Two Synchronous Neonatal Tumors: An Extremely Rare Case.

We report a case of a newborn with two synchronous tumors-sialoblastoma and hepatoblastoma-diagnosed at 20 weeks of gestation by magnetic resonance imaging (MRI) and ultrasonography (US). The aim of this study was to describe the management of this case together with a review of the literature. Our patient had a large facial tumor associated with extremely high alpha-fetoprotein levels. Diagnosis of the tumors was made by surgical biopsy, showing typical features in both. Sialoblastoma is a potentially aggressive tumor. In our case, the Ki67 index in the sialoblastoma was between 20 and 30%, indicating a possibly unfavorable behavior. The infant underwent surgery and chemotherapy in different steps. Complete surgical resection with clean margins is considered to be the best treatment option for sialoblastoma. Only four similar cases were previously reported. Timely management by a multidisciplinary team is essential in these difficult cases. In our patient, outcome was good at the time of this report.

The early onset of type 1 autoimmune hepatitis has a strong genetic influence: role of HLA and KIR genes.

We have previously reported a strong association between HLA-DRB1*1301 and type 1 pediatric autoimmune hepatitis (PAH) and between HLA-DR*0405 and adult autoimmune hepatitis (AAH). Because human killer cell immunoglobulin-like receptors are known to be associated with susceptibility to autoimmune diseases, we investigated the frequencies of HLA-A, B, C, DRB1 and KIR genes in 144 type 1 PAH and 86 AAH patients, which were compared with 273 healthy controls. We demonstrated in PAH the increased frequency of the functional form of KIR2DS4-Full Length (KIR2DS4-FL), which in combination with HLA-DRB1*1301 revealed a strong synergistic effect (odds ratio=36.5). PAH-KIR2DS4-FL+ subjects have shown an increased frequency of their putative HLA-C*02, 04 and 06 ligands. KIR analysis of PAH also revealed a decreased frequency of KIR2DL2 gene and its ligand. In contrast, AAH cases have shown a weaker increased frequency of KIR2DS4-FL, a lack of synergistic effect with HLA class II antigens and a moderate association with HLA-DRB1*0405. Of note, we demonstrated that liver T cells have a unique pattern of KIR expression. These results show a KIR gene involved in autoimmune hepatitis and suggest a stronger genetic influence for the early onset type I autoimmune hepatitis.

Combining analytical frameworks to assess livelihood vulnerability to climate change and analyse adaptation options.

Experts working on behalf of international development organisations need better tools to assist land managers in developing countries maintain their livelihoods, as climate change puts pressure on the ecosystem services that they depend upon. However, current understanding of livelihood vulnerability to climate change is based on a fractured and disparate set of theories and methods. This review therefore combines theoretical insights from sustainable livelihoods analysis with other analytical frameworks (including the ecosystem services framework, diffusion theory, social learning, adaptive management and transitions management) to assess the vulnerability of rural livelihoods to climate change. This integrated analytical framework helps diagnose vulnerability to climate change, whilst identifying and comparing adaptation options that could reduce vulnerability, following four broad steps: i) determine likely level of exposure to climate change, and how climate change might interact with existing stresses and other future drivers of change; ii) determine the sensitivity of stocks of capital assets and flows of ecosystem services to climate change; iii) identify factors influencing decisions to develop and/or adopt different adaptation strategies, based on innovation or the use/substitution of existing assets; and iv) identify and evaluate potential trade-offs between adaptation options. The paper concludes by identifying interdisciplinary research needs for assessing the vulnerability of livelihoods to climate change.

Immunohistochemical study of phospho-Stat3-ser727 expression in feline mammary gland tumours.

We describe the expression of pStat3-ser727 (signal transducer and activator of transcription 3 phosphorylated on serine 727) in normal, hyperplastic and neoplastic feline mammary gland tissue assessed by immunohistochemistry in 56 cats. The samples included 4 normal mammary non-lactating tissues, 13 hyperplastic lesions (9 lobular and 4 fibroepithelial) and 39 tumours (6 benign and 33 carcinomas). For immunohistochemistry, tissue sections were incubated with anti-pStat3-ser727 monoclonal antibodies and visualized with EnVision-DAB polymer. pStat3-ser727 positivity was quantified in a semi-quantitative manner, differentiating cytoplasmic and nuclear localization. Intense anti-pStat3-ser727 immunoreactivity was detected in epithelial neoplastic cells and in the fibro-component in two fibroepithelial hyperplastic lesions. The immunostaining was dot-like in the cytoplasm and homogeneous in the nuclei in both benign and malignant lesions. Statistically significant relations were observed between nuclear expression of pStat3-ser727 and the pleomorphism score (p = 0.006), mitotic activity (p < 0.0001), and histological grade (p < 0.0001). In contrast, no significant correlations were observed for cytoplasmic pStat3-ser727. These findings add new and interesting information on the potential role of the phosphorylated form of Stat3 in malignant lesions.

