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1.
Metabolic bone disorders after gastrectomy: inevitable or preventable?
Rino, Y, Aoyama, T, Atsumi, Y, Yamada, T, Yukawa, N
Surgery today. 2022;(2):182-188
Abstract
Some authors have suggested that a relationship exists between gastrectomy for gastric cancer and metabolic bone disorders. However, few studies have investigated metabolic bone disorders after gastrectomy for gastric cancer in detail. Thus, we reviewed the findings of our recent prospective study and those of other reports on this subject. Osteoporosis and osteomalacia have been observed after gastrectomy and appear to be caused by reduced food intake and absorption, and steatorrhea. Moreover, the incidence of fracture is high after gastrectomy, although subtotal or total gastrectomy and reconstruction for gastric cancer have not been identified as significant risk factors for decreased bone mineral density (BMD). Recently, we reported that the BMD decreased significantly within 12 months after gastrectomy for gastric cancer in both male and female patients, but there was no significant gender-related difference in the rate of change in BMD. More than 1 year after gastrectomy, the steep decrease in the BMD stabilized and normal levels of 1,25(OH)2 vitamin D3 were maintained, despite the lack of precursor for 1,25(OH)2 vitamin D3 synthesis after gastrectomy. Alendronate therapy might be effective and prevent postgastrectomy metabolic bone disorders; however, the optimal treatment and prevention strategy for this bone disorder has not been delineated.
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2.
Short-Term Efficacy and Quality of Life of Gastric Cancer Patients Undergoing Radical Gastrectomy Assisted by External Vision.
Zheng, J, Xue, Y, Li, C
Computational and mathematical methods in medicine. 2021;:4256347
Abstract
OBJECTIVE To evaluate the clinical effects and survival prognosis of radical gastrectomy assisted by external vision in gastric cancer. METHODS A total of 60 hospitalized gastric cancer patients from June 2016 to December 2018 were selected and divided into the observation group and control group according to different surgical procedures. The control group was treated with traditional open radical gastrectomy, while the observation group was treated with radical gastrectomy assisted by an external vision microscope. Relevant surgical indicators, visual analogue scale (VAS), postoperative complications, and life quality assessment were analyzed and compared between the two groups. RESULTS The incision length and intraoperative blood loss in the observation group were smaller than those in the control group, and the difference was statistically significant (P < 0.05); compared with the control group, the observation group had significantly shorter hospital stay, earlier postoperative first exhaust time, and lower gastric fluid volume at the 3rd day after surgery (P < 0.05). The pain scores of the observation group at 1, 4, and 12 weeks after surgery were lower than those of the control group (P < 0.05), and the difference was significant. The quality of life scores at the 1st week and 12th week after surgery showed that the dysphagia symptom scores of the observation group and the control group were significantly reduced but the two groups had significant differences in fatigue, physical function, pain score, postoperative pain, and overall quality of life. The observation group was significantly better than the control group (P < 0.05). Follow-up studies showed no significant difference between mortality and cancer recurrence (P > 0.05); the patients recovered well at postoperation, and the diet of the observation group was better than that of the control group (P < 0.05); gastric reflux and knife pain were less than those of the control group (P < 0.05). CONCLUSION Radical gastrectomy assisted by external vision for gastric cancer yields clinical benefits for gastric cancer patients, which not only dramatically shortened the length of hospital stay but also effectively ameliorated the quality of life of patients, all indicating that external vision-assisted surgery was significantly better than traditional gastrectomy in improving the postoperative quality of life of gastric cancer patients in the absence of increasing the risk of adverse events.
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3.
Effect of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Women: A Randomized Clinical Trial.
