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Purpose: Accurate prognostication may aid in the selection of patients who will benefit from surgery at recurrent WHO grade 4 glioma. This study aimed to evaluate the role of serial tumour volumetric measurements for prognostication at first tumour recurrence., Methods: We retrospectively analyzed patients with histologically-diagnosed WHO grade 4 glioma at initial and at first tumour recurrence at a tertiary hospital between May 2000 and September 2018. We performed auto-segmentation using ITK-SNAP software, followed by manual adjustment to measure serial contrast-enhanced T1W (CE-T1W) and T2W lesional volume changes on all MRI images performed between initial resection and repeat surgery., Results: Thirty patients met inclusion criteria; the median overall survival using Kaplan-Meier analysis from second surgery was 10.5 months. Seventeen (56.7%) patients received treatment post second surgery. Univariate cox regression analysis showed that greater rate of increase in lesional volume on CE-T1W (HR = 2.57; 95% CI [1.18, 5.57]; p = 0.02) in the last 2 MRI scans leading up to the second surgery was associated with a higher mortality likelihood. Patients with higher Karnofsky Performance Score (KPS) (HR = 0.97; 95% CI [0.95, 0.99]; p = 0.01) and who received further treatment following second surgery (HR = 0.43; 95% CI [0.19, 0.98]; p = 0.04) were shown to have a better survival., Conclusion: Higher rate of CE-T1W lesional growth on the last 2 MRI images prior to surgery at recurrence was associated with increase mortality risk. A larger prospective study is required to determine and validate the threshold to distinguish rapidly progressive tumour with poor prognosis., (© 2024. The Author(s).)

The recent legalization of cannabidiol (CBD) to treat neurological conditions such as epilepsy has sparked rising interest across global pharmaceuticals and synthetic biology industries to engineer microbes for sustainable synthetic production of medicinal CBD. Since the process involves screening large amounts of samples, the main challenge is often associated with the conventional screening platform that is time consuming, and laborious with high operating costs. Here, a portable, high-throughput Aptamer-based BioSenSing System (ABS 3 ) is introduced for label-free, low-cost, fully automated, and highly accurate CBD concentrations' classification in a complex biological environment. The ABS 3 comprises an array of interdigitated microelectrode sensors, each functionalized with different engineered aptamers. To further empower the functionality of the ABS 3 , unique electrochemical features from each sensor are synergized using physics-guided multidimensional analysis. The capabilities of this ABS 3 are demonstrated by achieving excellent CBD concentrations' classification with a high prediction accuracy of 99.98% and a fast testing time of 22 µs per testing sample using the optimized random forest (RF) model. It is foreseen that this approach will be the key to the realistic transformation from fundamental research to system miniaturization for diagnostics of disease biomarkers and drug development in the field of chemical/bioanalytics., (© 2022 Wiley-VCH GmbH.)

Background: Therapeutic synergism between radiotherapy and immune checkpoint blockade has been observed in preclinical models of hepatocellular carcinoma. We aimed to study the safety and efficacy of sequential radioembolisation with yttrium-90-resin microspheres (Y90-radioembolisation) followed by nivolumab in patients with advanced hepatocellular carcinoma., Methods: Patients with Child-Pugh A cirrhosis and advanced hepatocellular carcinoma not suitable for curative surgery were treated with Y90-radioembolisation followed by intravenous nivolumab 240 mg 21 days after Y90-radioembolisation and every 2 weeks thereafter. The primary endpoint, assessed in the per-protocol population, was the objective response rate, determined by RECIST version 1.1, defined as the proportion of patients with a confirmed complete or partial response observed for lesions both within and outside the Y90-radioembolisation field. This study is registered with ClinicalTrials.gov, NCT03033446 and has been completed., Findings: 40 patients were enrolled, of whom 36 received Y90-radioembolisation followed by nivolumab. One (3%) patient had a complete response and ten (28%) had a partial response; the objective response rate was 30·6% (95% CI 16·4-48·1). The most common treatment-related adverse events of any grade were pruritus (18 [50%] of 36 patients) and maculopapular rash (13 [36%]). Two (6%) patients experienced grade 3-4 treatment-related adverse events: one patient had a grade 3 increase in alanine aminotransferase levels, grade 3 bilirubin increase, and grade 4 increase in aspartate aminotransferase levels, while the other had a grade 3 maculopapular rash. Five (14%) patients had a treatment-related serious adverse event (Steven-Johnson syndrome, hepatitis E infection, fever, liver abscesses, and ascites)., Interpretation: Y90-radioembolisation followed by nivolumab resulted in an encouraging objective response rate in patients with advanced hepatocellular carcinoma, although the activity observed was not as high as the study was powered for. This strategy should be further evaluated in patients with Barcelona Clinic Liver Clinic (BCLC) stage B hepatocellular carcinoma that is ineligible or refractory to transarterial chemoembolisation and patients with BCLC C disease without extrahepatic spread., Funding: National Medical Research Council Singapore, Bristol-Myers Squibb, Sirtex., Competing Interests: Declaration of interests DT declares support for the current manuscript from Bristol-Myers Squibb, Sirtex, and NMRC Singapore (CIRG/1470/2017); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Ipsen, Eisai, and Bristol-Myers Squibb; and consulting fees from Novartis, Bristol-Myers Squibb, and Merck Sharpe Dohme. CSP declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche, Bristol-Myers Squibb, Ipsen, Lilly, AstraZeneca, and Roche; consulting fees from Bristol-Myers Squibb, Roche, Ipsen, Servier, Eisai, and AstraZeneca; a leadership or fiduciary role for Ministry of Health Singapore Medishield Life Cancer Drug committee; and stock or stock options with Bristol-Myers Squibb. DN declares support for the present manuscript from Sirtex; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Sirtex. JL declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bristol-Myers Squibb, Ipsen, and Bayer; and research funding from Bayer. PKHC declares grants or contracts from Sirtex Medical, Ipsen, IQVIA, New B Innovation, Perspectum, AMiLi, MiRXES, Genentech, and Engine Biosciences; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Sirtex Medical, Ipsen, Oncosil, Bayer, Roche, New B Innovation, Merck Sharpe Dohme, BTG Plc, Eisai, Abbott, AstraZeneca, IQVIA, Genentech, Worrell Guerbet, LEK Consulting, and COR2ED; and a leadership or fiduciary role, and stock or stock options for AVATAMED. TCW declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events and consulting fees from Sirtex. KL, AG, NKA, TSH, TH, FI, JL, MN, TCK, KSL, CHS, GGBB, HLH, NK, RL, BG, AC, THC, TCH, TL, JY, ZWW, and CCY declared no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

As 5G communication technology allows for speedier access to extended information and knowledge, a more sophisticated human-machine interface beyond touchscreens and keyboards is necessary to improve the communication bandwidth and overcome the interfacing barrier. However, the full extent of human interaction beyond operation dexterity, spatial awareness, sensory feedback, and collaborative capability to be replicated completely remains a challenge. Here, we demonstrate a hybrid-flexible wearable system, consisting of simple bimodal capacitive sensors and a customized low power interface circuit integrated with machine learning algorithms, to accurately recognize complex gestures. The 16 channel sensor array extracts spatial and temporal information of the finger movement (deformation) and hand location (proximity) simultaneously. Using machine learning, over 99 and 91% accuracy are achieved for user-independent static and dynamic gesture recognition, respectively. Our approach proves that an extremely simple bimodal sensing platform that identifies local interactions and perceives spatial context concurrently, is crucial in the field of sign communication, remote robotics, and smart manufacturing.

