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PURPOSE: Patients with advanced pancreatic cancer have a poor prognosis and there have been no improvements in survival since the introduction of gemcitabine in 1996. Pancreatic tumors often overexpress human epidermal growth factor receptor type 1 (HER1/EGFR) and this is associated with a worse prognosis. We studied the effects of adding the HER1/EGFR-targeted agent erlotinib to gemcitabine in patients with unresectable, locally advanced, or metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomly assigned 1:1 to receive standard gemcitabine plus erlotinib (100 or 150 mg/d orally) or gemcitabine plus placebo in a double-blind, international phase III trial. The primary end point was overall survival. RESULTS: A total of 569 patients were randomly assigned. Overall survival based on an intent-to-treat analysis was significantly prolonged on the erlotinib/gemcitabine arm with a hazard ratio (HR) of 0.82 (95% CI, 0.69 to 0.99; P = .038, adjusted for stratification factors; median 6.24 months v 5.91 months). One-year survival was also greater with erlotinib plus gemcitabine (23% v 17%; P = .023). Progression-free survival was significantly longer with erlotinib plus gemcitabine with an estimated HR of 0.77 (95% CI, 0.64 to 0.92; P = .004). Objective response rates were not significantly different between the arms, although more patients on erlotinib had disease stabilization. There was a higher incidence of some adverse events with erlotinib plus gemcitabine, but most were grade 1 or 2. CONCLUSION: To our knowledge, this randomized phase III trial is the first to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine. The recommended dose of erlotinib with gemcitabine for this indication is 100 mg/d.
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Epidemiological and experimental findings suggest that the development of gastric cancer (GC) is regulated by steroid hormones. In postmenopausal women and older men, the majority of steroid hormones are produced locally in peripheral tissue through the enzymatic conversion of steroid precursors. Therefore, using reverse transcription-quantitative polymerase chain reaction analysis, the mRNA expression of genes encoding steroidogenic enzymes, including steroid sulfatase (STS), hydroxy-delta-5-steroid dehydrogenase 3 beta- and steroid delta-isomerase 1 (HSD3B1), 17ß-hydroxysteroid dehydrogenase type 7 and aromatase (CYP19A1), was investigated in primary tumoral and adjacent healthy gastric mucosa from 60 patients with GC. Furthermore, the mRNA levels for estrogen receptor α, estrogen receptor ß (ESR2) and androgen receptor (AR), along with their coregulators, including proline, glutamate and leucine rich protein 1, CREB binding protein, nuclear receptor coactivator 1 (NCOA1), nuclear receptor corepressor 1 (NCOR1) and nuclear receptor subfamily 2 group F member 1 (NR2F1), were investigated. Additionally, the association between the mRNA expression of these genes and the clinicopathological features of patients with GC was examined. Significantly decreased levels of STS, HSD3B1, ESR2, AR, NCOA1 and NCOR1 mRNA, in addition to significantly increased levels of CYP19A1 mRNA were demonstrated in tumoral tissue samples compared with adjacent healthy gastric tissue samples. Deregulated expression of these genes in the analyzed tissue samples was associated with certain clinicopathological features of GC, such as age and localization of the tumor. The results of the current study suggest that all of the genes analyzed are expressed in tumoral and adjacent healthy gastric mucosa. In addition, the results indicate that abnormal expression of STS, ESR2, AR, NCOA1 and NCOR1 may serve a role in the development and progression of GC, and may be associated with specific clinicopathological features in patients with GC.
