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1.
MiR-17-5p enhances pancreatic cancer proliferation by altering cell cycle profiles via disruption of RBL2/E2F4-repressing complexes.
Zhu, Y, Gu, J, Li, Y, Peng, C, Shi, M, Wang, X, Wei, G, Ge, O, Wang, D, Zhang, B, et al
Cancer letters. 2018;:59-68
Abstract
The members of the miR-17-92 cluster are upregulated in various cancers and function as a cluster of oncogenic miRNA. Our study characterized a new function of miR-17-5p, a member of the miR-17-92 cluster, in regulating cell proliferation in pancreatic cancer. Our results indicate that miR-17-5p was up-regulated in pancreatic adenocarcinoma and directly targeted the retinoblastoma-like protein 2 (RBL2), a tumor suppressor belonging to the Rb family. High levels of miR-17-5p and low levels of RBL2 were associated with poor prognosis. RBL2 interacted with the transcription factor E2F4 and bound to the promoter regions of the E2F target genes. Disruption of the RBL2/E2F4 complex by miR-17-5p overexpression shifted the activity of E2F from gene repressing to gene activating, which induced cell cycle entry and proliferation. These results suggest that miR-17-5p promoted proliferation in pancreatic ductal adenocarcinoma cells (PDAC), and altered cell cycle profiles in vivo and in vitro, by disrupting the RBL2/E2F4-associated gene repressing complexes via direct targeting of RBL2. The new regulatory network, involving miR-17-5p and RBL2, emerges as a new target of PDAC treatment.
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2.
Risk factors for oesophageal cancer.
Xie, SH, Lagergren, J
Best practice & research. Clinical gastroenterology. 2018;:3-8
Abstract
The two main histological subtypes of oesophageal cancer, squamous cell carcinoma and adenocarcinoma, have distinct risk factor profiles. For oesophageal squamous cell carcinoma, tobacco smoking and excess alcohol use are the main risk factors. For adenocarcinoma, gastro-oesophageal reflux disease and obesity are main risk factors, whereas tobacco smoking is a moderately strong risk factor and infection with Helicobacter pylori decreases the risk. Dietary factors may influence the risk of both types of oesophageal cancer. Genetic factors are involved in the aetiology, but their influence is generally low. The striking male predominance in oesophageal adenocarcinoma is unexplained, although sex hormones may play a role. Risk prediction models combining information on multiple risk factors have shown promising potential in identifying high-risk individuals for targeted prevention and early detection, which should prompt further studies. More high-quality research efforts are warranted for better understanding of the aetiology of oesophageal cancer, particularly in developing countries.
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3.
Combination of arginine, glutamine, and omega-3 fatty acid supplements for perioperative enteral nutrition in surgical patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST): A prospective, randomized, double-blind study.
Ma, C, Tsai, H, Su, W, Sun, L, Shih, Y, Wang, J
Journal of postgraduate medicine. 2018;(3):155-163
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Abstract
BACKGROUND Perioperative enteral nutrition (EN) enriched with immune-modulating substrates is preferable for patients undergoing major abdominal cancer surgery. In this study, perioperative EN enriched with immune-modulating nutrients such as arginine, glutamine, and omega-3 fatty acids was evaluated for its anti-inflammatory efficacy in patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST) receiving curative surgery. MATERIALS AND METHODS This prospective, randomized, double-blind study recruited 34 patients with gastric adenocarcinoma or gastric GIST undergoing elective curative surgery. These patients were randomly assigned to the study group, receiving immune-modulating nutrient-enriched EN, or the control group, receiving standard EN from 3 days before surgery (preoperative day 3) to up to postoperative day 14 or discharge. Laboratory and inflammatory parameters were assessed on preoperative day 3 and postoperative day 14 or at discharge. Adverse events (AEs) and clinical outcomes were documented daily and compared between groups. RESULTS No significant differences were observed between the two groups in selected laboratory and inflammatory parameters, or in their net change, before and after treatment. AEs and clinical outcomes, including infectious complications, overall complications, time to first bowel action, and length of hospital stay after surgery, were comparable between treatment groups (all P > 0.05). CONCLUSION Immune-modulating nutrient-enriched EN had no prominent immunomodulation effect compared with that of standard EN.
