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)

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

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