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BACKGROUND: Total and partial gastric resection may affect the pharmacokinetics of drugs, especially orally administered a few days after surgery. Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) broadly used to treat postoperative pain, including patients after gastric resection. The aim of the research was to analyse the pharmacokinetics (PK) of orally administered ketoprofen in patients after gastrectomy. METHODS: The research was carried out on two groups of patients after total (TG; Roux-Y procedure) and partial (PG; Billroth II procedure) gastrectomy. The patients in group TG (n=15; mean [SD] age 61.86 [14.15] years; and BMI 24.20 [3.73] kg/m2) and group PG (n=5; mean [SD] age 62.40 [16.80] years; and BMI 23.98 [3.45] kg/m2) received ketoprofen in a single oral dose of 100mg. The measurement of ketoprofen plasma concentrations was made by means of the HPLC (high performance liquid chromatography) method. RESULTS: The PK parameters in group TG and PG were as follows: maximum plasma concentration (Cmax), 3.42 [0.99] and 4.66 [0.81] mg/l (p=0.0220); area under the plasma concentration-time curve from zero to infinity (AUC0-∞), 9.12 [2.78] and 9.17 [2.87] mg×h/ml (p=0.9734); area under the first moment curve from zero to the time of infinity (AUMC0-∞), 25.95 [8.52] and 26.53 [11.43] mg×h2/l (p=0.9056); time to reach maximum concentration (tmax), 0.47 [0.25] and 0.55 [0.27] h (p=0.5327), respectively. CONCLUSIONS: Lower concentrations of ketoprofen in patients after gastrectomy suggest that it might be necessary to apply higher dose of the analgesic.
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Antiinflamatorios no Esteroideos/farmacocinética , Cetoprofeno/farmacocinética , Administración Oral , Antiinflamatorios no Esteroideos/uso terapéutico , Área Bajo la Curva , Femenino , Gastrectomía/métodos , Humanos , Cetoprofeno/uso terapéutico , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/tratamiento farmacológicoRESUMEN
Steroid hormones have been shown to play a role in gastric carcinogenesis. Large amounts of steroid hormones are locally produced in the peripheral tissues of both genders. Type 5 of 17ß-hydroxysteroid dehydrogenase, encoded by the AKR1C3 gene, plays a pivotal role in both androgen and estrogen metabolism, and its expression was found to be deregulated in different cancers. In this study we measured AKR1C3 transcript and protein levels in nontumoral and primary tumoral gastric tissues, and evaluated their association with some clinicopathological features of gastric cancer (GC). We found decreased levels of AKR1C3 transcript (p < 0.0001) and protein (p = 0.0021) in GC tissues compared with the adjacent, apparently histopathologically normal, mucosa. Lower levels of AKR1C3 transcript were observed in diffuse and intestinal types of GC, whereas AKR1C3 protein levels were decreased in tumors with multisite localization, in diffuse histological type, T3, T4, and G3 grades. We also determined the effect of the histone deacetylase inhibitor sodium butyrate (NaBu) on AKR1C3 expression in EPG 85-257 and HGC-27 GC cell lines. We found that NaBu elevates the levels of both AKR1C3 transcript and protein in the cell lines we investigated. Together, our results suggest that decreased expression of AKR1C3 may be involved in development of GC and can be restored by NaBu.
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3-Hidroxiesteroide Deshidrogenasas/genética , Regulación hacia Abajo/genética , Regulación Neoplásica de la Expresión Génica/genética , Hidroxiprostaglandina Deshidrogenasas/genética , Neoplasias Gástricas/genética , Transcripción Genética/genética , Anciano , Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas , Ácido Butírico/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Neoplasias Gástricas/patologíaRESUMEN
In most populations, gastric cancer (GC) incidence is higher in men than in women, which may suggest the role of sex steroid hormones in gastric cancerogenesis. Both, androgens and estrogens can be synthetised in peripherial tissues. This process is controlled by expression of steroidogenic enzymes. Therefore, we evaluate the 17ß-hydroxysteroid dehydrogenase type 2 (HSD17B2) transcript and protein levels in gastric tumoral and nontumoral tissue. We also determined the association between HSD17B2 transcript and protein levels and some clinicopathological features in GC. We found significantly decreased levels of HSD17B2 transcript (P=0.00072) and protein (P=0.00017) in primary tumoral tissues of GC patients, as compared to nontumoral tissues. In patients above 60 years of age the amounts of HSD17B2 transcript (P=0.00044) and protein (P=0.00027) were significantly lower in tumoral than nontumoral tissues. Similarly, lower HSD17B2 levels, both in terms of the transcript and protein, were observed in tumoral tissues of male (P=0.013, P=0.0014), patients stomach (P=0.0062, P=0.045) and cardia (P=0.02, P=0.02) site of tumor, T3 (P=0.018, P=0.014) depth of invasion, N0 (P=0.017, P=0.045) lymph node metastasis, G3 (P=0.0027, P=0.014) malignancy grade. We also observed significantly reduced level of HSD17B2 transcript in tumoral tissue specimens of females (P=0.014), T4 depth of invasion (P=0.02), N3 lymph node metastasis (P=0.037) and G2 malignancy grade (P=0.045). Furthermore, diffuse GC histological types were associated with lower HSD17B2 protein level (P=0.024) than nontumoral tissues. We demonstrated that HSD17B2 transcript and protein levels are linked to some clinicopathological features in GC.
