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BACKGROUND: Helicobacter pylori (H. pylori) is a widespread microorganism related to gastric adenocarcinoma (AC). In contrast, it has been reported that an inverse association exists between H. pylori infection and esophageal carcinoma. The mechanisms underlying this supposedly protective effect remain controversial. AIM: To determine the prevalence of H. pylori infection in esophageal carcinoma patients, we performed a retrospective observational study of esophageal tumors diagnosed in our hospital. METHODS: We retrospectively reviewed the prevalence of H. pylori infection in a cohort of patients diagnosed with esophageal carcinoma. Concomitant or previous proton pump inhibitor (PPI) usage was also recorded. RESULTS: A total of 89 patients with esophageal carcinoma (69 males, 77.5%), with a mean age of 66 years (range, 26-93 years) were included. AC was the most frequent pathological variant (n = 47, 52.8%), followed by squamous cell carcinoma (n = 37, 41.6%). Fourteen ACs (29.8%) originated in the gastroesophageal junction and 33 (70.2%) in the esophageal body. Overall, 54 patients (60.7%) presented at stages III and IV. Previous H. pylori infection occurred only in 4 patients (4.5%), 3 with AC (6.3% of all ACs) and 1 with squamous cell carcinoma (2.7% of all squamous cell tumors). All patients with previous H. pylori infection had stage III-IV. Only one patient had received prior H. pylori eradication therapy, whereas 86 (96.6%) had received previous or concomitant PPI treatment. CONCLUSION: In our cohort of patients, and after histologic evaluation of paraffin-embedded primary tumors, we found a very low prevalence of previous H. pylori infection. We also reviewed the medical history of the patients, concluding that the majority had received or were on PPI treatment. The minimal prevalence of H. pylori infection found in this cohort of patients with esophageal carcinoma suggests a protective role.
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Neoplasias Esofágicas , Infecciones por Helicobacter , Helicobacter pylori , Inhibidores de la Bomba de Protones , Humanos , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/microbiología , Masculino , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/tratamiento farmacológico , Estudios Retrospectivos , Femenino , Anciano , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/patogenicidad , Persona de Mediana Edad , Prevalencia , Anciano de 80 o más Años , Adulto , Inhibidores de la Bomba de Protones/uso terapéutico , Adenocarcinoma/epidemiología , Adenocarcinoma/microbiología , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/microbiología , Estadificación de NeoplasiasRESUMEN
AIM: To determinate molecular changes in the downstream epidermal growth factor receptor signaling pathway using serial liquid biopsies in patients with metastatic colorectal tumors (mCRC) under anti-angiogenic treatment. PATIENTS AND METHODS: Determination of RAS mutation in primary tissue samples from colorectal tumors was performed in the 23 patients included in the study at diagnosis using quantitative-polymerase chain reaction. Sequential mutations were studied in circulating tumor (ct) DNA obtained from plasma samples. RESULTS: Twenty-three patients with RAS-mutated primary tumors were included. In the first ctDNA determination, 17 of these patients were found to have wild-type RAS status. Remarkably, three out of these 17 wild-type cases changed to RAS-mutated in subsequent ctDNA assays. CONCLUSION: Serial liquid biopsies in patients with mCRC might be a useful tool for identifying changes in the RAS mutation status in patients who had undergone previous anti-angiogenic therapy. The understanding of these changes might help to better define the landscape of mCRC and be the path to future randomized studies.
