Impact of Radiotherapy, Chemotherapy and Surgery in Multimodal Treatment of Locally Advanced Esophageal Cancer

Objectives: It was the aim of this study to assess our institutional experience with definitive chemoradiation (CRT) versus induction chemotherapy followed by CRT with or without surgery (C-CRT/S) in esophageal cancer. Methods: We retrospectively analyzed 129 institutional patients with locally advanced esophageal cancer who had been treated by either CRT in analogy to the RTOG 8501 trial (n = 78) or C-CRT/S (n = 51). Results: The median, 2-and 5-year overall survival (OS) of the entire collective was 17.6 months, 42 and 24%, respectively, without a significant difference between the CRT and C-CRT/S groups. In C-CRT/S patients, surgery statistically improved the locoregional control (LRC) rates (2-year LRC 73.6 vs. 21.2%; p = 0.003); however, this was translated only into a trend towards improved OS (p = 0.084). The impact of escalated radiation doses (>= 60.0 vs. <60.0 Gy) on LRC was detectable only in T1-3 N0-1 M0 patients of the CRT group (2-year LRC 77.8 vs. 42.3%; p = 0.036). Conclusion: Definitive CRT and a trimodality approach including surgery (C-CRT/S) had a comparable outcome in this unselected patient collective. Surgery and higher radiation doses improve LRC rates in subgroups of patients, respectively, but without effect on OS. Copyright (C) 2012 S. Karger AG, Base

Double Field Theory Formulation of Heterotic Strings

We extend the recently constructed double field theory formulation of the low-energy theory of the closed bosonic string to the heterotic string. The action can be written in terms of a generalized metric that is a covariant tensor under O(D,D+n), where n denotes the number of gauge vectors, and n additional coordinates are introduced together with a covariant constraint that locally removes these new coordinates. For the abelian subsector, the action takes the same structural form as for the bosonic string, but based on the enlarged generalized metric, thereby featuring a global O(D,D+n) symmetry. After turning on non-abelian gauge couplings, this global symmetry is broken, but the action can still be written in a fully O(D,D+n) covariant fashion, in analogy to similar constructions in gauged supergravities.Comment: 28 pages, v2: minor changes, version published in JHE

Massive Type II in Double Field Theory

We provide an extension of the recently constructed double field theory formulation of the low-energy limits of type II strings, in which the RR fields can depend simultaneously on the 10-dimensional space-time coordinates and linearly on the dual winding coordinates. For the special case that only the RR one-form of type IIA carries such a dependence, we obtain the massive deformation of type IIA supergravity due to Romans. For T-dual configurations we obtain a `massive' but non-covariant formulation of type IIB, in which the 10-dimensional diffeomorphism symmetry is deformed by the mass parameter.Comment: 21 page

Magnetic Flux-Based Nondestructive Evaluation Technologies for Assessing Corrosion Damage in External and Internal Post-Tensioned Tendons: Development Efforts and Evaluation Results

DTFH61-14-D-00011This report presents research work related to developing and evaluating magnetic flux-based nondestructive evaluation (NDE) technologies for detecting corrosion damage in external and internal post-tensioned (PT) tendons. For the external tendons, two types of magnetic main flux method (MMFM) systems\u2014a solenoid type and a permanent magnet type\u2014 were developed and validated in the laboratory and in the field. The solenoid-type MMFM system was the most accurate NDE method. Its lowest damage detection limit would be 0.4-percent section loss for the point measurement method and 1.0-percent section loss for the scan measurement method. The permanent-type MMFM system is suitable for locating potential problem areas containing more than 3.0-percent section loss in external PT tendons. It has more versatile applications in the field because of its simpler hardware and speedy operation. Ideally, both MMFM systems can be employed in sequence during the field investigations: the permanent magnet type identifies potentially problematic areas by quickly scanning all suspected tendons, followed by the point measurements in the suspicious areas with the solenoid type. A return flux method prototype was developed for the internal tendons. It reached the immediate goal of detecting relatively small section losses hidden in internal tendons in laboratory environments and proved its concept successfully. It could detect a section loss larger than 15.3-percent in internal mockup tendons surrounded by vertical rebars at 6.0-inch or wider spacing when the clear concrete cover was less than 7.5 inches for metal ducts and 6.5 inches for polyethylene ducts. Without interference from the vertical rebars, as little as 9.0-percent section loss could be identified at the 6.0-inch cover. However, poor results were obtained in the anchorage zone in the box girder specimen. It is recommended that the present prototype be further improved to make it a field-deployable NDE system

