Solid cancer, antiphospholipid antibodies, and venous thromboembolism

The pathogenic role of antiphospholipid antibodies (aPL) in the development of venous thromboembolism (VTE) in patients with malignancies has not been established. From May 2006 to April 2008, 258 consecutive patients with solid-organ malignancies who developed VTE (VTE+) were recruited. A group of 142 patients matched for age, sex and tumor type cancer patients without VTE (VTE-) and an age-and-sex matched group of 258 healthy subjects were also included. A second blood sample was taken in positive aPL patients at least 12 weeks later. Twenty-one (8.1%) VTE+ patients, 2 (1.4%) VTE- patients (p=0.006) and 2 (0.8%) healthy subjects (p<0.001) were positive for aPL. Persistent aPL positivity was observed in only 4 out of 15 available VTE+ patients. No differences in demographic characteristics, clinical pattern and outcome were observed in VTE+ patients according to aPL status. The low prevalence and transience of aPL positivity in patients with solid-organ malignancies with VTE argues against a pathogenic role in the development of thrombosis in this setting. The published evidence of the relationship between cancer, aPL, and thrombosis is reviewed.     

Identification of novel tumor suppressor proteases by degradome profiling of colorectal carcinomas

Proteolytic enzymes play important roles during tumor development and progression through their ability to promote cell growth or by facilitating the invasion of surrounding tissues. The human genome contains more than 570 protease-coding genes, many of them forming functional networks, which has forced the use of global strategies for the analysis of this group of enzymes. In this study, we have designed a new quantitative PCR-based device for profiling the entire degradome in human malignancies. We have used this method to evaluate protease expression levels in colorectal carcinomas with the finding that most proteases with altered expression in these tumors exert their function in the extracellular compartment. In addition, we have found that among genes encoding repressed proteases there was a higher proportion with somatic mutations in colorectal cancer when compared to genes coding for upregulated proteases (14% vs. 4%, p<0.05). One of these genes, MASP3, is consistently repressed in colorectal carcinomas as well as in colorectal cancer cell lines when compared to normal colonic mucosa. Functional analysis of this gene revealed that ectopic expression of MASP3 reduces cell proliferation in vitro and restrains subcutaneous tumor growth, whereas its downregulation induces an increase in the tumorigenic potential of colorectal cancer cells. These results provide new insights into the diversity of proteases associated with cancer and support the utility of degradome profiling to identify novel proteases with tumor-defying functions.     

Prognostic impact of chromosomal translocations in myelodysplastic syndromes and chronic myelomonocytic leukemia patients. A study by the spanish group of myelodysplastic syndromes

Chromosomal translocations are rare in the myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). With the exception of t(3q), translocations are not explicitly considered in the cytogenetic classification of the IPSS‐R and their impact on disease progression and patient survival is unknown. The present study was aimed at determining the prognostic impact of translocations in the context of the cytogenetic classification of the IPSS‐R. We evaluated 1,653 patients from the Spanish Registry of MDS diagnosed with MDS or CMML and an abnormal karyotype by conventional cytogenetic analysis. Translocations were identified in 168 patients (T group). Compared with the 1,485 patients with abnormal karyotype without translocations (non‐T group), the T group had a larger proportion of patients with refractory anemia with excess of blasts and higher scores in both the cytogenetic and global IPSS‐R. Translocations were associated with a significantly shorter survival and higher incidence of transformation into AML at univariate analysis but both features disapeared after multivariate adjustment for the IPSS‐R cytogenetic category. Patients with single or double translocations other than t(3q) had an outcome similar to those in the non‐T group in the intermediate cytogenetic risk category of the IPSS‐R. In conclusion, the presence of translocations identifies a subgroup of MDS/CMML patients with a more aggressive clinical presentation that can be explained by a higher incidence of complex karyotypes. Single or double translocations other than t(3q) should be explicitly considered into the intermediate risk category of cytogenetic IPSS‐R classification. © 2015 Wiley Periodicals, Inc.     

Paraparesia secundaria a metástasis intramedular como manifestación inicial de un carcinoma microcítico de pulmón

Intramedullary metastases (IM) are uncommon and rarely considered the initial presentation of malignancy. Lung and breast cancer account for most of the primary tumors. Magnetic resonance imaging may facilitate recognition of IM in patients with clinical features of myelopathy. A case of a unique intramedullary metastases as the presenting feature of an occult lung cancer is described.     

A case with persistent nephrogenic diabetes insipidus following parathyroidectomy for hyperparathyroidism

A 25-year-old woman with persistent nephrogenic diabetes insipidus (NDI) following parathyroidectomy for primary hyperparathyroidism is described. NDI is a well recognized complication of primary hyperparathyroidism, generally imputed to hypercalcemia, and promptly reversible after correcting it. In our case, the impaired concentrating ability of the renal tubule was irreversible after the removal of the parathyroid adenoma and the correction of the hypercalcemia, presumptively due to the morphological irreversible changes in the kidney. In addition, hypercalciuria persisted and was the cause of a compensatory hyperparathyroidism. Treatment with thiazide diuretic was effective to decrease relative hypercalciuria, thus reversing the compensatory hyperparathyroidism.     

Emergence and Dissemination of Quinolone-Resistant Escherichia coli in the Community

We studied the evolution of resistance to quinolones in Escherichia coli from 1992 to 1997 in Barcelona, Spain. An increasing proportion of quinolone-resistant E. coli (QREC) infections was observed. QREC strains were more common in patients with nosocomial infections but also increased in patients with community-acquired infections (9% in 1992 to 17% in 1996). Seventy (12%) of 572 episodes of E. coli bacteremia were due to QREC. Factors significantly associated with QREC bacteremia were the presence of underlying disease, recent exposure to antibiotics, and bacteremia of unknown origin. In the multivariate analysis, only prior exposure to antimicrobial agents (P < 0.001; odds ratio [OR] = 2), specifically, to quinolones (P < 0. 001; OR = 14), and the presence of a urinary catheter (P < 0.001; OR = 2) were significantly associated with QREC bacteremia. Among 16 QREC isolates from cultures of blood of community origin selected at random, 13 different pulsed-field gel electrophoresis patterns were recognized, showing the genetic diversity of these isolates and in turn indicating the independent emergence of QREC in the community. The prevalence of QREC in the feces of healthy people was unexpectedly high (24% in adults and 26% in children). A survey of the prevalence of QREC of avian and porcine origin revealed a very high proportion of QREC in animal feces (up to 90% of chickens harbored QREC). The high prevalence of QREC in the stools of healthy humans in our area could be linked to the high prevalence of resistant isolates in poultry and pork.