secondary outcomes focused on differences in depth of excision, R0-RR, IRR, en bloc resection rate, adverse events, and recurrence rate. Results: The COLDWATER study found higher muscularis mucosa resection in UCSP (81.72±62.81% vs. CCSP: 72.33±22.33%, P=0.003) with comparable submucosa presence (UCSP: 16.6%, CCSP: 12.5%, P=0.25). UCSP showed better outcomes regarding IRR (3.5% vs. 8.5%, P=0.05) and en bloc resection (98% vs. 93.5%, P=0.04). In CCSP, expert endoscopists achieved higher R0RR than non-experts, while UCSP showed no significant difference in R0RR across endoscopist's experience levels. Conclusions: UCSP achieves a more extensive excision of the muscularis mucosa compared to CCSP, even though it does not attain a deeper excision. Additionally, UCSP shows a higher en bloc resection rate, with lower rates of IRR, and emerges as a promising technique for training inexperienced endoscopists in polypectomy, given its experience-independent success in achieving R0 resection.

8.
Pharmaceutics ; 15(10)2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37896221

RESUMO

Hepatocellular carcinoma (HCC) stands as a significant contributor to global cancer-related mortality. Chronic inflammation, often arising from diverse sources such as viral hepatitis, alcohol misuse, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH), profoundly influences HCC development. Within this context, the interplay of extracellular vesicles (EVs) gains prominence. EVs, encompassing exosomes and microvesicles, mediate cell-to-cell communication and cargo transfer, impacting various biological processes, including inflammation and cancer progression. Toll-like receptor 4 (TLR4), a key sentinel of the innate immune system, recognizes both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), thereby triggering diverse signaling cascades and pro-inflammatory cytokine release. The intricate involvement of the TLR4 signaling pathway in chronic liver disease and HCC pathogenesis is discussed in this study. Moreover, we delve into the therapeutic potential of modulating the TLR4 pathway using EVs as novel therapeutic agents for HCC. This review underscores the multifaceted role of EVs in the context of HCC and proposes innovative avenues for targeted interventions against this formidable disease.

9.
Am J Case Rep ; 24: e939862, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37812585

RESUMO

BACKGROUND Desmoid tumors are a fibroblastic proliferation of soft tissues, with an extreme inclination for local dissemination and recurrence. Surgical excision is the usual treatment choice, with data regarding pharmaceutical treatment being scarce. CASE REPORT A 74-year-old female patient was admitted to "Laikon" General Hospital of Athens, Greece presenting with acute kidney injury secondary to diarrhea. The ultrasound, CT, and abdominal MRI performed showed a 12×6×10 cm tumorous liver lesion. Biopsy of the lesion revealed loosely organized, mesenchymal tissue with spindle cells, and myxoid stroma. Immunochemistry was positive for SMA and b-catenin. Right hemicolectomy was performed with tumor-free surgical margins (R0 resection) and tamoxifen was initiated. Six months after the last MRI (3 months after the use of tamoxifen), a follow-up MRI was performed. The tumor had increased to 14.2×11×12.3 cm, and at the next follow-up it had grown to 20.3×19 cm maximal dimensions; no new metastases were found. The patient received sorafenib and pazopanib. Our patient had PFS with sorafenib for more than 2 years and remained in a good performance status (ECOG 1). For Pazopanid, the median PFS for this treatment option was 6.5 months. CONCLUSIONS The results were good and show a promising method for the treatment of this rare but severe malignancy.


