RESUMEN
Genetic markers associated with colorectal cancer may be used in population screening for the early identification of patients at elevated risk of disease. We genotyped 3059 individuals with no cancer family history for eight markers previously associated with colorectal cancer. After colonoscopy, the genetic profile of cases with advanced colorectal neoplasia (213) was compared with the rest (2846). rs2066847 and rs6983267 were significantly associated with the risk of advanced colorectal neoplasia but with limited effect on their own [odds ratio (OR) 1.59; 95% confidence interval (CI) 1.02-2.41; p = 0.033 and OR 1.45; 95% CI 1.02-2.12; p = 0.044, respectively]. Cumulative effects, in contrast, were associated with high risk: the combination of rs2066847, rs6983267, rs4779584, rs3802842 and rs4939827 minimized the number of markers considered, while maximizing the relative size of the carrier group and the risk associated to it, for example, for at least two cumulated risk markers, OR is 2.57 (95% CI 1.50-4.71; corrected p-value 0.0079) and for three or more, OR is 3.57 (95% CI 1.91-6.96; corrected p-value 0.00074). The identification of cumulative models of - otherwise - low-risk markers could be valuable in defining risk groups, within an otherwise low-risk population (no cancer family history).
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Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Marcadores Genéticos , Anciano , Alelos , Estudios de Casos y Controles , Neoplasias Colorrectales/patología , Detección Precoz del Cáncer , Femenino , Frecuencia de los Genes , Pruebas Genéticas , Genotipo , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Oportunidad Relativa , Polonia/epidemiología , Polimorfismo de Nucleótido Simple , Vigilancia de la Población , RiesgoRESUMEN
BACKGROUND: The American Joint Committee on Cancer (AJCC) staging system has limited accuracy in predicting survival of gastric cancer patients with inadequate counts of evaluated lymph nodes (LNs). We therefore aimed to develop a prognostic nomogram suitable for clinical applications in such cases. METHODS: A total of 1511 noncardia gastric cancer patients treated between 1990 and 2010 in the academic surgical center were reviewed to compare the 7th and 8th editions of the AJCC staging system. A nomogram was developed for the prediction of 5-year survival in patients with less than 16 LNs evaluated (n = 546). External validation was performed using datasets derived from the Polish Gastric Cancer Study Group (n = 668) and the SEER database (n = 11,225). RESULTS: The 8th edition of AJCC staging showed better overall discriminatory power compared to the previous version, but no improvement was found for patients with < 16 evaluated LNs. The developed nomogram had better concordance index (0.695) than the former (0.682) or latest (0.680) staging editions, including patients subject to neoadjuvant treatment, and calibration curves showed excellent agreement between the nomogram-predicted and actual survival. High discriminatory power was also demonstrated for both validation cohorts. Subsequently, the nomogram showed the best accuracy for the prediction of 5-year survival through the time-dependent ROC curve analysis in the training and validation cohorts. CONCLUSIONS: A clinically relevant nomogram was built for the prediction of 5-year survival in patients with inadequate numbers of LNs evaluated in surgical specimens. The predictive accuracy of the nomogram was validated in two Western populations.
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Nomogramas , Neoplasias Gástricas , Humanos , Pronóstico , Estadificación de Neoplasias , Neoplasias Gástricas/patología , Ganglios Linfáticos/patologíaRESUMEN
Postoperative decline of renal function remains a common and unpredictable complication after abdominal aortic aneurysm (AAA) reconstruction. The oxidative stress that occurs during perioperative ischemia/reperfusion injury (I/R) may contribute to the development of this complication. In this study, the influence of intraoperative prostaglandin E (alprostadil) administration on erythrocyte and platelet antioxidants as well as postoperative kidney function modulation were verified. AAA patients were randomly divided into control and study/alprostadil groups. Blood samples were collected directly before aortic clamping and 5 min after aortic declamping. Superoxide dismutase, catalase, glutathione, glutathione peroxidase (GPx), and glutathione transferase (GST) were measured using spectrophotometry. During I/R, the activity of catalase (57.14+/-30.65 vs 128.35+/-91.94 U/mg protein; P < 0.009), GPx (0.21+/-0.18 vs 0.35+/-0.21 mU/g protein; P = 0.028), and GST (217.49+/-101.39 vs 310.66+/-88.86 mU/g protein; P = 0.0006) significantly increased in the control group. GST activity before the aortic clamping was significantly lower in the study/alprostadil group (2.84+/-2.28 vs 3.48+/-2.30 U/g Hb; P = 0.05). The activity of the selected antioxidants proved to be of a diagnostic value for predicting postoperative decline in renal function. In conclusion, during I/R after AAA reconstruction, activation of various erythrocyte and platelet antioxidants occurs. Perioperative administration of alprostadil is associated with disruption of this activation.
