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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.

e20619 Background: Non- small cell lung cancer (NSCLC) is one of the tumors with the highest mortality rate. The underlying metabolic alterations involved in its carcinogenesis are becoming more interesting. According to this, the analysis of the dysregulation of genes involved in lipid metabolism (LM) is subject to a growing research. To evaluate a profile of genes involved in lipid metabolism in NSCLC, we analyzed the correlation of this gene expression profile with different clinical-pathological variables. Methods: We performed a retrospective analysis of 22 genes related to LM in samples of NSCLC as well as clinical-pathological features. Advanced NSCLC patients enrolled from 2008 through 2015 were included. Clinical and pathological data were collected from medical reports. This study was approved in our ethical committee and all patients signed the consent inform. Samples were deparaffinated and RNA was extracted using RNeasy FFPE Kit (Qiagen Gmbh, Germany). A Taq-Man Low Density Array (Applied Biosystems) was specifically designed and gene-expression assays were performed in a HT-7900 Fast Real time PCR. RT-StatMiner software (Integromics Inc., Madison, USA) was used to detect and determine the quality control and differential expression analyses of data. Quantification of gene expression was calculated with the 2–ΔCt method. The Kaplan–Meier method was used for survival probabilities, and the log-rank test was to test differences between subgroups. Results: Ninety patients with advanced NSCLC were included. Median age was 64, 68/90 (75%) were male; 46/90 (51%) were ECOG 1; 68/90 (75%) adenocarcinoma vs 22/90 (24%) squamous; 47/90 (52%) smokers and 34% former smokers; metformine intake was presented in 9/90 (10%) and statins 24/90 (27%). In retrospective RT-PCR analysis including a lipid metabolism gene profile of 22 genes, we obtained an overexpression of 2 genes (an Acyl-CoA sintetase and a adipocine encoding gene). They were significantly correlated with overall poor survival in the multivariate analysis (table). These results were confirmed in an in silico validation using 994 NSCLC patients from TCGA study. Conclusions: This is the first study demonstrating a significant relation with a poor survival between a metabolic lipid gene profile expression and survival in advanced non- small cell lung cancer [Table: see text]

e20621 Background: Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overall survival (OS) greater than 2 years, are less than 10% in most series. Classical prognosis factors include stage, weight loss and ECOG, but more information is missing in the literature. Recently, EGFR, ALK and ROS 1 population (less than 20%) reach OS longer than 2 years. Immunotherapy has demonstrated very promising results with more LS compared to chemotherapy in first and second line setting. In this study, we focused in the analysis of LS patients with advanced NSCLC EGFR wt (wild type) and ALK nt (non-translocated), defined as those with OS greater than 36 months, in 7 hospitals in Madrid. Methods: In this serie, first of all, we will try to make a clinical, histopathological characterization collecting data from clinical reports according to a previously defined information. In a second step, we will carry out a genetic analysis of these patient samples comparing to an opposite extreme short survivors (SS) samples (OS less than 9 months). Initially, we used a NGS method of RNA-seq technology to identify differentiating profiles of gene expression between the two opposite populations. And finally, we confirmed this preliminary profile by RT-PCR in the rest of samples. Results: Ninety-six patients were initially included. The majority were men, smokers or former with adenocarcinoma and ECOG 0- 1. We have obtained a differential transcriptome expression between samples from 6 LS and 6 SS, resulting 13 over-expressed and 42 down-expressed genes in LS comparing to SS transcriptome expression. Some of the genes involved in this initial profile belong to different cellular pathways: Secretin Receptor, Surfactant Protein, Trefoil Factor 1, Serpin Family, Ca-bindings Protein channel and Toll like Receptor family. Finally, we carried on by RT-PCR in 40 samples of SS and LS survivors and only four genes were significantly down-regulated in SS compared to LS in the multivariate analysis. These 4 genes were related to Surfactant Proteins: SFTPA1 (p = 0.023), SFTPA2 (p = 0.027), SFTPB (p = 0.02) and SFTPC (p = 0.047). Conclusions: We present a sequential genetic analysis of a LS population with NSCLC EGFR wt (wild type) and ALK nt (non-translocated), obtaining a differential RNA seq- and RT-PCR gene profile based on different surfactant proteins expression. A further confirmation in a larger sample is ongoing.

