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Intra-tumoral vaccination is essential to maximize the benefit of MG1-IL12-ICV vaccine.

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Despite improvements in chemotherapy and radical surgical debulking, peritoneal carcinomatosis (PC) remains among the most common causes of death from abdominal cancers. Immunotherapies have been effective for selected solid malignancies, but their potential in PC has been little explored. Here, we report that intraperitoneal injection of an infected cell vaccine (ICV), consisting of autologous tumor cells infected ex vivo with an oncolytic Maraba MG1 virus expressing IL12, promotes the migration of activated natural killer (NK) cells to the peritoneal cavity in response to the secretion of IFNγ-induced protein-10 (IP-10) from dendritic cells. The recruitment of cytotoxic, IFNγ-secreting NK cells was associated with reduced tumor burden and improved survival in a colon cancer model of PC. Even in mice with bulky PC (tumors > 8 mm), a complete radiologic response was demonstrated within 8 to14 weeks, associated with 100% long-term survival. The impact of MG1-IL12-ICV upon NK-cell recruitment and function observed in the murine system was recapitulated in human lymphocytes exposed to human tumor cell lines infected with MG1-IL12. These findings suggest that an MG1-IL12-ICV is a promising therapy that could provide benefit to the thousands of patients diagnosed with PC each year. Cancer Immunol Res; 5(3); 211–21. ©2017 AACR.

A presente obra tem por objetivo colaborar na capacitação em Mediação Comunitária, a partir da experiência consolidada nos últimos 20 anos pelo Programa Justiça Comunitária, coordenado pelo Tribunal de Justiça do Distrito Federal e Territórios. Esta segunda edição se justifica, a fim de que possamos compartilhar novos aprendizados e percursos, resultantes de uma obra em permanente construção. O texto busca refletir em que medida a Mediação Comunitária contribui para a construção de uma comunidade mais participativa e uma justiça mais emancipadora. Ao traduzir uma prática social transformadora, a Mediação Comunitária promove protagonismo comunitário, assegurando habilidades e recursos para uma gestão cooperativa, responsável, autônoma e solidária de seus conflitos.

This work aims to collaborate in the training in Community Mediation, based on the experience consolidated in the last 20 years by the Community Justice Program, coordinated by the Court of Justice of the Federal District and Territories in Brazil. This second edition is justified, so that we can share new learnings and paths, resulting from a permanent work construction.

Here, we discuss recent updates and a continuing controversy in the diagnosis and management of Barrett's esophagus, specifically the recommendation that the irregular Z-line not be biopsied, the diminished status of ultrashort-segment Barrett's esophagus, the evidence basis for excluding and including the requirement of goblet cells for the diagnosis of Barrett's esophagus, and the conclusion that histologically confirmed low-grade dysplasia is best managed with endoscopic ablation rather than surveillance. We reference the American Gastroenterological Association and College of Gastroenterology and the British Society of Gastroenterology guidelines throughout, with the thesis that the field is converging on the concept of applying scarce medical resources to the diagnosis, surveillance, and therapy of patients most likely to derive benefit.

Despite improvements in chemotherapy and radical surgical debulking, peritoneal carcinomatosis (PC) remains among the most common causes of death from abdominal cancers. Immunotherapies have been effective for selected solid malignancies, but their potential in PC has been little explored. Here, we report that intraperitoneal injection of an infected cell vaccine (ICV), consisting of autologous tumor cells infected ex vivo with an oncolytic Maraba MG1 virus expressing IL12, promotes the migration of activated natural killer (NK) cells to the peritoneal cavity in response to the secretion of IFNγ-induced protein-10 (IP-10) from dendritic cells. The recruitment of cytotoxic, IFNγ-secreting NK cells was associated with reduced tumor burden and improved survival in a colon cancer model of PC. Even in mice with bulky PC (tumors > 8 mm), a complete radiologic response was demonstrated within 8 to14 weeks, associated with 100% long-term survival. The impact of MG1-IL12-ICV upon NK-cell recruitment and function observed in the murine system was recapitulated in human lymphocytes exposed to human tumor cell lines infected with MG1-IL12. These findings suggest that an MG1-IL12-ICV is a promising therapy that could provide benefit to the thousands of patients diagnosed with PC each year. Cancer Immunol Res; 5(3); 211–21. ©2017 AACR.

