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1.
Effectiveness and safety of underwater techniques in gastrointestinal endoscopy: a comprehensive review of the literature.
Maida, M, Sferrazza, S, Murino, A, Lisotti, A, Lazaridis, N, Vitello, A, Fusaroli, P, de Pretis, G, Sinagra, E
Surgical endoscopy. 2021;(1):37-51
Abstract
BACKGROUND Conventional endoscopic resection techniques such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), represent the standard of care for treatment of superficial gastrointestinal lesions. In 2012 a novel technique called underwater endoscopic mucosal resection (U-EMR) was described by Binmoeller and colleagues. This substantial variation from the standard procedure was afterwards applied at endoscopic submucosal dissection (U-ESD) and recently proposed also for peroral endoscopic myotomy (U-POEM) and endoscopic full-thickness resection (U-EFTR). METHODS This paper aims to perform a comprehensive review of the current literature related to supporting the underwater resection techniques with the aim to evaluate their safety and efficacy. RESULTS Based on the current literature U-EMR appears to be feasible and safe. Comparison studies showed that U-EMR is associated with higher "en-bloc" and R0 resection rates for colonic lesions, but lower "en-bloc" and R0 resection rates for duodenal non-ampullary lesions, compared to standard EMR. In contrast to U-EMR, little evidence supporting U-ESD are currently available. A single comparison study on gastric lesions showed that U-ESD had shorter procedural times and allowed a similar "en-bloc" resection rates compared to standard ESD. No comparison studies between U-ESD and ESD are available for colonic lesions. Finally, only some anecdotal experiences have been reported for U-POEM or U-EFTR, and the feasibility and effectiveness of these techniques need to be further investigated. CONCLUSIONS Further prospective studies are necessary to better explore the advantages of underwater techniques compared to the respective standards of care, especially in the setting of U-ESD where consistent data are lacking and where standardization of the technique is needed.
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2.
Home enteral nutrition and oral nutritional supplements in postoperative patients with upper gastrointestinal malignancy: A systematic review and meta-analysis.
Xueting, H, Li, L, Meng, Y, Yuqing, C, Yutong, H, Lihong, Q, June, Z
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3082-3093
Abstract
BACKGROUND The safety and potential benefits of home enteral route nutrition (HERN), referring specifically to home enteral nutrition (HEN) and oral nutritional supplements (ONS) in this article, after upper gastrointestinal (GI) resection are inconsistent. OBJECTIVE To evaluate the impact of HERN on nutritional status, complications, and quality of life (QOL) after upper GI resection. METHODS This systematic review was conducted in accordance with the PRISMA statement. Nine databases were searched from inception to October 2019. Randomized controlled trials (RCTs) comparing the impact of HERN after upper gastrointestinal resection were included. Relative risk/weighted mean difference/standardized mean difference (RR/WMD/SMD) and corresponding 95% confidence intervals (95% CI) were calculated using fixed- or random-effects models. RESULTS Overall, 15 RCTs involving 1059 patients were included. Compared with normal oral diet, HERN significantly prevented weight loss (-3.95 vs -5.82 kg; SMD: 1.98 kg; 95% CI: 1.24-2.73); improved added-level of albumin (3.48 vs 2.41 g/L; SMD: 1.36 g/L; 95% CI: 0.81-1.91), hemoglobin (6.54 vs -1.29 g/L; WMD: 7.45 g/L; 95% CI: 5.05-9.86), pre-albumin (37.59 vs 7.35 mg/L; WMD: 21.6 mg/L; 95% CI: 5.96-37.24), and transferrin (63.08 vs 50.45 mg/L; WMD: 16.44 mg/L; 95% CI: 13.51-19.38); and reduced the incidence of malnutrition or latent malnutrition (RR = 0.54; P < 0.01). Subgroup analysis based on the approach of HERN showed that weight loss in the HEN subgroup was significantly lower than that of the control group (WMD = 2.69, P < 0.01), while there was no significant difference between the ONS subgroup and the control group (P = 0.1). The same results were found in albumin. Physical function (WMD: 5.29; 95% CI: 1.86-8.73) and fatigue (WMD: -8.59; 95% CI: -12.61, -4.58) dimensions in QOL were significantly better in the HERN group. No significant differences in gastrointestinal and tube-related complications. CONCLUSION HERN improved nutritional status and some dimensions of QOL in upper GI malignancy patients after surgery, without increasing complications. Subgroup analysis showed that HEN experienced more benefits than ONS.