Background: During the ongoing COVID-19 pandemic, healthcare-associated transmission of respiratory viral infections (RVI) is a concern. To reduce the impact of SARS-CoV-2 and other respiratory viruses on patients and healthcare workers (HCWs) we devised and evaluated a multi-tiered infection control strategy with the goal of preventing nosocomial transmission of SARS-CoV2 and other RVIs across a large healthcare campus., Methods: From January-June 2020, a multi-tiered infection control strategy was implemented across a healthcare campus in Singapore, comprising the largest acute tertiary hospital as well as four other subspecialty centres, with more than 10,000 HCWs. Drawing on our institution's experience with an outbreak of Severe Acute Respiratory Syndrome (SARS) in 2003, this strategy included improved patient segregation and distancing, and heightened infection prevention and control (IPC) measures including universal masking. All symptomatic patients were tested for COVID-19 and common RVIs., Results: A total of 16,162 admissions campus-wide were screened; 7.1% (1155/16,162) tested positive for COVID-19. Less than 5% of COVID-19 cases (39/1155) were initially detected outside of isolation wards in multi-bedded cohorted wards. Improved distancing and enhanced IPC measures successfully mitigated onward spread even amongst COVID-19 cases detected outside of isolation. COVID-19 rates amongst HCWs were kept low (0.13%, 17/13,066) and reflected community acquisition rather than nosocomial spread. Rates of healthcare-associated-RVI amongst inpatients fell to zero and this decrease was sustained even after the lifting of visitor restrictions., Conclusion: This multi-tiered infection control strategies can be implemented at-scale to successfully mitigate healthcare-associated transmission of respiratory viral pathogens., (Copyright © 2020 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All rights reserved.)

Purpose: We present the strategy of a comprehensive cancer center organized to make operations pandemic proof and achieve continuity of cancer care during the COVID-19 pandemic., Methods: Disease Outbreak Response (DORS) measures implemented at our center and its satellite clinics included strict infection prevention, manpower preservation, prudent resource allocation, and adaptation of standard-of-care treatments. Critical day-to-day clinical operations, number of persons screened before entry, staff temperature monitoring, and personal protection equipment stockpile were reviewed as a dashboard at daily DORS taskforce huddles. Polymerase chain reaction swab tests performed for patients and staff who met defined criteria for testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were tracked. Descriptive statistics of outpatient attendances and treatment caseloads from February 3 to May 23, 2020, were compared with the corresponding period in 2019., Results: We performed COVID-19 swabs for 80 patients and 93 staff, detecting three cancer patients with community-acquired COVID-19 infections with no nosocomial transmission. Patients who required chemotherapy, radiotherapy, or surgery and patients who are on maintenance treatment continued to receive timely treatment without disruption. The number of intravenous chemotherapy treatments was maintained at 97.8% compared with 2019, whereas that of weekly radiotherapy treatments remained stable since December 2019. All cancer-related surgeries proceeded without delay, with a 0.3% increase in workload. Surveillance follow-ups were conducted via teleconsultation, accounting for a 30.7% decrease in total face-to-face clinic consultations., Conclusion: Through the coordinated efforts of a DORS taskforce, it is possible to avoid nosocomial SARS-CoV-2 transmissions among patients and staff without compromising on care delivery at a national cancer center.

The COVID-19 pandemic has disrupted current models of healthcare and adaptations will likely continue. With the gradual easing of lockdown measures worldwide, cancer centres must be prepared to implement novel means to prevent repeated waves of infection. There are two limitations unique to oncology - a higher susceptibility of patients to COVID-19 and the multidisciplinary approach required of cancer management. We describe the measures implemented in the largest cancer centre in Singapore to continue optimal cancer care in spite of the ongoing pandemic, with no nosocomial infections reported in our centre to date. We adopted a multipronged approach, with an overall committee supervising the entire COVID-19 management effort. A screening clinic was setup to triage patients prior to entry to the centre. Each Oncology Division within the cancer centre designed solutions tailored to the specific needs of their discipline. We explore in detail the screening criteria and workflow of the screening clinic, as well as modifications by individual divisions to reduce infection risk to patients and healthcare professionals. This approach can be modelled by other cancer centres during this prolonged COVID-19 pandemic., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Elsevier Ltd. All rights reserved.)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Aim: The survival benefit of using a non-cross resistant second-line chemotherapy in the third-line setting in metastatic gastroesophageal cancer is unproven. We evaluated the utility of third-line chemotherapy in patients treated at a single institution., Methods: Between 2010 and 2014, efficacy and toxicity data of patients who received three or more lines of systemic therapies for metastatic gastroesophageal adenocarcinoma at the National Cancer Centre Singapore was retrospectively analyzed., Results: Thirty-two (6%) patients received three or more lines of chemotherapy. The median age and ECOG performance status were 59 years (36-82) and 1 (0-2), respectively. Majority of patients (88%) had tumor located in the stomach and 13 patients (41%) had diffuse histology or poorly cohesive or signet ring cells. Four (12%) patients had HER2-positive disease. Prior therapy was platinum (100%), fluoropyrimidine (97%), taxane (63%), irinotecan (28%), anthracycline (13%) and ramucirumab (3%). Third-line therapy consisted of 24 (75%) monotherapy, 6 (19%) doublet, 1 (3%) triplet chemotherapy and 1 (3%) clinical trial. Monotherapy irinotecan (44%) was most common, followed by docetaxel (19%) and paclitaxel (9%). Of 22 patients evaluable for response, there was 1 (5%) partial response, 9 (41%) stable disease. Median overall survival was 18.3 weeks (4.3-65.1). Of 30 patients evaluable for toxicities, 17 (57%) experienced at least one grade 3 or 4 toxicities., Conclusion: The benefit of using non-cross resistant second-line regimens as third-line chemotherapy was small with moderate toxicity. Newer agents such as nivolumab or TAS-102 or clinical trial may be preferred., (© 2019 John Wiley & Sons Australia, Ltd.)