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Estradiol Deshidrogenasas/metabolismo , Regulación Enzimológica de la Expresión Génica/fisiología , Neoplasias Gástricas/enzimología , Estradiol Deshidrogenasas/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Caracteres Sexuales , Estómago/enzimología , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologíaRESUMEN
The recent ten to twenty years have seen a substantial progress in the diagnosis and treatment of breast cancer. A rapid development of various curative options has led to the improvement of treatment outcomes, while paying more and more attention to the aspects of quality of life and cosmetic effect. In our publication, we wish to outline certain trends in the development of modern treatment of breast cancer. Among topics discussed are new forms of molecular diagnostics, new approach to the idea of sentinel node biopsy, as well as new techniques for delivery of medical procedures, the increasing use of nomograms, progress in the techniques of breast conservative treatment, modern approach to occult breast lesions, the increasing use of neoadjuvant treatment and intraoperative radiotherapy.
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BACKGROUND: Tramadol/paracetamol is a fixed-dose combination prescribed for the relief of moderate to severe pain. The combination acts synergistically and guarantees the rapid onset of paracetamol and the prolonged analgesic effect of tramadol with good tolerability. These drugs are often used in various formulations in the treatment of patients with postoperative pain, e.g. after stomach resection. Gastrectomy leads to pathophysiological changes within the alimentary tract, which may affect the process of drug absorption. The aim of the research was an analysis of the pharmacokinetics of tramadol/paracetamol from effervescent and conventional tablets in patients after total gastrectomy. METHODS: The research was carried out on patients after gastrectomy with Roux-en-Y reconstruction. The patients received two tramadol/paracetamol fixed-dose combination tablets in a single orally administered dose of 75/650 mg (2 × 37.5/325 mg). The patients were subjected to one of the two study drug group with: I. effervescent tablet (ET) (n = 14; mean [SD] age, 63.4 [10.1] years; weight, 75.5 [15.3]kg; and BMI, 26.0 [4.6]kg/m(2)) and II. conventional tablet (CT) (n = 12; mean [SD] age, 66.8 [7.7] years; weight, 79.8 [17.8]kg; and BMI, 27.4 [5.3]kg/m(2)). Blood samples were collected within 10 h after the drug administration. The plasma concentrations of tramadol and paracetamol were measured with validated HPLC (high-performance liquid chromatography) method with UV detection. RESULTS: The comparison of the paracetamol and tramadol C(max) ratio for the ET group with that of the CT group gave ratios of 1.16 [90% confidence interval (CI) 1.06, 1.27] and 0.86 (90% CI 0.72, 1.02), respectively. The comparison of the paracetamol and tramadol AUC(0-t) ratio for the ET group with that of the CT group showed ratios of 0.99 (90% CI 0.88, 1.10) and 1.00 (90% CI 0.82, 1.22), respectively. The comparison of the difference for the effervescent and conventional formulation gave an estimated decrease in t(max) of 0.5 h for paracetamol and 0.13 h for tramadol. CONCLUSIONS: In view of the changes in the pharmacokinetics of paracetamol and tramadol in the patients after gastric resection for both formulations compared the conventional tablet seems to be more appropriate due to the comparable rate of absorption of both substances, higher concentrations of tramadol and comparable exposure to paracetamol.
