Overall survival of patients with recurrent pancreatic cancer treated with systemic therapy: a retrospective study

BACKGROUND: Only a few patients with pancreatic ductal adenocarcinoma (PDAC) recurring after curative resection and peri-operative (neoadjuvant and adjuvant) therapy are included in clinical trials of metastatic PDAC. As such, there is a paucity of data to guide treatment after relapse, and patients are treated similarly to those with de novo metastatic PDAC (mPDAC). We evaluated the patterns of chemotherapy use and over-all survival (OS) in patients with recurrent PDAC (rPDAC) following curative therapy. METHODS: In this retrospective study, the Indiana University pancreatic cancer database was used to identify patients with PDAC who underwent curative resection and subsequently developed recurrence. Demographics, tumor and treatment characteristics were collected. Patients were broadly divided into those who received chemotherapy for rPDAC and those who did not. Patients in the former category were further subdivided into those who received single agent therapy, any standard combination therapy (5-fluorouracil/irinotecan/oxaliplatin combination or gemcitabine/nab-paclitaxel) and those who received non-standard combinations. Survival analysis was performed by the Kaplan-Meier method. Log rank tests were used to determine differences in survival between treated rPDAC patients and those not treated. Cox regression analysis was employed to evaluate factors associated with OS. RESULTS: We identified 435 patients with resected PDAC treated between 2008 and 2014. Two hundred and twenty-three patients (51.2%) were diagnosed with rPDAC. Of these, 140 patients (63%) received chemotherapy whereas 71 patients (32%) did not receive chemotherapy. The 74 patients (53%) who received any standard, approved multiagent combination regimen had a median OS of 14 months compared to 8 months for the 47 patents (34%) who received other non-standard combinations and the 19 (13%) who received single agent therapy (P = 0.029). Multivariate cox regression analysis showed that margin negative resection, peri-operative therapy, radiotherapy and the use of any chemotherapy for rPDAC were associated with improved OS. CONCLUSION: Our findings support the use of standard approved multi-agent therapy in rPDAC. Patients derive significant benefit from these standard combination therapies with median OS that is comparable to what is observed with treatment for de novo mPDAC

Analytic treatment of geodesics in five-dimensional Myers-Perry space--times

We present the complete set of analytical solutions of the geodesic equation in the five-dimensional Myers-Perry space-time with equal rotation parameter in terms of the Weierstra{\ss}' elliptic and Weierstra{\ss}' zeta and sigma functions. We study the underlying polynomials in the polar and radial equations which depend on the parameters of the metric and conserved quantities of a test particle and characterize the motion by their zeros. We exemplify the efficiency of the analytical method on the orbits of test particles.Comment: 15 pages, 7 figures, to be published in PRD. Version with improved reference

Visualizing elements of Sha[3] in genus 2 jacobians

Mazur proved that any element xi of order three in the Shafarevich-Tate group of an elliptic curve E over a number field k can be made visible in an abelian surface A in the sense that xi lies in the kernel of the natural homomorphism between the cohomology groups H^1(k,E) -> H^1(k,A). However, the abelian surface in Mazur's construction is almost never a jacobian of a genus 2 curve. In this paper we show that any element of order three in the Shafarevich-Tate group of an elliptic curve over a number field can be visualized in the jacobians of a genus 2 curve. Moreover, we describe how to get explicit models of the genus 2 curves involved.Comment: 12 page

The orthogonal fitting procedure for determination of the empirical {\Sigma} - D relations for supernova remnants: application to starburst galaxy M82

The radio surface brightness-to-diameter ({\Sigma} - D) relation for supernova remnants (SNRs) in the starburst galaxy M82 is analyzed in a statistically more robust manner than in the previous studies that mainly discussed sample quality and related selection effects. The statistics of data fits in log {\Sigma} - log D plane are analyzed by using vertical (standard) and orthogonal regressions. As the parameter values of D - {\Sigma} and {\Sigma} - D fits are invariant within the estimated uncertainties for orthogonal regressions, slopes of the empirical {\Sigma} - D relations should be determined by using the orthogonal regression fitting procedure. Thus obtained {\Sigma} - D relations for samples which are not under severe influence of the selection effects could be used for estimating SNR distances. Using the orthogonal regression fitting procedure {\Sigma} - D slope {\beta} \approx 3.9 is obtained for the sample of 31 SNRs in M82. The results of implemented Monte Carlo simulations show that the sensitivity selection effect does not significantly influence the slope of M82 relation. This relation could be used for estimation of distances to SNRs that evolve in denser interstellar environment, with number denisty up to 1000 particles per cm3 .Comment: 14 pages, 3 figures, no changes, previous version had a typo in publication related comment, accepted for publication in Ap

Point vortices and classical orthogonal polynomials

Stationary equilibria of point vortices with arbitrary choice of circulations in a background flow are studied. Differential equations satisfied by generating polynomials of vortex configurations are derived. It is shown that these equations can be reduced to a single one. It is found that polynomials that are Wronskians of classical orthogonal polynomials solve the latter equation. As a consequence vortex equilibria at a certain choice of background flows can be described with the help of Wronskians of classical orthogonal polynomials.Comment: 20 pages, 12 figure

Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma

Phase III trials show sorafenib improves survival in advanced hepatocellular carcinoma (HCC). Because of narrow trial eligibility, results may not be generalizable to a broader HCC population. We sought to evaluate the effectiveness of initial sorafenib versus no treatment among Medicare beneficiaries with advanced HCC