Wang, DS, Hu, MT, Wang, ZQ, Ren, C, Qiu, MZ, Luo, HY, Jin, Y, Fong, WP, Wang, SB, Peng, JW, et al
JAMA network open. 2021;(4):e215250
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Abstract
IMPORTANCE The prevention of chemotherapy-induced nausea and vomiting has an important role in the overall management of cancer treatment. OBJECTIVE To evaluate whether adding aprepitant to palonosetron and dexamethasone can further prevent the incidence and severity of nausea and vomiting caused by FOLFIRI (fluorouracil, leucovorin, and irinotecan) or FOLFOX (fluorouracil, leucovorin, and oxaliplatin) chemotherapy regimens among women with gastrointestinal cancer at higher risk. DESIGN, SETTING, AND PARTICIPANTS This phase 3, double-blind, placebo-controlled randomized clinical trial recruited young women (age ≤50 years) who drank little or no alcohol and had gastrointestinal cancer for which they received FOLFOX or FOLFIRI chemotherapy. A total of 248 women were enrolled and assigned in the ratio 1:1 to intervention and control groups from August 4, 2015, to March 31, 2020. Intention-to-treat analysis was used to evaluate patient baseline characteristics and efficacy. The analysis was conducted on October 30, 2020. INTERVENTIONS Patients were randomly assigned to the aprepitant group (aprepitant, 125 mg, orally 60 minutes before initiation of chemotherapy on day 1 and 80 mg orally each morning of days 2 and 3; palonosetron, 0.25 mg, intravenously; and dexamethasone, 6 mg, orally 30 minutes before chemotherapy initiation on day 1) or the placebo group (placebo, 125 mg, orally 60 minutes before initiation of chemotherapy on day 1 and 80 mg orally on each morning of days 2 and 3; palonosetron, 0.25 mg, intravenously; and dexamethasone, 12 mg, orally 30 minutes before chemotherapy initiation on day 1). MAIN OUTCOMES AND MEASURES The primary end point was the complete response (CR) rate, defined as the proportion of patients without emesis episodes or rescue medication use during the overall phase of the first cycle. Other efficacy indicators, such as no vomiting and no nausea, were measured as the secondary and exploratory end points. RESULTS A total of 248 women from 4 clinical centers in China entered this study, and 243 patients (aprepitant regimen, 125 patients [51.4%]; placebo regimen, 118 patients [48.5%]) were evaluable for efficacy and safety; mean (SD) age of the total population was 40.1 (7.3) years. The CR rate was significantly higher in the aprepitant group vs the control group overall (107 [87.0%] vs 80 [66.7%]; P < .001) and in the acute (114 [92.7%] vs 91 [75.8%]; P = .001) and delayed (109 [88.6%] vs 84 [70.0%]; P = .001) phases of the trial. The incidence of adverse events was similar between the 2 groups (100 [80.0%] vs 96 [81.3%]; P = .79), and no grade 3 or 4 aprepitant treatment-related adverse events were observed. Multivariable analysis revealed that aprepitant use was the only independent factor associated with CR during the overall phase. CONCLUSIONS AND RELEVANCE The combination of aprepitant with palonosetron and dexamethasone provided increased antiemetic efficacy in the FOLFOX or FOLFIRI chemotherapy regimen and was well tolerated by younger women with gastrointestinal cancer who have a history of little or no alcohol consumption. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03674294.
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Enhanced Recovery after Surgery in Elderly Gastric Cancer Patients Undergoing Laparoscopic Total Gastrectomy.
Cao, S, Zheng, T, Wang, H, Niu, Z, Chen, D, Zhang, J, Lv, L, Zhou, Y
The Journal of surgical research. 2021;:579-586
Abstract
BACKGROUND The aim of this study was to evaluate the effects of the enhanced recovery after surgery (ERAS) program versus conventional perioperative care on the short-term postoperative outcomes among elderly patients with gastric cancer who are undergoing laparoscopic total gastrectomy. METHODS Elderly patients with gastric cancer (age ≥ 65 y) who are undergoing laparoscopic total gastrectomy were randomized to ERAS or conventional perioperative care groups. Short-term postoperative outcomes, including postoperative hospital stay, mortality, complications, readmission rate, and reoperation rate were compared between the two groups. In addition, blood samples were taken preoperatively (baseline) and on postoperative days 1, 3, and 5. Systemic human leukocyte antigen (HLA)-DR expression on monocytes and C-reactive protein (CRP) were analyzed. RESULTS Of the 171 eligible patients, 85 patients were assigned to receive ERAS program treatment (ERAS group) and 86 patients to receive conventional care (conventional group). The patients' characteristics were comparable. Postoperative hospital stay was shorter in the ERAS group than in the conventional group (11 [7-11] versus 13 [8-20] d, P < 0.001). Hospital mortality, overall morbidity, morbidity ≥ Clavien-Dindo (C-D) grade II, readmission rate, and reoperation rate did not show significant differences between the two groups. However, morbidity ≥ C-D grade IIIa was lower in the ERAS group than that in the conventional group (8.2% versus 18.6%, P = 0.047). The ERAS program shortened the number of days to postoperative first flatus, first defecation, semifluid diet, and soft bland diet. Moreover, the ERAS program increased the HLA-DR expression on monocytes and decreased the CRP levels on postoperative days 1, 3, and 5. CONCLUSIONS The ERAS program was feasible and effective for elderly patients with gastric cancer who are undergoing laparoscopic total gastrectomy. The benefits of ERAS were associated with improvement of impaired immune function and suppression of inflammatory reaction.