Assuntos
Fibromatose Agressiva , Neoplasias Hepáticas , Feminino , Humanos , Idoso , Fibromatose Agressiva/diagnóstico por imagem , Fibromatose Agressiva/cirurgia , Sorafenibe , Tamoxifeno , Neoplasias Hepáticas/diagnóstico por imagem
10.
BMC Cancer ; 12: 264, 2012 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-22892134

RESUMO

BACKGROUND: Palliative surgery followed by postoperative chemotherapy is a challenging approach in the treatment of stage IV gastric cancer yet patients must be carefully selected on the basis of likely clinical benefit. METHODS: The records of 218 patients with histological diagnosis of gastric adenocarcinoma who underwent palliative surgery followed by postoperative chemotherapy were retrospectively reviewed. Twelve potential prognostic variables including tumour DNA index and serum IgG anti- Helicobacter pylori (HP) antibodies were evaluated for their influence on overall survival by multivariate analysis. RESULTS: The median survival was 13.25 months [95% Confidence Interval (CI) 12.00, 14.50]. Three factors were found to have an independent effect on survival: performance status (PS) [PS 60-70 vs. 90-100 Hazard Ratio (HR) 1.676; CI 1.171-2.398, p = 0.005], liver metastases (HR 1.745; CI 1.318-2.310, p < 0.001), and DNA Index as assessed by Image cytometry (2.2-3.6 vs. >3.6 HR 3.059; CI 2.185-4.283, p < 0.001 and <2.2 vs. >3.6 HR; 4.207 CI 2.751-6.433 <0.001). HP infection had no statistically significant effect on survival by either univariate or multivariate analysis. CONCLUSION: Poor pre-treatment PS, the presence of liver metastasis and high DNA Index were identified factors associated with adverse survival outcome in patients with Stage IV gastric cancer treated with palliative gastrectomy and postoperative chemotherapy. HP infection had no influence on survival of these patients.


Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Adenocarcinoma/etiologia , Idoso , Infecções por Helicobacter/complicações , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ploidias , Prognóstico , Neoplasias Gástricas/etiologia
11.
Neuroendocrinology ; 92(4): 252-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20924166

RESUMO

OBJECTIVE: Although a number of familiar syndromes are associated with primary hyperparathyroidism (PHP), there is no information regarding the prevalence of PHP in other sporadic neuroendocrine diseases. The aim of this study is to investigate the prevalence of PHP in our group of patients with gastric carcinoid (GC) type 1 tumors. METHODS: Twenty-six patients with biopsy-proven GC type 1 tumors were retrospectively studied. The diagnosis of PHP was suspected following elevated or high-normal serum calcium levels and elevated or inappropriate normal parathyroid hormone levels. Further tests for the localization of the hyperfunctioning parathyroid glands included neck ultrasound, (99m)Tc-SESTAMIBI scanning, and cervical or upper mediastinal MR imaging studies. Four control groups were also studied: two age- and sex-matched groups of individuals with (n = 49) and without (n = 34) thyroid autoimmunity and normal endoscopy of the stomach, a third group with nongastric neuroendocrine tumors (n = 68), and a fourth group with atrophic gastritis and hypergastrinemia, without gastric endocrine tumors (n = 30). RESULTS: PHP was diagnosed in 4 (15.38%) patients with GC type 1 tumors compared to none of the 4 control groups. Three of the 4 patients with PHP were operated and proved to have a parathyroid adenoma. No statistically significant differences were observed between patients with or without PHP in mean gastrin and chromogranin A levels, number of lesions, ki-67 labeling index expression, and maximum GC type 1 tumor diameter. CONCLUSION: PHP seems to be relatively common, approximately 15% in the present cohort, in patients with GC type 1 tumors. PHP should be actively looked for in such patients and treated accordingly.


Assuntos
Tumor Carcinoide/complicações , Hiperparatireoidismo Primário/complicações , Neoplasias Gástricas/complicações , Adenoma/complicações , Adenoma/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/epidemiologia , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Adulto Jovem
12.
South Med J ; 102(10): 1061-4, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19738519

RESUMO

Diffuse malignant peritoneal mesothelioma (DMPM) represents 90% of all peritoneal forms of mesothelioma. It affects mainly patients 50-69 years old. In 50% of cases there is a history of asbestos exposure. The clinical presentation of the disease is not characteristic: nonspecific abdominal pain, weight loss, and abdominal distension are common. Ascites occurs in 90% of the patients. Bowel obstruction is a late manifestation. We present three patients with DMPM, without a history of asbestos exposure and without ascites, who presented with complete bowel obstruction. All patients underwent emergency operations, and palliative surgical procedures were performed. Each patient died within 3 to 6 months postoperatively.