Background: Attributes of the clinical learning environment (CLE) are a measure of quality in postgraduate medical education, and assessing the CLE is a component of the New Accreditation System being introduced in Singapore by the Accreditation Council for Graduate Medical Education International. There is a dearth of published studies of CLE quality in Singapore., Objective: Our study had 3 aims: (1) to measure the CLE in 1 Singaporean residency program; (2) to compare trainee perceptions by sex, training level, and experience; and (3) to identify areas for improvement., Methods: Between October and December 2017, we conducted a mixed assessment of the CLE in an internal medicine program in Singapore, using the Postgraduate Hospital Educational Environment Measure (PHEEM) and qualitative exploration using a focus group., Results: Of 153 IM residents, 136 (89%) provided PHEEM responses and 8 participated in the focus group. Total PHEEM scores and scores for the 3 subscales were higher than published data on the use of the PHEEM in international settings. Exploration of selected PHEEM responses via a focus group identified attributes associated with negative perceptions of the CLE: excessive workload, inadequate faculty presence in the CLE, and unmet trainee needs. It also suggested senior residents' clinical workloads, greater responsibilities, and pending examinations may contribute to their less positive perceptions of the CLE., Conclusions: Our analysis using the PHEEM showed overall positive perceptions of the CLE, along with areas for improvement amenable to interventions. Our approach has relevance to an accreditation model with ongoing evaluation of the CLE., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

Purpose: Since few studies have investigated whether the Distress Thermometer (DT) in Asian adolescent and young adult (AYA) cancer patients (between 15 and 39 years), we investigated the appropriateness of the DT as a screening tool for psychological symptom burden in these AYA patients and to evaluate AYA patients' distress across a trajectory of three time points longitudinally over a 6-month period., Methods: This was a prospective, longitudinal study. Recruited Asian AYA patients were diagnosed with lymphomas, sarcomas, primary brain malignancies, or germ cell tumors. Patients completed the DT, PedsQL Generic Core Scales, and the Rotterdam Symptom Checklist. Data were analyzed using STATA version 15., Results: Approximately half of the patients experienced clinically significant DT distress (distress score ≥ 4) early in their cancer journey with 43.1% patients presenting with distress at time of diagnosis and 47.7% patients 1 month after diagnosis. Among AYA patients > 24 years old, worry (68.3%), insurance/financial issues (61%), treatment decisions (43.9%), work/school issues (41.5%), nervousness (41.5%), and sadness (41.5%) were the top five identified problems. On the other hand, the top five identified problems among AYA ≤ 24 years were worry (54.2%), nervousness (41.7%), bathing/dressing problems (37.5%), work/school issues (33.3%), and fatigue (33.3%). DT scores were significantly associated with certain psychological symptom burden items such as worry (p < 0.001), depressed mood (p = 0.020), and nervousness (p = 0.015)., Conclusion: The DT is a useful screening tool for psychological distress in AYA cancer patients with clinically significant distress being identified in the early phases of the cancer journey.

Importance: Hand-foot syndrome (HFS) is a common adverse effect of capecitabine treatment., Objective: To compare the incidence and time to onset of grade 2 or greater HFS in patients receiving pyridoxine vs placebo and to identify biomarkers predictive of HFS., Design, Setting, and Participants: This single-center, randomized double-blind, placebo-controlled phase 3 trial conducted at National Cancer Centre Singapore assessed whether oral pyridoxine could prevent the onset of grade 2 or higher HFS in 210 patients scheduled to receive single-agent capecitabine chemotherapy for breast, colorectal, and other cancers., Interventions: Patients were randomized to receive concurrent pyridoxine (200 mg) or placebo daily for a maximum of 8 cycles of capecitabine, with stratification by sex and use in adjuvant or neoadjuvant vs palliative setting. Patients were withdrawn from the study on development of grade 2 or higher HFS or cessation of capecitabine., Main Outcomes and Measures: Primary end point was the incidence of grade 2 or higher HFS in patients receiving pyridoxine. Secondary end points included the time to onset (days) of grade 2 or higher HFS and identification of biomarkers predictive of HFS, including baseline folate and vitamin B12 levels, as well as genetic polymorphisms with genome-wide arrays., Results: In this cohort of 210 patients (median [range] age, 58 [26-82] years; 162 women) grade 2 or higher HFS occurred in 33 patients (31.4%) in the pyridoxine arm vs 39 patients (37.1%) in the placebo arm (P = .38). The median time to onset of grade 2 or higher HFS was not reached in both arms. In univariate analysis, the starting dose of capecitabine (odds ratio [OR], 1.99; 95% CI, 1.32-3.00; P = .001), serum folate levels (OR, 1.27; 95% CI, 1.10-1.47; P = .001), and red blood cell folate levels (OR, 1.25; 95% CI, 1.08-1.44; P = .003) were associated with increased risk of grade 2 or higher HFS. In multivariate analyses, serum folate (OR, 1.30; 95% CI, 1.12-1.52; P < .001) and red blood cell folate (OR, 1.28; 95% CI, 1.10-1.49; P = .001) were the only significant predictors of grade 2 or higher HFS. Grade 2 or higher HFS was associated with 300 DNA variants at genome-wide significance (P < 5 × 10-8), including a novel DPYD variant (rs75267292; P = 1.57 × 10-10), and variants in the MACF1 (rs183324967, P = 4.80 × 10-11; rs148221738, P = 5.73 × 10-10) and SPRY2 (rs117876855, P < 1.01 × 10-8; rs139544515, P = 1.30 × 10-8) genes involved in wound healing., Conclusions and Relevance: Pyridoxine did not significantly prevent or delay the onset of grade 2 or higher HFS. Serum and red blood cell folate levels are independent predictors of HFS., Trial Registration: clinicaltrials.gov Identifier: NCT00486213.

Background: The majority of patients with hepatocellular carcinoma (HCC) are inoperable and results with conventional chemotherapy are dismal. Many end up with no treatment options and resort to alternative medicine. The authors report the use of Coriolus versicolor (CV) in advanced HCC patients with poor liver function or who were unfit to receive standard therapy., Methods: Fifteen eligible cases were randomized 2:1 to either CV or placebo. The primary endpoint was the median time to progression (TTP) between both arms. Secondary endpoints include evaluating response rates, toxicity, quality of life (QOL), progression-free survival (PFS), and overall survival (OS). Further correlative studies were performed looking at the effect of CV on the immune system., Results: The median treatment duration was 1.5 cycles and 3 cycles on the placebo and CV arm, respectively. Median TTP was 2.5 (1.4-5.3) months compared to 4.2 (0.4-4.2) months in the CV and placebo arm, respectively, hazard ratio (HR) 0.70 (0.16-3.05 p = 0.634). Median PFS was 2.5 (1.4-5.3) months in the CV and 1.1 (0.4-4.2) months in the placebo arm, HR 0.42 (0.13-1.34, p = 0.144). Median OS was 6.5 (3.3-24.1) and 2.2 (0.8-23.3) months, respectively, HR 0.35 (0.10-1.25, p = 0.105). Social and emotional functioning scores were higher in the CV group compared to placebo group on treatment. CV subjects had less appetite loss and pain symptoms compared to placebo subjects during treatment., Conclusions: There was no difference in TTP with use of CV compared to placebo. CV subjects generally had better QOL on treatment compared to placebo subjects. The utility of this supplement in patients whose primary treatment goal is palliation should be further explored.

Introduction: Peritoneal carcinomatosis (PC) is increasingly being treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). We provide a review of a high-volume Asian institute's experience and survival outcomes with this procedure., Methods: Data were prospectively collected from 201 consecutive CRS and HIPEC procedures performed in a single institution between April 2001 and November 2015. Our primary endpoints were overall survival (OS) and disease-free survival (DFS), and secondary endpoints were morbidity and mortality., Results: 77% of patients were Chinese, 9% were Malay, 6% were Indian and 8% were other ethnicities. Primary tumours were colorectal (30%), ovarian (32%), appendiceal (20%), primary peritoneal (6.5%), mesothelioma (4.5%) and others (5%). The median peritoneal cancer index (PCI) was 12, and 92% of patients achieved a completeness of cytoreduction score (CC) of 0. High-grade morbidity occurred in 25.8% of cases, and there were no 30-day mortalities. At 5-years, the OS was 55.1% and DFS was 20.3%. Factors associated with improved OS on multivariate analysis were PCI <15 (p < 0.001) and a CC 0 (p = 0.016)., Conclusions: The combined treatment of CRS and HIPEC is beneficial and is associated with reasonable morbidity and mortality in Asian patients with PC from colorectal, ovarian, appendiceal, primary peritoneal and mesothelioma primaries. Complete cytoreduction and extent of disease are the most important prognostic factors for survival.