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3.
Malnutrition screening tools in gastrointestinal cancer: A systematic review of concurrent validity.
Deftereos, I, Djordjevic, A, Carter, VM, McNamara, J, Yeung, JM, Kiss, N
Surgical oncology. 2021;:101627
Abstract
OBJECTIVE Malnutrition is a significant problem in gastrointestinal (GI) cancer, and accurate screening and identification is essential to ensure appropriate nutrition intervention. This study aims to determine current evidence for concurrent validity of malnutrition screening tools in GI cancer. METHODS A systematic review was undertaken according to PRISMA guidelines, using four databases. Studies investigating the concurrent validity of malnutrition screening tools against a reference standard of Patient Generated Subjective Global Assessment (PG-SGA) or Subjective Global Assessment (SGA) in adult patients with GI cancer were identified. Screening, quality assessment using the QUADAS-2 checklist, and data extraction were performed by two independent reviewers. Concurrent validity ratings were applied using predefined criteria. RESULTS Six studies investigating concurrent validity of the Nutrition Risk Index (NRI), Malnutrition Universal Screening Tool (MUST), Malnutrition Screening Tool (MST) and Nutrition Risk Screening 2002 criteria (NRS-2002) were included. There was variation in concurrent validity ratings ranging from poor-good for all tools, depending on treatment type, stage and population characteristics. CONCLUSION Recommendations regarding the use of one tool over another could not be made. However, in the absence of a clear recommendation specific to GI cancer, screening tools that are well validated in general clinical populations should be utilised. The MST can be recommended based on validity data against the PG-SGA and SGA from other oncology populations. If indicated, malnutrition screening should then be followed by thorough nutritional assessment.
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4.
Autophagy and gastrointestinal cancers: the behind the scenes role of long non-coding RNAs in initiation, progression, and treatment resistance.
Shafabakhsh, R, Arianfar, F, Vosough, M, Mirzaei, HR, Mahjoubin-Tehran, M, Khanbabaei, H, Kowsari, H, Shojaie, L, Azar, MEF, Hamblin, MR, et al
Cancer gene therapy. 2021;(12):1229-1255
Abstract
Gastrointestinal (GI) cancers comprise a heterogeneous group of complex disorders that affect different organs, including esophagus, stomach, gallbladder, liver, biliary tract, pancreas, small intestine, colon, rectum, and anus. Recently, an explosion in nucleic acid-based technologies has led to the discovery of long non-coding RNAs (lncRNAs) that have been found to possess unique regulatory functions. This class of RNAs is >200 nucleotides in length, and is characterized by their lack of protein coding. LncRNAs exert regulatory effects in GI cancer development by affecting different functions such as the proliferation and metastasis of cancer cells, apoptosis, glycolysis and angiogenesis. Over the past few decades, considerable evidence has revealed the important role of autophagy in both GI cancer progression and suppression. In addition, recent studies have confirmed a significant correlation between lncRNAs and the regulation of autophagy. In this review, we summarize how lncRNAs play a behind the scenes role in the pathogenesis of GI cancers through regulation of autophagy.
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5.
Assessment of Nutritional Status and Nutrition Impact Symptoms in Patients Undergoing Resection for Upper Gastrointestinal Cancer: Results from the Multi-Centre NOURISH Point Prevalence Study.