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Acetaminofén/farmacocinética , Analgésicos/farmacocinética , Gastrectomía , Tramadol/farmacocinética , Acetaminofén/administración & dosificación , Anciano , Área Bajo la Curva , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Comprimidos , Tramadol/administración & dosificaciónRESUMEN
A decrease in ten-eleven translocation 1 (TET1) transcript and 5-Hydroxymethylcytosine (5hmC) levels has recently been demonstrated in primary gastric cancer (GC). However, little is known about TET1 protein levels in gastric tumoral and nontumoral tissue. Therefore, using reverse transcription, real-time quantitative polymerase chain reaction and western blotting analysis, we determined the TET1 transcript and protein levels in tumoral and nontumoral tissue from 38 patients with GC. We also assessed the association between the decrease in TET1 transcript and protein levels and some clinicopathological features in primary GC. We found significantly decreased levels of TET1 transcript (P=0.0023) and protein (P=0.00024) in primary tumoral tissues as compared to nontumoral tissues in patients with GC. Moreover, we also observed significantly lower amounts of TET1 transcript (P=0.03) and protein (P=0.00018) in tumoral tissues in patients aged>60. We also found significant lowered TET1 protein levels in male patients (P=0.0014), stomach (P=0.044) and cardia (P=0.013) tumor localization, T3 depth of invasion (P=0.019), N1 (P=0.012) and N3 lymph node metastasis (P=0.013) and G3 histological grade (P=0.0012). There were also significant decreases in TET1 transcript levels in female patients (P=0.042), intestinal histological types (P=0.0079) and T4 depth of invasion (P=0.037). Our results demonstrated that a decrease in TET1 transcript and protein levels is associated with some clinicopathological features in GC.
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Proteínas de Unión al ADN/genética , Mucosa Gástrica/metabolismo , Proteínas Proto-Oncogénicas/genética , Neoplasias Gástricas/metabolismo , Transcripción Genética , Factores de Edad , Anciano , Western Blotting , ADN Complementario/genética , Proteínas de Unión al ADN/biosíntesis , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxigenasas de Función Mixta , Clasificación del Tumor , Invasividad Neoplásica , Metástasis de la Neoplasia , Proteínas Proto-Oncogénicas/biosíntesis , Reacción en Cadena en Tiempo Real de la Polimerasa , Caracteres Sexuales , Estómago/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND: Sentinel lymph node biopsy (SLNB) is a standard staging procedure in breast cancer and skin melanoma patients. Radioactive colloid (RC) and blue dye are the routinely used markers for staining. The new dye used in this procedure, indocyanine green (ICG), seems to have true potential in near-infrared-guided SLNB. The aim of this study was to analyze 1-year morbidity after SLNB using RC and ICG or RC and ICG conjugated to human serum albumin (ICG:HSA) in breast cancer and skin melanoma patients. METHODS: Forty-nine patients diagnosed with breast cancer and 10 patients with skin melanoma underwent SLNB using ICG with RC and ICG:HSA with RC. A total of 47 SLNB patients without the need for additional lymphadenectomy were evaluated approximately 1 year (11-13 months) for the presence of tattoo, extremity swelling, nerve dysfunction/pain, range of motion, and stiffness. RESULTS: From the 47 patients examined, long-term morbidity was present in 3 (6.4%). In 1 patient, tattoo persisted for 11 months. Mild lymphedema was seen in 1 patient, and 1 patient exhibited minor functional deficit. CONCLUSIONS: Using ICG or ICG:HSA seems to be safe, and long-term morbidity in SLNB patients is low. However, skin discoloration may appear as it does after the use of blue dye, and an increased number of harvested nodes might be associated with an increased number of iatrogenic lymphedema.