Background: Treatment with sorafenib, although associated with inhibition of tumour growth and angiogenesis in in vivo studies, leads to up-regulation of pERK. The addition of MEK inhibition could potentially abrogate this effect and potentiate anti-tumour activity. This phase I study investigated the maximum tolerated dose (MTD), safety, tolerability, pharmacokinetics (PK) and biomarker correlates of selumetinib combined with sorafenib in patients with advanced hepatocellular carcinoma (HCC)., Methods: Patients with Child-Pugh (CP) score ≤7 were treated with 400 mg twice daily of sorafenib with escalating doses of selumetinib in a 3 + 3 study design. The dose-limiting toxicity (DLT) evaluation period was 28 days. PK of selumetinib was determined. Angiogenic effect was evaluated with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)., Results: Twenty-seven patients of Asian ethnicity were enrolled. The MTD was selumetinib 75 mg daily with sorafenib 400 mg twice daily. DLT included grade 3 transaminitis, diarrhoea and fatigue. Most common treatment-related adverse events at MTD (all grades) were diarrhoea (85%), rash (59%), hypertension (44%), fatigue (30%), anorexia (22%) and hand-foot syndrome (22%). Four patients (15%) had PR and 13 (48%) had SD. PR or SD was observed for ≥6 months in seven patients. The median overall survival was 14.4 months. Selumetinib exposures in combination with sorafenib were comparable to other monotherapy studies. A reduction in permeability-surface area product noted in DCE-MRI with treatment correlated with worse survival outcomes., Conclusion: The MTD of selumetinib was 75 mg daily when combined with sorafenib 400 mg twice a day in CP ≤7 HCC. Acceptable adverse events and encouraging anti-tumour activity warrant further evaluation. DCE-MRI findings deserve prospective evaluation., Clinicaltrialsgov Identifier: NCT01029418., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Meningiomas are usually low-grade, solitary lesions that rarely metastasize. In this group of central nervous system tumours, the higher grade subtypes are notorious for resistance to conventional chemo-radiation therapies. Recent studies have shown efficacy in the use of bevacizumab in patients with recurrent and, or progressive anaplastic meningioma. The authors report a case of a young patient with recurrent anaplastic meningioma who despite being treated with bevacizumab, progressed with disease dissemination to multiple extracranial sites. Although the majority of meningiomas are amendable to treatment, the higher grade subtypes remain therapeutically challenging. The unexpected resistance to anti-angiogenic therapy in this patient adds another layer of complexity to an elusive subset of a supposedly benign disease. This patient report reflects the need for in-depth studies, molecular characterization and overall, better disease understanding in order to improve prognosis for affected patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

There is an increasing demand for accurate prognostication for colorectal cancer (CRC). This study sought to assess prognostic potentials of methylation targets in the serum of CRC patients. A total of 165 CRC patients were enrolled in this prospective study. Promoter methylation levels of seven genes in pre-operative sera and matched tumor tissues were evaluated by quantitative methylation-specific PCR. Kaplan-Meier test, and univariate and multivariate Cox proportional hazards regression models were used for survival analyses. After a median follow-up of 56 months, 43 patients (28.7%) experienced tumor recurrence. In univariate survival analyses, serum methylation levels of SST and MA L were significantly predictive of cancer-specific death ( P <0.005 for both). The former was also a significant predictor for tumor recurrence ( P =0.007). Independent prognostic effects of serum methylation levels of SST were revealed by multivariate Cox regression model ( P =0.031 and P =0.003 for cancer death and recurrence, respectively). When focusing on stage II and III patients, prognostication with serum methylated SST remained significant. Methylated SST detected in all serum samples can be traced back to the matched primary tumor tissues. We believe that methylated SST detected in the pre-operative sera of CRC patients appear to be a novel promising prognostic marker and probably can be auxiliary to tumor staging system and serum carcinoembryonic antigen towards better risk stratification.

Background: The selection of patients for cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy infusion (HIPEC) is important, and relies heavily on imaging. However, it has been reported that Computer Tomographic (CT) scans may only achieve a low sensitivity of 33% for peritoneal disease. We propose a set of radiological criteria for pre-operative determination of resectability of peritoneal disease in peritoneal-based malignancies and validate this in our cohort of patients., Methods: A retrospective review of all patients who underwent laparotomy with a view for CRS and HIPEC, at the National Cancer Centre Singapore from January 2000 to April 2010, was performed. Intra-operative Peritoneal Cancer Index (PCI) scores were recorded. The pre-operative imaging was reviewed with a senior radiologist who was blinded, and recorded the radiological PCI scores (CT-PCI) and eight additional CT prognostic factors (CT-PF). The CT-PCI and CT-PF scores were then compared with the intra-operative findings to determine the radiological accuracy. The scores and the individual prognostic factors were then evaluated for their predictive ability for unresectability., Results: Comparison of the CT-PCI and PCI scores showed a concordance correlation coefficient at 0.52 (95% CI 0.34-0.7). Accuracy was increased with the addition CT-PF. The presence of omental caking and ascites were predictors of unresectability. We propose a scoring system which is able to predict for unresectable disease with a specificity of 80% and a sensitivity of 62%., Conclusion: With our proposed criteria, and scoring system, the selection of patients for CRS and HIPEC can be improved, and unnecessary exploratory operations avoided., (© 2016 The Royal Australian and New Zealand College of Radiologists.)

Introduction: Peritoneal carcinomatosis (PC) is increasingly being treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), with or without early post-operative intraperitoneal chemotherapy (EPIC). We compared the morbidities, overall survival (OS) and disease free survival (DFS) between two groups of patients who underwent CRS and HIPEC alone and with EPIC at our institution., Methods: A retrospective review of 111 patients with PC who were treated with CRS + HIPEC or CRS + HIPEC + EPIC in a single institution between January 2008 and April 2014 was performed. EPIC with 5-fluorouracil or paclitaxel was utilised, depending on the primary tumour., Results: Patients who received EPIC had a higher proportion of grade III and above post- operative complications (58% versus 25%; p = 0.048) and a longer duration of hospitalisation (16 days versus 13 days; p = 0.019) than patients without EPIC. There were no significant OS and DFS differences between the EPIC and no EPIC groups (log-rank p = 0.231 and p = 0.144, respectively)., Conclusion: The use of EPIC after CRS + HIPEC for PC potentially results in increased morbidity and longer hospitalisation, and is unlikely to affect survival outcomes. Based on our experience, EPIC is not recommended after CRS and HIPEC.