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The role of vitamin D in hepatic metastases from colorectal cancer.
Shaw, E, Massaro, N, Brockton, NT
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2018;(3):259-273
Abstract
Colorectal cancer (CRC) represents a significant health burden worldwide, comprising approximately 10% of annual cancer cases globally. Hepatic metastases are the most common site of CRC metastasis, and are the leading cause of death in CRC patients. There is strong epidemiologic evidence for an inverse association between vitamin D status and risk of CRC; however, the role of vitamin D in the natural history of liver metastases has not yet been investigated. Several researchers have proposed hallmarks of metastases; crucially, metastases can be blocked by interrupting just one rate-limiting step. Vitamin D status has been implicated in each proposed hallmark of metastasis. The aim of this review is to examine the potential role for vitamin D in reducing the development of hepatic metastases from CRC and outline the candidate mechanisms by which vitamin D may mediate these effects. The results of ongoing randomised intervention trials are eagerly awaited to determine whether addressing vitamin D insufficiency in CRC patients could reduce the occurrence of liver metastases, and the consequent morbidity and mortality.
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Enhanced recovery after surgery in gastric cancer: which are the main achievements from the Italian experience?
Fumagalli Romario, U, Weindelmayer, J, Coratti, A, Cossu, A, Gianotti, L, Rausei, S, Sansonetti, A, De Pascale, S, ,
Updates in surgery. 2018;(2):257-264
Abstract
In the last years, the concept of 'enhanced recovery after surgery' (ERAS) has become a routine in the perioperative care of patients undergoing colorectal resection. The application of ERAS programs in gastric surgery had a more difficult penetration into clinical practice, mainly for the introduction of radical changes in the traditional postoperative management. The aim of the study was to analyze the rate of compliance to a standardized ERAS protocol in different Italian centers and evaluate the results in terms of postoperative outcomes. From April 2015 to July 2017, a prospective observational study was conducted among seven centers participating in the Italian Group for Research for Gastric Cancer (GIRCG), in patient candidates to elective gastrectomy for cancer. A standardized ERAS perioperative protocol was approved by all centers. Compliance to the protocol was then evaluated and postoperative outcomes (morbidity and mortality rate, duration of hospital stay and readmission rate) were analyzed. Two-hundred and seventy unselected patients operated on for gastric cancer were enrolled. The median age was 73 years; 40.4% of patients were female; 24.1% had a nutritional risk score ≥ 3. Perioperative chemotherapy was used in 23.7% of cases. Total gastrectomy was performed in 57.4% of patients; minimally invasive approach was adopted in 28.1% of patients. Adherence to the protocol varied between 23 and 88% for single items. It was quite low for pre- and intraoperative items, mainly for items related to nutritional care. Postoperative complications occurred in 35.5% of patients, mortality was 0.7%. Median length of hospital stay was 8 days (range 4-72) and the readmission rate was 6.3%. There is a growing attention on the implementation of ERAS protocol for gastric cancer surgery, but several elements of this protocol are still not routinely adopted, among them items regarding nutritional care.
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Recovery of Food Intake after Gastrectomy for Gastric Cancer: Based on a Large-Scale Gastric Cancer Cohort.