e14737 Background: Lung cancer is the leading cause of cancer death worldwide. Although most of the knowledge about metabolic dysregulation in cancer focuses on carbohydrates, the importance of alterations related to lipid metabolism is starting to be recognized. There is increasing data on lipid metabolism and non-small lung cancer, but much less is known about this in small cell lung cancer (SCLC). In order to improve our knowledge of these alterations we evaluated a genetic profile related to lipid metabolism and studied clinical outcomes. Methods: We performed a retrospective analysis of 22 genes related to lipid metabolism in 37 tumoral tissue samples of SCLC patients and evaluated clinical features and outcomes. Advanced SCLC patients enrolled from November 1, 2008 through December 31, 2015 were included in this analysis. Clinical data were collected from medical records at the time of enrollment. The study was approved by an Ethics Comittee and all patients signed an Informed Consent form. We used formalin-fixed, paraffin- embedded tumor tissue. Samples were deparaffinated and total RNA was extracted. A Taq-Man Low Density Array (Applied Biosystems) was specifically designed and gene-expression assays were performed in a HT-7900 Fast Real time PCR. RT-StatMiner software was used to detect and determine the quality control and differential expression analyses of data. Results: We included 37 patients, 73 % males and 27 % women, with a median age of 62. 29 patients (78%) had stage IV tumor and nearly all of them (92%) were treated with platinum- based chemotherapy. 11 % (4/37) received thoracic radiotherapy and 5% (2/37) received whole brain radiotherapy. 6 patients (16%) were on chronic treatment with metformin and 15 (40%) on statins. We performed a multivariable analysis and found that overexpression of two metabolic genes (a mitochondrial enzyme and a lipid metabolism regulator) led to longer overall survival. (HR 0.13 (0.04-0.42), p 0.0019, padjusted 0.04 and HR 0.11 (0.03-0.35) p 0.0006, padjusted 0.01, respectively). Conclusions: These genes contribute to normal functioning and regulation of lipid metabolism and could be considered as potential prognostic biomarkers. There is no previous evidence of association between levels of expression of these genes and overall survival in SCLC. Validation in a larger series of patients is ongoing.

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.

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/m2 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.

[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. © 2012 Elsevier Inc. All rights reserved., Funded by Fondo de Investigaciones SanitariasPI021094 and Fundación Mutua Madrileña. P. Cejas is supported by Asociación Española Contra el Cáncer programa PAO 2010, and V. M. García is supported by Fundación Para la Investigación Biomédica del Hospital La Paz grant REX 09.

This work is licensed under a Creative Commons Attribution 4.0 International License.-- et al., Radiation has a limited but relevant role in the adjuvant therapy of gastric cancer (GC) patients. Since Chk1 plays a critical function in cellular response to genotoxic agents, we aimed to analyze the role of Chk1 in GC as a biomarker for radiotherapy resistance. We analyzed Chk1 expression in AGS and MKN45 human GC cell lines by RT-QPCR and WB and in a small cohort of human patient's samples. We demonstrated that Chk1 overexpression specifically increases resistance to radiation in GC cells. Accordingly, abrogation of Chk1 activity with UCN-01 and its expression with shChk1 increased sensitivity to bleomycin and radiation. Furthermore, when we assessed Chk1 expression in human samples, we found a correlation between nuclear Chk1 accumulation and a decrease in progression free survival. Moreover, using a luciferase assay we found that Chk1's expression is controlled by p53 and RB/E2F1 at the transcriptional level. Additionally, we present preliminary data suggesting a posttranscriptional regulation mechanism, involving miR-195 and miR-503, which are inversely correlated with expression of Chk1 in radioresistant cells. In conclusion, Chk1/microRNA axis is involved in resistance to radiation in GC, and suggests Chk1 as a potential tool for optimal stratification of patients susceptible to receive adjuvant radiotherapy after surgery., This work was supported by Instituto de Salud Carlos III–Fondo de Investigación Sanitaria (PS09/1988 to ISP; PI11-00949, pI014-1495 and Feder Funds to RP); Comunidad Autónoma de Madrid-Universidad Autónoma de Madrid (CCG10-UAM/BIO-5871 to ISP); Fundación Leticia Castillejo Castillo and Ministerio de Ciencia e Innovación (SAF2012-30862 to RSP), Spain. JBI was supported by a fellowship from Catedra Isaac Costero, funded by Banco Santander UAM and is a doctoral student from a double doctorate program in Molecular Biosciences (UAM) and in Biomedical Sciences, (UNAM) and received fellowship CVU:607546 from CONACYT.

