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Abstract: Immunohistochemical loss of the succinate dehydrogenase subunit B (SDHB) has recently been reported as a surrogate biomarker of malignancy in sporadic and familial pheocromocytomas and paragangliomas through the activation of hypoxia pathways. However, data on the prevalence and the clinical implications of SDHB immunoreactivity in ileal neuroendocrine tumors are still lacking. Thirty-one consecutive, advanced primary midgut neuroendocrine tumors and related lymph node or liver metastases from 24 males and seven females were immunohistochemically assessed for SDHB. All patients were G1 tumors (Ki-67 labeling index ⩽2%). SDHB immunohistochemistry results were expressed as immunostaining intensity and scored as low or strong according to the internal control represented by normal intestinal cells. Strong positivity for SDHB, with granular cytoplasmatic reactivity, was found in 77% of primary tumors (T), whilst low SDHB expression was detected in 90% of metastases (M). The combined analysis (T+M) confirmed the loss of SDHB expression in 82% of metastases compared to 18% of primary tumors. SDHB expression was inversely correlated with Ki-67 labeling index, which accounted for 1.54% in metastastic sites and 0.7% in primary tumors. A correlation between SDHB expression loss, increased Ki-67 labeling index and biological aggressiveness was shown in advanced midgut neuroendocrine tumors, suggesting a role of tumor suppressor gene. [ABSTRACT FROM AUTHOR]

An innovative three-step procedure for the synthesis of linear phased arrays with nonuniformly spaced elements is presented. The main objective is to obtain an array with a minimal number of elements and an optimal efficiency of the amplifiers driving the elements. The procedure consists of three steps. First of all, a periodic array with a single-amplitude tapering and as much phase tapering as there are required shaped patterns is derived. Then, starting from the results of the first step, an equiamplitude nonperiodic array, with a number of phase tapering equal to the number of required patterns and with a minimum number of radiators is synthesized. Finally, a numerical optimization permits refining the results so as to satisfy the design constraints. [ABSTRACT FROM PUBLISHER]

Large cell carcinomas (LCCs) of the lung are heterogeneous and may be of different cell lineages. We analyzed 56 surgically resected lung tumors classified as LCC on the basis of pure morphologic grounds, using a panel of immunophenotypic markers (adenocarcinoma [ADC]-specific, thyroid transcription factor-1, cytokeratin 7, and napsin A; squamous cell carcinoma [SQCC]-specific, p63, cytokeratin 5, desmocollin 3, and Δnp63) and the quantitative analysis of microRNA-205 (microRNA sample score [mRSS]). Based on immunoprofiles 19 (34%) of the cases were reclassified as ADC and 14 (25%) as SQCC; 23 (41%) of the cases were unclassifiable. Of these 23 cases, 18 were classified as ADC and 5 as SQCC according to the mRSS. Our data show that an extended panel of immunohistochemical markers can reclassify around 60% of LCCs as ADC or SQCC. However, a relevant percentage of LCCs may escape convincing immunohistochemical classification, and mRSS could be used for further typing, but its clinical relevance needs further confirmation. [ABSTRACT FROM AUTHOR]

In this article, an algorithm able to deal at the same time with wire frame and surface patch models for the method of moments in time domain is presented. After a unified theory combining both models, attention is focused on stability dependence issues on the time basis function chosen and on other algorithm parameters. An accurate analysis of time interpolation functions and of their time filtering properties is provided. © 2011 Wiley Periodicals, Inc. Int J RF and Microwave CAE, 2011. [ABSTRACT FROM AUTHOR]

BACKGROUND: [ABSTRACT FROM AUTHOR]

High efficiency, compactness, light weight and low return loss are of high importance in antennas, especially in space applications. In this contribution a modified nondominated sorting genetic algorithm (NSGA-II) is applied to the design of Horn antennas for discrete lens applications to achieve a Pareto-optimal solution. Horn design is aimed not only towards higher possible efficiency but also towards large band and compactness. © 2011 Wiley Periodicals, Inc. Int J RF and Microwave CAE, 2011. [ABSTRACT FROM AUTHOR]

Background: Small intestine neuroendocrine tumors (SI-NETs) belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2) as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. Methodology/Principal Findings: A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC), to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. Conclusion: Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA) for the risk of recurrence after radical operation of these tumors. [ABSTRACT FROM AUTHOR]