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Adenocarcinoma , ADN Tumoral Circulante , Neoplasias Colorrectales , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , ADN Tumoral Circulante/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Humanos , Biopsia Líquida , MutaciónRESUMEN
AIM: VITAL, a phase II single-arm study, aimed to evaluate efficacy and safety of panitumumab addition to 5-fluorouracil (5-FU), mitomycin-C (MMC) and radiotherapy (RT) in patients with localized squamous cell carcinoma of the anal canal (SCCAC). METHODS: Adult, treatment-naïve SCCAC patients (Stage T2-T4, any N, M0) and ECOG-PS ≤2, received panitumumab (6 mg/kg, day 1 and Q2W; 8 weeks), 5-FU (1000 mg/m2 /d, days 1-4 and 29-32), MMC (10 mg/m2 , days 1 and 29) and RT 45 Gy (1.8 Gy/fraction) to the primary tumor and mesorectal, iliac and inguinal lymph nodes, plus 10-15 Gy boost dose to the primary tumor and affected lymph nodes. The primary objective was disease free survival rate (DFS) at 3-years (expected 3-year DFS rate: 73.7 ± 12%). RESULTS: Fifty-eight patients (31 women; median age: 59 years; ECOG-PS 0-1:98%; TNM II [29%] (T2 or T3/N0/M0)/IIIA (T1-T3/N1/M0 or T4/N0/M0) [21%]/IIIB (T4/N1/M0 or any T/N2 or N3/M0) [47%]/nonevaluable [4%]) were included. The median follow-up was 45 months. The 3-year DFS rate was 61.1% (95% CI: 47.1, 72.4). The 3-year overall survival rate was 78.4% (95% CI: 65.1, 87.1). Eighteen patients (31.0%) required a colostomy within 2 years posttreatment. Grade 3-4 toxicities were experienced by 53 (91%) patients. Most common grade 3-4 treatment-related events were radiation skin injury (40%) and neutropenia (24%). No toxic deaths occurred. Improved efficacy in colostomy-free survival and complete response rate was observed in human papilloma virus positive patients. CONCLUSIONS: Panitumumab addition to MMC-5FU regimen in SCCAC patients increases toxicity and does not improve patients' outcomes. RT plus MMC-5FU remains the standard of care for localized SCCAC patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Ano/terapia , Quimioradioterapia Adyuvante/efectos adversos , Terapia Neoadyuvante/efectos adversos , Neutropenia/epidemiología , Radiodermatitis/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Ano/mortalidad , Quimioradioterapia Adyuvante/métodos , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Mitomicina/efectos adversos , Terapia Neoadyuvante/métodos , Neutropenia/diagnóstico , Neutropenia/etiología , Panitumumab/administración & dosificación , Panitumumab/efectos adversos , Proctectomía , Radiodermatitis/diagnóstico , Radiodermatitis/etiología , Índice de Severidad de la Enfermedad , Tasa de SupervivenciaAsunto(s)
Neoplasias Pancreáticas/mortalidad , Anciano , Anciano de 80 o más Años , Paclitaxel Unido a Albúmina/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Comorbilidad , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Diabetes Mellitus/epidemiología , Dieta , Resistencia a Antineoplásicos , Detección Precoz del Cáncer , Fluorouracilo/administración & dosificación , Predisposición Genética a la Enfermedad , Humanos , Irinotecán/administración & dosificación , Leucovorina/administración & dosificación , Terapia Neoadyuvante , Metástasis de la Neoplasia , Oxaliplatino/administración & dosificación , Cuidados Paliativos , Pancreatectomía , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/etiología , Neoplasias Pancreáticas/terapia , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Pronóstico , Radiocirugia , Factores de Riesgo , España/epidemiología , GemcitabinaRESUMEN
BACKGROUND: Oxaliplatin is a chemotherapy agent active against digestive tumors. Peripheral neuropathy is one of the most important dose-limiting toxicity of this drug. It occurs in around 60-80% of the patients, and 15% of them develop severe neuropathy. The pathophysiology of oxaliplatin neurotoxicity remains unclear. SCN9A is a gene codifying for a subtype sodium channel (type IX, subunit α) and mutations in this gene are involved in neuropathic perception. In this study we investigated whether SCN9A genetic variants were associated with risk of neurotoxicity in patients diagnosed of cancer on treatment with oxaliplatin. METHODS: Blood samples from 94 patients diagnosed of digestive cancer that had received oxaliplatin in adjuvant or metastatic setting were obtained from three hospitals in Madrid. These patients were classified into two groups: "cases" developed oxaliplatin-induced grade 3-4 neuropathy (n = 48), and "controls" (n = 46) had no neuropathy or grade 1. The neuropathy was evaluated by an expert neurologist and included a clinical examination and classification according to validated neurological scales: National Cancer Institute Common Toxicity Criteria (NCI-CTC), Oxaliplatin-Specific Neurotoxicity Scale (OSNS) and Total Neuropathy score (TNS). Genotyping was performed for 3 SCN9A missense polymorphisms: rs6746030 (R1150W), rs74401238 (R1110Q) and rs41268673 (P610T), and associations between genotypes and neuropathy were evaluated. RESULTS: We found that SCN9A rs6746030 was associated with protection for severe neuropathy (OR = 0.39, 95% CI = 0.16-0.96; p = 0.041). Multivariate analysis adjusting for diabetes provided similar results (p = 0.036). No significant differences in neuropathy risk were detected for rs74401238 and rs41268673. CONCLUSION: SCN9A rs6746030 was associated with protection for severe oxaliplatin-induced peripheral neuropathy. The validation of this exploratory study is ongoing in an independent series.
