Metastatic colorectal cancer: optimizing treatment with anti-EGFR monoclonal antibody

Colorectal cancer remains a major cause of morbidity and mortality worldwide despite substantial improvement in the standard of care. Although surgical resection in selected patients may potentially be curative, systemic therapy is the only choice of treatment for most patients with metastatic colorectal cancer. Anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody has established its role in the systemic therapy of metastatic colorectal cancer through multiple well-designed clinical trials and yet, the optimal use of anti-EGFR monoclonal antibody is undefined. This article serves to review the available evidence for anti-EGFR monoclonal antibodies and to speculate optimal strategy for their uses.published_or_final_versio

Children born prematurely: Cognitive outcomes and preliminary findings for subsequent intervention

Well-established evidence shows that children born preterm/low birth weight (LBW) are at increased risk of academic difficulties (Lee, Yeatman, Luna, & Feldman, 2011; Pritchard et al., 2009) and, despite global IQ scores within the normal range, nonetheless display lower academic performance than their same age peers (Bhutta, Cleves, Casey, Cradock, & Anand, 2002; Kerr-Wilson, Mackay, Smith, & Pell, 2011). This is not fully understood and previous attempts to improve these circumstances through means of cognitive intervention have met with little success. Therefore, the current thesis investigates possible underlying mechanisms of this intellectual disparity and tests the effectiveness of one potential intervention. In doing so, the studies presented focus specifically on fluid intelligence (Taub, 2002). The investigation through fluid intelligence is relatively novel in the current literature and therefore worthy of further exploration. Normal individual differences in fluid intelligence have been explained with reference to information processing parameters. Previous studies have shown that children born preterm/LBW have impairments in basic processes identified with executive function (Aarnoudse-Moens, Smidts, Oosterlaan, Duivenvoorden, & Weisglas-Kuperus, 2009; Mulder, Pitchford, Hagger, & Marlow, 2009). However, the current study is the first to test whether differences in fluid intelligence, as measured by the Cattell Culture Fair Tests, between preterm (n = 217) and typically developing children (n = 145) could be accounted for by differences in working memory and cognitive flexibility, as measured by the digit span tasks and the Wisconsin Card Sorting Test respectively. Results indicate that the seven to nine years old preterm cohort performed less well on measures of fluid intelligence than their peers across all age groups and their differences were partially mediated by both working memory and cognitive flexibility in a multiple mediation analysis. It also identified at least one year of developmental delay in fluid intelligence between the clinical group and their peers. Provided with evidence from Study 1 and parallel research suggesting that computerized working memory training may enhance working memory and fluid intelligence in non-clinical groups (Jaeggi, Buschkuehl, Jonides, & Perrig, 2008; Klingberg, Forssberg, & Westerberg, 2002; Studer et al., 2009), the second goal of this thesis was to conduct a preliminary study to investigate the feasibility of cognitive training for children born preterm/LBW. Therefore, in the second study, the utility of a brief adaptive working memory span training program (Buschkuehl, Jaeggi, Kobel, & Perrig, 2008) was tested in typically developing children. Sixty-three children, aged seven to nine years, were randomly assigned to one of three groups: Intervention, active control and passive control. The intervention group was trained in the adaptive version of the working memory span task and the active control group was trained in the nonadaptive version. Both groups trained for 15 minutes each day for a duration of 20 days. Participants in the passive control group participated only in pre and post assessments. All participants were assessed using the digit span and spatial span tasks for measuring working memory, the Stroop task for measuring executive control, a reaction time task for measuring processing speed and the Raven’s Standard Progressive Matrices for measuring fluid intelligence. Results indicate that children in the intervention group improved on their trained task and demonstrated significant far transfer effects on the assessment of fluid intelligence compared to both control groups. However, no near transfer to other measures was found. The reason behind the occurrence of far transfer effect without evidence of near transfer effects was unclear. However, given that the adaptive complex working memory training task was not in any way similar to the fluid intelligence measure, significant differences in fluid intelligence gains were unlikely to have been a consequence of practice or general familiarity effects but, rather, a consequence of the training. Although Study 1 identified that working memory and cognitive flexibility partially mediate birth status-related differences in Gf, the impact of these variables on academic performance in children born preterm is still unknown. Nonetheless, current evidence of far transfer to fluid intelligence after adaptive complex working memory span training provides support for the utility of WM training and modifiability in Gf. This in turn provides a preliminary evidence-base approach for psychologists to work toward providing neuro-remediation treatment options to targeted clinical groups, such as those born preterm with fluid intelligence deficiencies. In combination, the outcomes of these two studies provide both a theoretical contribution to our understanding of the deficits observed in children born preterm and an applied contribution to beginning the process of developing appropriate intervention programmes suitable for this clinical group in the future, with hopeful prospects for improving cognitive outcomes