Background Cancer patients search for information about prognosis and treatment. Internet has become a major source of medical information. Its impact on oncology patients is not well known. Patients and methods Three hundred and eighty questionnaires were distributed to cancer patients and companions and 293 were returned. The type of information they obtained online, its usefulness, and its impact on the patient–physician relationship as well as other sources of searching were demanded. Student t-tests, chi-square tests, and multivariate regression logistic analysis were carried out. Results Internet use was low (27% patients, 58% relatives). Cancer-specific information was the principal research (41% and 70%). For 61% patients, the information had been useful. Information provided by clinicians was the primary reason to not use Internet (37% and 67%). Twenty-two percent patients discussed it with clinicians. Among other sources, health professional (62% and 51%) and printed materials (18% and 25%) were the most demanded. Conclusions Cancer patients and carers reported a low use of the Internet for searching medical information, although it helps patients to better cope with cancer. To discuss this information may strengthen the patient–physician relationship. Physicians should ensure that their patients receive reliable online information.

Gastric cancer is the major cause of cancer-related deaths worldwide. The majority of them are classified as sporadic, whereas the remaining 10% exhibit familial clustering. Hereditary diffuse gastric cancer (HDGC) syndrome is the most important condition that leads to hereditary gastric cancer. However, other hereditary cancer syndromes, such as hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, Peutz-Jeghers syndrome, Li-Fraumeni syndrome and hereditary breast and ovarian cancer, entail a higher risk compared to the general population for developing this kind of neoplasia. In this review, we describe briefly the most important aspects related to clinical features, molecular biology and strategies for prevention in hereditary gastric associated to different cancer syndromes.

Purpose: Preoperative chemoradiotherapy (CRT) is the treatment of choice for rectal cancer (RC), but half of the patients do not respond, suffer unnecessary toxicities, and surgery delays. We aimed to develop a model that could predict a clinically meaningful response to CRT by using formalin-fixed paraffin-embedded (FFPE) biopsies. Experimental Design: We first carried out an exploratory screening of candidate genes by using SAGE technology to evaluate dynamic changes in the RC transcriptome in selected refractory patients before and after CRT. Next, 53 genes (24 from SAGE and 29 from the literature) were analyzed by qPCR arrays in FFPE initial biopsies from 94 stage II/III RC patients who were preoperatively treated with CRT. Tumor response was defined by using Dworak's tumor regression grade (2–3–4 vs. 0–1). Multivariate Cox methods and stepwise algorithms were applied to generate an optimized predictor of response and outcome. Results: In the training cohort (57 patients), a 13-gene signature predicted tumor response with 86% accuracy, 87% sensitivity, and 82% specificity. In a testing cohort (37 patients), the model correctly classified 6 of 7 nonresponders, with an overall accuracy of 76%. A signature-based score identified patients with a higher risk of relapse in univariate (3-year disease-free survival 64% vs. 90%, P = 0.001) and multivariate analysis (HR = 4.35 95% CI: 1.2–15.75, P = 0.02), in which it remained the only statistically significant prognostic factor. Conclusions: A basal 13-gene signature efficiently predicted CRT response and outcome. Multicentric validation by the GEMCAD collaborative group is currently ongoing. If confirmed, the predictor could be used to improve patient selection in RC studies. Clin Cancer Res; 17(12); 4145–54. ©2011 AACR.