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Antineoplásicos/efectos adversos , Biomarcadores de Tumor/genética , Neoplasias del Sistema Digestivo/tratamiento farmacológico , Canal de Sodio Activado por Voltaje NAV1.7/genética , Compuestos Organoplatinos/efectos adversos , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Polimorfismo Genético/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Digestivo/patología , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Oxaliplatino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/genética , Pronóstico , Tasa de SupervivenciaRESUMEN
Cancer stem cells (CSCs) are a very heterogeneous subpopulation of "stem-like" cancer cells that have been identified in many cancers, including leukemias and solid tumors. It is believed that CSCs drive tumor growth, malignant behavior and are responsible for the initiation of metastatic spread. In addition, CSCs have been implicated in chemotherapy and radiotherapy resistance. Current evidence supports the theory that CSCs share at least two main features of normal stem cells: self-renewal and differentiation, properties that contribute to tumor survival even in the presence of aggressive chemotherapy; however, the mechanism(s) governing the unique biology of CSCs remain unclear. In the field of gastrointestinal cancer, where we face very low survival rates across different tumor types, unraveling the role of CSCs in gastrointestinal tumors should improve our knowledge of cancer biology and chemoresistance, ultimately benefiting patient survival. Towards this end, much effort is being invested in the characterization of CSCs as a means of overcoming drug resistance and controlling metastatic spread. In this review we will cover the concept of CSCs, the current evidence for CSCs in gastrointestinal tumors and future research directions.
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Neoplasias Gastrointestinales/patología , Células Madre Neoplásicas , Animales , Diferenciación Celular , Autorrenovación de las Células , Quimioradioterapia , Resistencia a Antineoplásicos , Neoplasias Gastrointestinales/terapia , HumanosRESUMEN
Oxaliplatin is one of the main drugs used in digestive tumors treatment. Peripheral neuropathy is a well-recognized dose-limiting toxicity of OXL. Two types of neuropathy have been described with this agent: acute or transient and chronic or persistent, with different etiology, clinical manifestations and prognosis. This paper is an exhaustive review about the main aspects of oxaliplatin induced peripheral neuropathy, focus in clinical features, treatment, prevention strategies and future approach.
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Antineoplásicos/efectos adversos , Neoplasias del Sistema Digestivo/complicaciones , Compuestos Organoplatinos/efectos adversos , Enfermedades del Sistema Nervioso Periférico/etiología , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Neoplasias del Sistema Digestivo/tratamiento farmacológico , Humanos , Incidencia , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Oxaliplatino , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/epidemiología , Enfermedades del Sistema Nervioso Periférico/prevención & control , Enfermedades del Sistema Nervioso Periférico/terapia , Factores de RiesgoRESUMEN
Lung cancer is currently one of the most common malignancies in the world and peritoneal involvement is rare in these types of tumors. Clinical manifestations of these metastases are also uncommon and include intestinal perforation and obstruction. The present study reviewed certain aspects of the complication of peritoneal involvement and illustrated it with four cases of patients that were diagnosed with primary lung carcinoma and secondary peritoneal carcinomatosis (PC). The outcome of these patients is poor and they rarely respond to chemotherapy. Surgery is successful in the majority of cases.
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Malignant fibrous histiocytoma is an aggressive tumor, the most common soft-tissue sarcoma of adult age. It is usually located in the extremities and retroperitoneum, and very rarely there is skeletal involvement. Surgery is the preferred treatment in early disease; in advanced disease, chemotherapy is the main therapeutic strategy. We present a 25-year-old female patient diagnosed with a vertebral mass in T5 with a severely compromised spinal cord. She underwent surgical decompression and the pathological findings were consistent with malignant fibrous histiocytoma. After several surgical treatments she had pulmonary progression and was therefore started on chemotherapy. She had a very poor response to most of the administered regimens until she initiated trabectedin 1 mg/m 2 every three weeks. She showed a significant improvement with a major response of the lung metastases. This report indicates that trabectedin is an active drug in advanced, previously treated metastatic malignant fibrous histiocytoma.