Asunto(s)
Alprostadil/administración & dosificación , Aneurisma de la Aorta Abdominal/cirugía , Plaquetas/metabolismo , Eritrocitos/metabolismo , Enfermedades Renales/sangre , Daño por Reperfusión/sangre , Vasodilatadores/administración & dosificación , Anciano , Antioxidantes/metabolismo , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/patología , Humanos , Riñón/irrigación sanguínea , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/etiología , Enfermedades Renales/patología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Oxidorreductasas/sangre , Daño por Reperfusión/etiología , Daño por Reperfusión/patologíaRESUMEN
Recent studies demonstrated that selected hormones/adipokines may be involved into the regulation of bone metabolism and bone marrow-derived hematopoietic stem/progenitor cells (HSPCs) mobilization in humans. Interestingly, in obese individuals significantly higher numbers of spontaneously circulating stem cells are also observed. Therefore in this study we comprehensively examined plasma and AT (subcutaneous and visceral/omental) levels of hormones/adipokines involved in HSPCs mobilization in lean, overweight and obese individuals as well as verified their potential associations with concentrations of HSPCs chemoattractant, stromal-derived factor-1 (SDF-1). Blood and AT samples (35 subcutaneous and 35 omental) were obtained from individuals undergoing elective surgery. Plasma and AT-derived interstitial fluid levels of resistin, visfatin, osteocalcin and SDF-1 were measured using ELISA. In our study obese patients had almost significantly (P<0.06) higher plasma visfatin and resistin levels as well as lower osteocalcin concentrations (P<0.04) than lean individuals. Osteocalcin and resistin concentrations were strongly associated with levels of SDF-1 and metalloproteinases (MMP 2 and 9). AT levels of all examined substances were significantly lower than the corresponding levels in the plasma (in all cases at least P<0.05), and depot-specific differences in the concentrations of these factors were found only in terms of osteocalcin and SDF-1. In addition, subcutaneous and visceral/omental concentrations of osteocalcin and visfatin, but not of resistin, were associated with values of such parameters as age, body mass or adiposity indexes (BMI and BAI, respectively) and/or waist-to-hip ratio (WHR). In summary, our study showed that in obese individuals the biochemical constellation of adipokines/hormones involved in the process of HSPCs mobilization resembles this observed during pharmacological HSPCs mobilization. Moreover, our study offers further indirect translational evidence for existence of a biochemical cross-talk between bone and AT metabolism (so called - bone-fat- axis) in humans.