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Verde de Indocianina/efectos adversos , Biopsia del Ganglio Linfático Centinela/efectos adversos , Biopsia del Ganglio Linfático Centinela/métodos , Espectroscopía Infrarroja Corta/métodos , Neoplasias de la Mama/patología , Femenino , Estudios de Seguimiento , Humanos , Complicaciones Posoperatorias/etiología , Albúmina Sérica , Piel/patologíaRESUMEN
There are several findings suggesting the protective role of estrogens in gastric carcinogenesis. Extragonadal 17ß-estradiol (E2) may be formed during estrone (E1) reduction to E2 by 17-ß-hydroxysteroid dehydrogenase type 1 (HSD17B1). Therefore, we studied the HSD17B1 transcript and protein levels in primary nontumoral and tumoral gastric tissue from the same 21 patients with gastric cancer (GC). We also assessed the effect of 5-Aza-2'-deoxycytidine (5-dAzaC), on the methylation status of HSD17B1 and its expression and conversion of E1 to E2 in HGC-27 and EPG 85-257 GC cells. We identified the presence of HSD17B1 transcript and protein in HGC-27 and EPG 85-257 GC cells as well as in primary nontumoral and tumoral tissues from patients with GC. Moreover, we found that 5-dAzaC significantly up-regulated the HSD17B1 transcript and protein levels, which is associated with increased conversion of E1 to E2 in HGC-27 and EPG 85-257 GC cells. The changes in HSD17B1 expression in both HGC-27 and EPG 85-257 cells were accompanied by 5-dAzaC induced DNA demethylation in the 5' flanking region. Our results demonstrated that HSD17B1 expression and its ability to convert the weak estrogen E1 to the more potent E2 can be associated with DNA methylation in the 5' flanking region in GC cells.
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Estradiol Deshidrogenasas/metabolismo , Estradiol/biosíntesis , Neoplasias Gástricas/enzimología , Anciano , Azacitidina/análogos & derivados , Azacitidina/farmacología , Línea Celular Tumoral , Metilación de ADN/efectos de los fármacos , Decitabina , Estrona/metabolismo , Femenino , Humanos , Masculino , Metilación/efectos de los fármacos , Regulación hacia ArribaRESUMEN
With the development of near-infrared (NIR) technology, real-time utility of NIR and its fluorophores has gained vast interest among surgeons of various sub-disciplines. The purpose of this review is to assess and explore the most recent developments in NIR-guided surgery in an upper gastrointestinal (UGI) surgical setting. Queries of PubMed and Medline literature databases was performed for experimental and clinical studies relevant to NIR use in the context of UGI surgery. NIR-guided UGI surgeries have been reported to be valuable in: (1) esophageal anastomosis; (2) sentinel lymph node biopsy in gastric cancer; (3) detection of liver and pancreatic tumors; and (4) detection of extra bile duct and bile duct injuries. Although NIR technology has shown tremendous promise in UGI surgery, its full clinical translation and wider adaptation remains to be seen.
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Procedimientos Quirúrgicos del Sistema Digestivo/tendencias , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/cirugía , Rayos Infrarrojos , Cirugía Asistida por Computador/tendencias , Termografía/tendencias , HumanosRESUMEN
PURPOSE: The aim of the study was to assess sentinel lymph node biopsy (SLNB) results in colon cancer (CC) regarding basic anthropometric features of the studied population and their derivatives calculated using mathematical formulas. METHODS: One hundred three SLNBs in CC have been analysed. Various indicators were calculated for every patient using mathematical formulas: BMI, Roher's index, lean body weight, body fat percentage and body weight/ideal body weight for a given height ratios using the following formulas: Broca's, Broca's ideal weight, Broca-Brugsch, Lorenz's, Potton's, Devine's, Robinson's, Miller's and Hamwi. The results were compared with accuracy, sensitivity and false negative results percentage by means of ROC curves and the test for structure indicators (for determined cut-off points). RESULTS: No statistically significant relationship between the results and patients' sex or age were found. ROC curve analysis did not reveal statistically significant relationships between the obtained results and indicators calculated on the basis of growth and weigh (all p > 0.05). The analyses of sensitivity and accuracy with determined cut-off point, in spite of differences amounting to 19 % (analysis of lean body weight/weight ratio), showed no statistical significance for any of the relationships (all p > 0.05). CONCLUSIONS: No indicator with high diagnostic and prognostic value has been found. The problem of qualifying patients for SLNB in CC in regard of the anthropometric features of the population and body composition assessment formulas remains open and requires further analysis on larger populations.