The role of primary tumor resection in colorectal cancer patients with asymptomatic, synchronous unresectable metastasis: Study protocol for a randomized controlled trial

BACKGROUND: Approximately 20 % of all patients with colorectal cancer are diagnosed as having Stage IV cancer; 80 % of these present with unresectable metastatic lesions. It is controversial whether chemotherapy with or without primary tumor resection (PTR) is effective for the treatment of patients with colorectal cancer with unresectable metastasis. Primary tumor resection could prevent tumor-related complications such as intestinal obstruction, perforation, bleeding, or fistula. Moreover, it may be associated with an increase in overall survival. However, surgery delays the use of systemic chemotherapy and affects the systemic spread of malignancy. METHODS/DESIGN: Patients with colon and upper rectal cancer patients with asymptomatic, synchronous, unresectable metastasis will be included after screening. They will be randomized and assigned to receive chemotherapy with or without PTR. The primary endpoint measure is 2-year overall survival rate and the secondary endpoint measures are primary tumor-related complications, quality of life, surgery-related morbidity and mortality, interventions with curative intent, chemotherapy-related toxicity, and total cost until death or study closing day. The authors hypothesize that the group receiving PTR following chemotherapy would show a 10 % improvement in 2-year overall survival, compared with the group receiving chemotherapy alone. The accrual period is 3 years and the follow-up period is 2 years. Based on the inequality design, a two-sided log-rank test with α-error of 0.05 and a power of 80 % was conducted. Allowing for a drop-out rate of 10 %, 480 patients (240 per group) will need to be recruited. Patients will be followed up at every 3 months for 3 years and then every 6 months for 2 years after the last patient has been randomized. DISCUSSION: This randomized controlled trial aims to investigate whether PTR with chemotherapy shows better overall survival than chemotherapy alone for patients with asymptomatic, synchronous unresectable metastasis. This trial is expected to provide evidence so support clear treatment guidelines for patients with colorectal cancer with asymptomatic, synchronous unresectable metastasis. TRIAL REGISTRATION: Clinicaltrials.gov NCT01978249

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Gastric Juvenile Polyposis with High-Grade Dysplasia in Pachydermoperiostosis

Pachydermoperiostosis (PDP) is the primary form of hypertrophic osteoarthropathy. It is a very rare disease consisting of pachydermia, digital clubbing and radiologic periostosis. Various digestive symptoms in PDP are seen in 11–49% of patients and juvenile polyps may be found at gastric endoscopy. We report here the history of a patient with PDP who was referred for assessment of severe anemia. Endoscopy of the upper digestive tract showed multiple polyps of the stomach with two huge lesions exhibiting foci of high-grade dysplasia. This observation suggests that PDP can be considered as a precancerous condition of the stomach and systematic screening using endoscopy should be considered in these patients

Inactivation of the FLCN Tumor Suppressor Gene Induces TFE3 Transcriptional Activity by Increasing Its Nuclear Localization

Germline mutations in a tumor suppressor gene FLCN lead to development of fibrofolliculomas, lung cysts and renal cell carcinoma (RCC) in Birt-Hogg-Dubé syndrome. TFE3 is a member of the MiTF/TFE transcription factor family and Xp11.2 translocations found in sporadic RCC involving TFE3 result in gene fusions and overexpression of chimeric fusion proteins that retain the C-terminal DNA binding domain of TFE3. We found that GPNMB expression, which is regulated by MiTF, was greatly elevated in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Since TFE3 is implicated in RCC, we hypothesized that elevated GPNMB expression was due to increased TFE3 activity resulting from the inactivation of FLCN.TFE3 knockdown reduced GPNMB expression in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Moreover, FLCN knockdown induced GPNMB expression in FLCN-restored renal cancer cells. Conversely, wildtype FLCN suppressed GPNMB expression in FLCN-null cells. FLCN inactivation was correlated with increased TFE3 transcriptional activity accompanied by its nuclear localization as revealed by elevated GPNMB mRNA and protein expression, and predominantly nuclear immunostaining of TFE3 in renal cancer cells, mouse embryo fibroblast cells, mouse kidneys and mouse and human renal tumors. Nuclear localization of TFE3 was associated with TFE3 post-translational modifications including decreased phosphorylation.Increased TFE3 activity is a downstream event induced by FLCN inactivation and is likely to be important for renal tumor development. This study provides an important novel mechanism for induction of TFE3 activity in addition to TFE3 overexpression resulting from Xp11.2 translocations, suggesting that TFE3 may be more broadly involved in tumorigenesis