Liver resection for non-colorectal, non-neuroendocrine metastases: analysis of a multicenter study from Argentina.

BACKGROUND AND AIM: Resection of colorectal liver metastases has become a standard of care, although the value of this procedure in non-colorectal non-neuroendocrine (NCRNNE) metastases remains controversial and is still a matter of debate. The aim of the study was to determine the utility of liver resection in the long-term outcome of patients with NCRNNE metastases. MATERIAL AND METHODS: The records of 106 patients who underwent liver resection for NCRNNE metastases in the period 1989 to 2006 at 5 HPB Centers in Argentina were analyzed. Patient demographics, tumor characteristics, type of resection, long-term outcome and prognostic factors were analyzed. Depending on primary tumor sites, a comparative analysis of survival was performed. RESULTS: Mean age was 54 (17-76). Hepatic metastases were solitary in 62.3% and unilateral in 85.6%. Primary tumor sites: Urogenital (37.7%), sarcomas (21.7%), breast (17.9%), gastrointestinal (6.6%), melanoma (5.7%), and others (10.4%). Fifty-one major hepatectomies and 55 minor resections were performed. Twenty patients underwent synchronous resections. An R0 resection could be achieved in 89.6%. Perioperative mortality was 1.8%. Overall, 1-year, 3-year, and 5-year survival rates were 67%, 34%, and 19%, respectively. Survival was significantly longer for metastases of urogenital (p=0.0001) and breast (p=0.003) origin. Curative resections (p=0.04) and metachronous disease (p=0.0001) were predictors of better survival. CONCLUSIONS: Liver resection is an effective treatment for NCRNNE liver metastases; it gives satisfactory long-term survival especially in metachronous disease, in patients with metastases from urogenital and breast tumors and when R0 procedures can be performed.

Expression of Stat3 in feline mammary gland tumours and its relation to histological grade.

The expression of Stat3 (signal transducer and activator of transcription 3) in normal and neoplastic feline mammary gland tissue was assessed by immunohistochemistry in 72 cats. The samples included 3 normal nonlactating mammary tissues, 17 hyperplastic lesions (11 lobular and 6 fibroepithelial) and 52 neoplasms (5 benign and 47 malignant). For immunohistochemistry, tissue sections were incubated with anti-Stat3 monoclonal antibody and visualized with EnVision-DAB polymer. Stat3 positivity was assessed in a semiquantitative manner. Normal mammary tissue showed occasional cytoplasmic and nuclear positivity, although the number of positive cells was lower than in the hyperplastic specimens. In neoplastic tissue, high numbers of neoplastic cells with a moderate to intense cytoplasmic and nuclear positivity were observed. Selected variations in the staining pattern correlated with malignancy. Moreover, a positive association was seen between the histological grade and the Stat3 score (p < 0.0001; correlation coefficient 0.750). A linear regression model showed a positive association between mitotic count and Stat3 expression (p < 0.001). These results further support published data found in humans regarding to the relation between the expression of Stat3 and malignancy.

Co-culture with human fibroblasts increases the radiosensitivity of MCF-7 mammary carcinoma cells in collagen gels.

The growth and differentiation of normal and neoplastic epithelial cells may be regulated by the presence of adjacent normal tissues and cells, particularly stromal fibroblasts. However, the influence of normal fibroblast-tumor cell interactions on the response of malignant epithelial cells to radiation has not been adequately investigated nor has the possible role played by a 3-D environment in such modulation. We addressed this question by embedding MCF-7 mammary carcinoma cells into a collagen lattice, alone or mixed with HSF human dermal fibroblasts, and kept the gels anchored to the plastic surface or suspended in the culture medium. Some gels served as controls and others were irradiated with 6 MV photons fractionated into 3 daily doses totaling 5 or 10 Gy. After 2 or 7 days from the last treatment (7 or 12 days in culture, respectively), gels were processed in 1 of 2 ways: overall cell survival was determined by the MTT assay, while the survival of MCF-7 cells was selectively detected by a clonogenicity assay. Under these experimental conditions, we found that, in the presence of HSF fibroblasts, the growth of MCF-7 cells was restrained and radiosensitivity increased compared with MCF-7 cells cultured alone. For example, while the average number of MCF-7 foci/gel recovered from control gels with MCF-7 cells alone was 2,460 on day 7 and 3, 290 on day 12 of culture, it was 4 to 5 times lower (p < 0.001) in control gels with mixed MCF-7 and HSF cells. Radiation affected severely the survival of MCF-7 cells in all experimental groups but not sufficiently to mask the differences. For example, following exposure to the low dose of 5 Gy, the average number of MCF-7 foci/gel recovered from MCF-7-containing gels was 590 on day 7 and 329 on day 12 of culture, whereas numbers from the gels containing mixed MCF-7 and HSF cells were only 218 and 73, respectively (p < 0. 003 in both cases). HSF fibroblasts did not grow in our system, but they contracted strongly anchored and floating gels.