Schisandrin B as a Hormetic Agent for Preventing Age-Related Neurodegenerative Diseases

Oxidative stress and mitochondrial dysfunction have been implicated in the pathogenesis of neurodegenerative diseases, with the latter preceding the appearance of clinical symptoms. The energy failure resulting from mitochondrial dysfunction further impedes brain function, which demands large amounts of energy. Schisandrin B (Sch B), an active ingredient isolated from Fructus Schisandrae, has been shown to afford generalized tissue protection against oxidative damage in various organs, including the brain, of experimental animals. Recent experimental findings have further demonstrated that Sch B can protect neuronal cells against oxidative challenge, presumably by functioning as a hormetic agent to sustain cellular redox homeostasis and mitoenergetic capacity in neuronal cells. The combined actions of Sch B offer a promising prospect for preventing or possibly delaying the onset of neurodegenerative diseases, as well as enhancing brain health

Global Pattern of Nasopharyngeal Cancer: Correlation of Outcome With Access to Radiation Therapy

Purpose: This study aimed to estimate the treatment outcome of nasopharyngeal cancer (NPC) across the world and its correlation with access to radiation therapy (RT). Methods and Materials: The age-standardized mortality (ASM) and age-standardized incidence (ASI) rates of NPC from GLOBOCAN (2012) were summarized, and [1−(ASM/ASI)] was computed to give the proxy relative survival (RS). Data from the International Atomic Energy Agency (IAEA) and the World Bank were used to assess the availability of RT in surrogate terms: the number of RT equipment units and radiation oncologists per million population. Results: A total of 112 countries with complete valid data were analyzed, and the proxy RS varied widely from 0% to 83% (median, 50%). Countries were categorized into Good, Median, and Poor outcome groups on the basis of their proxy RS (55%). Eighty percent of new cases occurred in the Poor outcome group. Univariable linear regression showed a significant correlation between outcome and the availability of RT: proxy RS increased at 3.4% (P<.001) and 1.5% (P=.001) per unit increase in RT equipment and oncologist per million population, respectively. The median number of RT equipment units per million population increased significantly from 0.5 in the Poor, to 1.5 in the Median, to 4.6 in the Good outcome groups, and the corresponding number of oncologists increased from 1.1 to 3.3 to 7.1 (P<.001). Conclusions: Nasopharyngeal cancer is a highly treatable disease, but the outcome varies widely across the world. The current study shows a significant correlation between survival and access to RT based on available surrogate indicators. However, the possible reasons for poor outcome are likely to be multifactorial and complex. Concerted international efforts are needed not only to address the fundamental requirement for adequate RT access but also to obtain more comprehensive and accurate data for research to improve cancer outcome.postprin

Intraperitoneal chemotherapy for gastric cancer with peritoneal carcinomatosis: is HIPEC the only answer?

Gastric cancer with peritoneal carcinomatosis is notorious for its dismal prognosis. While the pathophysiology of peritoneal dissemination is still controversial, the rapid downhill course is universal. Patients usually suffer abdominal distension, intestinal obstruction and various complications before they succumb after a median of 3 - 6 months. Although not adopted in most international treatment guidelines, intraperitoneal chemotherapy has growing evidence compared with conventional systemic chemotherapy for the treatment of peritoneal carcinomatosis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is well-established for clinical benefit but is technically demanding with substantial treatment-related morbidities and mortality. On the other hand, normothermic intraperitoneal chemotherapy in the form of bidirectional neoadjuvant treatment is promising with various newer chemotherapeutic agents. Regardless of the treatment technique applied, the essential element of success is meticulous patient selection and availability of expertise. Future direction is along the line of personalized treatment with the application of translational science.published_or_final_versio

Radiation recall after capecitabine in a patient with recurrent nasopharyngeal carcinoma: a case report

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The International Atomic Energy Agency global initiatives on nasopharyngeal cancer treatment

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Policy proposals to select African states to optimize benefits from China's interest and investment in Africa

published_or_final_versionInternational and Public AffairsMasterMaster of International and Public Affair

Genetic linkage of beta and gamma subunits of epithelial sodium channel to systolic blood pressure in southern Chinese

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Efficacy and safety of afatinib in Chinese patients with EGFR-mutated metastatic non-small-cell lung cancer (NSCLC) previously responsive to first-generation tyrosine-kinase inhibitors (TKI) and chemotherapy: comparison with historical cohort using erlotinib

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