Context.--Colorectal cancer is the leading cause of morbidity and death among gastrointestinal tumors and ranks fourth after lung, breast, and ovarian cancers. Despite a continuous refinement of the T (tumor), N (node), and M (metastasis) staging system to express disease extent and define prognosis, and eventually to guide treatment, the outcome of patients with colorectal cancer may vary considerably even within the same tumor stage. Therefore, the need for new factors, either morphologic or molecular, that could more precisely stratify patients into different risk categories is clearly warranted. Objectives.--To present the state of the art with regard to the colorectal cancer staging system and to discuss confusing and/or challenging issues, including the assessment of peritoneal membrane involvement, vascular invasion, tumor deposits, and pathologic tumor response to neoadjuvant chemoradiotherapy. Data Sources.--Literature review of relevant articles indexed in PubMed (US National Library of Medicine) and primary material from the authors' institutions. Conclusions.--Two emerging needs exist for the TNM system, namely, further stratification of patients with the same tumor stage and incorporation of nonanatomic factors, the latter including molecular and treatment factors. The identification and classification of morphologic features encountered in the pathologic examination of colorectal cancer specimens may be difficult and a source of subjective variability. Enhanced pathologic analysis, agreed-upon standard protocols, and standardization should improve the completeness and accuracy of pathology reports. [ABSTRACT FROM AUTHOR]

Reports on the case of a 38-year-old woman complaining of persistent chest pain. Description of the woman's condition; Medical examination of the patient; How a radiograph showed an irregularity on the sternum; Discovery of Langerhans' cell histiocytosis.

Acinar cell carcinoma (ACC) of the pancreas are known to be rare and difficult to be recognize because they mimic other unrelated tumors (neuroendocrine, solid pseudopapillary) with different clinical behavior. Especially in the setting of inoperable patients, fine needle aspiration cytology (FNAC), core needle biopsy (FNAB) and immunocyto/histochemistry (ICC/IHC) play a crucial role in the differential diagnosis. The biological material available for ICC tests obtained by minimal invasive procedures is usually limited. Aim of the current study was to evaluate diagnostic panel based on a limited number of ICC markers for typing preoperatively ACC of the pancreas. Of 1820 needle sampling procedures performed and related to pancreatic lesions, 21 cases were extracted with a confirmed diagnosis of ACC on histology. Of them,12 were pure ACC and 9 mixed acinar-neuroendocrine carcinoma (MANEC). Smears of ACC, MANEC and a control group composed of 34neuroendocrine, 7solid pseudopapillary, 50ductal and 4 adenosquamous carcinoma were assessed with an ICC panel made up of BCL10, trypsin, synaptophysin, chromograninA, β-catenin. On cytology, BCL10 sensitivity and specificity for ACC was 100%. Trypsin correctly recognized 90% of the cases. Synaptophysin was helpful to correctly identify all the cases with a mixed neuroendocrine component. No significant cross-reaction was observed between BCL10 and trypsin in any of the control group case. BCL10 is a determinant marker for the diagnosis of acinar cell carcinoma and mixed acinar neuroendocrine cell carcinoma of the pancreas in a pre-operative citologic/histologic setting. [ABSTRACT FROM AUTHOR]

Summary: Background: Indeterminate non-calcified lung nodules are frequent when low-dose spiral computed tomography (LD-CT) is used for lung cancer screening. We assessed the diagnostic utility of a non-invasive work-up protocol for nodules detected at baseline in volunteers enrolled in our single-centre screening trial, and followed for at least 1 year. Methods: 5201 high-risk volunteers, recruited over 1 year from October 2004, underwent baseline LD-CT; 4821 (93%) returned for the first repeat LD-CT. Nodules ≤5mm underwent repeat LD-CT at 1 year; nodules 5.1–8mm underwent LD-CT 3 months later; lesions >8mm received combined CT-positron emission tomography (CT-PET). A subset of nodules >8mm was studied by CT with contrast. Protocol failures were delayed diagnosis with disease progression beyond stage I, and negative surgical biopsy. Results: 2754 (53%) volunteers presented one or more non-calcified nodules. Ninety-two lung cancers were diagnosed: 55 at baseline and 37 at annual screening (66% stage I). Among the 37 incident cancers, 17 had a baseline nodule that remained stage I, 7 had a baseline nodule that progressed beyond stage I, and 13 presented a new malignant nodule. Baseline and annual cancers were 79 (1.5%) and 13 (0.2%), respectively. In 15 of 104 (14%) invasive diagnostic procedures, the lesion was benign. Sensitivity, and specificity were 91 and 99.7%, respectively, for the entire protocol; 88 and 93% for CT-PET; and 100 and 59% for CT with contrast. Conclusions: The protocol limits invasive diagnostic procedures while few patients have diagnosis delay, supporting the feasibility of lung cancer screening in high-risk subjects by LD-CT. Nevertheless further optimization of the clinical management of screening-detected nodules is necessary. [Copyright &y& Elsevier]

A letter to the editor is presented in response to the article "Intratumoral T Cells, Recurrence, and Survival in Epithelial Ovarian Cancer," by L. Zhang, J.R. Conejo-Garcia and D. Katsaros in the January 16, 2003 issue.