Serial interferon-gamma release assays during treatment of active tuberculosis in young adults

<p>Abstract</p> <p>Background</p> <p>The role of interferon-γ release assay (IGRA) in monitoring responses to anti-tuberculosis (TB) treatment is not clear. We evaluated the results of the QuantiFERON-TB Gold In-tube (QFT-GIT) assay over time during the anti-TB treatment of adults with no underlying disease.</p> <p>Methods</p> <p>We enrolled soldiers who were newly diagnosed with active TB and admitted to the central referral military hospital in South Korea between May 1, 2008 and September 30, 2009. For each participant, we preformed QFT-GIT assay before treatment (baseline) and at 1, 3, and 6 months after initiating anti-TB medication.</p> <p>Results</p> <p>Of 67 eligible patients, 59 (88.1%) completed the study protocol. All participants were males who were human immunodeficiency virus (HIV)-negative and had no chronic diseases. Their median age was 21 years (range, 20-48). Initially, 57 (96.6%) patients had positive QFT-GIT results, and 53 (89.8%), 42 (71.2%), and 39 (66.1%) had positive QFT-GIT results at 1, 3, and 6 months, respectively. The IFN-γ level at baseline was 5.31 ± 5.34 IU/ml, and the levels at 1, 3, and 6 months were 3.95 ± 4.30, 1.82 ± 2.14, and 1.50 ± 2.12 IU/ml, respectively. All patients had clinical and radiologic improvements after treatment and were cured. A lower IFN-γ level, C-reactive protein ≥ 3 mg/dl, and the presence of fever (≥ 38.3°C) at diagnosis were associated with negative reversion of the QFT-GIT assay.</p> <p>Conclusion</p> <p>Although the IFN-γ level measured by QFT-GIT assay decreased after successful anti-TB treatment in most participants, less than half of them exhibited QFT-GIT reversion. Thus, the reversion to negativity of the QFT-GIT assay may not be a good surrogate for treatment response in otherwise healthy young patients with TB.</p

Quality of life and mortality from a nephrologist's view: a prospective observational study

<p>Abstract</p> <p>Background</p> <p>Although health-related quality of life (HRQOL) is a potential independent predictor of mortality, nephrologists have shown little interest in HRQOL with respect to mortality in chronic kidney disease (CKD). The aim of this article is to evaluate the impact of HRQOL on mortality in the elderly, who are likely to develop or already have CKD.</p> <p>Methods</p> <p>Among 1,000 randomly sampled participants aged more than 65 years (sourced from the Korean Longitudinal Study on Health and Ageing), 944 subjects were evaluated for HRQOL. HRQOL was assessed using a 36-item Short-Form health survey (SF36). A cumulative survival rate was calculated according to tertiles of SF36 scores and classified by the presence of CKD (estimated GFR <60 ml/min/1.73 m²).</p> <p>Results</p> <p>Among 944 subjects, 46.6% had CKD. CKD patients had lower total and physical component scores compared with subjects without CKD. The 3-year cumulative survival rate was 90.0% (non-CKD vs. CKD: 92.6% vs. 87.4%, <it>P </it>= 0.005 by log rank test). After adjusting for multiple variables, a reduced SF36 score (physical and mental components) was a strong predictor of all-cause mortality. Physical components were consistently able to predict mortality after CKD classification, but mental components were statistically significant only in the CKD group.</p> <p>Conclusion</p> <p>In addition to traditional risk factors of mortality, nephrologists should be aware of HRQOL as a predictor of mortality and should make efforts to improve HRQOL in CKD patients.</p