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Composición Corporal/fisiología , Índice de Masa Corporal , Neoplasias del Colon/patología , Estadificación de Neoplasias/métodos , Biopsia del Ganglio Linfático Centinela/métodos , Adulto , Anciano , Antropometría , Estudios de Cohortes , Estudios de Evaluación como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Teóricos , Invasividad Neoplásica , Polonia , Curva ROC , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
AIM: This paper describes our experience of 20 cases identified in the FEA vacuum core biopsy. BACKGROUND: Screening mammography has contributed to the increased recognition of early cancer, premalignant and preinvasive breast lesions. A premalignant lesion called FEA (flat epithelial atypia), although rarely recognized as the only lesion in the core biopsy, is a major challenge in clinical proceedings. Increasing recognition is associated with an increasing use of the vacuum core biopsy as a tool for verifying nonpalpable lesions identified by mammography, and suspected of being breast cancer. MATERIALS AND METHODS: Of 4326 mammotome biopsies performed at our institution in 2000-2006, FEA was diagnosed in 20 patients (0.46%). These patients underwent surgery for reexcsion. Data were collected for clinical, radiological and pathological findings to assess factors associated with the underestimation of invasive lesions. RESULTS: Among 20 patients with FEA diagnosis, the mean age was 59.6, range 52-71. When compared to the ADH group (mean age 55.45), the FEA patients were found to be statistically significantly older (p = 0.0002). Two patients 2/20 (10%) showed underestimation, with invasive cancer on the final pathology were G1 tubular cancer T1b, and G2 lobular cancer T1a. CONCLUSION: Although FEA is rarely diagnosed as the only lesion in a core biopsy, the ever more common use of this diagnostic technique forces us to establish a clear clinical practice. The problem is the underestimation of invasive lesions in the case of primary diagnosis of FEA. It seems that some percent of these cases can be identified by certain radiological or pathological features, thus helping implement appropriate clinical management.
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BACKGROUND: With the introduction of mammography screening, we are more often dealing with the diagnosis of precancerous and preinvasive breast lesions. An increasing number of patients are observed to show a premalignant change of ADH (atypical ductal hyperplasia). It also involves a wider use of the vacuum assisted core biopsy as a tool for verifying nonpalpable changes identified by mammography. AIM: This paper describes our experience of 134 cases of ADH diagnosed at Mammotome(®) vacuum core needle biopsy. MATERIAL AND METHODS: Of 4326 mammotomic biopsies performed at our institution in 2000-2006, ADH was diagnosed in 134 patients (3.1%). Patients underwent surgery to remove the suspected lesion. All histopathological blocks were again reviewed by one pathologist. Clinical, radiological and pathological data were collected for statistical evaluation. RESULTS: Underestimation of invasive changes occurred in 12 patients (9%). The only clinicopathologic feature of statistical significance radiologically and pathologically was the presence of radial scar in the mammography. CONCLUSIONS: More frequent diagnosis of precancerous changes in the mammotomic breast biopsy forces us to establish a clear clinical practice. The problem is the underestimation of invasive changes. The occurrence of radial scar on mammography for diagnosis of the presence of ADH increases the risk of invasive changes.
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Ever since Kitai first performed fluorescent navigation of sentinel lymph nodes (SLNs) using indocyanine green (ICG) dye with a charge-couple device and light emitting diodes, the intraoperative use of near infrared fluorescence has served a critical role in increasing our understanding in various fields of surgical oncology. Here the authors review the emerging role of the ICG fluorophore in the development of our comprehension of the lymphatic system and its use in SLN mapping and biopsy in various cancers. In addition, they introduce the novel role of ICG-guided video angiography as a new intraoperative method of assessing microvascular circulation. The authors attempt to discuss the promising potential in addition to assessing several challenges and limitations in the context of specific surgical procedures and ICG as a whole. PubMed and Medline literature databases were searched for ICG use in clinical surgical settings. Despite ICG's significant impact in various fields of surgical oncology, ICG is still in its nascent stages, and more in-depth studies need to be carried out to fully evaluate its potential and limitations.