Purpose: The use of trastuzumab, a monoclonal antibody targeting the HER2 protein, in combination with 5-fluorouracil/platinum-based chemotherapy improves survival in patients with HER2-positive advanced gastric cancer. In addition, TS-one (S-1)/platinum is also used as a standard of care in Asian countries. However, little is known about the combination of S-1/cisplatin chemotherapy and trastuzumab in patients with HER2-positive advanced gastric/gastroesophageal junction (GEJ) cancer., Methods: We conducted a single-arm, two-stage, open-label, multicenter phase II study. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 mg/kg and 6 mg/kg on day 1 of subsequent cycles. Cisplatin was administered intravenously at 60 mg/m(2) on day 1 of each cycle after trastuzumab. S-1 was administered orally [based on body surface area (BSA)] twice a day for 14 days in a 3-weekly cycle. Patients with BSA of <1.25 received a total of 80 mg of S-1, those with BSA ≥1.5 received 120 mg, and the remaining received 100 mg daily in two divided doses., Results: All evaluable patients experienced tumor reduction during the trial. The primary end point (overall survival rate) was 59.3 %, with a clinical benefit rate of 66.7 %. Median progression-free survival was 7.4 months; 62.6 % patients were free from disease progression at 6 months. Median overall survival was 14.6 months, and the median time to treatment failure was 6.0 months., Conclusion: The combination of trastuzumab with S-1 and cisplatin demonstrated good activity, was generally well tolerated, and is a feasible treatment option in the first-line treatment of HER2-positive advanced gastric/GEJ cancers.

Background: The treatment of glioblastoma multiforme (GBM) is an unmet clinical need. The 5-year survival rate of patients with GBM is less than 3%. Temozolomide (TMZ) remains the standard first-line treatment regimen for gliomas despite the fact that more than 90% of recurrent gliomas do not respond to TMZ after repeated exposure. We have also independently shown that many of the Asian-derived glioma cell lines and primary cells derived from Singaporean high-grade glioma patients are indeed resistant to TMZ. This issue highlights the need to develop new effective anti-cancer treatment strategies. In a recent study, wild-type epidermal growth factor receptor (wtEGFR) has been shown to phosphorylate a truncated EGFR (known as EGFRvIII), leading to the phosphorylation of STAT proteins and progression in gliomagenesis. Despite the fact that combination of EGFR targeting drugs and rapamycin has been used before, the effect of mono-treatment of Nimotuzumab, rapamycin and combination therapy in human glioma expressing different types of EGFR is not well-studied. Herein, we evaluated the efficacy of dual blockage using monoclonal antibody against EGFR (Nimotuzumab) and an mTOR inhibitor (rapamycin) in Caucasian patient-derived human glioma cell lines, Asian patient-derived human glioma cell lines, primary glioma cells derived from the Mayo GBM xenografts, and primary short-term glioma culture derived from high-grade glioma patients., Methods: The combination effect of Nimotuzumab and rapamycin was examined in a series of primary human glioma cell lines and glioma cell lines. The cell viability was compared to TMZ treatment alone. Endogenous expressions of EGFR in various GBM cells were determined by western blotting., Results: The results showed that combination of Nimotuzumab with rapamycin significantly enhanced the therapeutic efficacy of human glioma cells compared to single treatment. More importantly, many of the Asian patient-derived glioma cell lines and primary cells derived from Singaporean high-grade gliomas, which showed resistance to TMZ, were susceptible to the combined treatments., Conclusions: In conclusion, our results strongly suggest that combination usage of Nimotuzumab and rapamycin exert higher cytotoxic activities than TMZ. Our data suggest that this combination may provide an alternative treatment for TMZ-resistant gliomas regardless of the EGFR status.

Introduction: Compared with intravenous chemotherapy, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival in patients with recurrent colorectal disease confined to the peritoneum. We report our experience with CRS and HIPEC for colorectal cancer patients with peritoneal carcinomatosis, evaluating prognostic factors for disease-free survival (DFS), overall survival (OS), and perioperative morbidity and mortality., Methods: All patients who underwent CRS and HIPEC were included in our study. Clinical characteristics, operative data, and 30-day morbidity and mortality were collected and evaluated., Results: Between January 2001 and December 2012, there were 35 consecutive patients who underwent CRS and HIPEC at our institution. Thirty-three patients (94%) had optimal cytoreduction. No 30-day mortality was reported, but 14 patients had postoperative complications. The median DFS was 9.4 months (95% confidence interval 5.5-18.7 months), and DFS at 1 year, 3 years, and 5 years were 43.8%, 22.3%, and 22.3%, respectively. The median OS was calculated to be 27.1 months (95% confidence interval 15.3-39.1), and the OS at 1 year, 3 years, and 5 years were 83.7%, 38.2%, and 19.1%, respectively., Conclusion: CRS and HIPEC can provide survival benefit, with reasonable morbidity and mortality for Asian patients with peritoneal carcinomatosis from colorectal cancer. Patient selection and perioperative management of the patients are key to the success of the procedure., (Copyright © 2014. Published by Elsevier Taiwan.)

Background: This phase II, open-label, randomised study evaluated whether patients with metastatic pancreatic cancer receiving erlotinib/gemcitabine derived survival benefits from increasing the erlotinib dose., Methods: After a 4-week run-in period (gemcitabine 1000 mg m(-2) once weekly plus erlotinib 100 mg per day), patients with metastatic pancreatic cancer who developed grade 0/1 rash were randomised to receive gemcitabine plus erlotinib dose escalation (150 mg, increasing by 50 mg every 2 weeks (maximum 250 mg); n=71) or gemcitabine plus standard-dose erlotinib (100 mg per day; n=75). The primary end point was to determine whether overall survival (OS) was improved by increasing the erlotinib dose. Secondary end points included progression-free survival (PFS), incidence of grade ⩾2 rash, and safety., Results: Erlotinib dose escalation induced grade ⩾2 rash in 29 out of 71 (41.4%) patients compared with 7 out of 75 (9.3%) patients on standard dose. Efficacy was not significantly different in the dose-escalation arm compared with the standard-dose arm (OS: median 7.0 vs 8.4 months, respectively, hazard ratio (HR), 1.26, 95% confidence interval (CI): 0.88-1.80; P=0.2026; PFS: median 3.5 vs 4.5 months, respectively, HR, 1.09, 95% CI: 0.77-1.54; P=0.6298). Incidence of adverse events was comparable between randomised arms., Conclusion: The erlotinib dose-escalation strategy induced rash in some patients; there was no evidence that the higher dose translated into increased benefit.