BackgroundIntraductal papillary neoplasms of the biliary tract (IPNB) and intracholecystic papillary neoplasms (ICPN) are rare tumours characterized by intraluminal papillary growth that can be associated with invasive carcinoma. Their natural history remains poorly understood. This study examines clinicopathological features and outcomes.MethodsPatients who underwent surgery for IPNB/ICPN (2008–2014) were identified. Descriptive statistics and survival data were generated.ResultsOf 23 patients with IPNB/ICPN, 10 were male, and the mean age was 68 years. The most common presentations were abdominal pain (n = 10) and jaundice (n = 9). Tumour locations were: intrahepatic (n = 5), hilar (n = 3), the extrahepatic bile duct (n = 8) and the gallbladder (n = 7). Invasive cancer was found in 20/23 patients. Epithelial subtypes included pancreatobiliary (n = 15), intestinal (n = 7) and gastric (n = 1). The median follow‐up was 30 months. The 5‐year overall (OS) and disease‐free survivals (DFS) were 51% and 57%, respectively. Decreased OS (P = 0.09) and DFS (P = 0.05) were seen in patients with tumours expressing MUC1 on immunohistochemistry (IHC).ConclusionIPNB/ICPN are rare precursor lesions that can affect the entire biliary epithelium. At pathology, the majority of patients have invasive carcinoma, thus warranting a radical resection. Patients with tumours expressing MUC1 appear to have worse OS and DFSs.

Reflux esophagitis is an important clinical diagnosis; however, the histologic findings can be nonspecific and overlap with other entities. Various benign changes can produce diagnostic difficulties for pathologists. In this review, the typical histologic findings of gastroesophageal reflux disease (GERD) of the esophagus are discussed, along with the issues relating to clinical correlation and technical aspects of endoscopic biopsies and specimen processing. The literature has been reviewed to discuss histologic definitions of GERD as well as current and developing controversies in the area of GERD. Histologic features are not entirely sensitive or specific for GERD. Awareness of these problems is essential; clinical and endoscopic information can be very useful in distinguishing GERD from other inflammatory lesions.

A 63-yr-old woman, known case of ulcerative colitis, was diagnosed with sclerosing cholangitis 2 years back. She was admitted for investigation of abdominal discomfort, fatigue with elevated alkaline phosphatase and deranged liver function test. Imaging studies (computerised tomography and magnetic resonance imaging) demonstrated a normal biliary tree with focal hepatic lesion which was showing features of cholangiocarcinoma. Ultrasound guided biopsy of the lesion surprisingly revealed non caseating granulomata. Granulomatous hepatitis occurs in less than 1 percent of cases of inflammatory bowel disease. A clinical diagnosis of isolated granulomatous hepatitis was established as the lesion remained stable on follow up and no other cause for it was identified on further investigation. Although the differential diagnosis of focal hepatic lesion in patients with ulcerative colitis with sclerosing cholangitis is wide, granulomatous hepatitis presenting as focal mass lesion mimicking cholangiocarcinoma has never been described previously.