Deftereos, I, Yeung, JMC, Arslan, J, Carter, VM, Isenring, E, Kiss, N, On Behalf Of The Nourish Point Prevalence Study Group,
Nutrients. 2021;(10)
Abstract
BACKGROUND Identification and treatment of malnutrition are essential in upper gastrointestinal (UGI) cancer. However, there is limited understanding of the nutritional status of UGI cancer patients at the time of curative surgery. This prospective point prevalence study involving 27 Australian tertiary hospitals investigated nutritional status at the time of curative UGI cancer resection, as well as presence of preoperative nutrition impact symptoms, and associations with length of stay (LOS) and surgical complications. METHODS Subjective global assessment, hand grip strength (HGS) and weight were performed within 7 days of admission. Data on preoperative weight changes, nutrition impact symptoms, and dietary intake were collected using a purpose-built data collection tool. Surgical LOS and complications were also recorded. Multivariate regression models were developed for nutritional status, unintentional weight loss, LOS and complications. RESULTS This study included 200 patients undergoing oesophageal, gastric and pancreatic surgery. Malnutrition prevalence was 42% (95% confidence interval (CI) 35%, 49%), 49% lost ≥5% weight in 6 months, and 47% of those who completed HGS assessment had low muscle strength with no differences between surgical procedures (p = 0.864, p = 0.943, p = 0.075, respectively). The overall prevalence of reporting at least one preoperative nutrition impact symptom was 55%, with poor appetite (37%) and early satiety (23%) the most frequently reported. Age (odds ratio (OR) 4.1, 95% CI 1.5, 11.5, p = 0.008), unintentional weight loss of ≥5% in 6 months (OR 28.7, 95% CI 10.5, 78.6, p < 0.001), vomiting (OR 17.1, 95% CI 1.4, 207.8, 0.025), reduced food intake lasting 2-4 weeks (OR 7.4, 95% CI 1.3, 43.5, p = 0.026) and ≥1 month (OR 7.7, 95% CI 2.7, 22.0, p < 0.001) were independently associated with preoperative malnutrition. Factors independently associated with unintentional weight loss were poor appetite (OR 3.7, 95% CI 1.6, 8.4, p = 0.002) and degree of solid food reduction of <75% (OR 3.3, 95% CI 1.2, 9.2, p = 0.02) and <50% (OR 4.9, 95% CI 1.5, 15.6, p = 0.008) of usual intake. Malnutrition (regression coefficient 3.6, 95% CI 0.1, 7.2, p = 0.048) and unintentional weight loss (regression coefficient 4.1, 95% CI 0.5, 7.6, p = 0.026) were independently associated with LOS, but no associations were found for complications. CONCLUSIONS Despite increasing recognition of the importance of preoperative nutritional intervention, a high proportion of patients present with malnutrition or clinically significant weight loss, which are associated with increased LOS. Factors associated with malnutrition and weight loss should be incorporated into routine preoperative screening. Further investigation is required of current practice for dietetics interventions received prior to UGI surgery and if this mitigates the impact on clinical outcomes.
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6.
Molecular Modeling Study of c-KIT/PDGFRα Dual Inhibitors for the Treatment of Gastrointestinal Stromal Tumors.