Indicaciones y resultados del trasplante hepático con donante vivo relacionado en el tratamiento de la insuficiencia hepática aguda / Indications and results of hepatic transplatation using living-related donor in the treatment of acute hepatic insufficiency

La técnica de trasplante hepático(TH)con donante vivo relacionado(DVR)es un recurso valioso para resolver la escacez de donantes y la aplicabilidad del TH en niños con insuficiencia hepática aguda(IHA)Se analizan las indicaciones y resultados del TH con DVR en niñops con IHA y hepatopatía crónica severa(HCS)Entre junio de 1995 y Junio de 1998 se realizaron en nuestro centro 107 TH en 104 pacientes(77 adultos y 27 niños)De los 27 pacientes pediátricos 13(48 por ciento)fueron transplantados con DVR.La edad media fue de 38 meses con un rango de 7 meses a 9 años.De los 13 pacientes transplantados con DVR,4 presentaron complicaciones postrasplante:trombosis arterial que requirió postrsplante en un caso,fístula biliar y absceso abdominal que requirió reexploración en otro y estenosis de la anstomosis billiar tratados con dilatación percutánea en dos casos.Dos pacientes fallecieron,uno de ellos a los 18 meses del trasplante.La curva de sobrevida actuarial al año de todos los niños trasplantados con DVR(Kaplan-Meier) fue de 90 por ciento u para los 14 con DC fue del 88 por ciento

Indicaciones y resultados del trasplante hepático con donante vivo relacionado en el tratamiento de la insuficiencia hepática aguda / Indications and results of hepatic transplatation using living-related donor in the treatment of acute hepatic insufficiency

La técnica de trasplante hepático(TH)con donante vivo relacionado(DVR)es un recurso valioso para resolver la escacez de donantes y la aplicabilidad del TH en niños con insuficiencia hepática aguda(IHA)Se analizan las indicaciones y resultados del TH con DVR en niñops con IHA y hepatopatía crónica severa(HCS)Entre junio de 1995 y Junio de 1998 se realizaron en nuestro centro 107 TH en 104 pacientes(77 adultos y 27 niños)De los 27 pacientes pediátricos 13(48 por ciento)fueron transplantados con DVR.La edad media fue de 38 meses con un rango de 7 meses a 9 años.De los 13 pacientes transplantados con DVR,4 presentaron complicaciones postrasplante:trombosis arterial que requirió postrsplante en un caso,fístula biliar y absceso abdominal que requirió reexploración en otro y estenosis de la anstomosis billiar tratados con dilatación percutánea en dos casos.Dos pacientes fallecieron,uno de ellos a los 18 meses del trasplante.La curva de sobrevida actuarial al año de todos los niños trasplantados con DVR(Kaplan-Meier) fue de 90 por ciento u para los 14 con DC fue del 88 por ciento

Fibroblasts regulate the migration of MCF7 mammary carcinoma cells in hydrated collagen gel.

We have defined a tissue culture method suitable to study cell-cell interactions in an environmental set close to in vivo conditions. It consists of heterotypic cell populations mixed together inside a collagen gel in a chamber slide for a period of up to 14 days. When the three-dimensional system is saturated, cells will start to move on the plastic surface as monolayers surrounding the gel, with a characteristic speed depending on cell type. Usually fibroblasts move fast, while epithelial cells demonstrate a much lower pace of migration. At any given time gel contraction can be measured, and thus the rate of cell expansion, by knowing the distance from the edge of the gel to the leading edge of cell migration. By using this approach it was found that MCF7 mammary carcinoma cells display a great variety of morphologies following their mixture with different fibroblastic cell lines. In particular, when MCF7 cells were mixed with fibroblasts from human fetus, dog thymus and rat kidney, they migrated up to the leading edge of the fibroblastic front as isolated single cells or as cellular aggregates, many of which became necrotic in time, or took on an elongated morphology. Selective necrosis of MCF7 cells was also induced with serum concentration of 15% and 20% FCS, but only when they were mixed with fibroblasts. No necrosis was induced in MCF7 cells cultured alone. From these observations it is suggested that necrosis may sometimes favor the detachment and infiltration of resistant epithelial tumor cells by increasing their autonomous behaviour. Fibroblasts seem to be instrumental in regulating this process.