Kératose précancéreuse palpébrale [Eyelid precancerous keratosis].

A 25-year-old-male patient had one keratinized tumor on the inferior right eyelid, first observed 5 months before. Its size had been increasing for the last three weeks. The visual function was normal. Clinical examination disclosed a papillomatous lesion on the cutaneous middle part of the eyelid. A surgical excision was performed under local anesthesia. The histopathological study found a papillomatous epidermal proliferation with both structural and cytological atypias, concluding with a precancerous keratosis of the eyelid.

Increased neuroendocrine cells in resected metastases compared to primary colorectal adenocarcinomas.

Neuroendocrine differentiation has been described in rectal adenocarcinomas receiving neoadjuvant therapy prior to radical surgery, but its clinical relevance is controversial and no data are currently available in colorectal carcinoma metastases as compared to primary tumors. The presence of chromogranin A positive tumor cells was investigated by means of immunohistochemistry on surgical specimens from 54 primary colorectal carcinomas and their corresponding metastases, resected at diagnosis or during tumor progression. In 47 patients, tumor metastases were resected 1 month to 12 years after chemotherapy and/or radiotherapy, while in the remaining seven patients no additional therapy after primary surgery was performed. In primary tumors, neuroendocrine differentiation was found in 12/54 cases (22.2%) as compared to 25/54 metastatic lesions (46.3%; p?=?0.01). The presence of neuroendocrine phenotype was not correlated with any clinical pathological parameter nor with a different proliferation index. However, patients having neuroendocrine cells in the primary tumor had a significantly shorter survival from the time of metastatic spread than those having not (33.3 vs. 55.5 months; p?=?0.04). In summary, our data show that colorectal carcinoma metastases contain a higher percentage of neuroendocrine differentiated cells as compared to their corresponding primaries, a finding possibly related to the influence of chemotherapy in neuroendocrine differentiation during colorectal carcinoma progression.

Klinisch-immunologische Teste--Standortbestimmung 1976

[Clinical-immunological tests; current state].

Up-regulation of placental leptin by human chorionic gonadotropin.

Leptin, the 16,000 molecular weight protein product of the obese gene, was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, leptin has been suggested to be involved in other functions during pregnancy, particularly in placenta, in which it was found to be expressed. In the present work, we have found that recombinant human chorionic gonadotropin (hCG) added to BeWo choriocarcinoma cell line showed a stimulatory effect on endogenous leptin expression, when analyzed by Western blot. This effect was time and dose dependent. Maximal effect was achieved at hCG 100 IU/ml. Moreover, hCG treatment enhanced leptin promoter activity up to 12.9 times, evaluated by transient transfection with a plasmid construction containing different promoter regions and the reporter gene luciferase. This effect was dose dependent and evidenced with all the promoter regions analyzed, regardless of length. Similar results were obtained with placental explants, thus indicating physiological relevance. Because hCG signal transduction usually involves cAMP signaling, this pathway was analyzed. Contrarily, we found that dibutyryl cAMP counteracted hCG effect on leptin expression. Furthermore, cotransfection with the catalytic subunit of PKA and/or the transcription factor cAMP response element binding protein repressed leptin expression. Thereafter we determined that hCG effect could be partially blocked by pharmacologic inhibition of MAPK pathway with 50 microM PD98059 but not by the inhibition of the phosphatidylinositol 3-kinase pathway with 0.1 microm wortmannin. Moreover, hCG treatment promoted MAPK kinase and ERK1/ERK2 phosphorylation in placental cells. Finally, cotransfection with a dominant-negative mutant of MAPK blocked the hCG-mediated activation of leptin expression. In conclusion, we provide some evidence suggesting that hCG induces leptin expression in trophoblastic cells probably involving the MAPK signal transduction pathway.

Immune Microenvironment in Colorectal Cancer: A New Hallmark to Change Old Paradigms

Impact of immune microenvironment in prognosis of solid tumors has been extensively studied in the last few years. Specifically in colorectal carcinoma, increased knowledge of the immune events around these tumors and their relation with clinical outcomes have led to consider immune microenvironment as one of the most important prognostic factors in this disease. In this review we will summarize and update the current knowledge with respect to this intriguing and complex new hallmark of cancer, paying special attention to infiltration by T-infiltrating lymphocytes and their subtypes in colorectal cancer, as well as its eventual clinical translation in terms of long-term prognosis. Finally, we suggest some possible investigational approaches based on combinatorial strategies to trigger and boost immune reaction against tumor cells.