We present the case of a patient with a solitary left frontoparietal brain metastasis of melanoma previously treated with surgery. Three months later, the patient was admitted to the emergency room in a confusional state with meningeal signs. A cerebrospinal fluid (CSF) test and magnetic resonance imaging findings suggested a subarachnoid haemorrhage (SAH) and/or meningeal carcinomatosis. The results of a cytological examination of the CSF showed neoplastic epithelial cells consistent with metastatic melanoma cells. Resection of metastatic posterior fossa lesions is often cited as a risk factor for leptomeningeal dissemination, however, when the resection is limited to the anterior fossa, this complication is relatively rare. In contrast, SAH may be a complication of leptomeningeal dissemination and responsible for acute meningeal syndrome. Treatment with high doses of corticoids did not show any improvement, and intrathecal chemotherapy was not possible due to the patient's poor functional status. She succumbed 1 week after admission.

e13565Background: In last years, the relationship among antinuclear antibodies (ANAs) and cancer has been widely studied. Anti-centromere protein –F (Anti-CENP-F), a subtype of ANAs targeted to nuc...

e21128Background: Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overall survival (OS) greater than 2 years, are less than 10% in most series. Classical prognosis factors ...

The median age at diagnosis of colorectal cancer is during the seventh decade, and the incidence of the disease increases continuously with age. However, as the age increases, the possibilities of receiving adequate cancer treatment diminish and the mortality rises. So, there is a huge need for defined treatment strategies in elderly patients with colorectal carcinoma. The geriatric population is a very heterogeneous group where patients with an excellent health status coexist with the patients with both co-morbidities and functional dependency. Therefore, it is necessary to personalize each treatment according to the degree of vulnerability of the elderly patients. It is essential to set up a multidimensional geriatric assessment in order to consider not only the stage of the disease, but also all the factors that may influence the survival and interfere with the treatment. The aim of this review is to discuss the potential benefits and issues of chemotherapy in the elderly patients affected with colorectal cancer.

High-grade gliomas are the most common primary malignant brain tumours. Surgery, radiotherapy and chemotherapy are the cornerstone of actual treatment. In spite of large therapeutic efforts, overall survival is still poor. New molecular data allow a new molecular classification for high-grade gliomas and open a therapeutic window for targeted therapy. Molecular diagnostic tools may provide a basis for receptor-based therapies and enough information to personalise future treatments. In this regard, epidermal growth factor receptor (EGFR) is a target that will play a critical role in the management of glioma patients. This review summarises basic and preclinical data that support future use of therapies against EGFR.

Summary We report a case of an unusual presentation of a complicated community-acquired pneumonia resembling lung cancer in an adult male with a long history of fever and consumption syndrome. Chest X-ray showed a right lower lobe consolidation and CT of the chest confirmed those findings. The bronchoscopy demonstrated a mass obstructing the right lower lobe orifice and narrowing the intermedius and right bronchus. Although the picture resembled a lung cancer, two biopsies were consistent with chronic inflammation and features of squamous metaplasia. He received several courses of empiric antibiotics (moxifloxacin and macrolides) without improvement. Cultures yielded Streptococcus pneumoniae and the antibiogram indicated exhibited resistance to moxifloxacin. We started with Amoxicilin–Clavulanic with a clear clinical and radiological improvement. This is the first case report in USA of a community-acquired pneumonia resistant to moxifloxacin.