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Tejido Adiposo/metabolismo , Quimiocina CXCL12/análisis , Citocinas/análisis , Nicotinamida Fosforribosiltransferasa/análisis , Obesidad/metabolismo , Osteocalcina/análisis , Resistina/análisis , Adulto , Movilización de Célula Madre Hematopoyética , Humanos , Persona de Mediana Edad , Sobrepeso/metabolismoRESUMEN
OBJECTIVE: The aim of this study was to evaluate the efficacy of adjuvant chemotherapy with etoposide, Adriamycin and cisplatin (EAP) after potentially curative resections for gastric cancer. METHODS: After surgery, patients were randomly assigned to the EAP or control arm. Chemotherapy included 3 courses, administered every 28 days. Each cycle consisted of doxorubicin (20 mg/m(2)) on days 1 and 7, cisplatin (40 mg/m(2)) on days 2 and 8, and etoposide (120 mg/m(2)) on days 4, 5, and 6. RESULTS: Of 309 eligible patients, 141 were allocated to chemotherapy and 154 to the supportive care group. Four (2.8%) treatment-related deaths were recorded, including 3 due to septic complications of myelosuppression and 1 due to cardiocirculatory failure. Grade 3 or 4 toxicities were found in 17 (22%) patients. According to the intention-to-treat analysis, the median survival was 41.3 months (95% confidence interval, 24.5-58.2) and 35.9 months (95% confidence interval, 25.5-46.3) in the chemotherapy and control group, respectively (p = 0.398). Subgroup analysis revealed survival benefit from chemotherapy in patients with tumors infiltrating the serosa and in those with 7-15 metastatic lymph nodes. CONCLUSION: Three cycles of EAP regimen postoperatively offer no survival advantage in gastric cancer patients.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/cirugía , Anciano , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Gastrectomía , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/cirugía , Análisis de SupervivenciaRESUMEN
BACKGROUND/AIMS: Endosonography (EUS) is rarely used in the routine diagnostic of portal hypertension in patients with cirrhosis even though it has significantly higher sensitivity for detection of varices than gastroduodenoscopy. The aim of this cross-sectional study was to assess the features of portal hypertension identified with EUS and to analyze the effect of variceal ligation on the prevalence of "deep" varices in subjects with cirrhosis. METHODOLOGY: A cohort of 121 patients was divided into 2 groups depending on whether they had a history of variceal bleeding treated with ligation or not. RESULTS: "Deep" oesophageal varices and large (> 5 mm) gastric varices occurred significantly more common in patients with previous banding. Also, large "deep" gastric varices occurred significantly more common in the banded group with no or small varices than in the not-banded group with similar endoscopy. Sixty percent of banded patients who had grade II/III oesophageal varices on endoscopy had large "deep" gastric varices comparing to 20% of not-banded with the same endoscopical findings (p = 0.04). CONCLUSION: Previous banding may increase the risk of the development of large "deep" oesophageal and gastric varices. Thus potential new indication for EUS in patients with cirrhosis could be a follow-up examination after successful eradication of varices.
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Endosonografía , Várices Esofágicas y Gástricas/diagnóstico por imagen , Várices Esofágicas y Gástricas/terapia , Hipertensión Portal/diagnóstico por imagen , Distribución de Chi-Cuadrado , Circulación Colateral , Estudios Transversales , Endoscopía Gastrointestinal , Várices Esofágicas y Gástricas/etiología , Femenino , Humanos , Hipertensión Portal/complicaciones , Ligadura/efectos adversos , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Factores de Riesgo , Resultado del TratamientoRESUMEN
The expression of p53 was immunohistochemically determined in sets of biopsies from primary and recurrent colorectal (12) and gastric (17) tumours that had progressed to more advanged stages in the following 6-54 months. At presentation 7 carcinomas overexpressed p53 protein in the cell nucleus and 22 tumours had normal, undetectable levels of p53. In most patients, the p53 phenotype was maintained during the process of tumour progression. In two gastric and two colorectal carcinomas p53 overexpression was subsequently detected in recurrent tumour growth at the primary site and was also associated with the development of metastases. These results suggests that in some cases p53 alterations may contribute to the conversion to malignancy and in others to tumour progression and metastatic capacity.
