Surgical Management of Locally Recurrent Rectal Cancer

Developments in chemotherapeutic strategies and surgical technique have led to improved loco regional control of rectal cancer and a decrease in recurrence rates over time. However, locally recurrent rectal cancer continues to present considerable technical challenges and results in significant morbidity and mortality. Surgery remains the only therapy with curative potential. Despite a hostile intra-operative environment, with meticulous pre-operative planning and judicious patient selection, safe surgery is feasible. The potential benefit of new techniques such as intra-operative radiotherapy and high intensity focussed ultrasonography has yet to be thoroughly investigated. The future lies in identification of predictors of recurrence, development of schematic clinical algorithms to allow standardised surgical technique and further research into genotyping platforms to allow individualisation of therapy. This review highlights important aspects of pre-operative planning, intra-operative tips and future strategies, focussing on a multimodal multidisciplinary approach

The BraveNet prospective observational study on integrative medicine treatment approaches for pain

BACKGROUND: Chronic pain affects nearly 116 million American adults at an estimated cost of up to $635 billion annually and is the No. 1 condition for which patients seek care at integrative medicine clinics. In our Study on Integrative Medicine Treatment Approaches for Pain (SIMTAP), we observed the impact of an integrative approach on chronic pain and a number of other related patient-reported outcome measures. METHODS: Our prospective, non-randomized, open-label observational evaluation was conducted over six months, at nine clinical sites. Participants received a non-standardized, personalized, multimodal approach to chronic pain. Validated instruments for pain (severity and interference levels), quality of life, mood, stress, sleep, fatigue, sense of control, overall well-being, and work productivity were completed at baseline and at six, 12, and 24 weeks. Blood was collected at baseline and week 12 for analysis of high-sensitivity C-reactive protein and 25-hydroxyvitamin D levels. Repeated-measures analysis was performed on data to assess change from baseline at 24 weeks. RESULTS: Of 409 participants initially enrolled, 252 completed all follow-up visits during the 6 month evaluation. Participants were predominantly white (81%) and female (73%), with a mean age of 49.1 years (15.44) and an average of 8.0 (9.26) years of chronic pain. At baseline, 52% of patients reported symptoms consistent with depression. At 24 weeks, significantly decreased pain severity (−23%) and interference (−28%) were seen. Significant improvements in mood, stress, quality of life, fatigue, sleep and well-being were also observed. Mean 25-hydroxyvitamin D levels increased from 33.4 (17.05) ng/mL at baseline to 39.6 (16.68) ng/mL at week 12. CONCLUSIONS: Among participants completing an integrative medicine program for chronic pain, significant improvements were seen in pain as well as other relevant patient-reported outcome measures. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0118634

EEG artifacts reduction by multivariate empirical mode decomposition and multiscale entropy for monitoring depth of anaesthesia during surgery

Electroencephalography (EEG) has been widely utilized to measure the depth of anaesthesia (DOA) during operation. However, the EEG signals are usually contaminated by artifacts which have a consequence on the measured DOA accuracy. In this study, an effective and useful filtering algorithm based on multivariate empirical mode decomposition and multiscale entropy (MSE) is proposed to measure DOA. Mean entropy of MSE is used as an index to find artifacts-free intrinsic mode functions. The effect of different levels of artifacts on the performances of the proposed filtering is analysed using simulated data. Furthermore, 21 patients' EEG signals are collected and analysed using sample entropy to calculate the complexity for monitoring DOA. The correlation coefficients of entropy and bispectral index (BIS) results show 0.14 ± 0.30 and 0.63 ± 0.09 before and after filtering, respectively. Artificial neural network (ANN) model is used for range mapping in order to correlate the measurements with BIS. The ANN method results show strong correlation coefficient (0.75 ± 0.08). The results in this paper verify that entropy values and BIS have a strong correlation for the purpose of DOA monitoring and the proposed filtering method can effectively filter artifacts from EEG signals. The proposed method performs better than the commonly used wavelet denoising method. This study provides a fully adaptive and automated filter for EEG to measure DOA more accuracy and thus reduce risk related to maintenance of anaesthetic agents.This research was financially supported by the Center for Dynamical Biomarkers and Translational Medicine, National Central University, Taiwan, which is sponsored by Ministry of Science and Technology (Grant Number: NSC102-2911-I-008-001). Also, it was supported by Chung-Shan Institute of Science and Technology in Taiwan (Grant Numbers: CSIST-095-V301 and CSIST-095-V302) and National Natural Science Foundation of China (Grant Number: 51475342)

MicroRNA expression in colorectal cancer.