Assuntos
Obstrução Intestinal/etiologia , Mesotelioma/diagnóstico , Neoplasias Peritoneais/diagnóstico , Adulto , Evolução Fatal , Humanos , Ileostomia , Masculino , Mesotelioma/cirurgia , Pessoa de Meia-Idade , Neoplasias Peritoneais/cirurgia
13.
Anticancer Res ; 28(1B): 543-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18383900

RESUMO

BACKGROUND: Most patients with pancreatic adenocarcinoma are diagnosed with locally advanced (unresectable) or metastatic disease. The aim of this study was to investigate possible prognostic factors of survival in such patients. PATIENTS AND METHODS: Two hundred and fifteen patients were studied retrospectively. Twenty-four potential prognostic variables (demographics, clinical parameters, biochemical markers, treatment modality) were examined. RESULTS: Mean survival was 29.0 weeks. 21.9% survived more than 36 weeks. On multivariate analysis, 10 factors had an independent effect on survival: tumour localisation, metastasis, performance status, jaundice, weight loss, C reactive protein, CEA, CA 19-9, palliative surgery and chemotherapy. Patients managed only with palliative care had a hazard ratio of 8.94 versus those offered a combination of palliative surgery and chemotherapy. CONCLUSION: Many factors could be used as predictors of survival in patients with advanced or metastatic pancreatic cancer. Chemotherapy and palliative surgery are associated with increased survival, and should be offered to all eligible patients.


Assuntos
Adenocarcinoma/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos Retrospectivos , Fatores de Risco
14.
Endocrinol Metab Clin North Am ; 47(3): 645-660, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30098721

RESUMO

Gastric carcinoids, formally named gastric neuroendocrine neoplasms (NENs), are derived from enterochromaffin-like cells of the stomach and are increasingly diagnosed. A majority are designated as type I (related to autoimmune gastritis) and type II (related to gastrinoma) neoplasms that develop secondary to gastrin hypersecretion. Types I and II gastric carcinoids are mostly small-sized (1-2 cm), multiple, low-malignancy potential lesions mainly confined to the gastric mucosa/submucosa. These lesions have an indolent course and low metastatic potential. In contrast, type III gastric carcinoids are single, larger-sized (>2 cm), non-gastrin-related lesions that infiltrate the muscular layers associated with local and distant metastases.


Assuntos
Tumor Carcinoide/patologia , Tumor Carcinoide/terapia , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/terapia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Tumor Carcinoide/tratamento farmacológico , Neoplasias Gastrointestinais/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico
15.
Front Genet ; 8: 65, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28611823

RESUMO

The fundamental role of human Toll-like receptors (TLRs) and NOD-like receptors (NLRs), the two most studied pathogen recognition receptors (PRRs), is the protection against pathogens and excessive tissue injury. Recent evidence supports the association between TLR/NLR gene mutations and susceptibility to inflammatory, autoimmune, and malignant diseases. PRRs also interfere with several cellular processes, such as cell growth, apoptosis, cell proliferation, differentiation, autophagy, angiogenesis, cell motility and migration, and DNA repair mechanisms. We briefly review the impact of TLR4 and NOD1/NOD2 and their genetic variability in the process of inflammation, tumorigenesis and DNA repair, focusing in the gastrointestinal tract. We also review the available data on new therapeutic strategies utilizing TLR/NLR agonists and antagonists for cancer, allergic diseases, viral infections and vaccine development against both infectious diseases and cancer.