Independent evaluation of a simple clinical prediction rule to identify right ventricular dysfunction in patients with shortness of breath

BACKGROUND: Many patients have unexplained persistent dyspnea after negative computed tomographic pulmonary angiography (CTPA). We hypothesized that many of these patients have isolated right ventricular (RV) dysfunction from treatable causes. We previously derived a clinical decision rule (CDR) for predicting RV dysfunction consisting of persistent dyspnea and normal CTPA, finding that 53% of CDR-positive patients had isolated RV dysfunction. Our goal is to validate this previously derived CDR by measuring the prevalence of RV dysfunction and outcomes in dyspneic emergency department patients. METHODS: A secondary analysis of a prospective observational multicenter study that enrolled patients presenting with suspected PE was performed. We included patients with persistent dyspnea, a nonsignificant CTPA, and formal echo performed. Right ventricular dysfunction was defined as RV hypokinesis and/or dilation with or without moderate to severe tricuspid regurgitation. RESULTS: A total of 7940 patients were enrolled. Two thousand six hundred sixteen patients were analyzed after excluding patients without persistent dyspnea and those with a significant finding on CTPA. One hundred ninety eight patients had echocardiography performed as standard care. Of those, 19% (95% confidence interval [CI], 14%-25%) and 33% (95% CI, 25%-42%) exhibited RV dysfunction and isolated RV dysfunction, respectively. Patients with isolated RV dysfunction or overload were more likely than those without RV dysfunction to have a return visit to the emergency department within 45 days for the same complaint (39% vs 18%; 95% CI of the difference, 4%-38%). CONCLUSION: This simple clinical prediction rule predicted a 33% prevalence of isolated RV dysfunction or overload. Patients with isolated RV dysfunction had higher recidivism rates and a trend toward worse outcomes

An estimate for the Morse index of a Stokes wave

Stokes waves are steady periodic water waves on the free surface of an infinitely deep irrotational two dimensional flow under gravity without surface tension. They can be described in terms of solutions of the Euler-Lagrange equation of a certain functional. This allows one to define the Morse index of a Stokes wave. It is well known that if the Morse indices of the elements of a set of non-singular Stokes waves are bounded, then none of them is close to a singular one. The paper presents a quantitative variant of this result.Comment: This version contains an additional reference and some minor change

Locoregional and systemic therapy for hepatocellular carcinoma

The management of hepatocellular carcinoma (HCC) remains challenging due to late presentation and the presence of accompanying liver dysfunction. As such, most patients are not eligible for curative resection and liver transplant. Management in this scenario depends on a number of factors including hepatic function, tumor burden, patency of hepatic vasculature and patients' functional status. Based on these, patients can be offered catheter based intra-arterial therapy for intermediate stage disease and in more advanced disease, sorafenib. Given recent data, regorafenib is now an option following failure of sorafenib. Catheter directed intra-arterial therapy takes advantage of tumor hypervascularity and the unique dual blood supply of the liver, as hepatic tumors receive arterial perfusion via the hepatic artery while the rest of the liver is supplied by the portal vein. This allows selective embolization and delivery of chemotherapeutic agents to the tumor. Compared to best supportive care, intra-arterial therapy offers a survival benefit in intermediate stage HCC and is the recommended approach for treatment. None of the catheter based approaches; including bland embolization, conventional trans-arterial chemoembolization (cTACE), drug eluting bead trans-arterial chemoembolization (DEB-TACE) or trans-arterial radioembolization (TARE) offers a clear advantage over the other, although DEB-TACE may be characterized by less systemic toxicity. All of these approaches are contraindicated in patients with portal vein thrombosis (PVT). On the other hand, intra-arterial, radio embolization, with Yttrium-90 (Y90) can be offered to patients with PVT. The place of this modality in management of HCC is still being investigated. The role of sorafenib in advanced HCC is not in doubt, as until recently, it was the only systemic therapy approved for the management in this setting. This is despite multiple trials evaluating other agents. The addition of sorafenib to catheter-based therapy in intermediate stage disease has also failed to show any benefit. The modest survival benefit with sorafenib and the failure of other targeted agents suggest that it is important to look beyond inhibition of angiogenesis in advanced HCC. Identification of key drivers and mediators of HCC remains paramount for successful drug development. In line with this, it is refreshing that the excitement that has followed developments in cancer immunotherapy is finding its way to HCC with early trials of anti-PD1 monoclonal antibodies showing sufficient activity that phase III trials are now ongoing for Pembrolizumab and Nivolumab in advanced HCC. Future drug development efforts will focus on defining the feasibility of combining different treatment approaches targeting multiple important modulators of HCC

UGC 7388: a galaxy with two tidal loops

We present the results of spectroscopic and morphological studies of the galaxy UGC7388 with the 8.1-m Gemini North telescope. Judging by its observed characteristics, UGC7388 is a giant late-type spiral galaxy seen almost edge-on. The main body of the galaxy is surrounded by two faint (\mu(B) ~ 24 and \mu(B) ~ 25.5) extended (~20-30 kpc) loop-like structures. A large-scale rotation of the brighter loop about the main galaxy has been detected. We discuss the assumption that the tidal disruption of a relatively massive companion is observed in the case of UGC7388. A detailed study and modeling of the observed structure of this unique galaxy can give important information about the influence of the absorption of massive companions on the galactic disks and about the structure of the dark halo around UGC7388.Comment: 8 pages, 5 figure