Primary intracranial germ cell tumours (ICGCT) are a rare group of brain tumours arising predominantly in the paediatric and pre-adult population, accounting for up to 9.5% of paediatric brain tumours in East Asia. The National Cancer Centre Singapore (NCCS) is a tertiary referral centre for patients from all over South-East Asia. Our study aims to describe the characteristics of ICGCT patients in South-East Asia. Data on all patients with ICGCT who were seen at the Therapeutic Radiology Department of NCCS from 2000 to 2013 were collected retrospectively. Patient demographics, disease characteristics and treatment outcomes were analysed. Characteristics and survival of our patients were similar to other centres. Pure germinomas demonstrated 5 year overall survival (OS) and disease-free survival (DFS) rates of 89.2% (95% confidence interval [CI] 60.2-97.5) and 85.2% (95%CI 60.8-95.0) respectively. Secreting germinomas, non-germinomatous germ cell tumours and mixed germ cell tumours were evaluated together and demonstrated 5 year OS of 70.6% (95%CI 41.0-87.3) and DFS of 61.4% (95%CI 31.9-81.3). Patients ⩽ 12 years had marginally better 5 year OS than their older counterparts (81.0% [95%CI 49.5-93.9] versus 77.9% [95%CI 47.3-92.0], respectively). Patients who underwent extended field radiotherapy had longer OS and DFS than those who received local field irradiation. Treatment outcomes of our ICGCT patients are comparable with those in other Asian and Western centres. Extended field radiotherapy is a pivotal component of ICGCT treatment. Adding chemotherapy confers no extra survival benefit in treating germinomas. Treatment of mixed germ cell tumours and non-germinomatous germ cell tumours involves a multidisciplinary approach that varies for each histological subtype., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: An increasing number of patients are presenting with peritoneal carcinomatosis and more centers are performing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). While morbidity and mortality are shown to be acceptable, quality of life after surgery should be assessed., Methods: 63 patients who had CRS and HIPEC from 2001 to 2012 and who were still alive and on follow up were included. The EORTC-QLQ-C30 was administered to the patients., Results: Median age was 53 years (14-71). 44% had ovarian primaries, 21% had appendicael primaries and 19% had colorectal primaries. Median follow-up was 1.08 years (0.06-9.8). The median time from surgery to the questionnaire was 1.3 years (0.24-10.18). There was no statistical difference in scores when comparing by age, gender, recurrence, gender, PCI score, presence of a complication and type of primary cancer. Scores were highest less than 6 months after surgery, dropped subsequently but rose again after 2 years. Our patients had better scores compared to a control group of outpatient cancer patients at our institution as well as the reference EORTC group., Conclusions: In keeping with previous quality of life studies done for CRS and HIPEC patients, we have shown that our patients can achieve a good quality of life after CRS and HIPEC even with recurrent disease., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder, with heterogeneous manifestations that pose major diagnostic and management challenges and incur considerable chronic disease burden on patients, their caregivers and healthcare systems. This survey of clinical practice in the Asia-Pacific region highlights priorities for improving TSC management in the region. The prevalence of TSC in non-Caucasians is uncertain and more data are needed to assess its impact and health-economic burden. There are unmet needs for access to genetic testing and earlier diagnosis and intervention. TSC management is multidisciplinary and largely based on experience, backed by international guidelines; however, physicians in the Asia-Pacific region feel isolated and lack local or regional guidance and support structures to implement best-practice. Raising awareness of TSC and increasing trans-regional collaboration are particular priorities. Understanding of TSC pathophysiology has enabled the development of targeted therapies. Encouraging data indicate that mammalian target of rapamycin (mTOR) inhibitors can ameliorate TSC-related lesions and may potentially change the treatment paradigm. Ultimately, improving outcomes for TSC patients in the region requires greater collaboration and a holistic, patient-focused, continuum of care that is maintained through the transition from pediatric to adult care., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Aim: Combined temozolomide (TMZ) and radiation therapy (RT) is often used as initial treatment for anaplastic glioma. However, there is no prospective randomized data available that proves the efficacy of the combination for anaplastic glioma. In this retrospective study we aimed to compare the outcome of patients who had combined TMZ and RT with those who had RT alone for the initial treatment of anaplastic glioma in our centers., Methods: Patients with anaplastic astrocytoma or oligoastrocytoma treated at our centers between 2000 and 2010 were reviewed. Only patients who received initial RT or concurrent TMZ and RT (TMZ-RT) were included., Results: Of 62 patients, 55 were less than 66-years old; 36 (58.1%) had a tumor resection and 26 had a biopsy only. An oligodendroglial component in their tumor histology was present in 21 patients (33.9%). At a median follow up of 20.7 months for all patients, median progression-free survival was similar for the two treatment groups (RT alone: 16.7 months (95% CI 9.4, 34.8 months) versus TMZ-RT: 14.8 months (95% CI 8.6, 28.6 months, P = NS). Median overall survival was 27.4 months (95% CI 10.6, not estimable [NE] months) for patients who had RT alone and 34.1 months (95% CI 19.8, 42.1 months) for those who had TMZ-RT., Conclusion: No significant benefit of combined TMZ with RT compared to RT alone was observed as the initial treatment of anaplastic glioma. Prospective randomized trials are needed to evaluate the optimal treatment for this disease., (© 2012 Wiley Publishing Asia Pty Ltd.)

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival in selected patients with peritoneal carcinomatosis. We review our institutional experience with the procedure and evaluate the overall survival (OS) and disease-free survival (DFS) rates in 100 consecutive patients., Methods: Data were prospectively collected from 100 consecutive patients with peritoneal carcinomatosis treated by CRS and HIPEC at the National Cancer Centre Singapore between April 2001 and May 2012. Our primary end points were OS and DFS., Results: Of the 100 patients, 84 were of Chinese ethnicity, 3 were Malay, 6 were Indian, and 7 were of other ethnicities. Primary tumors were ovarian cancer (n=39), colorectal cancer (n=28), primary peritoneal (n=6), appendiceal cancer (n=20), and mesothelioma (n=7). Median follow-up duration was 21 months. At 5 years, the DFS was 26.3% and OS was 50.9%. Factors influencing OS and DFS were cytoreductive score, primary cancer, and disease-free interval of more than 12 months on univariate analysis. The only factors that remained significant for prognosis after multivariate analysis were primary cancer and cytoreductive score. Thirty-day morbidity was 56%, and there were no 30-day mortalities., Conclusions: CRS and HIPEC can be safely carried out in Asian patients with peritoneal carcinomatosis from ovarian, colorectal, appendiceal, mesothelioma, and primary peritoneal origins. Overall, the ovarian, appendiceal, mesothelioma, and primary peritoneal cancer patients tended to do better than the colorectal patients, but careful patient selection ensuring that optimal cytoreduction can be achieved is essential for the success of this procedure.

Objective: To identify methylated genes in serum with diagnostic potentials for early colorectal cancer (CRC)., Methods: Serum methylation levels of up to 12 genes were measured in two sets of serum samples with the second set from 26 stage I CRC patients and 26 age/gender-matched controls., Results: Serum methylation levels of TAC1, SEPT9, and EYA4 were significant discriminants between stage I CRC and healthy controls. Combination of TAC1 and SEPT9 rendered 73.1% sensitivity with 92.3% specificity., Conclusion: Serum methylation levels of TAC1. SEPT9 and EYA4 may be useful biomarkers for early detection of CRC though a validation study is necessary.

Purpose: The liver and peritoneum are common sites of colorectal metastases. Hepatectomy for colorectal liver metastases (CLM) is considered gold standard treatment. We attempt to compare the survival outcomes for CLM patients after hepatectomy to that of patients with colorectal peritoneal metastases (CPM) who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)., Methods: A retrospective review of patients with CPM and CLM who underwent surgery between January 2003 and May 2011 was performed. The overall (OS) and disease-free survivals (DFS) were compared., Results: There were 22 patients with CPM who underwent CRS and HIPEC and 186 patients who underwent hepatectomy for CLM. Patients with CPM had a 3-year OS of 39 % and DFS of 27.7 %. CLM patients showed a 3-year OS of 58.5 % and a DFS of 28.8 %. Most recurrences for CPM occurred within 2 years, while CLM patients continue to develop systemic recurrences over 3 years, showing a gradual decline in DFS and OS during this period of time., Conclusion: Our results show that CRS and HIPEC for CPM confer good OS and DFS rates and that the DFS after CRS and HIPEC is comparable to that after hepatectomy for CLM.