Cylindrical post-based waveguide filters are a relevant component of antenna feeding networks. Their synthesis performed via automatic optimization based on full-wave analyses can be very time consuming. In this article a novel fast-design approach based on Levy's and Moore's algorithms and an artificial neural network (ANN) architecture is presented. © 2006 Wiley Periodicals, Inc. Int J RF and Microwave CAE, 2006. [ABSTRACT FROM AUTHOR]

Summary: Objective: Large cell neuroendocrine carcinoma of the lung are considered aggressive. However, reported prognoses are heterogeneous and the optimum treatment remains undefined. We retrospectively evaluated outcomes in a series of patients with a pathological diagnosis of large cell neuroendocrine lung carcinoma, who underwent lung resection. We also assessed the utility of chemotherapy in a small subgroup. Patients and methods: The clinical records of 144 consecutive patients were reviewed in a multicenter study. Survival times, assessed from the day of surgery until death or most recent follow-up, were estimated by the Kaplan–Meier method, and compared by the log rank test. Results: There were 117 men and 27 women of median age 63 years. Twelve wedge resections, 3 segmentectomies, 95 lobectomies, 7 bilobectomies and 24 pneumonectomies were performed. Induction chemotherapy was given in 21 and postoperative chemotherapy in 24. Pathologically, 73 (50%) were stage I, 29 (20%) stage II, 40 (28%) stage III and 2 stage IV. Postoperative mortality was 2.8% and morbidity 26%. Overall 5-year survival was 42.5%: 52% for stage I, 59% for stage II and 20% for stage III (p =0.001 log-rank test on Kaplan–Meier curves). A trend to better outcome was associated with preoperative or postoperative chemotherapy in stage I disease (p =0.077) compared to no chemotherapy. The response rate to induction chemotherapy was 80% in the 15 patients with data available. Conclusion: large cell neuroendocrine carcinoma of the lung are confirmed as aggressive but are also chemosensitive. Our experience suggests that chemotherapy may improve prognosis in stage I disease. [Copyright &y& Elsevier]

In this paper the electromagnetic coupling between a corrugated horn and a reflector dish is analyzed with a new hybrid perturbative technique. This coupling may produce significant modifications especially in the return loss and in the cross-polar pattern of the feed. The hybrid perturbative approach combines three different techniques: a mode matching (MM) technique for the propagation inside the horn, a method of moments (MoM) technique for the radiation of the horn taking into account the external part of the horn itself, and a fast Gaussian beam asymptotic physical optics (FGBAPO) technique for the interactions between the feed and the reflector. Some measurements and the comparison with rigorous numerical results demonstrate the accuracy of the new hybrid technique and the effects of this electromagnetic coupling on the feed performance. [ABSTRACT FROM AUTHOR]

Background Low-dose spiral CT of the chest effectively detects early-stage lung cancer in high-risk individuals. The high rate of benign nodules and issues of making a differential diagnosis are critical factors that currently hamper introduction of large-scale screening programmes. We investigated the efficacy of repeated yearly spiral CT and selective use of positron emission tomography (PET) in a large cohort of high-risk volunteers. Methods We enrolled 1035 individuals aged 50 years or older who had smoked for 20 pack-years or more. All patients underwent annual low-dose CT, with or without PET, for 5 years. Lesions up to 5 mm were deemed non-suspicious and low-dose CT was repeated after 12 months (year 2). Findings By year 2, 22 cases of lung cancer had been diagnosed (11 at baseline, 11 at year 2). 440 lung lesions were identified in 298 (29%) participants, and 95 were recalled for high-resolution contrast CT. PET scans were positive in 18 of 20 the identified cancer cases. Six patients underwent surgical biopsy for benign disease because of false-positive results (6% of recalls, 22% of invasive procedures). Complete resection was achieved in 21 (95%) lung cancers, 17 (77%) were pathological stage I (100% at year 2), and the mean tumour size was 18 mm. There were no interval lung cancers in the 2.5 years of followup (average time on study from randomisation to last contact), although 19 individuals were diagnosed with another form of cancer (two deaths and 17 non-fatal admissions). [ABSTRACT FROM AUTHOR]