RESUMEN
BACKGROUND: Gastric cancer is one of the most frequent neoplasms and a leading cause of the death world-wide. In recent years, epidemiological and animal studies demonstrated a link between gastric cancer and chronic infection with H. pylori. The exact mechanism responsible for the development of gastric cancer in H. pylori-infected patients still remains unclear. There is evidence that the up-regulation of certain growth factors could play an important role in the promotion of the gastric carcinogenesis. AIMS: The present study was designed to determine the gene expression of major known growth factors such as transforming growth factor alpha (TGFalpha), hepatocyte growth factor (HGF) and gastrin in the gastric cancer tissue, the surrounding mucosa and, for comparison, in the normal gastric mucosa. Furthermore, the luminal and plasma levels of gastrin in patients with gastric cancer were determined. In addition, the gene and protein expressions of apoptosis-related proteins such as Bax and Bcl-2 were investigated by reverse transcription-polymerase chain reaction and Western blot. Twenty-five gastric cancer patients and 40 age- and gender-matched control subjects hospitalized with non-ulcer dyspepsia were included into this study. RESULTS: An overall H. pylori-seropositivity among gastric cancer patients was about 72% and was significantly higher than in the controls (56%). The prevalence of CagA-positive strains was also significantly higher among gastric cancer patients than in controls (56% vs. 32%). The gene expression of HGF and TGFalpha was detected more frequently in gastric cancer tissue samples than in normal gastric mucosa (52% vs. 12% for HGF and 48% vs. 24% for TGFalpha). The extent of protein expression in Western blotting analysis for HGF and TGFalpha correlated with the mRNA expression of these factors. Gene expression of gastrin was detected in the antrum of all tested patients and in the majority (84%) of gastric cancer patients. The median plasma and luminal concentrations of gastrin in gastric cancer patients were significantly higher than in controls. The gene expression of bcl-2 was detected in all (100%) and that of proapoptotic bax only in 56% of gastric cancer samples. In comparison to the surrounding non-tumorous tisssue, the gene expression of bax was significantly down-regulated and the gene expression of bcl-2 was up-regulated in gastric cancer tissue. At the protein level, Bax was not detectable and Bcl-2 was seen in 80% of gastric cancer samples. CONCLUSIONS: It is concluded that the patients infected with H. pylori, especially with CagA-positive strains, are at a higher risk of developing a gastric cancer. An increased production and release of gastrin, as well as an over-expression of growth factors such as HGF and TGFalpha, might contribute to the gastric carcinogenesis. In addition, a dysregulation of the Bax/Bcl-2 system with significant up-regulation of Bcl-2 is observed in gastric cancer.
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ADN de Neoplasias/genética , Gastrinas/biosíntesis , Regulación Neoplásica de la Expresión Génica , Infecciones por Helicobacter/complicaciones , Factor de Crecimiento de Hepatocito/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteínas Proto-Oncogénicas/biosíntesis , Neoplasias Gástricas/genética , Factor de Crecimiento Transformador alfa/biosíntesis , Adulto , Anciano , Apoptosis , Estudios de Casos y Controles , Regulación hacia Abajo , Femenino , Gastrinas/análisis , Helicobacter pylori/patogenicidad , Factor de Crecimiento de Hepatocito/análisis , Humanos , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas/análisis , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Factor de Crecimiento Transformador alfa/análisis , Regulación hacia Arriba , Proteína X Asociada a bcl-2RESUMEN
The aim of this study was to assess whether thoracic radiotherapy (TRT) is necessary for those patients (pts) with limited small cell lung cancer (SCLC) who obtained CR after induction chemotherapy (ChT). The analysis include retrospective material of 124 consecutive pts with limited SCLC. All pts had induction ChT (3-5 courses): 78 with CAVE (cyclophosphamide, doxorubicine, etoposide) and 46--with other regimens without etoposide. After induction ChT 55 pts were irradiated on tumor and mediastinum and in 69 the same ChT was continued for 6-8 courses or till progression. After induction ChT CR was obtained in 31 pts, PR in 67 and NR in 26. TRT significantly increased the number of CR among those pts who did not achieve satisfactory tumor response after induction ChT. The median survival was 24 months for those patients who obtained CR, 12 months for those who obtained PR and 9 months for those who did not respond. In the group of patients who obtain CR, survival was the same for those treated with ChT alone and for those treated with ChT and TRT. We conclude that in the treatment of individual patient with limited SCLC TRT is indicated for those who did not obtain CR after ChT. Whether patients in whom CR after chemotherapy was obtained can further gain by application of TRT is worth further randomised studies.