Eom, BW, Kim, J, Kim, DH, Kim, YI, Yoon, HM, Cho, SJ, Lee, JY, Kim, CG, Choi, IJ, Kim, YW, et al
Digestive surgery. 2018;(3):220-229
Abstract
BACKGROUND This study was aimed at evaluating the food intake and nutritional status of patients who underwent gastrectomy for gastric cancer based on a large-scale gastric cancer cohort. METHODS An observational prospective cohort study for gastric cancer has been conducted since 2010. From the cohort data, we selected the data for patients who completed at least 2 days of 3-day diet diaries and who underwent subtotal gastrectomy (STG) or total gastrectomy (TG). As a control group, patients who underwent endoscopic submucosal dissection were also included. The collected diet data were converted to macro- and micronutrients using computerized software, and the nutrient intakes were compared. RESULTS Among 6,556 patients who participated in the cohort study from 2011 to 2016, 1,289 patients who completed at least 2 days of 3-day diet diaries were included in this study. During the postoperative 3-month period, body weight was significantly decreased in the and TG groups. However, there was no difference in nutrient intake among the 3 groups except vitamin D and calcium intake. Similar results were observed during the postoperative 12 months period. CONCLUSIONS Postoperative body weight loss and anemia might originate from altered absorptive function and metabolic change after gastrectomy rather than decreased nutrient intake.
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Roux-en-Y or Billroth II Reconstruction After Radical Distal Gastrectomy for Gastric Cancer: A Multicenter Randomized Controlled Trial.
So, JB, Rao, J, Wong, AS, Chan, YH, Pang, NQ, Tay, AYL, Yung, MY, Su, Z, Phua, JNS, Shabbir, A, et al
Annals of surgery. 2018;(2):236-242
Abstract
OBJECTIVE The aim of the study was to compare the clinical symptoms between Billroth II (B-II) and Roux-en-Y (R-Y) reconstruction after distal subtotal gastrectomy (DG) for gastric cancer. BACKGROUND Surgery is the mainstay of curative treatment for gastric cancer. The technique for reconstruction after DG remains controversial. Both B-II and R-Y are popular methods. METHODS This is a prospective multicenter randomized controlled trial. From October 2008 to October 2014, 162 patients who underwent DG were randomly allocated to B-II (n = 81) and R-Y (n = 81) groups. The primary endpoint is Gastrointestinal (GI) Symptoms Score 1 year after surgery. We also compared the nutritional status, extent of gastritis on endoscopy, and quality of life after surgery between the 2 procedures at 1 year. RESULTS Operative time was significantly shorter for B-II than for R-Y [mean difference 21.5 minutes, 95% confidence interval (95% CI) 3.8-39.3, P = 0.019]. The B-II and R-Y groups had a peri-operative morbidity of 28.4% and 33.8%, respectively (P = 0.500) and a 30-day mortality of 2.5% and 1.2%, respectively (P = 0.500). GI symptoms score did not differ between R-Y versus B-II reconstruction (mean difference -0.45, 95% CI -1.21 to 0.31, P = 0.232). R-Y resulted in a lower median endoscopic grade for gastritis versus B-II (mean difference -1.32, 95% CI -1.67 to -0.98, P < 0.001). We noted no difference in nutritional status (R-Y versus B-II mean difference -0.31, 95% CI -3.27 to 2.65, P = 0.837) and quality of life at 1 year between the 2 groups too. CONCLUSION Although BII is associated with a higher incidence of heartburn symptom and higher median endoscopic grade for gastritis, BII and RY are similar in terms of overall GI symptom score and nutritional status at 1 year after distal gastrectomy.
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Irreversible Electroporation in pancreatic ductal adenocarcinoma: Is there a role in conjunction with conventional treatment?