Background: Tamoxifen reduces the risk of breast cancer in women at high risk for the disease but increases the risk for endometrial tumors and venous thromboembolisms, possibly in a dose-dependent fashion. We compared the effects of tamoxifen at 1 mg/day and 5 mg/day with those of the standard dose of 20 mg/day on breast cancer proliferation using a surrogate endpoint marker (Ki-67 expression) and blood biomarkers associated with breast cancer, cardiovascular disease, and bone fracture risk.Methods: We randomly assigned 120 women with estrogen receptor (ER)-positive breast cancer to tamoxifen at 1, 5, or 20 mg/day for 4 weeks. Expression of the tumor proliferation marker Ki-67 and of biomarkers of breast cancer (insulin-like growth factor-I, sex hormone-binding globulin), cardiovascular disease (cholesterol, triglycerides, ultrasensitive C-reactive protein, fibrinogen, antithrombin-III), and bone fracture (type I collagen C-telopeptide) risk were determined before (baseline) and after treatment. All levels were compared with those in two nonrandomized control groups (34 women with ER-negative breast cancer and 29 additional women with ER-positive breast cancer). Data were analyzed by analysis of covariance. All statistical tests were two-sided.Results: Expression of Ki-67 decreased in all three tamoxifen groups, with no difference in the magnitude of reduction among groups (P =.81). Relative to baseline, Ki-67 expression decreased by a median of 15.0% (95% confidence interval = 0.0% to 24.1%) among the tamoxifen groups but increased by 12.8% (95% confidence interval = 0.0% to 19.6%) among the nonrandomized control groups. Several blood biomarkers showed dose-response relationships with tamoxifen, including decreased insulin-like growth factor-I, increased sex hormone-binding globulin, and decreased low-density lipoprotein-cholesterol, ultrasensitive C-reactive protein, fibrinogen, and antithrombin-III levels.Conclusions: The effects on Ki-67 expression of lower doses of tamoxifen were comparable to those achieved with the standard dose, although the effects on blood biomarkers were variable. The effects of lower doses of tamoxifen should be assessed further in randomized trials. [ABSTRACT FROM AUTHOR]

We present a very interesting case of lung adenocarcinoma carrying an uncommon EGFR exon 19 insertion with concomitant PIK3CA mutation showing dramatic and persisting improvement upon erlotinib therapy, after progression during PI3K inhibitor. [ABSTRACT FROM AUTHOR]

Distinguishing between malignant mesothelioma and reactive mesothelial hyperplasia is often inestimable, but may be a challenging gauntlet for pathologists. A 62-year-old man underwent appendectomy after the identification of a peritoneal mass and the histological examination showed mesothelial proliferation along the appendix surface with no clear images of infiltration. After a few months the patient developed mediastinal and supraclavicular lymphadenopathies, and a nodal biopsy showed mesothelial cell proliferation invading lymphatic sinuses, consistent with the cells seen in the abdominal cavity. Since overt morphologic criteria for malignancy were lacking and reactive mesothelial cell deposits have been documented in lymph nodes, a molecular investigation of the CDKN2A (henceforth simply p16) gene status via fluorescence in situ hybridization was performed, which showed homozygous deletion in 100% tumor cells. These data ruled out the hypothesis of reactive mesothelial cells inclusion in lymph nodes, thus confirming the diagnosis of epithelioid malignant mesothelioma. [ABSTRACT FROM AUTHOR]

The ability of cancer cells to attach to laminin has been correlated with their metastatic potential and highly metastatic cancer cells seem to express on their surface significantly more laminin receptors than do their much less metastatic or benign counterparts. The expression of 67-kDa laminin receptors (LR) was investigated in a group of 75 patients who underwent gastrectomy for advanced gastric cancer, with special reference to the possible role in the tumor progression and in the overall survival. The tumor LR expression was immunohistochemically determined in paraffin-embedded sections using the MLuC5 monoclonal antibody which recognizes the 67-kDa LR and the avidin-biotin immunoperoxidase method. Of the 75 cases analyzed, 43 cases (57.3%) displayed a positive reaction. The cumulative 5-year survival rate was 72.6% (95% CI 52.5–85.3) for patients without expression of LR and 46.6% (29.8–61.8) for those with positive LR expression. A significant association between LR expression and depth of tumor invasion (0.022) was found. By univariate analysis the presence of laminin receptors seemed to be associated with a higher risk of death [RR 1.72 (95% CI 0.71–4.20], but this effect disappeared after controlling for depth of tumor invasion. In conclusion, these results suggest that tumor expression of laminin receptors could be correlated with tumor aggressiveness. However, the prognostic significance of laminin receptor expression is already provided by the depth of tumor invasion. [ABSTRACT FROM AUTHOR]