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Carcinoma de Células Pequeñas/mortalidad , Neoplasias Pulmonares/mortalidad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/radioterapia , Terapia Combinada , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Inactivation of the p53 tumour-suppressor gene is the commonest genetic abnormality in human cancers. This results in a conformational change in the p53 protein, and a consequent prolongation in its half-life; thereby permitting the identification of p53 immunoreactivity in malignant cells. Such reactivity is observed in up to 57% of gastric carcinomas, and is a proven indicator of poor prognosis. We have investigated the use of p53 immunohistochemistry in the diagnosis of malignancy in pre-operative gastric biopsy specimens. Using a three-stage immunoperoxidase technique, p53 expression was examined in 117 gastric biopsies obtained during flexible upper gastrointestinal endoscopy: 80 of these biopsies were from known gastric carcinomas, 20 from benign gastric disorders and 17 from normal gastric mucosa. Of the gastric cancers 40% (n = 32) exhibited overexpression of p53. No reactivity was observed in any of the biopsies of gastric ulcers, polyps or normal mucosa. The expression of p53 by gastric carcinomas improved the diagnostic accuracy of conventional histopathology from 86% to 92.5%; with 5% of biopsies incorrectly diagnosed and 2.5% of an equivocal appearance. These results demonstrate that the detection of p53 is a highly specific marker of gastric malignancy, and that such a technique can easily be performed on biopsies obtained at endoscopy.
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Biomarcadores de Tumor/análisis , Neoplasias Gástricas/diagnóstico , Proteína p53 Supresora de Tumor/análisis , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Adenoma/diagnóstico , Adenoma/patología , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Gastroscopía , Humanos , Técnicas para Inmunoenzimas , Neoplasias Gástricas/patologíaRESUMEN
OBJECTIVE: To evaluate the prognostic value of p53 in colorectal cancer. DESIGN: A retrospective study to investigate the correlation between p53 in tumour tissue and the course of patients' disease. PATIENTS: One hundred and two patients who underwent radical surgery for colorectal cancer and were followed up for a minimum of 5 years, or until death, were included in this study. METHODS: The p53 expression in tumour tissue was studied by immunohistochemistry using CM1 polyclonal rabbit antibody and formalin-fixed, paraffin-embedded material. RESULTS: p53 accumulation was detected in 46% (47/102) of the tumours. There was no significant difference in long-term survival between the patients with p53 positive and negative tumours (P=0.86). Five-year survival rates were 55% for p53 positive tumours compared with 56% for patients with p53 negative tumours. However, patients with p53 overexpressing tumours showed a higher local recurrence rate than those having carcinomas with undetectable levels of p53, 23% versus 9% respectively; the 2-year actuarial rates of 26% and 9% were statistically different (P=0.015). CONCLUSION: The results suggest that in colorectal carcinoma accumulation of p53 is not associated with a difference in long-term prognosis. However, this phenomenon might be useful in the identification of patients with a high risk of local recurrence.
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Neoplasias Colorrectales/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adulto , Anciano , Biomarcadores/análisis , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
OBJECTIVE: To evaluate the role of 5T4 antigen in gastric cancer progression and prognosis. DESIGN: A prospective study of 5T4 antigen expression in primary, secondary and recurrent gastric carcinoma, the relationship to selected prognostic parameters and the course of disease. PATIENTS: Eighty six patients operated on for gastric cancer. TISSUE: One hundred and twenty two gastric tumours were studied, including 86 primary carcinomas, 32 coexisting lymph node metastases and four recurrent carcinomas. METHODS: Immunohistochemistry using 5T4 monoclonal antibody on frozen sections. RESULTS: The 5T4 antigen was detected in 41% of primary gastric tumours including early gastric cancer. A strong relationship was found between 5T4 positivity and tumour histology. Thus, 52% of gastric carcinomas of intestinal type expressed 5T4 antigen compared with 28% of the diffuse type (P = 0.028). Among 16 sets of primary gastric carcinomas and regional lymph node metastases, coordinate 5T4 expression was seen in 14 cases; the other two showed acquisition of positivity on metastatic tumour cells (carcinomas of diffuse type). 5T4 antigen was detected more frequently in carcinomas with p53 accumulation compared with those with undetectable p53 levels (P = 0.015). The presence of 5T4 in cancer cells was correlated with poor short-term prognosis (24% vs 49% of 2 year survival for 5T4 positive and negative tumours respectively, P = 0.024). The effect on survival was evident in the p53 negative group, with patients 5T4 positive showing worse survival (28% vs 60% in 2 years). CONCLUSIONS: Our results suggest that the assessment of 5T4 expression in gastric carcinoma can be helpful in identifying patients with poor short-term prognosis.
