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A study was conducted to assess the percentage of individual placental mass that is associated with fetal survival in twin-twin transfusion syndrome after selective photocoagulation of communicating vessels. The findings contribute to the understanding of normal and pathologic monochorionic twin gestations, in the counseling of patients, and potentially to the improvement of surgical treatment of twin-twin transfusion syndrome.

The twin-twin transfusion syndrome is most likely to happen if the placenta contains deep anastomoses rather than superficial anastomoses, according to an examination of 131 placentas. All 85 placentas with deep anastomoses resulted in twin-twin transfusion syndrome compared to only 1 of the 18 placentas with superficial anastomoses. Twin-twin transfusion syndrome occurs when one twin receives most of the nutrients and grows at the expense of the other twin.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis largely owing to inefficient diagnosis and tenacious drug resistance. Activation of pancreatic stellate cells (PSCs) and consequent development of dense stroma are prominent features accounting for this aggressive biology1,2. The reciprocal interplay between PSCs and pancreatic cancer cells (PCCs) not only enhances tumour progression and metastasis but also sustains their own activation, facilitating a vicious cycle to exacerbate tumorigenesis and drug resistance3–7. Furthermore, PSC activation occurs very early during PDAC tumorigenesis8–10, and activated PSCs comprise a substantial fraction of the tumour mass, providing a rich source of readily detectable factors. Therefore, we hypothesized that the communication between PSCs and PCCs could be an exploitable target to develop effective strategies for PDAC therapy and diagnosis. Here, starting with a systematic proteomic investigation of secreted disease mediators and underlying molecular mechanisms, we reveal that leukaemia inhibitory factor (LIF) is a key paracrine factor from activated PSCs acting on cancer cells. Both pharmacologic LIF blockade and genetic Lifrdeletion markedly slow tumour progression and augment the efficacy of chemotherapy to prolong survival of PDAC mouse models, mainly by modulating cancer cell differentiation and epithelial–mesenchymal transition status. Moreover, in both mouse models and human PDAC, aberrant production of LIF in the pancreas is restricted to pathological conditions and correlates with PDAC pathogenesis, and changes in the levels of circulating LIF correlate well with tumour response to therapy. Collectively, these findings reveal a function of LIF in PDAC tumorigenesis, and suggest its translational potential as an attractive therapeutic target and circulating marker. Our studies underscore how a better understanding of cell–cell communication within the tumour microenvironment can suggest novel strategies for cancer therapy. A systematic proteomic investigation of disease mediators secreted by pancreatic stellate cells identifies leukaemia inhibitory factor (LIF) as a key factor that acts on cancer cells, promoting tumour progression and chemoresistance.

Patients with advanced gastric or gastro-oesophageal junction cancer that progresses on chemotherapy have poor outcomes. We compared pembrolizumab with paclitaxel in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine.

Aim:New approaches are required to improve compliance in older patients with problems in swallowing traditional formulations. A novel memantine orodispersible tablet (ODT) was formulated, and its bioavailability and taste acceptability were evaluated. Materials & methods:In vitrocharacterization of ODT comprised dispersion in simulated saliva prior to dissolution assay in a limited volume of biorelevant media. A single oral dose of 20-mg memantine ODT exhibits similar bioavailability to that of an immediate release 20-mg tablet in a healthy population under fasting conditions. Results:90 confidence interval for Cmaxwas of 96.78–106.52 and 98.27–104.78 for AUC0–72. An applied palatability survey showed exceptional acceptance of the formulation. Conclusion:Memantine microspheres prepared by a solid-dispersion technique results in ODT with adequate biopharmaceutical performance.

ABSTRACTCarcinosarcoma is a rare subtype of pancreatic neoplasm including both carcinomatous and sarcomatous components. Fewer than 30 cases have been reported to the Surveillance, Epidemiology, and End Results Program database. Given such rarity, definitive treatment guidelines are not well defined. We report a case of pancreatic carcinosarcoma diagnosed in our institution, review tumor clinicopathological characteristics, and describe our medical and surgical management strategy.

Abstract Purpose: To determine the anti-tumor activity DX-8951f when administered as a 30-minute infusion daily for 5 days every 3 weeks to patients with previously untreated metastatic gastric cancer, and to evaluate toxicities and pharmacokinetics (PK) of DX-8951f in this patient population. Patients and methods: Forty-one patients were enrolled. All had previously untreated metastatic gastric cancer. DX-8951f was administered until disease progression or unacceptable toxicity. Responses were assessed after every 2 courses using RECIST criteria. Results: Thirty-nine patients were evaluable. Two patients achieved a partial response (PR) and 18 achieved stable disease (SD), including five patients with unconfirmed PR. A total of 141 courses of therapy were delivered (median 3, range 1–10). The most common drug-related toxicity was neutropenia. Non-hematologic toxicities were mostly mild to moderate; the most common were nausea, vomiting and anorexia. Plasma concentrations of DX-8951 (the anhydrous form of DX-8951f) were well described using a linear 2-compartment PK model. All concentrations and dose events were simultaneously modeled and explained by the population PK model. There was no evidence of non-linearity in the elimination PK, auto-inhibition or induction of DX-8951 clearance over the five days of administration. Conclusions: DX-8951f had modest activity against metastatic gastric cancer and its PK was dose-proportional. The toxicity profile was predictable and manageable. Further development of this agent is warranted.

Fragmentation patterns of cell-free DNA from urine differ between healthy individuals and those with cancer.

The article focuses on the Municipal Action Guide on Supporting Foster Youth Transitions to Adulthood which aims to help the role of city officials on its campaign to help foster youth. It mentions that the guide offers strategies that can be taken by city officials in partnership with states, county agencies and other local service providers to address needs of foster youth. The guide also provides examples of actions done from various cities that support foster youth transition.