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Antineoplásicos Alquilantes/uso terapéutico , Dioxoles/uso terapéutico , Histiocitoma Fibroso Maligno/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias de la Columna Vertebral/tratamiento farmacológico , Tetrahidroisoquinolinas/uso terapéutico , Adulto , Antineoplásicos Alquilantes/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Dioxoles/administración & dosificación , Esquema de Medicación , Femenino , Histiocitoma Fibroso Maligno/química , Histiocitoma Fibroso Maligno/diagnóstico , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/secundario , Imagen por Resonancia Magnética , Neoplasias de la Columna Vertebral/química , Neoplasias de la Columna Vertebral/diagnóstico , Tetrahidroisoquinolinas/administración & dosificación , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/patología , Tomografía Computarizada por Rayos X , TrabectedinaRESUMEN
Cancer is a global problem that accounts for almost 13% of deaths worldwide, a number similar to the 7 million deaths each year from HIV/AIDS, TB and malaria combined According to Globocan it is estimated that by 2020, there will be between 15 and 17 million new cases of cancer every year, 60% of which will be in developing countries. Moreover, the survival rates in these regions are often half those of developed countries. However, cancer is potentially the most preventable disease; with current resources, one-third of tumors could be preventable, and another one-third of newly diagnosed cancer patients could experience increased survival or early-stage detection. There have been proposed several strategies and programs to ameliorate cancer prevention and treatment in less developed countries. If all these proposed strategies are taken into consideration, worldwide cancer care, control and survival in low-income countries may improve in the years to come.
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Países en Desarrollo , Neoplasias/epidemiología , Humanos , Neoplasias/etiología , Neoplasias/prevención & controlRESUMEN
Surgical resection remains the only option of cure for patients with colorectal liver metastases, and no patient should be precluded from surgery. There is much controversy not only regarding the most appropriate therapeutic approach in the neoadjuvant setting but also after surgery is performed. Many patients will experience early relapses but others will be long survivors. We need to establish reliable prognostic and predictive factors to offer a tailored treatment. Several prognostic factors after metastasectomy have been identified: high C-reactive protein levels, a high neutrophil-lymphocyte ratio, elevated neutrophil count and low serum albumin are related to a worst outcome. Elevated CEA and Ki 67 levels, intrahepatic and perihepatic lymph node invasion are also some of the markers related to a worst outcome. In contrast, the administration of preoperative chemotherapy has been associated with a better prognosis after hepatectomy. The administration of adjuvant chemotherapy should be done taking in consideration these factors. Regarding predictive factors, determination of ERCC1, TS, TP and DPD and UGT1 polymorphisms assessment could be considered prior to chemotherapy administration. This would avoid treatment related toxicities and increase this population quality of life.
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Neoplasias Colorrectales/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Quimioterapia Adyuvante , Neoplasias Colorrectales/tratamiento farmacológico , Humanos , Ganglios Linfáticos/patología , Medicina de Precisión , Pronóstico , Resultado del TratamientoRESUMEN
BACKGROUND: Squamous cell carcinoma (SCC) is the predominant histological type in men, and adenocarcinoma is the most common subtype in women in the world. The incidence of SCC is decreasing in men, while the incidence of adenocarcinoma (AC) is stable or slightly increasing in western countries. There is active research on the AC subtype but SCC remains poorly studied. CONCLUSIONS: In this review, we have studied different aspects of the SCC subtype, including epidemiology, clinical features, pathology, molecular biology markers, and new therapeutic targets, treatments and prognosis implications.
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Carcinoma de Células Escamosas , Neoplasias Pulmonares , Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Humanos , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , PronósticoRESUMEN
Changes in magnetic resonance imaging (MRI) during neoadjuvant chemotherapy (NAC) have been reported as predictive of pathology outcome in triple-negative and HER2-positive breast cancer. The purpose of our study was to evaluate the relevance of breast cancer subtype for MRI response in 24 women before and during NAC in our centre. Our results show that a reduction greater than 23% is associated with a pathological complete response (pCR) in Her-2-positive and ER-negative/Her2-negative breast cancer, and suggest a trend correlation between higher ADC values and pCR in these subtypes in comparison with ER-positive/Her2-negative breast cancers. Higher proliferating tumours respond better to chemotherapy and our study suggests that changes in MRI during NAC are predictive of pCR in these breast cancer subtypes.