Human pluripotent stem cells can serve as an accessible and reliable source for the generation of functional human cells for medical therapies. In this study, we used a conventional lentiviral transduction method to derive human-induced pluripotent stem (iPS) cells from primary human fibroblasts and then generated neural stem cells (NSCs) from the iPS cells. Using a dual-color whole-body imaging technology, we demonstrated that after tail vein injection, these human NSCs displayed a robust migratory capacity outside the central nervous system in both immunodeficient and immunocompetent mice and homed in on established orthotopic 4T1 mouse mammary tumors. To investigate whether the iPS cell-derived NSCs can be used as a cellular delivery vehicle for cancer gene therapy, the cells were transduced with a baculoviral vector containing the herpes simplex virus thymidine kinase suicide gene and injected through tail vein into 4T1 tumor-bearing mice. The transduced NSCs were effective in inhibiting the growth of the orthotopic 4T1 breast tumor and the metastatic spread of the cancer cells in the presence of ganciclovir, leading to prolonged survival of the tumor-bearing mice. The use of iPS cell-derived NSCs for cancer gene therapy bypasses the sensitive ethical issue surrounding the use of cells derived from human fetal tissues or human embryonic stem cells. This approach may also help to overcome problems associated with allogeneic transplantation of other types of human NSCs., (Copyright © 2012 AlphaMed Press.)

Tumor-tropic neural stem cells (NSCs) can be used in the Trojan horse approach as cellular vehicles for targeted delivery of therapeutic agents to distant tumor sites. To realize this cancer therapy potential, it is important to have a renewable source to generate large quantities of uniform human NSCs. Here, we reported that NSCs derived from HES1 human embryonic stem cell line were capable of migrating into intracranial glioma xenografts after systemic injection or after intracranial injection at a site distant from the tumor. To test whether the HES1-derived NSCs can be used for cancer gene therapy, we used a baculoviral vector to introduce the herpes simplex virus thymidine kinase suicide gene into the cells and demonstrated that baculovirus-mediated transgene expression may last for at least 3 weeks in NSCs. After being injected into the cerebral hemisphere opposite the tumor site and in the presence of ganciclovir, NSCs expressing the suicide gene were able to inhibit the growth of human glioma xenografts and prolong survival of tumor-bearing mice. Our findings suggest that human embryonic stem cells could potentially serve as a clinically viable source for production of cellular vehicles suitable for targeted anticancer gene therapy.

Using neural stem cells (NSCs) with tumor tropic migratory capacity to deliver therapeutic genes is an attractive strategy in eliminating metastatic or disseminated tumors. While different methods have been developed to isolate or generate NSCs, it has not been assessed whether induced pluripotent stem (iPS) cells, a type of pluripotent stem cells that hold great potential for regenerative medicine, can be used as a source for derivation of NSCs with tumor tropism. In this study, we used a conventional lentivirus transduction method to derive iPS cells from primary mouse embryonic fibroblasts and then generated NSCs from the iPS cells. To investigate whether the iPS cell derived NSCs can be used in the treatment of disseminated brain tumors, the cells were transduced with a baculoviral vector containing the herpes simplex virus thymidine kinase suicide gene and injected into the cerebral hemisphere contralateral to a tumor inoculation site in a mouse intracranial human glioma xenograft model. We observed that NSCs expressing the suicide gene were, in the presence of ganciclovir, effective in inhibiting the growth of the glioma xenografts and prolonging survival of tumor-bearing mice. Our findings provide evidence for the feasibility of using iPS cell derived NSCs as cellular vehicles for targeted anticancer gene therapy.

Aim: To analyze the outcome of patients who received concurrent capecitabine (Xeloda) and radiation (XRT) compared to the established concurrent 5-fluorouracil (5-FU) with radiation (5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers., Methods: All patients with gastric cancers who received adjuvant treatment at the National Cancer Centre Singapore between 1996 and 2006 were reviewed. Treatment outcomes of patients who received XRT were compared with those who had 5FU-RT or chemotherapy alone as adjuvant therapy for gastric cancers., Results: A total of 108 patients were reviewed. Median age at diagnosis was 60. The majority of the patients (64.8%) had advanced stage III and IV disease (with no distant metastasis). All except 4 patients had D2 gastrectomy. Twenty one patients (19.4%) had positive surgical resection margins. Thirty three patients received XRT compared with 52 who had 5FU-RT and 23 who received chemotherapy alone. For the patients in the chemotherapy-only group, all had fluoropyrimidine-based therapy, with added cisplatin in 7 patients and epirubicin in 2 patients. Median recurrence-free survival was longer for the XRT group (52 mo) compared to the 5FU-RT (35 mo) and chemotherapy-only groups (25 mo) (P = 0.48). The patients in the XRT group achieved similar median overall survival (53 mo) as the 5FU-RT (54 mo) and the chemotherapy-only groups (44 mo) (P = 0.5)., Conclusion: Capecitabine with concurrent radiation was as effective as concurrent 5FU with radiation or fluoropyrimidine-based chemotherapy alone when used as adjuvant treatment in patients with gastric cancers.

Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis characterized by progressive histiocytic proliferation with multiorgan involvement, typically of the kidney, skin, brain, and lung, and less frequently, the heart and retro-orbital tissue. Fluorine-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) plays an important role in the management of this disease. It has been reported that FDG PET imaging allows accurate evaluation of the extent of the disease at baseline, as well as assessment of response to any specific therapy. In this case, a 57-year-old Chinese man presented with functional decline and a urinary tract infection. He had a prior history of xanthogranulomas of bilateral canthal masses. On imaging, he was found to have left hydronephrosis, diffuse urothelial thickening, increased density of the perinephric fat, mural thickening of the descending aorta and soft tissue masses along the posterior wall of the right atrium extending into the region of the interatrial septum and involving the right atrioventricular groove. Histopathology revealed retroperitoneal fibrosis. An IV contrast-enhanced FDG PET scan showed increased activity in a previously unidentified brain stem mass and the shafts of bilateral femora. Varying levels of FDG uptake were seen in the other lesions.

Introduction: Randomized placebo-controlled phase III trials failed to show a survival benefit with the addition of gefitinib to platinum-based combination chemotherapy as first-line therapy in unselected patients with advanced non-small cell lung cancer (NSCLC). We conducted a retrospective analysis of the outcome in never smokers with advanced NSCLC who received gemcitabine-carboplatin-gefitinib (GCI) as first-line therapy and compared these patients with a historical control group who received gemcitabine-carboplatin (GC) alone in our center., Methods: Never-smoker patients with chemonaive stage IIIB or IV NSCLC were treated with GCI. These patients were compared with a historical control group of never smokers who had been treated with GC alone as the first-line therapy., Results: A total of 80 patients were reviewed: 51 patients were treated with GCI and 29 with GC. Most patients were women, and adenocarcinoma was the most common histologic subtype. The response rate for patients in the GCI group was 62.7% (95% confidence interval [CI] = 48.08-75.87), which was higher than that of the GC group, 27.6% (95% CI = 12.73-47.24). The GCI group showed a significant improvement in progression-free survival compared with the GC group (hazard ratio of 0.19, 95% CI = 0.105-0.351, p < 0.001). The median overall survival for the patients on GCI was 20.5 months compared 14.1 months (p = 0.05) for patients on GC., Conclusion: The addition of gefitinib to first-line chemotherapy improved progression-free survival and overall survival when used as a first-line therapy in never smokers with advanced NSCLC in this retrospective study. A prospective randomized phase III study is needed to confirm this finding.