We have with great interest read the pharmacogenetic study by Abraham and colleagues ([1][1]) reporting SNPs associated with paclitaxel-induced neuropathy. The identification of markers predictive of sensory neuropathy is an important clinical problem for taxanes, vinca-alkaloids, platinum compounds

Permanent central venous catheters (CVC), such as Port-a-Cath®, Hickmann® or PICC®, are widely used in oncology patients for cancer treatment. Thrombosis is a frequent complication that should be ruled out, as it is associated with potentially severe infection and hemodynamic consequences. This is the case report of a male patient who was undergoing chemotherapy for colon cancer. The patient presented with an atrial mass secondary to a CVC-related organized thrombus located inside the atrial cavity. The mass was inducing a massive right-to-left intracardial shunt due to a persistent foramen ovale and signs of respiratory failure that required surgical intervention to remove the intracardial mass.

Introduccion. El tratamiento curativo del cancer gastrico es la cirugia. La tasa de recidivas con esta terapia es del 40%–70%. Hasta ahora, la administracion de quimioterapia adyuvante ha sido ineficaz en demostrar un descenso en la tasa de recidivas. A la vista de los resultados del estudio INT-0116, pacientes intervenidos de cancer gastrico estadios desde I-B (T1N1 o T2a/b N0) a IV (T4N1,2,3 M0/T1,2,3 N3M0) recibieron tratamiento combinado quimiorradioterapico segun el esquema de McDonalds en nuestro servicio.

Se ha visto que los canceres de cabeza y cuello tienen multiples anomalias geneticas que influyen en el desarrollo y comportamiento del tumor y pueden ser utiles para la creacion de nuevas terapias.

La cistitis hemorragica se define como un sangrado vesical difuso agudo o insidioso. Las causas potenciales de hemorragia vesical son numerosas; incluyen toxicos quimicos (agentes al quilantes como las oxazofosforinas, el busulfan, tiotepa, derivados de toloudina y de anilinas como los insecticidas y drogas de diseno), agentes immunes (penicilinas, el danazol), radioterapia externa o intersticial, virus (adenovirus tipo 11, virus BK y virus deInfluenza A), asi como diversas etiologias idiopaticas (amiloidosis en la artritis reumatoide). El diagnostico y tratamiento de esta complicacion a menudo resulta problematico. Por otro lado, la hemorragia vesical secundaria a infecciones bacterianas, fungicas y parasitarias no esta directamente recogida en esta revision. Por tanto nos centraremos en las causas de cistitis hemorragica no debidas a infecciones de origen tumoral.

e16504 Background: In the CHAARTED and STAMPEDE clinical trials, Docetaxel combined with androgen-deprivation therapy (ADT) increased overall survival in mHSPC patients. Despite the increasing use of this strategy in clinical practice, there is a lack of information about the best treatment choice after progression. Methods: We retrospectively analyzed 96 patients with mHSPC treated with Docetaxel plus ADT in 18 Spanish centers (July 2014 to December 2016). The objectives of the study were to describe baseline and progression characteristics, as well as second-line treatment choice and its outcomes. Results: The median age was 66.7 years. 33.3% patients had visceral metastases at diagnosis and 81% had a Gleason Score 8-10. After a median follow-up of 12.2 months, 35.4% of patients developed castration-resistant prostate cancer (CRPC). The median time to CRPC was 15.4 months. 36.3% of patients had visceral progressive disease. 27 patients received subsequent treatment after progression: 9 (33.3%) were treated with chemotherapy (2 docetaxel, 6 cabazitaxel, 1 carboplatin-etoposide), and 18 (66.6%) received androgen receptor axis-targeted agents (12 enzalutamide, 6 abiraterone). Median progression-free survival was similar with hormonal therapies (4.3 months) than chemotherapy (3.5 months) as second line. Treatment choice was influenced by pattern of progression (visceral vs non visceral) and time to develop CRPC (≤ 12 vs > 12 months). Hormonal therapies were more frequent for non-visceral disease (75% vs 25%) or patients with longer time to develop CRPC (89% vs 11%). Chemotherapy was preferred in patients with visceral progressive disease (83.3% vs 16.7%). In patients with a time to CRPC less than 12 months both treatments were used equally (44.5 vs 55.5%). Conclusions: In our cohort, androgen receptor axis-targeted agents were used more frequently than chemotherapy after progression to chemo-hormonal therapy. Despite the low number of patients that received treatment at progression, our results suggest that the characteristics at the time of progression, such as pattern of progression and time to develop CRPC, could influence treatment choice.