Aims and Background: Sputum has been examined for the identification of potential biomarkers for the non-invasive diagnosis of lung cancer. However, no definitive biomarkers with reliable accuracy have been identified yet. The main objective of this work was to evaluate the utility of magnetic resonance spectroscopy (MRS) in the analysis of sputum for the non-invasive diagnosis of lung cancer. Methods: Induced sputum samples from lung cancer patients (n = 9) and control subjects (n = 6) were collected for proton (1H) MRS analysis. Samples from two cancer patients and one control subject were discarded as these samples were confirmed to contain only saliva by cytologic examination. Only the true sputum specimens containing alveolar macrophages were analyzed by 1H MRS. To facilitate MRS analysis, sputum samples were dispersed in 2M sodium chloride solution buffered with phosphate-buffered-saline (PBS). MR spectra were obtained using a one-pulse sequence with presaturation of the water resonance. Results: Glucose was found to be absent in sputum samples obtained from lung cancer patients. Spectra of sputum samples collected from control subjects showed presence of glucose signal except for one whose sputum cytology indicated the presence of atypia. The absence of glucose in sputum from cancer patients could be attributed to an increased rate of glycolysis in the lung cancer cells. The present observation, albeit on a small sample size, showed a better sensitivity (100%) and overall accuracy (92%) compared to sputum cytology (sensitivity = 50%; overall accuracy = 70%). Conclusions: Absence of glucose in sputum could be an indicator of lung cancer and the present methodology can be a valuable addition to the non-invasive diagnostics of lung cancer.

As a tool for deliberately planning for and optimizing the ways in which we design our environments, Health Impact Assessment (HIA) holds promise for achieving environmental justice and health equity. This case study describes the application of HIA to updating a rural county's General Plan. Humboldt County, California is currently considering three development plans to accommodate future population growth, and the described HIA process successfully identified and analyzed potential health outcomes associated with each. Although the General Plan Update process is not yet complete as of this writing, the HIA has already accomplished one of its initial goals, which was to build awareness of health impacts related to planning decisions among county agencies, project decision-makers, participating community members, and the general public. Another noteworthy outcome of this process, which is intended to aid in planning future equitable and just communities, was the development of the “Rural Healthy D...

e15137 Background: p-STAT3 is a transcription factor which is associated with poor prognosis in multiple cancers. Overexpression of p-STAT3 by immunohistochemistry (IHC) in tumors of patients with mCRC is associated with more aggressive disease and decreased survival. Concordance of p-STAT3 expression in primary and metastatic tumors was assessed to determine the temporal heterogeneity of expression and correlation with clinical outcomes. Methods: Patients with tissue available from both primary and liver metastases were identified retrospectively. Tissue microarrays (TMA) were constructed using 2 x 2mm cores. Nuclear p-STAT3 expression intensity by IHC was graded as absent, low, or high. Primary outcome was concordance of p-STAT3 expression between primary and metastatic sites. Secondary outcome was correlation of p-STAT3 expression with disease outcomes. Results: 91 patients were identified: 55% were male, median age at diagnosis was 63, 60% had left-sided disease and 81% of metastases were synchronous. Expression of p-STAT3 in primary tumors was 23% high, 47% low and absent in 30% compared to 29% high, 50% low, and 21% absent in metastases. Concordant expression was observed in 23% of patients whereas it increased in 46% and decreased in 31% from primary to metastasis. Pearson’s correlation was 0.119 indicating a weak concordance. After a median follow-up of 7 years, 50 of 91 patients died. One-year and 5-year survival rates were 92% and 44% respectively, while the median overall survival (mOS) was 4.7 years [95%CI 3.1-6.4]. No significant prognostic correlation between primary or metastatic p-STAT3 expression and mOS was found. Conclusions: There was low concordance of p-STAT3 expression in primary and metastatic tumors of patients with mCRC. Tumor staining heterogeneity due to sampling of small cores included in TMA and predominance of synchronous metastases may play a role. Further research in the use of p-STAT3 as a biomarker in patients with mCRC is needed.

The main idea of the authors’ research is to perform quantitative analysis of a text collection during the process of its preparation and transformation into a digital library for a website. They use as a case study the digital library of the website on Mixtec culture that we maintain. The authors propose using the concept of the text document search image (TDSI). For creating TDSIs they make analysis of word frequencies in the documents and distinguish between the Zipf’s distribution that is typical for meaningful words and distributions approximated by an ellipse typical for auxiliary words. The authors also describe some analogies of these distributions in architecture and in urban planning. We describe a toolkit DDL that allows for TDSI creation and show its application for the mentioned website and for the corpus of dialogs with railway office information system.