Keretsu, S, Ghosh, S, Cho, SJ
International journal of molecular sciences. 2020;(21)
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common Mesenchymal Neoplasm of the gastrointestinal tract. The tumorigenesis of GISTs has been associated with the gain-of-function mutation and abnormal activation of the stem cell factor receptor (c-KIT) and platelet-derived growth factor receptor alpha (PDGFRα) kinases. Hence, inhibitors that target c-KIT and PDGFRα could be a therapeutic option for the treatment of GISTs. The available approved c-KIT/PDGFRα inhibitors possessed low efficacy with off-target effects, which necessitated the development of potent inhibitors. We performed computational studies of 48 pyrazolopyridine derivatives that showed inhibitory activity against c-KIT and PDGFRα to study the structural properties important for inhibition of both the kinases. The derivative of phenylurea, which has high activities for both c-KIT (pIC50 = 8.6) and PDGFRα (pIC50 = 8.1), was used as the representative compound for the dataset. Molecular docking and molecular dynamics simulation (100 ns) of compound 14 was performed. Compound 14 showed the formation of hydrogen bonding with Cys673, Glu640, and Asp810 in c-KIT, and Cys677, Glu644, and Asp836 in PDGFRα. The results also suggested that Thr670/T674 substitution in c-KIT/PDGFRα induced conformational changes at the binding site of the receptors. Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed based on the inhibitors. Contour map analysis showed that electropositive and bulky substituents at the para-position and the meta-position of the benzyl ring of compound 14 was favorable and may increase the inhibitory activity against both c-KIT and PDGFRα. Analysis of the results suggested that having bulky and hydrophobic substituents that extend into the hydrophobic pocket of the binding site increases the activity for both c-KIT and PDGFRα. Based on the contour map analysis, 50 compounds were designed, and the activities were predicted. An evaluation of binding free energy showed that eight of the designed compounds have potential binding affinity with c-KIT/PDGFRα. Absorption, distribution, metabolism, excretion and toxicity (ADMET) and synthetic feasibility tests showed that the designed compounds have reasonable pharmaceutical properties and synthetic feasibility. Further experimental study of the designed compounds is recommended. The structural information from this study could provide useful insight into the future development of c-KIT and PDGFRα inhibitors.
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7.
Efficacy and Safety of Low-Molecular-Weight Heparin on Prevention of Venous Thromboembolism after Laparoscopic Operation for Gastrointestinal Malignancy in Japanese Patients: A Multicenter, Open-Label, Prospective, Randomized Controlled Trial.
Obitsu, T, Tanaka, N, Oyama, A, Ueno, T, Saito, M, Yamaguchi, T, Takagi, A, Rikiyama, T, Unno, M, Naitoh, T, et al
Journal of the American College of Surgeons. 2020;(5):501-509.e2
Abstract
BACKGROUND The risk of venous thromboembolism (VTE) after surgery for malignancy in Japanese patients is unclear; therefore, standard prevention protocols have not been established, especially for minimally invasive procedures. We aimed to investigate the additional effect of low molecular weight heparin (LMWH) on prevention of VTE after laparoscopic surgery for gastrointestinal malignancy. STUDY DESIGN From February 2013 to January 2017, 400 patients scheduled for laparoscopic surgery were included. Cases were randomly allocated to the physical therapy group (Control group; 201 patients) or to the combination-therapy group (LMWH group; 199 patients), in which enoxaparin sodium (20 mg [= 2000 IU] twice a day) was administered for 1 week postoperatively in addition to the physical therapy. A diagnosis of VTE was made by contrast-enhanced CT or ultrasonography when symptomatic or D-dimer was ≥10 μg/mL. RESULTS VTE was observed in 1.2% and 4.0% of patients in the LMWH and Control groups, respectively (odds ratio [OR] 0.3, 95% confidence interval [CI] 0.03-1.53). Pulmonary embolism was confirmed only in the Control group (1.7%). No major bleeding occurred in either group. Logistic multiple regression analysis revealed that surgical time extension (OR 1.02, 95% CI 1.00-1.04) was a risk factor of VTE, while administration of LMWH (OR 0.21, 95% CI 0.03-0.99), male sex (OR 0.12, 95% CI 0.01-0.60), and early cancer (OR 0.17, 95% CI 0.02-0.82) reduced the risk of VTE. CONCLUSIONS Postoperative LMWH administration is safe. The additional effect of LMWH administration on the physical therapy was not statistically proven in this study. However, it could be useful for the patients with risk factors such as female sex, long operation time, and higher cancer stage.
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8.
Blue rubber bleb nevus syndrome with the complication of intussusception: A case report and literature review.