Purpose: Paclitaxel, a widely used chemotherapeutic drug, can cause peripheral neuropathies leading to dose reductions and treatment suspensions and decreasing the quality of life of patients. It has been suggested that genetic variants altering paclitaxel pharmacokinetics increase neuropathy risk, but the major causes of interindividual differences in susceptibility to paclitaxel toxicity remain unexplained. We carried out a whole-exome sequencing (WES) study to identify genetic susceptibility variants associated with paclitaxel neuropathy. Experimental Design: Blood samples from 8 patients with severe paclitaxel-induced peripheral neuropathy were selected for WES. An independent cohort of 228 cancer patients with complete paclitaxel neuropathy data was used for variant screening by DHPLC and association analysis. HEK293 cells were used for heterologous expression and characterization of two novel CYP3A4 enzymes. Results: WES revealed 2 patients with rare CYP3A4 variants, a premature stop codon (CYP3A4*20 allele) and a novel missense variant (CYP3A4*25, p.P389S) causing reduced enzyme expression. Screening for CYP3A4 variants in the independent cohort revealed three additional CYP3A4*20 carriers, and two patients with missense variants exhibiting diminished enzyme activity (CYP3A4*8 and the novel CYP3A4*27 allele, p.L475V). Relative to CYP3A4 wild-type patients, those carrying CYP3A4 defective variants had more severe neuropathy (2- and 1.3-fold higher risk of neuropathy for loss-of-function and missense variants, respectively, P = 0.045) and higher probability of neuropathy-induced paclitaxel treatment modifications (7- and 3-fold higher risk for loss-of-function and missense variants, respectively, P = 5.9 × 10−5). Conclusion: This is the first description of a genetic marker associated with paclitaxel treatment modifications caused by neuropathy. CYP3A4 defective variants may provide a basis for paclitaxel treatment individualization. Clin Cancer Res; 21(2); 322–8. ©2014 AACR.

Colorectal cancer (CRC) is one of the most frequent cancer in first world. Two hereditary CCR syndrome have been described: familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer. A recently described biallelic mutation of MYH, is responsible for adenomatous polyposis with an increased risk of CRC and is responsible for 30–40 % of adenomatous polyposis cases in which an APC mutation cannot be found. However, there is no clear consensus in the literature as whether a monoallelic mutation increases the risk for colorectal cancer. In addition, some authors have indicated that the spectrum of extracolonic lesions in MYH associated polyposis (MAP) might be far different from that observed in FAP and could be more similar to Lynch syndrome spectrum. In this review we are going to describe some general and specific aspects of MAP, including genetic topics, clinical features, different phenotypes and strategies to reduce CCR risk.

Colorectal cancer treatment has experienced important advances in the last 5 years. New targeted therapies have been included in the classical regimens based on 5-fluorouracil, oxaliplatin, or irinotecan. This new approach has brought great revolution in the treatment of this type of cancer. Bevacizumab (Avastin), a new antivascular endothelial growth factor drug, has been shown to improve overall survival in combination with chemotherapy in first-line and second-line settings as compared with standard chemotherapy regimens alone. This case report demonstrates our experience with bevacizumab in a colon cancer patient with liver, lung, and regional lymph node metastases who had a relapse in the liver after adjuvant treatment with capecitabine (Xeloda). The addition of bevacizumab to the FOLFOX4 regimen resulted in a partial response that provided an opportunity for salvage hepatic surgery.

recurrence appeared. The patient was diagnosed with primary classic Kaposi’s Sarcoma (Type I) limited to the supraglottis. Conclusion Classic-type Kaposi’s sarcoma is usually slow growing and does not impair quality of life and survival in the short term, but aggressive forms may be life threatening and should be treated urgently. Systemic chemotherapy with pegylated liposomal doxorubicin is an affective and well-tolerated strategy also for limited-stage disease with rapid progression, however.