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5.
Computational design and experimental substantiation of conformationally constrained peptides from the complex interfaces of transcriptional enhanced associate domains with their cofactors in gastric cancer.
Zhang, D, Wu, H, Zhao, J
Computational biology and chemistry. 2021;:107569
Abstract
Transcriptional enhanced associate domains (Teads) are the downstream effectors of the hippo signaling pathway and have been recognized as attractive druggable targets of gastric cancer. The biological function of Teads is regulated by diverse cofactors. In this study, the intermolecular interactions of Teads with their cognate cofactors were systematically characterized at structural, thermodynamic and dynamic levels. The Teads possess a double-stranded helical hairpin that is surrounded by three independent structural elements β-sheet, α-helix and Ω-loop of cofactor proteins and plays a central role in recognition and association with cofactors. A number of functional peptides were split from the hairpin region at Tead-cofactor complex interfaces, which, however, cannot maintain in native conformation without the support of protein context and would therefore incur a considerable entropy penalty upon competitively rebinding to the interfaces. Here, we further used disulfide and hydrocarbon bridges to cyclize and staple the hairpin and helical peptides, respectively. The chemical modification strategies were demonstrated to effectively constrain peptide conformation into active state and to largely reduce peptide flexibility in free state, thus considerably improving their affinity. Since the cyclization and stapling only minimize the indirect entropy cost but do not influence the direct enthalpy effect upon peptide binding, the designed conformationally constrained peptides can retain in their native selectivity over different cofactors. This is particularly interesting because it means that the cyclized/stapled, affinity-improved peptides can specifically compete with their parent Teads for the cofactor arrays as they share consistent target specificity.
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A novel irradiation stent versus conventional irradiation stent for malignant dysphagia: A prospective randomized controlled trial.
Zhu, GY, Lu, J, Wang, C, Guo, JH
Journal of cancer research and therapeutics. 2021;(5):1261-1268
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Abstract
AIM: To evaluate whether a novel irradiation stent (NIS) could decrease the rate of recurrent dysphagia, compared to the conventional irradiation stent (CIS) in patients with malignant dysphagia. MATERIALS AND METHODS We performed an open-label randomized controlled trial of participants with malignant dysphagia. A total of 94 participants were parallelly allocated into the NIS group or the NIS group between April 2019 and April 2020. The primary endpoint was the rate of recurrent dysphagia. The secondary endpoints included technical success, clinical success, overall survival, and adverse events. RESULTS The technical success rate and the clinical success rate was 100.0% (47/47) in both groups. The median follow-up period was 189 days (range 14-422 days). Recurrent dysphagia was observed in 12.8% (6/47) of patients in the NIS group and 31.9% (15/47) in the CIS group (P = 0.026). Tissue/tumor growth occurred in 4 patients (8.5%) after NIS placement and 12 (25.5%) after CIS placement (P = 0.028). Stent migration occurred in 2 patients (4.3%) after NIS placement and 3 (6.4%) after CIS placement (P = 0.646). No food obstruction was found in both groups. The median overall survival was 177 days (95% confidence interval [CI] 139-214) in the NIS group and 168 days (95% CI 153-183) in the CIS group (P = 0.932). The incidence of severe adverse events was comparable between the two groups (21.3% vs. 17.0%, P = 0.600). CONCLUSIONS In patients with malignant dysphagia, compared with CIS, NIS could decrease the rate of tissue/tumor growth without increase the rate of stent migration and therefore decrease the rate of recurrent dysphagia.
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FOLFIRINEC: a randomized phase II trial of mFOLFIRINOX vs platinum-etoposide for metastatic neuroendocrine carcinoma of gastroenteropancreatic or unknown origin.
Hadoux, J, Afchain, P, Walter, T, Tougeron, D, Hautefeuille, V, Monterymard, C, Lorgis, V, Thuillier, F, Baudin, E, Scoazec, JY, et al
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2021;(7):824-829
Abstract
BACKGROUND Poorly differentiated neuroendocrine carcinomas (NEC) are rare diseases with a poor prognosis. Platinum-etoposide (PE) has been the recommended first-line treatment for decades. FOLFIRINEC (NCT04325425) is a national multicenter randomized phase II study which aims to challenge this standard regimen. METHODS The primary objective is to compare the median progression-free survival (PFS) under mFOLFIRINOX versus PE. The secondary objectives are to evaluate the objective response rates (ORR), median overall survival (OS), safety and quality of life. The associated real-time translational study will establish a molecular profile for each patient enrolled. MAIN INCLUSION CRITERIA ARE NEC of gastroenteropancreatic (GEP) or unknown origin, metastatic and RECIST 1.1 evaluable disease, tumor sample available and no contraindication to chemotherapy. Patients will be randomized 1:1 between PE every 21 days for 6-8 cycles and mFOLFIRINOX every 14 days for up to 12 cycles and stratified according to center, performance status, Ki67 and pathological subtype. This trial will randomize 218 patients (24 months of follow-up) to have 80% power to detect an improvement of the median PFS from 5 months under PE to 7.5 months under mFOLFIRINOX (HR of 0.67, α =5%, two-sided). An intermediate analysis is planned at 50% of events. Recruitment started on October 20, 2020.