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Colorantes Fluorescentes , Verde de Indocianina , Neoplasias/cirugía , Servicio de Oncología en Hospital/tendencias , Biopsia del Ganglio Linfático Centinela/tendencias , Angiografía/métodos , Angiografía/tendencias , Humanos , Periodo Intraoperatorio , Biopsia del Ganglio Linfático Centinela/métodosRESUMEN
PURPOSE: Although the importance of sentinel node biopsy (SNB) in colon cancer (CC) has not been clearly established, this method is proposed as potentially enabling more appropriate staging by means of immunohistochemistry (IHS). The aim of the study was to evaluate the SNB method used in CC treatment taking into consideration the results of the IHS examination. MATERIALS AND METHODS: In the period from May 2005 to September 2010 in the 1st Department of Surgical Oncology and General Surgery, Wielkopolska Cancer Centre, 100 SNB in CC were performed. Sentinel nodes (SN) were identified intraoperatively with the use of Patent Blue dye. In the case of negative hematoxylin and eosin staining, the SN material was subjected to immunohistochemical examination. Finally, the histopathological findings of sentinel and non-sentinel lymph nodes were compared with the results of the immunohistochemical staining. RESULTS: At least one SN was identified in 99 of 100 patients (99%). The SN was the only place of metastases in 12.1% (12/99) of the patients. The accuracy of SNB in determining the regional lymph node status was 93.9% (93/99). The sensitivity of the method was 83.3% (30/36). The false-negative rate amounted to 16.7% (6/36). Upstaging obtained by the implementation of the immunohistochemical method was 10% (7/70). CONCLUSIONS: The application of the immunohistochemical staining enables upstaging of some patients, potentially benefiting from adjuvant chemotherapy. For full and definitive assessment of SNB in CC, further research is required especially in terms of additional factors determining a patient's eligibility for this procedure.
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Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Biopsia del Ganglio Linfático Centinela , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Factibilidad , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios ProspectivosRESUMEN
Gastrectomy leads to pathophysiological changes within the alimentary tract, which may affect drug absorption and pharmacokinetic parameters (PK). The need to apply orally administered analgesics in this group of patients is often related with alternative application of currently available generic products. Thus, from the clinical point of view it is necessary to evaluate the PK of these drugs to confirm their equivalence. The aim of the study was therefore an analysis of the pharmacokinetics of paracetamol from two generic products in patients after total gastric resection. The research was carried out on two groups of patients after gastrectomy with Roux-en-Y reconstruction (n = 30; mean [SD] age, 63.0 [11.5] years; weight, 67.6 [13.7] kg; and height, 166.4 [9.1] cm). The patients received paracetamol in a single orally administered dose of 1,000 mg. Blood samples were collected within 6 h of drug administration. The concentration of paracetamol and paracetamol glucuronide in the blood plasma was marked by means of a validated high-pressure liquid chromatography with ultraviolet detection (HPLC-UV). The main PK for paracetamol in group 1 (n = 17) and 2 (n = 13) were as follows: C(max), 9.46 (3.66) and 12.79 (5.32) µg/ml, respectively (p = 0.0517); AUMC(0-t), 77.64 (30.37) and 51.01 (15.76) µg h(2)/ml (p = 0.0046); AUC(0-inf), 41.61 (23.52) and 30.28 (9.74) µg h/ml (p = 0.0862); t(max), 1.68 (0.63) and 0.50 (0.25) h (p < 0001). The obtained C(max) and AUC values in patients after gastrectomy were reduced in comparison with healthy subjects. Total gastrectomy therefore affected the pharmacokinetics of paracetamol administered in tablets. In our patients, we also observed significant differences between the PK of paracetamol and two generic preparations. These two drugs can thus be used interchangeably, but with caution.
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Acetaminofén/farmacocinética , Medicamentos Genéricos/farmacocinética , Gastrectomía , Dolor Postoperatorio/metabolismo , Acetaminofén/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Gastrectomía/efectos adversos , Gastrectomía/métodos , Humanos , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/tratamiento farmacológico , ComprimidosRESUMEN
BACKGROUND: Sentinel node biopsy (SNB) is a gold standard in staging of early breast cancer. Nowadays, routine mapping of lymphatic tract is based on two tracers: human albumin with radioactive technetium, with or without blue dye. Recent years have seen a search for new tracers to examine sentinel node as well as lymphatic network. One of them is indocyanine green (ICG) visible in infrared light. AIM: The aim of this study is to evaluate clinical usage of ICG in comparison with standard tracer, i.e. nanocoll, in SNB of breast cancer patients. MATERIALS AND METHODS: In the 1st Department of Surgical Oncology and General Surgery, Greater Poland Cancer Centre, Poznan, 13 female breast cancer patients have benn operated since September 2010. All these patients had sentinel node biopsy with nanocoll (human albumin with radioactive technetium), and with indocyanine green. The feasibility of this new method was assessed in comparison with the standard nanocoll. RESULTS: A lymphatic network between the place of injection of ICG and sentinel node was seen in infrared light. An area where a sentinel node was possibly located was confirmed by gamma probe. Sensitivity of this method was 100%. CONCLUSION: SNB using ICG is a new, promising diagnostics technique. This procedure is not without drawbacks; nevertheless it opens new horizons in lymphatic network diagnostics.