16.
Medicine (Baltimore) ; 96(1): e5883, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28072751

RESUMO

RATIONALE: We are reporting the first-to our knowledge-case of duodenal Plexiform Fibromyxoma causing obscure upper gastrointestinal bleeding. PATIENT CONCERNS: Plexiform fibromyxoma triggered recurrent upper gastrointestinal bleeding episodes in a 63-year-old man who remained undiagnosed, despite multiple hospitalizations, extensive diagnostic workups and surgical interventions (including gastrectomies), for almost 17 years. DIAGNOSES-INTERVENTIONS: During hospitalization for the last bleeding episode, an upper gastrointestinal endoscopy revealed an intestinal hemorrhagic nodule. The lesion was deemed unresectable by endoscopic means. An abdominal computerized tomography disclosed no further lesions and surgery was decided. The lesion at operation was found near the edge of the duodenal stump and treated with pancreas-preserving duodenectomy (1st and 2nd portion). OUTCOMES: Postoperative recovery was mainly uneventful and a 20-month follow-up finds the patient in good health with no need for blood transfusions.Plexiform fibromyxomas stand for a rare and widely unknown mesenchymal entity. Despite the fact that they closely resemble other gastrointestinal tumors, they distinctly vary in clinical management as well as the histopathology. Clinical awareness and further research are compulsory to elucidate its clinical course and prognosis.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Duodenais , Duodeno , Fibroma , Hemorragia Gastrointestinal , Neoplasias Duodenais/complicações , Neoplasias Duodenais/patologia , Neoplasias Duodenais/fisiopatologia , Neoplasias Duodenais/cirurgia , Duodeno/diagnóstico por imagem , Duodeno/patologia , Endoscopia do Sistema Digestório/métodos , Fibroma/complicações , Fibroma/patologia , Fibroma/fisiopatologia , Fibroma/cirurgia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
17.
Front Genet ; 8: 20, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28289428

RESUMO

Helicobacter pylori (H. pylori) is a Gram negative bacterium that colonizes the stomach of almost half human population. It has evolved to escape immune surveillance, establishes lifelong inflammation, predisposing to genomic instability and DNA damage, notably double strand breaks. The epithelial host cell responds by activation of DNA damage repair (DDR) machinery that seems to be compromised by the infection. It is therefore now accepted that genetic damage is a major mechanism operating in cases of H. pylori induced carcinogenesis. Here, we review the data on the molecular pathways involved in DNA damage and DDR activation during H. pylori infection.

18.
Infect Control Hosp Epidemiol ; 23(11): 653-9, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12452292

RESUMO

OBJECTIVE: To determine the diagnostic accuracy of an index of underlying disease severity (Horn's index) in identifying patients with a high probability of having nosocomial Clostridium difficile diarrhea as a complication of antimicrobial therapy. DESIGN: A prospective cohort study of 252 adult patients admitted to the hospital and receiving antibiotics. Risk facctors for C. difficile diarrhea were first determined retrospectively in a different cohort of 300 hospitalized patients (primary cohort) and then prospectively in this cohort of 252 hospitalized patients receiving antibiotics (secondary cohort). At the time of hospital admission, disease was rated by clinicians as mild (1), moderate (2), severe (3), or extremely severe (4) using a modified Horn's index. Multivariable logistic regression analysis was used to determine the odds ratio (OR) for C. difficile diarrhea associated with increasing levels of disease severity. SETTING: An urban teaching hospital affiliated with a medical school in Boston, Massachusetts. RESULTS: The incidence of nosocomial C. difficile diarrhea was 8.7% in the primary cohort and 11% in the secondary cohort In the prospective cohort study (secondary cohort), the OR for C. difficile diarrhea associated with extremely severe disease was 17.6 (95% confidence interval, 5.8 to 53.5). The sensitivity, specificity, and positive and negative predictive values of a Horn's index score of 3 or more (severe to extremely severe disease) as a predictor of nosocomial C. difficile diarrhea were 79%, 73%, 27%, and 96%, respectively. CONCLUSIONS: These findings provide a means of early stratification of hospitalized patients receiving antibiotics according to their risk for nosocomial C. difficile diarrhea. Patients with severe to extremely severe disease at the time of admission may benefit from careful monitoring of antibiotic prescribing and early attention to infection control issues. In the future, these "high-risk" patients may benefit from prophylaxis studies of novel agents being developed to prevent C. difficile diarrhea.