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Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Imagen por Resonancia Magnética , Terapia Neoadyuvante , Estadificación de Neoplasias , Receptor ErbB-2/metabolismoRESUMEN
PURPOSE: Management of locally advanced rectal cancer (RC) consists of neoadjuvant chemoradiotherapy (CRT) with fluoropyrimidines, followed by total mesorectal excision. We sought to evaluate the expression of selected genes, some of which were derived from a previous undirected SAGE (serial analysis of gene expression)-based approach, before and after CRT, to identify mechanisms of resistance. METHODS: This retrospective cohort study included 129 consecutive patients. Quantitative polymerase chain reaction of 53 candidate genes was performed on the biopsy specimen before treatment and on the surgical specimen after CRT. A paired-samples t test was performed to determine genes that were significantly changed after CRT. The result was correlated with patients' disease-free survival. RESULTS: Twenty-two genes were significantly upregulated, and two were significantly downregulated. Several of the upregulated genes have roles in cell cycle control; these include CCNB1IP1, RCC1, EEF2, CDKN1, TFF3, and BCL2. The upregulation of TFF3 was associated with worse disease-free survival on multivariate analyses (hazard ratio, 2.64; P=.027). Patients whose surgical specimens immunohistochemically showed secretion of TFF3 into the lumen of the tumoral microglands had a higher risk of relapse (hazard ratio, 2.51; P=.014). In vitro experiments showed that DLD-1 cells stably transfected with TFF3 were significantly less sensitive to 5-fluorouracil and showed upregulation of genes involved in the transcriptional machinery and in resistance to apoptosis. CONCLUSION: Upregulation of TFF3 after CRT for RC is associated with a higher risk of relapse. The physiological role of TFF3 in restoring the mucosa during CRT could be interfering with treatment efficacy. Our results could reveal not only a novel RC prognostic marker but also a therapeutic target.
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Adenocarcinoma/metabolismo , Quimioradioterapia Adyuvante , Proteínas de Neoplasias/metabolismo , Recurrencia Local de Neoplasia , Péptidos/metabolismo , Neoplasias del Recto/metabolismo , Neoplasias del Recto/terapia , Adenocarcinoma/genética , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Línea Celular Tumoral , Quimioradioterapia Adyuvante/métodos , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos/genética , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Proteínas de Neoplasias/genética , Péptidos/genética , Reacción en Cadena de la Polimerasa , Pronóstico , Análisis por Matrices de Proteínas/métodos , Neoplasias del Recto/genética , Estudios Retrospectivos , Transfección/métodos , Factor Trefoil-3 , Regulación hacia Arriba , Adulto JovenRESUMEN
Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. More than 30% patients present with metastases at diagnoses and will require systemic chemotherapy. In recent years many anti-EGFR targets have been developed. Among them, panitumumab, a fully human IgG2 monoclonal antibody has shown important benefits in the treatment of this disease.
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We present the case of a 70-year-old woman with emphysematous cystitis. She was a diabetic patient and she was on chemotherapy treatment for a breast cancer. She complaint of severe asthenia and pain in her right lower extremity, but no fever or urinary symptoms. A computed tomography (CT) scan was suggestive of severe emphysematous cystitis. Emphysematous cystitis is a rare clinically entity, more commonly seen in diabetic, immunocompromised patients. A conservative treatment approach using antibiotics and bladder catheterization is typically successful, with a complication rate less than 20%.
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A 40-year-old woman with liver metastasis resulting from colorectal adenocarcinoma suffered from a severe hypersensitivity reaction to cetuximab. She also experienced grade 3 skin toxicity. The administration of cetuximab was suspended, and she was offered panitumumab as an alternative treatment. Whereas she did not experience another infusion reaction, her skin rash worsened with the administration of panitumumab, a fully human anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (MAb).