Hu, Z, Lin, X, Zhong, J, He, Q, Peng, Q, Xiao, J, Chen, B, Zhang, J
Medicine. 2020;(28):e21199
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Abstract
RATIONALE Blue rubber bleb nevus syndrome (BRBNS) is an extremely rare disorder characterized by multifocal venous malformations involving various organs such as the skin and gastrointestinal tract. Severe complications of BRBNS, such as intussusception, volvulus, and intestinal infarction are rarer and require surgery. This report describes a 33-year-old male of BRBNS complicated with intussusception that was successfully diagnosed and treated with surgery. PATIENT CONCERNS A 33-year-old Chinese man presented with persistent, colicky pain accompanied by nausea, abdominal distension, and dizziness. The patient presented with sporadic bluish nodules on his skin involving his head, neck, thorax, abdomen, and planta pedis. DIAGNOSES BRBNS with the complication of intussusception. INTERVENTIONS An emergency laparotomy was performed, and postoperative management included blood transfusions and oral iron supplementation for 2 weeks. OUTCOMES The patient's postoperative course of hospitalization was uneventful. During the 4-month follow-up, the patient showed no signs of intussusception recurrence. LESSONS Patients diagnosed with BRBNS who present with acute abdominal pain and distension should raise suspicion for the presence of intussusception, which requires emergent surgical intervention.
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SARC-CalF-assessed risk of sarcopenia and associated factors in cancer patients.
Souza, VF, Ribeiro, TSC, Marques, RA, Petarli, GB, Pereira, TSS, Rocha, JLM, Guandalini, VR
Nutricion hospitalaria. 2020;(6):1173-1178
Abstract
Introduction: sarcopenia is considered a risk factor for cancer patients, as it increases mortality and post-surgical complications, and reduces response to treatment and quality of life. Objective: to identify the risk of sarcopenia by SARC-CalF, as well as the factors associated with this outcome in patients with cancer of the gastrointestinal tract (GIT) and adnexal glands. Methods: this cross-sectional study included patients with cancer of the GIT and adnexal glands, without edema or ascites, of both sexes and aged ≥ 20 years. Conventional anthropometric variables and handgrip strength (HGS) were measured. The risk of sarcopenia was assessed through the SARC-CalF questionnaire, and nutritional status by the Patient-Generated Subjective Global Assessment (PG-SGA). The data analysis was performed using the SPSS® software, 22.0, with a significance of 5 %. Results: seventy patients took part in the study. Of these, 55.7 % were female, 52.9 % were aged over 60 years, and 64.3 % were non-white. PG-SGA identified 50.0 % of patients as well-nourished and 50.0 % as having some degree of malnutrition. The prevalence of risk of sarcopenia was 28.6 %. There were different correlations between the SARC-CalF score and anthropometric variables (p < 0.05) according to life stage (adults and elderly). After a linear regression analysis the measures that most influenced the SARC-CalF score were arm circumference (AC) and adductor pollicis muscle thickness in the dominant hand (DAPMT) for adults, while for the elderly current weight and DAPTM (p < 0.05) were more relevant. Conclusion: SARC-CalF identified 28.6 % of patients at risk for sarcopenia and was associated with body weight and anthropometric variables indicative of muscle reserve in adults and the elderly.
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10.
Perioperative body composition changes in the multimodal treatment of gastrointestinal cancer.
Aoyama, T
Surgery today. 2020;(3):217-222
Abstract
Surgical resection and perioperative adjuvant therapy are widely accepted standard treatments for gastrointestinal cancer. However, body composition changes, such as weight loss and skeletal muscle loss, are unavoidable during these treatments. Several studies have shown that perioperative body composition changes are affected by multimodal treatment for gastrointestinal cancer. This review summarizes the background, current status, and future perspectives of perioperative body composition changes in the multimodal treatment of gastrointestinal cancer. Recent studies have described the body composition changes observed in the early period after surgery and during adjuvant therapy. Changes in the body composition might affect adjuvant chemotherapy toxicity after surgery and postoperative complications after neoadjuvant therapy. The mechanisms underlying body composition changes during multimodal therapy are multifactorial and include systemic inflammation, reduced nutrient intake, and physical inactivity. Several approaches have been tested to maintain the body composition, and especially prevent skeletal muscle wasting, during multimodal therapy. Although the ideal approach for managing body composition changes in gastrointestinal cancer patients remains unclear, recent studies support the combination of multiple approaches rather than a single approach.