The article reports that the youth employment rate continues to decline in 2009. It states that the low employment rate could cause adverse effects on the earning potential and future employment status of the youth. It mentions that the American Recovery and Reinvestment Act of 2009 (ARRA) allotted 1.2 billion dollars funding to stimulate youth and older youth employment. It also notes the establishment of the Reengaging Disconnected Youth through Economic Efforts learning community.

The article reports that 12 cities were selected by the National League of Cities' (NLC) Youth, Education, and Families Institute (YEF Institute) to take part in the Reengaging Disconnected Youth Through Economic Recovery Efforts learning community. The chosen cities will focus on how the funds of the American Recovery and Reinvestment Act (ARRA) should be use to strengthen the employment efforts for youth it their locality. The cities selected include Moines, Iowa and Hartford, Connecticut.

The article focuses on the Institute for Youth, Education and Families (YEF Institute) sponsored by the National League of Cities in the U.S. It states that the program is supported by the Charles Stewart Mott Foundation, and municipal leaders seeking to reengage disconnected youth through the use of economic recovery resources. The project is designed to help cities be more strategies in reengaging youth who are out of school.

The article reports on the meeting of the Municipal Network for Disconnected Youth (MNDY) of the National League of Cities (NLC) in Baltimore, Maryland. Among the main highlights of the event were visits to the Harbor City High School and Baltimore's Youth Opportunity Center. The goal of the meeting was to investigate sustainability techniques for reengaging school dropouts who lack connections to family and are out of work.

The article reports that the National League of Cities (NLC) will provide technical assistance to several cities from across the U.S. as part of an initiative of its Institute for Youth, Education and Families. NLC aims to help municipal leaders reengage disconnected youth through collaboration. The cities include Denver, Colorado; Hartford, Connecticut; Newark, New Jersey; Orlando, Florida; Roanoke, Virginia; and St. Louis, Missouri.

Savona: Karyopharm: Consultancy, Equity Ownership; Celgene: Consultancy; Gilead: Consultancy; Incyte: Consultancy. Kolibaba:Celgene: Research Funding. Conkling:Celgene: Research Funding. Rifkin:Celgene: Scientific Advisory Board Other; Millennium/Takeda: Scientific Advisory Board, Scientific Advisory Board Other; Onyx/Amgen: Scientific Advisory Board, Scientific Advisory Board Other. Laille:Celgene: Employment, Equity Ownership. Kellerman:Celgene: Employment. Ukrainskyj:Celgene: Employment, Equity Ownership. Dong:Celgene: Employment. Skikne:Celgene: Employment, Equity Ownership.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

Darinaparsin is an organic arsenic molecule constructed of dimethylated arsenic linked to glutathione (N-[S-(dimethylarsino)-N-L-gamma-glutamyl-L-cysteinyl]-glycine). It has a multifaceted mechanism of action, inducing G2/M cell cycle arrest and apoptosis mediated through disruption of mitochondrial functions, increased reactive oxygen species production, and modulation of signal transduction pathways. In addition, darinaparsin has anti-angiogenic activity. It has significant activity in a broad spectrum of hematologic and solid tumors in preclinical models, including human cell lines resistant to arsenic trioxide. It is active in heavily treated patients with refractory lymphoma when administered IV 300 mg/m2 for 5 days on a 28 day cycle, and is very well tolerated. Preclinically it is orally highly bioavailable. Oral administration may be of importance in potential utility in lymphoma in continuous metronomic dosing.Two Phase I studies of oral darinaparsin are being conducted in patients diagnosed with relapsed or refractory advanced tumors. The first protocol is a Phase I, dose-escalation, oral administration study designed to determine the MTD of darinaparsin capsules. The dosing schedule is a regimen of 2 doses per week for 3 weeks followed by 1 week of rest, starting at 300 mg twice weekly. A second Phase I study, having a similar design and objective, evaluates several dosing regimens, including dosing capsules three times per week increasing dosing frequency to daily dosing for 3 weeks, with 1 week of rest. For each study 28 days constitutes one cycle. Standard methods for evaluation of toxicity, escalation and efficacy are being used.These two studies have thus far enrolled 19 and 17 patients, respectively. In total there are 24 male and 12 female patients. The median age is 59 years, with a range from 38 to 82 years. To date, MTD has not been reached in either study. The dose continues to be escalated and is currently at 900mg / day twice weekly in the 1st study, and 300 mg daily every day in the 2nd study. Bioavailability has been very high (>75%). All patients were heavily pretreated and refractory. Of 27 evaluable patients thus far in the two trials, 2 had a partial response and 15 had prolonged stable disease, including lymphoma (NHL), head and neck, colon, and pancreatic cancers. The duration of responses has been 3 – 8 + months. Safety and tolerability has been very good and comparable to that of IV darinaparsin. SAEs were atrial fibrillation and congestive heart failure, each occurring in one patient, and dyspnea, occurring in two patients. No QT prolongation has been observed. Dose escalation continues in both studies and updated results will be presented.Darinaparsin is a novel organic arsenic molecule that has demonstrated clinical activity in refractory lymphoma when given IV. When given orally by capsule, the drug is well tolerated and demonstrates early signs of activity.Buck: ZIOPHARM Oncology: Employment. Wallner:ZIOPHARM Oncology: Employment. Lewis:ZIOPHARM Oncology: Employment, Membership on an entity's Board of Directors or advisory committees.

Abstract 4759

The article reports that several groups of city and school district leaders from six communities in South Carolina, Tennessee, California and Georgia met in Washington, D.C. to launch collaboration efforts to combat childhood obesity. The National League chosen the communities of Cities (NLC) Institute for Youth, Education and Families and the American Association of School Administrators to receive technical assistance in developing wellness programs.

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