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Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/metabolismo , Glicoproteínas de Membrana/metabolismo , Neoplasias Gástricas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Técnicas para Inmunoenzimas , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/metabolismo , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Análisis de SupervivenciaRESUMEN
5T4 oncofetal antigen is defined by a monoclonal antibody raised against human placental trophoblast, and recognizes a 72 kD glycoprotein expressed in many different carcinomas but detected only at low levels in some normal epithelia. Analysis of the patterns of expression of 5T4 oncofetal antigen in colorectal carcinomas has indicated a significant association between the presence of the antigen in tumor cells and metastatic spread. The 5T4 antigen expression of 72 epithelial ovarian carcinomas has been investigated by immunohistochemistry; 71% of the carcinomas demonstrated positive 5T4 immunoreactivity in adenocarcinoma cells and/or associated stromal tissue. In order to assess any relationship to prognosis, the 5T4 phenotypes were analyzed with respect to various clinicopathologic features of the tumors and the clinical outcome of the patients assessed by survival and disease-free interval. There was a significant correlation between 5T4 expression and more advanced stage of disease (FIGO stages III and IV) (P < 0.001) and with poorly differentiated tumors (P = 0.036) compared to well or moderately differentiated tumors. Patients with tumors expressing 5T4 were less likely to respond well to adjuvant therapy (P = 0.030) and had a significantly worse outlook in terms of survival (P = 0.033) and disease-free interval (P = 0.033). This significance was not demonstrated as acting independently of FIGO stage and tumor differentiation.
RESUMEN
Numerous epidemiological studies demonstrated the association between Helicobacter pylori (H. pylori) infection and gastric cancer but the mechanism of the involvement of H. pylori in gastric cancerogenesis remains virtually unknown. This study was designed to determine the seropositivity of H. pylori and cytotoxin associated gene A (CagA), serum gastrin and gastric lumen gastrin levels under basal conditions and following stimulation with histamine in gastric cancer patients and controls. 100 gastric cancer patients aging from 21 to 60 years and 300 gender- and age-adjusted controls hospitalized with non-ulcer dyspepsia (NUD) entered this study. 13C-Urea Breath Test (UBT), serum immunoglobulin (IgG) antibodies to H. pylori and CagA were used to assess the H. pylori infection and serum levels of IL-1beta, IL-8 and TNFalpha were measured by enzyme-linked immunosorbent assay (ELISA) to evaluate the degree of gastric inflammation by H. pylori . Gastrin-17 mRNA and gastrin receptors (CCK(B)) mRNA expression in gastric mucosal samples taken by biopsy from the macroscopically intact fundic and antral mucosa as well as from the gastric tumor was determined using RT-PCR. The overall H. pylori seropositivity in gastric cancer patients at age 21-60 years was about 92%, compared, respectively, to 68%, in controls. A summary odds ratio (OR) for gastric cancer in H. pylori infected patients was about 5.0 . The H. pylori CagA seropositivity in gastric cancer patients was about 58.5% compared to 32.4% in controls, giving the summary OR for gastric cancer in CagA positive patients about 8.0. The prevalence of H. pylori- and H. pylori CagA-seropositivity was significantly higher in cancers than in controls, irrespective of the histology of gastric tumor (intestinal, diffuse or mixed type). Median IL-1beta and IL-8 reached significantly higher values in gastric