Assuntos
Antibacterianos/efeitos adversos , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/epidemiologia , Infecção Hospitalar/epidemiologia , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Hospitais de Ensino , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Boston/epidemiologia , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/microbiologia , Estudos de Coortes , Infecção Hospitalar/microbiologia , Diarreia/microbiologia , Feminino , Hospitais Urbanos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
19.
FEMS Immunol Med Microbiol ; 41(3): 237-42, 2004 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-15196573

RESUMO

Clostridium difficile is a major cause of infectious diarrhoea in hospitalised patients. Surface layer proteins (SLPs) are the most abundant surface localised proteins expressed by C. difficile. The aim of this study was to examine the humoral immune response to C. difficile SLPs and its potential role in protection from C. difficile associated diarrhoea (CDAD). Serum antibodies to SLPs from C. difficile were measured by ELISA in a cohort of 146 patients (55 patients with CDAD, 34 asymptomatic carriers, and 57 controls). No significant difference was detected in serum IgM, IgA or IgG antibody levels between cases, carriers or control groups at any of the time points tested. However, patients with recurrent episodes of C. difficile diarrhoea had significantly lower IgM-anti-SLP levels than patients with a single episode on days 1, 3, 6 and 9 (p = 0.05, p = 0.009, p = 0.02, p = 0.049). The adjusted odds ratio for recurrent diarrhoea associated with a low day 3 serum IgM anti-SLP antibody level was 24.5 (95% confidence interval; 1.6-376.3). Further studies which examine the specific anti-SLP antibody responses to the colonising strain are warranted to determine if immune responses to C. difficile SLPs play a role in protection from CDAD.


Assuntos
Anticorpos Antibacterianos/sangue , Proteínas de Bactérias/imunologia , Clostridioides difficile/imunologia , Infecções por Clostridium/imunologia , Glicoproteínas de Membrana/imunologia , Infecções por Clostridium/microbiologia , Diarreia/imunologia , Diarreia/microbiologia , Enterocolite Pseudomembranosa/imunologia , Enterocolite Pseudomembranosa/microbiologia , Humanos , Imunoglobulina M/sangue
20.
Eur J Endocrinol ; 168(2): 185-93, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23132699

RESUMO

OBJECTIVE: To study the clinical presentation, diagnostic approach, response to treatment, and the presence of other pathologies in patients with gastric carcinoid type 1 (GC 1) tumors. DESIGN AND METHODS: Retrospective analysis of 111 patients from four institutions and a mean follow-up of 76 months. RESULTS: The main indications for gastroscopy were upper gastrointestinal tract symptoms. The mean number of lesions, maximum tumoral diameter, and percentage of cells expressing Ki-67 labeling index were 3.6±3.8, 8±12.1 mm and 1.9±2.4% respectively. Serum gastrin and chromogranin A (CgA) levels were elevated in 100/101 and 85/90 patients respectively. Conventional imaging studies demonstrated pathology in 9/111 patients. Scintigraphy with radiolabeled octreotide was positive in 6/60 without revealing any additional lesions. From the 59 patients who had been followed-up without any intervention, five developed tumor progression. Thirty-two patients were treated with long-acting somatostatin analogs (SSAs), leading to a significant reduction of gastrin and CgA levels, number of visible tumors, and CgA immune-reactive tumor cells in 28, 19, 27, and 23 treated patients respectively. Antrectomy and/or gastrectomy were initially performed in 20 patients and a complete response was achieved in 13 patients. The most common comorbidities were vitamin B12 deficiency, thyroiditis, and parathyroid adenomas. CONCLUSIONS: Most GCs1 are grade 1 (82.7%) tumors presenting with stage I (73.9%) disease with no mortality after prolonged follow-up. Ocreoscan did not provide further information compared with conventional imaging techniques. Treatment with SSAs proved to be effective for the duration of administration.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Tumor Carcinoide/patologia , Octreotida/uso terapêutico , Neoplasias Gástricas/patologia , Biomarcadores Tumorais/sangue , Tumor Carcinoide/sangue , Tumor Carcinoide/tratamento farmacológico , Cromogranina A/sangue , Feminino , Seguimentos , Gastrinas/sangue , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/tratamento farmacológico , Resultado do Tratamento
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