Municipal distribution of bladder cancer mortality in Spain: Possible role of mining and industry

BACKGROUND Spain shows the highest bladder cancer incidence rates in men among European countries. The most important risk factors are tobacco smoking and occupational exposure to a range of different chemical substances, such as aromatic amines. METHODS This paper describes the municipal distribution of bladder cancer mortality and attempts to "adjust" this spatial pattern for the prevalence of smokers, using the autoregressive spatial model proposed by Besag, York and Molliè, with relative risk of lung cancer mortality as a surrogate. RESULTS It has been possible to compile and ascertain the posterior distribution of relative risk for bladder cancer adjusted for lung cancer mortality, on the basis of a single Bayesian spatial model covering all of Spain's 8077 towns. Maps were plotted depicting smoothed relative risk (RR) estimates, and the distribution of the posterior probability of RR>1 by sex. Towns that registered the highest relative risks for both sexes were mostly located in the Provinces of Cadiz, Seville, Huelva, Barcelona and Almería. The highest-risk area in Barcelona Province corresponded to very specific municipal areas in the Bages district, e.g., Suría, Sallent, Balsareny, Manresa and Cardona. CONCLUSION Mining/industrial pollution and the risk entailed in certain occupational exposures could in part be dictating the pattern of municipal bladder cancer mortality in Spain. Population exposure to arsenic is a matter that calls for attention. It would be of great interest if the relationship between the chemical quality of drinking water and the frequency of bladder cancer could be studied.

Identification of tumor-associated antigens by large-scale analysis of genes expressed in human colorectal cancer.

Despite the high prevalence of colon cancer in the world and the great interest in targeted anti-cancer therapy, only few tumor-specific gene products have been identified that could serve as targets for the immunological treatment of colorectal cancers. The aim of our study was therefore to identify frequently expressed colon cancer-specific antigens. We performed a large-scale analysis of genes expressed in normal colon and colon cancer tissues isolated from colorectal cancer patients using massively parallel signal sequencing (MPSS). Candidates were additionally subjected to experimental evaluation by semi-quantitative RT-PCR on a cohort of colorectal cancer patients. From a pool of more than 6000 genes identified unambiguously in the analysis, we found 2124 genes that were selectively expressed in colon cancer tissue and 147 genes that were differentially expressed to a significant degree between normal and cancer cells. Differential expression of many genes was confirmed by RT-PCR on a cohort of patients. Despite the fact that deregulated genes were involved in many different cellular pathways, we found that genes expressed in the extracellular space were significantly over-represented in colorectal cancer. Strikingly, we identified a transcript from a chromosome X-linked member of the human endogenous retrovirus (HERV) H family that was frequently and selectively expressed in colon cancer but not in normal tissues. Our data suggest that this sequence should be considered as a target of immunological interventions against colorectal cancer.

What is the presentation of renal angiomyolipomas?

Renal angiomyolipomas (AMLs) are commonly benign tumours formed by fat, blood vessels and non-striated muscle, which tend to be associated with neuroendocrine syndromes, or turn up sporadically.

Reseccion intestinal masiva. Proceso de adaptacion nutricional

INTRODUCTION Massive small bowel resection (MSBR) with a remnant jejunum shorter than 60 cm produces severe water, electrolytes, vitamins and protein-caloric depletion. While waiting for a viable intestinal transplantation, most of MSBR patients depend on total parenteral nutrition (TPN). CLINICAL CASE 32 years old male, with MSBR due to sectioning trauma of the superior mesenteric artery root. First surgical intervention: jejunostomy with small bowel, right colon, and spleen resection. Six months later: jejunocolic anastomosis with 12-cm long jejunum remnant and prophylactic cholecystectomy. NUTRITIONAL INTERVENTION: 1st phase. Hemodynamic stabilization and enteral stimulation (6 months): TPN + enteral nutrition with elemental formula + oral glucohydroelectrolitic solution (OGHS) + 15 g/d of oral glutamine + omeprazol. Clinical course indicators: biochemistry, I/L balance. 2a phase. Digestive adaptation with colonic integration (8 months): replacement of TPN by part-time peripheral PN. Progressive cooked diet complemented with pancreatic poly-enzyme preparation, omeprazol, OGHS, glutamine, elemental formula. Clinical course indicators: biochemistry, diuresis, weight and feces. 3a phase. Auto-sufficiency without parenteral dependence: fragmented free oral diet supplemented with pancreatic poly-enzyme preparation, mineralized beverages, enteral formula supplement, Ca and Mg oral supplements, oral multivitamin and mineral preparation, monthly IM vitamin B12. Current situation actual (52 months): slight ponderal gain, diuresis > liter/day, 2-3 normal feces, no clinical signs of any deficiency and normal blood levels of micronutrients. CONCLUSION It may be possible to withdraw from PN in MSBR considering, as in this case, favorable age and etiology and early implementation of an appropriate protocol of remnant adaptation.