Small cell lung cancer is the most aggressive lung cancer subtype. The standard treatment approach is based on cisplatin regimens. Although response rates to treatment are approximately 60-80%, the median survival is still very poor. Excision repair cross complementation group 1 (ERCC1) is an enzyme that removes cisplatin-induced DNA adducts and has been related with prognosis and cisplatin response. Topotecan is the standard treatment as second-line therapy and it is an inhibitor of topoisomerase I (TOP I). We selected 76 patients with small cell lung (SCLC) to analyze the ERCC1 and TOP I mRNA expression. ERCC1 was studied both by quantitative PCR and immunohistochemistry. A significant association was found between the inmunohistochemistry expression of ERCC1 and the lack of platinum response (p=0.001). Moreover, low levels of TOP I RNA were shown to be linked to cisplatin response (p=0.002). In the survival analysis, a significant correlation between a better PFS with a low TOP I RNA expression as well as a negative ERCC1 inmunostaining were found, in both cases with a significant p-value (p=0.02 and 0.009, respectively). In summary, our results suggest the use of ERCC1 immunohistochemistry and TOP I mRNA analysis to predict cisplatin response and prognosis in SCLC patients.

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.

TNM and histological subtype are the most important prognostic criteria in gastric cancer. In this study, we have tried to identify an immunohistochemical protein profile involved in gastric recurrence after a radical surgery.In this paper, protein panels involved in gastric carcinogenesis and progression was analyzed by immunohistochemistry expression: p53, Ki-67, Bcl-2, COX-2, c-erb-B2, EPO-R, E-cadherin, and β-catenin in 44 gastrectomy samples coming from gastrectomy pieces of patients diagnosed and operated on adenocarcinoma of the stomach followed by adjuvant treatment based on MacDonald chemoradiation regimen. An immunostaining profile that could predict the relapse after the end of adjuvant treatment was tried to find. These results have shown that the expression of the adverse prognostic protein profile based on positive p53 immunohistochemical expression and non-conserved E-cadherin/B-catenin staining is associated with tumor recurrence and a poor disease-free survival in operated gastric cancer patients with curative intent followed by adjuvant chemoradiation according to MacDonald's regimen. A protein profile based on immunohistochemical expression of p53 and E-cadherin-B-catenin that has a significant correlation to disease-free survival was identified in gastric cancer samples.

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).

Chemotherapy-induced peripheral neuropathy (CIN) is a common toxicity of anticancer treatment and its incidence is growing. It significantly affects quality of life and is a dose-limiting factor that interferes with treatment. Its diagnosis can be established in clinical terms but some complementary tests can help when the diagnosis is difficult. There is still no proven method to prevent it that has become a standard of care in spite of the huge amount of investigation carried out in recent years. There are promising strategies that could help reduce the burden of this complication. This review will suggest an approach to the diagnosis of these disorders and provide an update on new therapies.

Bevacizumab has been shown to be effective combined with chemotherapy for first-line treatment of advanced colorectal cancer, but little information is available about its efficacy and safety in patients who may be candidates for surgery at any time during the disease. The case history of a female patient with colorectal cancer, undergoing surgery for liver metastases and bilateral surgery for lung metastases at different time-points during her disease, is reported. Perioperative bevacizumab administration caused no complications either associated with surgery, in the early postoperative period, or in the subsequent months.

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.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.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).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.