cancer patients (9.31 and 30.8 pg/ml) than in controls (0.21 and 3.12, respectively). In contrast, median serum gastrin in cancers (as total group) was several folds higher (62.6 pM) than in controls (19.3 pM). Also median luminal gastrin concentration in gastric cancer patients was many folds higher (310 pM) than in controls (20 pM). This study shows for the first time that cancer patients are capable of releasing large amounts of gastrin into the gastric lumen to increase luminal hormone concentration to the level that was recently reported to stimulate the growth of H. pylori. There was no any correlation between plasma gastrin levels and gastric luminal concentration of gastrin suggesting that: 1) luminal gastrin originates from different source than plasma hormone, most probably from the cancer cells, 2) cancer cells are capable of expressing gastrin and releasing it mainly into the gastric juice and 3) the gastric cancer cells are equipped with gastrin-specific (CCK(B)) receptor so they exhibit the self-growth promoting activity in autocrine fashion. This notion is supported by direct detection of gastrin mRNA and gastrin receptor (CCK(B)-receptors) mRNA using RT-PCR in cancer tissue. To our knowledge this is the first study showing an important role of gastrin as self-stimulant of cancer cells in patients infected with H. pylori. Basal and histamine maximally stimulated acid outputs were significantly lower in gastric cancer patients than in controls despite of enhanced gastrin release, particularly in cancer patients and this might reflect the mucosal inflammatory changes (increased serum levels of proinflammtory interleukins - IL-1beta and IL-8), that are known to increase gastrin release. We conclude that: 1) H. pylori infected patients, particularly those showing CagA-seropositivity, are at greatly increased risk of development of gastric cancer, 2) H. pylori-infected cancer patients produce significantly more IL-1beta and IL-8 that might reflect an H. (ABSTRACT TRUNCATED)
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Antígenos Bacterianos , Gastrinas/fisiología , Infecciones por Helicobacter/metabolismo , Helicobacter pylori , Neoplasias Gástricas/microbiología , Adulto , Anticuerpos Antibacterianos/sangre , Proteínas Bacterianas/inmunología , Femenino , Ácido Gástrico/metabolismo , Infecciones por Helicobacter/sangre , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/patologíaRESUMEN
Seasonal accumulation of duodenal ulcer recurrences suggests that maintenance therapy could be limited to the more risky periods. We carried out a 2-year, multi-centre, randomized, double blind study in 250 patients in whom the last ulcer proved to be healed at the endoscopy on entry. One-hundred-and-twenty-six patients in group A were given pirenzepine 2 X 25 mg while 124 in group B had 2 X 50 mg daily from the beginning of January to the end of March, and from the beginning of September to the end of November for two consecutive years. Test endoscopies were performed each year at the end of February, May and November. Both groups proved to be well comparable. Thirty-five patients dropped out from group A in the first and 10 in the second year; in group B 27 and 29, respectively. As the effect did not show any dose relation, the four yearly cycles were summarized. Recurrence rate checked in May was 22.1% while in both pirenzepine protected months it was 11.3% (p less than 0.0005) and 13.4% (p less than 0.001), respectively. We conclude that pirenzepine administered in the risky seasons prevents the peak ulcer incidence and reduces the recurrence rate to a level lower than in the non-risky season. Thus pirenzepine is effective in ulcer prevention even if administered in an interrupted manner.