de Liguori Carino, N, O'Reilly, DA, Siriwardena, AK, Valle, JW, Radhakrishna, G, Pihlak, R, McNamara, MG
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2018;(10):1486-1493
Abstract
BACKGROUND The incidence of pancreatic ductal adenocarcinoma (PDAC) is rapidly increasing. Up to 30% of patients present with locally advanced disease and therefore are not candidates for surgery. Locally advanced pancreatic cancer (LAPC) is an emerging entity lacking in level III evidence-based recommendations for its treatment. Currently, systemic chemotherapy is the main treatment for LAPC. However, due to lack of response or disease progression, downsizing of the tumour, making it resectable is successful in only a small proportion of patients. Radiotherapy is often advocated to improve local disease control if there is stability following chemotherapy. Recently, Irreversible Electroporation (IRE), a novel non-thermal ablation technique, has been proposed for the treatment of LAPC. AIMS AND METHODS This narrative review aims to explore the potential role and timing for the use of IRE in patients with LAPC. RESULTS To date, there is limited and inconsistent level I and II evidence available in the literature regarding the use of IRE for the treatment of PDAC. DISCUSSION Although some of the preliminary experience of the use of IRE in patients with LAPC is encouraging, it should only be used after conventional evidence-based treatments and/or within the research context.
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Nutritional Recovery after Open and Laparoscopic Distal Gastrectomy for Early Gastric Cancer: A Prospective Multicenter Comparative Trial (CCOG1204).
Matsushita, H, Tanaka, C, Murotani, K, Misawa, K, Ito, S, Ito, Y, Kanda, M, Mochizuki, Y, Ishigure, K, Yaguchi, T, et al
Digestive surgery. 2018;(1):11-18
Abstract
BACKGROUND Little information from prospective clinical trials is available on the influences of surgical approaches on postoperative body compositions and nutritional status. We designed a prospective non-randomized trial to compare postoperative chronological changes in body composition and nutritional status between laparoscopic and open distal gastrectomy for stage I gastric cancer (GC). METHODS Body compositions and nutritional indicators in blood tests were measured at the baseline and at the 1st, 3rd, 6th, and 12th postoperative months (POM). The primary end point was the decrease relative to the baseline in the body muscle mass at POM 6. RESULTS Ninety-six patients for the laparoscopic group and 52 for the open group were eligible for data analysis. No significant differences were found in any baseline demographics, body compositions, and nutritional indicators between the groups. The changes of body muscle mass at POM 6 were similar in both groups. Overall, no significant differences between the groups were observed in any of the body composition and nutritional indicators during the first year after surgery. CONCLUSIONS Postoperative body compositions and nutritional status were not affected by surgical approaches during the first 12 months after surgery in patients who underwent distal gastrectomy for stage I GC.
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Pancreatic enzyme supplementation after gastrectomy for gastric cancer: a randomized controlled trial.
Catarci, M, Berlanda, M, Grassi, GB, Masedu, F, Guadagni, S
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2018;(3):542-551
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Abstract
BACKGROUND Gastrectomy for gastric cancer is a significant cause of secondary exocrine pancreatic insufficiency. Pancreatic enzyme replacement therapy may influence nutritional status and quality of life after gastrectomy, but the pertinent clinical research to date remains controversial. A randomized controlled trial to test this hypothesis was carried out. METHODS After gastrectomy, 43 patients with gastric cancer were randomly assigned to a normal diet (Normal-d; n = 21) or to a pancreatic enzyme supplementation diet (PES-d; n = 22) and were followed up during a 12-month period, assessing nutritional status and quality of life through body mass index (BMI), instant nutritional assessment (INA) class status, serum pre-albumin (SPA) values, and GastroiIntestinal Quality of Life Index (GIQLI). RESULTS BMI was not significantly influenced by the type of diet; INA class status was significantly improved in the PES-d arm, particularly during the first 3 months after gastrectomy; SPA levels increased in both arms at 6 months after gastrectomy, reaching significantly higher values in the PES-d arm at 12 months. GIQLI was not significantly influenced by the type of diet throughout the follow-up period; however, this index significantly improved in the PES-d arm between the first and third month after gastrectomy. CONCLUSIONS PES-d improves nutritional status and quality of life after gastrectomy for gastric cancer, particularly within 3 months from the operation. A larger, multicenter trial is necessary to address the potential influence of several confounding variables such as disease stage and adjuvant treatments.