Combined low initial DNA damage and high radiation-induced apoptosis confers clinical resistance to long-term toxicity in breast cancer patients treated with high-dose radiotherapy

BACKGROUND. Either higher levels of initial DNA damage or lower levels of radiation-induced apoptosis in peripheral blood lymphocytes have been associated to increased risk for develop late radiation-induced toxicity. It has been recently published that these two predictive tests are inversely related. The aim of the present study was to investigate the combined role of both tests in relation to clinical radiation-induced toxicity in a set of breast cancer patients treated with high dose hyperfractionated radical radiotherapy. METHODS. Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma treated with high-dose hyperfractioned radical radiotherapy. Acute and late cutaneous and subcutaneous toxicity was evaluated using the Radiation Therapy Oncology Group morbidity scoring schema. The mean follow-up of survivors (n = 13) was 197.23 months. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radiation-induced apoptosis (RIA) at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide. RESULTS. Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46). Radiation-induced apoptosis increased with radiation dose (median 12.36, 17.79 and 24.83 for 1, 2, and 8 Gy respectively). We observed that those "expected resistant patients" (DSB values lower than 1.78 DSB/Gy per 200 Mbp and RIA values over 9.58, 14.40 or 24.83 for 1, 2 and 8 Gy respectively) were at low risk of suffer severe subcutaneous late toxicity (HR 0.223, 95%CI 0.073-0.678, P = 0.008; HR 0.206, 95%CI 0.063-0.677, P = 0.009; HR 0.239, 95%CI 0.062-0.929, P = 0.039, for RIA at 1, 2 and 8 Gy respectively) in multivariate analysis. CONCLUSIONS. A radiation-resistant profile is proposed, where those patients who presented lower levels of initial DNA damage and higher levels of radiation induced apoptosis were at low risk of suffer severe subcutaneous late toxicity after clinical treatment at high radiation doses in our series. However, due to the small sample size, other prospective studies with higher number of patients are needed to validate these results.

Increased expression of urokinase-type plasminogen activator mRNA determines adverse prognosis in ErbB2-positive primary breast cancer.

PURPOSE: To evaluate and validate mRNA expression markers capable of identifying patients with ErbB2-positive breast cancer associated with distant metastasis and reduced survival. PATIENTS AND METHODS: Expression of 60 genes involved in breast cancer biology was assessed by quantitative real-time PCR (qrt-PCR) in 317 primary breast cancer patients and correlated with clinical outcome data. Results were validated subsequently using two previously published and publicly available microarray data sets with different patient populations comprising 295 and 286 breast cancer samples, respectively. RESULTS: Of the 60 genes measured by qrt-PCR, urokinase-type plasminogen activator (uPA or PLAU) mRNA expression was the most significant marker associated with distant metastasis-free survival (MFS) by univariate Cox analysis in patients with ErbB2-positive tumors and an independent factor in multivariate analysis. Subsequent validation in two microarray data sets confirmed the prognostic value of uPA in ErbB2-positive tumors by both univariate and multivariate analysis. uPA mRNA expression was not significantly associated with MFS in ErbB2-negative tumors. Kaplan-Meier analysis showed in all three study populations that patients with ErbB2-positive/uPA-positive tumors exhibited significantly reduced MFS (hazard ratios [HR], 4.3; 95% CI, 1.6 to 11.8; HR, 2.7; 95% CI, 1.2 to 6.2; and, HR, 2.8; 95% CI, 1.1 to 7.1; all P < .02) as compared with the group with ErbB2-positive/uPA-negative tumors who exhibited similar outcome to those with ErbB2-negative tumors, irrespective of uPA status. CONCLUSION: After evaluation of 898 breast cancer patients, uPA mRNA expression emerged as a powerful prognostic indicator in ErbB2-positive tumors. These results were consistent among three independent study populations assayed by different techniques, including qrt-PCR and two microarray platforms.

Genetic analysis of caveolin-1 and eNOS genes in colorectal cancer.

Caveolae are involved in physical compartmentalization between different groups of signaling events. Its main component, CAV1, modulates different pathways in cellular physiology. The emerging evidence pointing to the role of CAV1 in cancer led us to study whether different alleles of this gene are associated with colorectal cancer (CRC). Since one of the most characterized enzymes regulated by CAV1 is eNOS, we decided to include both genes in this study. We analyzed five SNPs in 360 unrelated CRC patients and 550 controls from the general population. Two of these SNPs were located within eNOS and three within the CAV1 gene. Although haplotype distribution was not associated with CRC, haplotype TiA (CAV1) was associated with familiar forms of CRC (p<0.05). This was especially evident in CRC antecedents and nuclear forms of CRC. If both CG (eNOS) and TiA (CAV1) haplotypes were taken together, this association increased in significance. Thus, we propose that CAV1, either alone or together with eNOS alleles, might modify CRC heritability.