Objective To evaluate preoperative diagnosis of low-grade urothelial carcinoma (LGUC) and urothelial neoplasms of unknown malignant potential (UMP UN) of the upper urinary tract (UUT) and its role in disease management, especially in the context of nephron-sparing treatment possibilities. Study design Wash and brush ureteral specimens of LGUC/UMP UN of the UUT with histopathologic correlation were retrieved at our institution for 7 years and studied along with 7 ureteral specimens from nonneoplastic ureteral lesions. Results Of 30 specimens from 25 LGUC/UMP UN, 5 were negative for tumor cells and 3 showed cytologic atypia. The remaining 22 contained tumor cells with characteristic features of urothelial carcinoma, including hard and soft criteria. The 4 hard criteria included branching stromal cores, dyshesive cell networks, 3-dimensional papillary clusters with stromal core and atypia associated with CK20-positive cells. The 2 soft criteria were hypercellularity and atypia in CK20-negative cells. All LGUC/UMP UN of the UUT were associated with at least 1 hard criterion or both soft criteria. Conclusion Branching stromal cores, 3-dimensional papillary clusters, dyshesive cell networks and CK20-positive atypia immunostaining appear specific for LGUC/UMP UN of the UUT but are seen in few cases. Combined soft and hard criteria will increase sensitivity to 83%.

We investigated the pattern of reactivity of calretinin and CD34 in normal and pathological endometria.Various endometrial tissues were submitted for calretinin and CD34 immunostaining.Calretinin reactivity was limited to the endometrial stromal cells (ESC) of the superficial zone of the functionalis layer (FL) in the proliferative phase, and was extensive in all stages of the secretory phase. The ESC of the post-menopausal, ectopic, hyperplastic or neoplastic endometria showed negative or focal weak reactivity for calretinin. In dysfunctional uterine bleeding (DUB) with a normal or an abnormal histopathological appearance on routine stain, there were varying degrees of focal to extensive decreases in calretinin reactivity. The foci of negative calretinin reactivity in the FL displayed varying reactivity for CD34 and appeared to be continuous with the basalis layer (BL). Endometrial polyps were often reactive for CD34, but not reactive for calretinin.Immunostaining for calretinin and CD34 is helpful in the diagnosis of endometrial polyp and hyperplasia. In DUB, with or without abnormal histopathological findings, there were alterations of the zonal pattern of calretinin reactivity in the FL. This alteration appears to be an expansion of the stroma of the BL into the FL, resulting in a 'disordered endometrial stroma'.

Papillary renal cell carcinoma (PRCC) can display extensive areas of solid and non-papillary architecture and extensive areas with oncocytic cytoplasm. Eleven oncocytic renal cell neoplasms (ORCN) with histopathological features posing a diagnostic problem between renal cell carcinoma (RCC) with oncocytic features and renal oncocytoma (RO) were identified. The neoplasms were well circumscribed or encapsulated tumors with solid and diffuse growth pattern. Very occasional papillae were seen in four and tumoral necrosis in two of 11. Six ORCN displayed a CD117+/progesterone receptor (PR)+ immunophenotype (feature shared by RO) and five tumors displayed a CD117-/PR- immunophenotype (feature shared by RCC). The CD117-/PR- ORCN also displayed alpha-methylacyl-coenzyme A racemase and RCC antigen reactivity as well as varying reactivity for cytokeratin 7, vimentin and CD10 (features of oncocytic PRCC). These five cases had tumor sizes ranging from 1 to 6 cm. Two patients in the latter group developed progression of the disease with metastases. In conclusion, oncocytic PRCC with solid architecture is a rare type of RCC. The carcinoma often poses differential diagnostic problems with RO and has similar immunohistochemical properties to the common type of PRCC. Cytogenetic and molecular studies have not been performed yet for this variant of RCC.