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Úlcera Duodenal/prevención & control , Pirenzepina/administración & dosificación , Adulto , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Cooperación del Paciente , Distribución Aleatoria , Recurrencia , Estaciones del AñoRESUMEN
Mutations of the tumour-suppressor p53 gene are a very frequent event in many human cancers. In normal cells and tissue, p53 protein has a very short half-life and attains such a low level that is not detectable immunohistochemically. In contrast, the altered forms, present in 30 to 80% of different neoplasms, are more stable and accumulate to concentration that can be detected by immunohistochemistry. Changes in the p53 gene product can be immunogenic. Thus a simple procedures as immunohistochemistry or Elisa test which stratifies cancer patients into those with and without p53 accumulation or p53 auto- antibodies can be analyzed for useful correlations with clinical and histopathological data. The p53 studies have demonstrated that in gastric carcinoma the expression of p53 protein can be properly assessed prior to surgery, using immunohistochemistry on a small tissue samples obtained during endoscopy. It has been shown that p53 assessment in this carcinoma can be helpful in identifying patients at high risk for metastatic spread, including regional lymph node involvement, and in the discrimination of those patients with especially poor prognosis. Furthermore it was demonstrated that in stomach p53 accumulation is a marker of malignancy. Thus, when combined with routine procedures, a simple test as p53 immunohistochemistry might allow better planing of appropriate treatment strategies and help in the pre-operative diagnosis of gastric carcinoma. Further studies are required to determine the clinical significance of p53 serum antibodies in gastric cancer.
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Carcinoma de Células Escamosas/genética , Neoplasias Gástricas/genética , Proteína p53 Supresora de Tumor/genética , Anticuerpos Antineoplásicos/inmunología , Carcinoma de Células Escamosas/inmunología , Genes Supresores de Tumor/genética , Humanos , Neoplasias Gástricas/inmunologíaRESUMEN
Argon plasma coagulation (APC) has been introduced for the local endoscopic treatment of gastrointestinal malignancy recently. It is mainly used as a palliative therapy, especially in case of stenosis. Despite a lot of publications concerning APC the clinical usefulness of this method in a small malignant tumors remains unclear. The patient with early diagnosed carcinoma of gastric, efficiently treated using argon plasma coagulation is described.
Asunto(s)
Coagulación con Láser/métodos , Neoplasias Gástricas/cirugía , Anciano , Endoscopía Gastrointestinal , Humanos , Masculino , Cuidados Paliativos , Neoplasias Gástricas/diagnósticoRESUMEN
The difficulties in diagnosis of abdominal actinomycosis are presented. Clinical manifestations and colonoscopy suggested malignancy. Final diagnosis was made on the basis of pathological assessment of resected sigmoid. Authors underline that in case of "negative" pathomorphological results of material obtained during endoscopy from lesions suspected, benign disease should be consider including anctinomycosis and intraoperative pathomorphological examination should be performed.
Asunto(s)
Absceso Abdominal/diagnóstico , Actinomicosis/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Radiotherapy in patients with squamous cell lung cancer produced an increase of urinary magnesium and calcium secretion. This is probably due to the cytolysis of malignant cells and shifting of the acid--base balance toward acidity values. This interpretation is justified by the significant correlation between the regression of tumor and increased secretion of the intercellular cation--magnesium.
Asunto(s)
Calcio/orina , Carcinoma de Células Escamosas/orina , Radioisótopos de Cobalto/administración & dosificación , Neoplasias Pulmonares/orina , Magnesio/orina , Adulto , Anciano , Calcio/efectos de la radiación , Carcinoma de Células Escamosas/radioterapia , Ritmo Circadiano/fisiología , Ritmo Circadiano/efectos de la radiación , Femenino , Humanos , Neoplasias Pulmonares/radioterapia , Magnesio/efectos de la radiación , Masculino , Persona de Mediana Edad , Dosificación Radioterapéutica , Factores de TiempoRESUMEN
The comparison between results of chemotherapy (ChT) and ChT plus radiotherapy (RT) was performed in the group of 124 patients with limited SCLC. After induction ChT 25% pts obtained CR, 54%-PR and 21% did not respond. In 69 pts ChT was continued and in 55 others RT was added to ChT. The number of patients in whom tumor response was observed increased significantly after addition of RT to ChT. The degree of complete response had important impact on survival time. The pts who obtained CR had significantly longer survival time than those who achieved only PR or NR. Median survival time was very similar in both groups (13 months after ChT alone and 15 months after ChT plus RT). This was also true for the groups of patients who obtained CR after completion of treatment. Achievement of complete response is the most important factor for good prognosis. RT is indicated in those patients who achieved only PR after induction ChT.