In many filtering applications, direct-coupled cavity filters are often used for their symmetry and handling easiness. In this paper, a method is described for the design of these filtering devices by using an artificial neural network (ANN). Starting from design requirements, the procedure discussed herein directly determines the geometric dimensions of the filtering device with good accuracy and very short processing time. ©1999 John Wiley & Sons, Inc. Int J RF and Microwave CAE 9: 287–296, 1999. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) is a leading cause of cancer-related death in males worldwide. Exacerbated inflammation and angiogenesis have been largely demonstrated to contribute to PCa progression. Diverse naturally occurring compounds and dietary supplements are endowed with anti-oxidant, anti-inflammatory and anti-angiogenic activities, representing valid compounds to target the aberrant cytokine/chemokine production governing PCa progression and angiogenesis, in a chemopreventive setting. Using mass spectrometry analysis on serum samples of prostate cancer patients, we have previously found higher levels of carnitines in non-cancer individuals, suggesting a protective role. Here we investigated the ability of Acetyl-L-carnitine (ALCAR) to interfere with key functional properties of prostate cancer progression and angiogenesis in vitro and in vivo and identified target molecules modulated by ALCAR. Methods: The chemopreventive/angiopreventive activities ALCAR were investigated in vitro on four different prostate cancer (PCa) cell lines (PC-3, DU-145, LNCaP, 22Rv1) and a benign prostatic hyperplasia (BPH) cell line. The effects of ALCAR on the induction of apoptosis and cell cycle arrest were investigated by flow cytometry (FC). Functional analysis of cell adhesion, migration and invasion (Boyden chambers) were performed. ALCAR modulation of surface antigen receptor (chemokines) and intracellular cytokine production was assessed by FC. The release of pro-angiogenic factors was detected by a multiplex immunoassay. The effects of ALCAR on PCa cell growth in vivo was investigated using tumour xenografts. Results: We found that ALCAR reduces cell proliferation, induces apoptosis, hinders the production of pro inflammatory cytokines (TNF-α and IFN-γ) and of chemokines CCL2, CXCL12 and receptor CXCR4 involved in the chemotactic axis and impairs the adhesion, migration and invasion capabilities of PCa and BPH cells in vitro. ALCAR exerts angiopreventive activities on PCa by reducing production/release of pro angiogenic factors (VEGF, CXCL8, CCL2, angiogenin) and metalloprotease MMP-9. Exposure of endothelial cells to conditioned media from PCa cells, pre-treated with ALCAR, inhibited the expression of CXCR4, CXCR1, CXCR2 and CCR2 compared to those from untreated cells. Oral administration (drinking water) of ALCAR to mice xenografted with two different PCa cell lines, resulted in reduced tumour cell growth in vivo. Conclusions: Our results highlight the capability of ALCAR to down-modulate growth, adhesion, migration and invasion of prostate cancer cells, by reducing the production of several crucial chemokines, cytokines and MMP9. ALCAR is a widely diffused dietary supplements and our findings provide a rational for studying ALCAR as a possible molecule for chemoprevention approaches in subjects at high risk to develop prostate cancer. We propose ALCAR as a new possible "repurposed agent' for cancer prevention and interception, similar to aspirin, metformin or beta-blockers. [ABSTRACT FROM AUTHOR]

A straightforward method for the design of microwave filtering devices by using neural networks is proposed. Starting from the filter requirements, this technique is able to perform the synthesis of microwave filters with good accuracy and high computational efficiency. The neural-network training set is generated by applying the finite-element (FE) approach. © 1998 John Wiley & Sons, Inc. Microwave Opt Technol Lett 19: 36–38, 1998. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the subclassification of Primary Tumor Stage 4 Tumors (pT4) category in colorectal cancer.

The article cites a study on colorectal cancer spread through small vessels of the organs concerned. According to researchers, in such tumors, vascular invasion by neoplastic cells are considered to be a strong adverse prognostic factor. Tumors are caused by the overexpression of fascin, cytoplasmic actin-binding protein normally accumulated in endothelial cells.

Presents a letter to the editor concerning Akt phosphor and gefitinib efficacy in patients with advanced non-small-cell lung cancer.