RESUMEN
Malignant ascites is a common manifestation of advanced cancers, and treatment options are limited. The trifunctional antibody catumaxomab (anti-epithelial cell-adhesion molecule x anti-CD3) represents a targeted immunotherapy for the intraperitoneal (i.p.) treatment of malignant ascites secondary to epithelial cancers. In this phase II/III trial (EudraCT 2004-000723-15; NCT00836654), cancer patients (n = 258) with recurrent symptomatic malignant ascites resistant to conventional chemotherapy were randomized to paracentesis plus catumaxomab (catumaxomab) or paracentesis alone (control) and stratified by cancer type (129 ovarian and 129 nonovarian). Catumaxomab was administered as an i.p. infusion on Days 0, 3, 7 and 10 at doses of 10, 20, 50 and 150 mug, respectively. The primary efficacy endpoint was puncture-free survival. Secondary efficacy parameters included time to next paracentesis, ascites signs and symptoms and overall survival (OS). Puncture-free survival was significantly longer in the catumaxomab group (median 46 days) than the control group (median 11 days) (hazard ratio = 0.254: p < 0.0001) as was median time to next paracentesis (77 versus 13 days; p < 0.0001). In addition, catumaxomab patients had fewer signs and symptoms of ascites than control patients. OS showed a positive trend for the catumaxomab group and, in a prospectively planned analysis, was significantly prolonged in patients with gastric cancer (n = 66; 71 versus 44 days; p = 0.0313). Although adverse events associated with catumaxomab were frequent, they were manageable, generally reversible and mainly related to its immunologic mode of action. Catumaxomab showed a clear clinical benefit in patients with malignant ascites secondary to epithelial cancers, especially gastric cancer, with an acceptable safety profile.
Asunto(s)
Anticuerpos Biespecíficos/uso terapéutico , Ascitis/complicaciones , Ascitis/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/complicaciones , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Esquema de Medicación , Humanos , Persona de Mediana Edad , ParacentesisRESUMEN
BACKGROUND: Treatment of breast fibroadenoma remains a subject of clinical discussion. Recommended methods include clinical observation or surgical excision of the lesion. The procedure involves hospitalisation and anaesthesia, leaving a scar on the breast. AIM: The aim of this study was to present the Centre's experience in removing lesions radiologically suspicious of fibroadenoma by means of an ultrasound-guided vacuum-assisted core-needle biopsy as an alternative to a classical surgery. MATERIALS AND METHODS: Between March 2007 and April 2010, 196 ultrasound-guided vacuum-assisted biopsies were performed in the Mammotome Biopsy Laboratory of the 1st Surgical Oncology and General Surgery Department at the Greater Poland Cancer Centre in Poznan. The procedure was delivered to female patients aged 17-91 years (mean 40.8, median 39). Qualified for removal were ultrasound identified lesions described as fibroadenomas. RESULTS: The average size of excised lesions according to pre-biopsy ultrasound image was 13.53 ± 8.92 mm (median 11 mm, range 4-60 mm). In 184 cases (93.9%), benign lesions were found in the final histopathologic examination. Pre-cancer lesions were found in 10 cases, and invasive lesions in two cases. Overall, after follow-up ultrasound examination, four patients were qualified for subsequent surgical resection of lesions that had been left behind. CONCLUSION: Vacuum core-needle biopsy is an effective tool enabling removal of breast fibroadenomas. It combines features of a lesion resection and histopathologic material collection providing an access with minimum invasiveness.