Although rare, cardiotoxicity is a significant complication of cancer treatment. The incidence and severity of cardiovascular side effects are dependent on the type of drugs used, dose and schedule employed, and age of patients, as well as the presence of coexisting cardiac diseases and previous mediastinal irradiation. Classically, anthracyclines are among one of the most active agents in oncology, but their use is often hampered by their cumulative dose-limiting cardiotoxicity. In the past decade, combination therapy with new drugs such as taxanes or anti- EGFR, and Her-2 therapy as a single agent have also resulted in unexpected cardiotoxicity. Cardiac damage can be secondary to an alteration of cardiac rhythm, changes in blood pressure and ischaemia, and can also alter the ability of the heart to contract and/or relax. The clinical spectrum of these toxicities can range from subclinical abnormalities to being catastrophic, life-threatening and sometimes fatal. Knowledge of this toxicity can aid clinicians to choose the optimal and least toxic regimen suitable for an individual patient. In this work we present an exhaustive review of the cardiovascular side effects associated to new anticancer drugs, from new formulations of anthracyclines to tyrosine kinase inhibitors and monoclonal antibodies.

Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPx) is the only known enzyme able to reduce lipid peroxides bound to cell membranes. Moreover it has been involved in apoptosis and can influence intracellular signaling. To investigate the possible relationship between PHGPx and human cancer we have quantified PHGPx expression levels by real-time quantitative PCR and immunohistochemistry in tissue samples of human breast invasive ductal carcinoma from 34 patients compared with their own controls of benign breast tissue. PHGPx expression levels were compared with the clinical and pathological data of these patients. The results showed that PHGPx expression levels are downregulated in poorly differentiated (grade 3) breast invasive ductal carcinoma (P=0.0043). PHGPx expression levels decreased gradually with tumor grade from grade 1 to grade 3. We also found a downregulation of PHGPx in cases that showed p53 accumulation compared with cases without p53 immunostaining (P=0.0011). PHGPx was also downregulated in cases without progesterone receptors (PR) immunostaining compared with cases with PR immunostaining (P=0.0165). Grade 3, p53 immunostaining and absence of PR immunostaining are poor prognostic factors. These results suggest that PHGPx downregulation could be related with a poorer prognosis in breast invasive ductal carcinoma.

La carcinomatosis leptomeningea constituye una seria complicacion de los tumores solidos y hematologicos extraneurales y ocasional en las neoplasias primarias del sistema nervioso y que cuenta con una mediana de supervivencia inferior a 6 meses. El cancer de mama, pulmon y gastrico asi como el melanoma, el linfoma y la leucemia son las neoplasias mas comunes implicadas en la invasion leptomeningea. Esta complicacion se presenta con sintomas y signos sugestivos de alteracion de pares craneales. El liquido cefalorraquideo (LCR) normalmente presenta pleocitosis, aumento de las proteinas e hipoglucorraquia. Los hallazgos tipicos de la resonancia magnetica nuclear consisten en incrementos focales de la captacion de gadolinio. Finalmente el diagnostico se confirma mediante el examen patologico del LCR. Se han desarrollado diversas estrategias de radioterapia y quimioterapia, sin embargo, pese a estas intervenciones la mayoria de los pacientes fallecen dentro de los 6 meses del diagnostico siendo la mediana de supervivencia en estudios recientes de 6 a 16 semanas.

Reactive Oxygen Species (ROS) result from cell metabolism as well as from extracellular processes. ROS exert some functions necessary for cell homeostasis maintenance. When produced in excess they play a role in the causation of cancer. ROS mediated lipid peroxides are of critical importance because they participate in chain reactions that amplify damage to biomolecules including DNA. DNA attack gives rise to mutations that may involve tumor suppressor genes or oncogenes, and this is an oncogenic mechanism. On the other hand, ROS production is a mechanism shared by many chemotherapeutic drugs due to their implication in apoptosis control. The ROS mediated cell responses depend on the duration and intensity of the cells exposing to the increased ROS environment. Thus the status redox is of great importance for oncogenetic process activation and it is also implicated in tumor susceptibility to specific chemotherapeutic drugs. Phospholipid Hydroperoxide Glutathione Peroxidase (PH-GPx) is an antioxidant enzyme that is able to directly reduce lipid peroxides even when they are bound to cellular membranes. This article will review the relevance of oxidative stress, particularly of lipid peroxidation, in cell response with special focus in carcinogenesis and cancer therapy that suggests PH-GPx as a potentially important enzyme involved in the control of this processes.