Especialista en Enfermería Quirúrgica Cuenca

They were continued, at National Institute of Nuclear Physics, Frascati National Laboratories-Italy, the systematic studies about detection of new elements, some even with isotopic composition different from natural one, after prolonged electrolysis of Pd wires. The electrolytic solution adopted is the, unusual, used from our experimental group since 1999. In short, it was a mixture of both heavy ethyl alcohol (C2H5OD at 90-95%) and water (D2O, at 10-5%), with Th salts at micromolar concentration and Hg at even lower concentration (both of spectroscopic purity). The liquid solutions, before use, were carefully vacuum distilled (and on line 100nm filtered) at low temperatures (30-40°C) and analysed by ICP-MS. The pH was kept quite mild (acidic at about 3-4). The cathode is Pd (99.9% purity) in the shape of long (60cm) and thin wires (diameter only 0.05mm). Before use, it is carefully cleaned and oxidised by Joule heating in air following a (complex) procedure from us continuously improved (since 1995). Before and after use, some pieces of it, about 50% of total length, are ICP-MS analysed. The anode is a Pt wire (purity>99.99%), 0.250mm diameter. The cell adopted is usually a borosilicate chemical glass (like SCHOTT-DURAN, Germany), filling volume about 750cc. Recently (since July 2004) an ultra-pure quartz cylinder (volume about 1050cc) was adopted in order to rule out possibilities of corrosion effects from the cell. The sample older and details of cell are made only of PTFE, as detailed at ICCF10 and ICCF11.

Gastrointestinal stromal tumors (GIST) are relatively rare tumors arising in the gastrointestinal tract. Clinical presentations of GIST are related to the site of origin, tumor size, and presence of ulceration. Surgery followed by adjuvant treatment with the BCR-ABL tyrosine kinase inhibitor, imatinib, for 3 years, in high-risk tumors is the only curative modality. Neoadjuvant treatment with imatinib may be considered in the setting of locally advanced primary borderline resectable/unresectable disease. Treatment with imatinib in patients with metastatic or unresectable disease is associated with significant improvements in overall survival (OS) from 18 to 57 months. In patients with metastatic disease, those responding to imatinib therapy may be considered for surgery and this may be beneficial if resection of the primary and metastatic disease is feasible and if imatinib is continued post resection. Other locoregional treatments such as radiofrequency ablation (RFA) and hepatic artery embolization (HAE) with or without chemotherapy may achieve long-lasting disease control and may be considered in highly selected patients. In patients with primary or secondary resistance to imatinib, second-line treatment with sunitinib and third-line treatment with regorafenib is recommended. However, despite all of these advances, few patients with metastatic disease are cured and further trials of novel agents or combinations are required.

The insoluble powder recovered at the bottom of our electrolytic cell, after several electrolytic deuterium loading/deloading cycles, was analysed by an ICP-MS analyser. The electrolyte was constituted of a deuterated hydro-alcoholic solution; Sr and Hg salts were added to such a solution at micromolar concentration; the cathode was a long and thin Pd wire. The ICP-MS analyses of the insoluble powder were motivated from the recent results of Y. Iwamura and collaborators at Mitsubishi Heavy Industries-Researh Center (Yokohama, Japan) showing reproducible "transmutation" of Sr into Mo (isotopic composition different from natural one) and Cs into Pr, when a special multilayer Pd sheet was subjected to a prolonged Deuterium gas flowing. Some of our results look partially in agreement with Y. Iwamura report. Other unexpected elements were also detected with an isotopic distribution close to the natural one. The production of stable isotopes by Selective Channel Photofission, according to the model of A.Takahashi (Osaka University, Japan), can help for understanding. Further works, hopefully also from other Laboratories, are needed to clarify this kind of results.