Journal articleColorectal cancer is a common disease entity with a multi-factorial aetiology which remains poorly understood. It is estimated that in 2008, colorectal cancerwas responsible for 8% of all cancer deaths, making it the fourth most common cause of death from cancer [10]. Prognosis is heavily linked to stage at diagnosis. The major cause of death is development of metastasis in liver, abdominal lymph nodes,and lung, forwhich there is no cure [21]. According to the most recently defined American Joint Committee on Cancer (AJCC) system for colonic adenocarcinoma, 5-year stage-specific survivals were 93.2% for stage I disease compared with 8.1% for stage IV [34], highlighting a need for novel early detection strategies. Colorectal cancer, at least theoretically, is a disease entity which is amenable to early detection, since it exhibits a stepwise progression of carcinogenesis from benign polyps to adenocarcinoma, over a period of time. The majority of national screening programmes currently centre on the use of colonoscopy or faecal immunohistochemistry/occult blood testing. Colonoscopy is an expensive, invasive procedure which carries a significant risk of intestinal perforation (1:700). Faecal testing ismore cost effective and less invasive but sacrifices sensitivity and specificity. Carcinoembryonic antigen, the only blood test currently available, exhibits low sensitivity and specificity. Hence, there is greatneed for new biomarkers for early detection of CRC

Mesenchymal stem cells in the colorectal tumor microenvironment: Recent progress and implications

Mesenchymal stem cells (MSCs) are nonhematopoietic multipotent adult stem cells. They have been shown to have a natural tropism for many tumors types, including colorectal, and are capable of escaping host immune surveillance. MSCs are known to engraft at tumors and integrate into their architecture, potentially as carcinoma-associated fibroblasts. In contrast with other malignancies, our understanding of the interactions between colorectal cancer cells and MSCs remains limited. Considering the established importance of inflammation in the colorectal cancer primary tumor microenvironment and the role of stromal cells in this process, there is a potential wealth of information to be gleaned from further investigation of interactions between these cell populations. Epithelialmesenchymal transition is central to colorectal cancer progression and MSCs have also been implicated in this process. This review explores the current knowledge (both in vitro and in vivo) of interactions between colorectal cancer cells and MSCs. It highlights potential effects of cell source, number and ratio on outcome of in vivo studies and explores strategies to more accurately explore their role in the primary tumor microenvironment. As our understanding of the underlying molecular processes in colorectal cancer develops, elucidation of these interactions will be central to development of novel therapeutic strategies for this prevalent disease

Screening of exosomal microRNAs from colorectal cancer cells

BACKGROUND: Cells release extracellular membrane vesicles including microvesicles known as exosomes. Exosomes contain microRNAs (miRNAs) however the full range within colorectal cancer cell secreted exosomes is unknown.OBJECTIVE: To identify the full range of exosome encapsulated miRNAs secreted from 2 colorectal cancer cell lines and to investigate engineering of exosomes over-expressing miRNAs.METHODS: Exosomes were isolated from HCT-116 and HT-29 cell lines. RNA was extracted from exosomes and microRNA array performed. Cells were engineered to express miR-379 (HCT-116-379) or a non-targeting control (HCT-116-NTC) and functional effects were determined. Exosomes secreted by engineered cells were transferred to recipient cells and the impact examined.RESULTS: Microvesicles 40-100 nm in size secreted by cell lines were visualised and confirmed to express exosomal protein CD63. HT-29 exosomes contained 409 miRNAs, HCT-116 exosomes contained 393, and 338 were common to exosomes from both cell lines. Selected targets were validated. HCT-116-379 cells showed decreased proliferation (12-15% decrease, pFunding support was received from Breast Cancer Research and the Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT Grant CCRC13GAL.peer-reviewe