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Adenocarcinoma/terapia , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Neoplasias Colorrectales/terapia , Receptores ErbB/inmunología , Adulto , Anticuerpos Monoclonales/uso terapéutico , Esquema de Medicación , Receptores ErbB/antagonistas & inhibidores , Femenino , Humanos , Panitumumab , Enfermedades de la Piel/inducido químicamenteRESUMEN
Male breast cancer accounts for around 1% of all breast cancer cases, but the incidence has increased over the past 25 years. The rarity of this entity precludes prospective randomized clinical trials. Although breast carcinoma in both genders share certain characteristics, notable differences have emerged. Familial cases usually have BRCA2 rather than BRCA1 mutations. Klinefelter syndrome is the strongest risk factor for developing male breast carcinoma. Men tend to be diagnosed at an older age than women. Presentation is usually a painless lump, but is often late, with more than 40% of individuals having stage III or IV disease. When survival is adjusted for age at diagnosis and stage of disease, outcomes for male and female patients with breast cancer is similar. Surgery is usually mastectomy with axillary clearance or sentinel node biopsy. Because 90% of tumors are hormonal receptor positive, tamoxifen is standard adjuvant therapy. Indications for radiotherapy and chemotherapy are similar to female breast cancer. For metastatic disease, hormonal therapy is the main treatment, but chemotherapy can also provide palliation.
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Neoplasias de la Mama Masculina/genética , Neoplasias de la Mama Masculina/terapia , Antineoplásicos/uso terapéutico , Ensayos Clínicos como Asunto , Terapia Combinada , Femenino , Humanos , Masculino , Mastectomía , Radioterapia , Factores de RiesgoRESUMEN
BACKGROUND: KRAS mutations in colorectal cancer primary tumors predict resistance to anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody therapy in patients with metastatic colorectal cancer, and thus represent a true indicator of EGFR pathway activation status. METHODOLOGY/PRINCIPAL FINDINGS: KRAS mutations were retrospectively studied using polymerase chain reactions and subsequent sequencing of codons 12 and 13 (exon 2) in 110 patients with metastatic colorectal tumors. These studies were performed using tissue samples from both the primary tumor and their related metastases (93 liver, 84%; 17 lung, 16%). All patients received adjuvant 5-Fluorouracil-based polychemotherapy after resection of metastases. None received anti-EGFR therapy. Mutations in KRAS were observed in 37 (34%) of primary tumors and in 40 (36%) of related metastases, yielding a 94% level of concordance (kappa index 0.86). Patients with primary tumors possessing KRAS mutations had a shorter disease-free survival period after metastasis resection (12.0 vs 18.0 months; P = 0.035) than those who did not. A higher percentage of KRAS mutations was detected in primary tumors of patiens with lung metastases than in patients with liver metastases (59% vs 32%; p = 0.054). To further evaluate this finding we analyzed 120 additional patients with unresectable metastatic colorectal cancer who previously had their primary tumors evaluated for KRAS mutational status for clinical purposes. Separately, the analysis of these 120 patients showed a tendency towards a higher degree of KRAS mutations in primary tumors of patients with lung metastases, although it did not reach statistical significance. Taken together the group of 230 patients showed that KRAS was mutated significantly more often in the primary tumors of patients with lung metastases (57% vs 35%; P = 0.006). CONCLUSIONS/SIGNIFICANCE: Our results suggest a role for KRAS mutations in the propensity of primary colorectal tumors to metastasize to the lung.
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Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundario , Mutación/genética , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Proteínas Proto-Oncogénicas p21(ras)RESUMEN
BACKGROUND: Venous thromboembolism (VTE) is one of the most common complications in cancer patients. It is not only associated with both reduced survival and a high number of recurrences, but an idiopathic VTE also increases the likelihood of a cancer diagnosis. METHODS: Between January 2000 and October 2005 we reviewed the medical history of 88 patients who were admitted to a tertiary hospital and presented both a diagnosis of VTE and any type of tumour. The information collected included the type of tumour, the temporal association between tumour diagnosis and VTE, anticoagulation treatment applied and percentage of recurrences. RESULTS: Ten patients (11.4%) presented the VTE prior to the cancer diagnosis; only half of them underwent a posterior tumour screening routine. Fifteen patients (17%) were diagnosed simultaneously and 71% presented the VTE after the tumour was detected. In 47 patients (53.4%) no risk factors for VTEs were detected. Twenty-nine patients (31.7%) presented a recurrent VTE, mainly during chemotherapy treatment (66%). Less than half of the patients (47.57%) were receiving treatment with low-molecular- weight heparins (LMWH). CONCLUSIONS: Idiopathic VTEs may be the first manifestation of an occult neoplasia, but tumour screening is scheduled in only a few patients. Regarding the high incidence of recurrent VTE in cancer populations, a high percentage is attributed to the underuse of LMWH, whose efficacy in preventing recurrent phenomena is superior to oral dicumarinics.