Aim: To analyze the outcome of elderly patients compared with the younger age group patients who were diagnosed with gastrointestinal stromal tumours (GIST) at our institution., Methods: Patients diagnosed with GISTs were analyzed according to two age groups, those who were at least age 65 and less than age 65., Results: A total of 49 patients were reviewed. Median age at diagnosis was 59. 18 patients (36.7%) were of age at least 65 or above. Of these 11 patients presented with localized disease. Five patients subsequently developed recurrence with metastatic disease. The median recurrence free survival was 18.5 months. This was not significantly different compared to the younger age group patient (P=0.598). On univariate analysis, the presence of co-morbidities was found to be significantly associated with decrease recurrence-free survival (P=0.046). 13 patients (72.2.%) of the elderly age group had metastatic disease. 8 of these patients had metastasis at diagnosis and 5 developed metastasis at recurrence. The median progression-free survival for these patients was 33 months and there was no significant difference compared to the younger age group patient (P=0.887). On univariate analysis, low albumin was associated with low progression survival (P=0.047). The median overall survival for the elderly patients was 37.6 months. There was no significant difference compared to the younger age group patient (P=0.119). Presence of co-morbidity was associated with lower overall survival in the elderly age group in the multivariate analysis (P=0.037)., Conclusion: The elderly with GIST can achieve a similar outcome as younger patients. Presence of co-morbidity was found to affect the survival of elderly patients with GIST.

This paper introduces a two-stage approach to the detection of people eating and/or drinking for the purposes of surveillance of daily life. With the sole use of wearable accelerometer sensor attached to somebody's (man or a woman) wrists, this two-stage approach consists of feature extraction followed by classification. At the first stage, based on the limb's three dimensional kinematics movement model and the Extended Kalman Filter (EKF), the realtime arm movement features described by Euler angles are extracted from the raw accelerometer measurement data. In the latter stage, the Hierarchical Temporal Memory (HTM) network is adopted to classify the extracted features of the eating/drinking activities based on the space and time varying property of the features, by making use of the powerful modelling capability of HTM network on dynamic signals which is varying with both space and time. The proposed approach is tested through the real eating and drinking activities using the three dimensional accelerometers. Experimental results show that the EKF and HTM based two-stage approach can perform the activity detection successfully with very high accuracy.

Background and Objectives: The purpose of this study was to confirm our hypothesis that the development of functional intestinal obstruction in carcinomatosis peritonei (CP) is related to cytokine-mediated inhibition of the Akt pathway and to investigate the phenomenon of relative adrenal insufficiency in CP., Methods: Human adrenocortical cells (NCI-H295R) were treated with serum derived from eight cancer patients who had intestinal obstruction and functional adrenal insufficiency. Serum from three normal healthy subjects and three who had CP but without intestinal obstruction or adrenal insufficiency were used as controls. The differential effects of serum on the treated cells were studied using Western blot analysis. Cortisol production of these treated cells was assayed with cortisol ELISA kits., Results: Phosphorylation of Akt at Ser473 and Ser308 in cells was significantly reduced when treated with serum from patients with intestinal obstruction but not controls. Phosphorylation of PDK1 at Ser241, mTOR downstream targets like p70S6 at Thr421/Ser424 and Thr389, and lastly 4EBP-1 at Ser70 a downstream target of p70S6 was reduced by approximately 50%, 40%, and 70%, respectively. There was enhanced phosphorylation of elF4E an initiating factor in protein translation in cells treated with patient serum compared to controls. Cortisol synthesis was stimulated upon treatment with patient serum but not with control serum., Conclusion: Inhibition of Akt phosphorylation is a mechanism that could play a major role in the development of intestinal obstruction in carcinomatosis peritonei. The identification of the mediating cytokines will lead to the development of cogent targeted therapeutic strategies.

This study attempted to evaluate the usefulness of the International Prognostic Index (IPI) as a prognostic model in patients treated with R-CHOP (rituximab, cyclophosphamide, vincristine, adriamycin and prednisolone) chemotherapy. We compared 279 patients with DLBCL. Among them, 183 received CHOP while 96 received R-CHOP. Results showed that there were no statistically significant differences between the two groups of patients in terms of both the patient and the lymphoma characteristics. The estimated 2-year survival was significantly higher among patients treated with R-CHOP compared to CHOP alone (85.6% vs. 64.7%, P = 0.004). Both the IPI and age-adjusted IPI were less useful as prognostic models in patients receiving R-CHOP compared to CHOP. In the multivariate analysis, age >or= 60, elevated serum LDH, low serum albumin and advanced stages of disease were each independently associated with decreased survival in patients treated with CHOP. In contrast, among those treated with R-CHOP, only male sex and advanced stage of disease were each independently associated with decreased survival. Using these two factors, patients treated with R-CHOP could be separated into three prognostic groups with 5-year estimated survival ranging from 47% to 100% (P < 0.0001). In summary, we can conclude that with the significant improvement in survival following the use of rituximab, the relevance of previously recognized prognostic factors has to be reassessed and re-evaluated.

Aim: We aimed to compare the frequencies, clinical characteristics, and prognostic factors of peripheral T-cell lymphoma (PTCL) vs. extra-nodal natural killer (NK)/T-cell lymphoma and to characterize the subtypes of extra-nodal NK/T-cell lymphoma., Methods: We reviewed 97 consecutive patients with PTCL and extra-nodal NKT lymphoma from 2000 to 2006. During this period, a total of 780 patients with malignant lymphomas were treated in our center. The diagnostic criteria used were based on the WHO classification system of malignant lymphomas., Results: Extra-nodal-NK/T-cell lymphoma and PTCL comprised 5.0% (39/780) and 7.4% (58/780) of all cases. Of the PTCL cases, histology was PTCL-NOS in 25, anaplastic large cell in 11, angioimmunoblastic T cell in 18 and other subtypes in four patients. Compared with PTCL, extra-nodal NK/T-cell lymphoma was associated with a significantly inferior rates of complete remission (33% vs. 53%, P = 0.05) and 3 yr overall survival (29.5% vs. 47.5%, P = 0.003). On multivariate analysis, extra-nodal NK/T-cell histology was independently associated with decreased survival. Further analysis into this subtype showed the nasal variant (n = 25) differed significantly from extra-nasal variant (n = 14) in terms of stage at presentation (stages III/IV, 36% vs. 79%), international prognostic index scores (high intermediate or high IPI scores, 24% vs. 64%), complete remission rates (48% vs. 7%), and median survival (10 months vs. 1 month, P < 0.0001)., Conclusions: Extra-nodal NK/T-cell lymphoma was associated with a poorer prognosis compared with PTCL and is likely to comprise two distinct variants with different clinical behavior and prognosis.