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Comparison of efficacy of pharmacological therapies for gastric endoscopic submucosal dissection-induced ulcers: a systematic review and network meta-analysis.
Gao, H, Li, L, Zhang, C, Tu, J, Geng, X, Wang, J, Zhou, X, Jing, J, Pan, W
Expert review of gastroenterology & hepatology. 2020;(3):207-220
Abstract
Objectives: This study aimed to compare the efficacy of various anti-ulcer medications in preventing delayed bleeding and promoting ulcer healing after ESD.Methods: Asystematic search was conducted for articles up to August2019. The treatments of iatrogenic ulcer were analyzed by Bayesian network meta-analysis.Results: The analysis included 28 studies. Six treatments were compared. For the prevention of delayed bleeding, potassium-competitive acid blocker (P-CAB) alone was superior to proton-pump inhibitor (PPI) alone [RR = 1.02, 95%CI (1.00, 1.05)]. Treatments based on P-CAB tended to be better than the non-P-CAB groups [RR = 1.05, 95%CI (1.03, 1.07)]. Concerning the ulcer healing rate at 4 weeks, the combined treatment of PPI and mucoprotective agent (MP) was superior to PPI alone [RR = 1.81, 95%CI (1.19, 2.76)] and P-CAB alone [RR = 2.75, 95%CI (1.02, 7.44)]. At 8 weeks, PPI+MP and P-CAB+MP tend to be superior to than the other four groups. The healing effect of MP-based therapies was better than that of non-MP groups at 4 weeks [RR = 1.63, 95%CI (1.32, 2.01)] and 8 weeks [RR = 1.06, 95%CI (1.02, 1.11)].Conclusion: P-CAB may prevent delayed bleeding, but not significantly. MP agents have the potential to heal post-ESD ulcers.
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FOLFIRINOX for the Treatment of Advanced Gastroesophageal Cancers: A Phase 2 Nonrandomized Clinical Trial.
Park, H, Jin, RU, Wang-Gillam, A, Suresh, R, Rigden, C, Amin, M, Tan, BR, Pedersen, KS, Lim, KH, Trikalinos, NA, et al
JAMA oncology. 2020;(8):1231-1240
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Abstract
IMPORTANCE Standard first-line regimens for patients with metastatic gastroesophageal adenocarcinomas have an approximate 40% objective response rate (ORR). The combination of leucovorin, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) has been efficacious as first-line therapy for other gastrointestinal cancers, such as pancreatic and colon cancers. OBJECTIVE To evaluate the clinical activity and safety of FOLFIRINOX as first-line treatment for patients with advanced gastroesophageal adenocarcinoma. DESIGN, SETTING, AND PARTICIPANTS This is an open-label, single-arm phase 2 study of first-line FOLFIRINOX in patients with advanced gastroesophageal adenocarcinoma. Estimated sample size included 41 patients with ERBB2-negative disease with 90% power to detect an ORR of 60% or greater with α of .10. No enrollment goal was planned for ERBB2-positive patients, but they were allowed to receive trastuzumab in combination with FOLFIRINOX. INTERVENTIONS Starting doses were fluorouracil, 400 mg/m2 bolus, followed by 2400 mg/m2 over 46 hours; leucovorin, 400 mg/m2; irinotecan, 180 mg/m2; and oxaliplatin, 85 mg/m2. Trastuzumab was administered as a 6 mg/kg loading dose, followed by 4 mg/kg every 14 days in patients with ERBB2-positive disease. MAIN OUTCOMES AND MEASURES The primary end point was ORR by the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included safety profile, progression-free survival (PFS), overall survival (OS), and duration of response. RESULTS From November 2013 to May 2018, 67 patients were enrolled (median [range] age, 59.0 [34-78] years; including 56 [84%] men), and 26 of 67 (39%) had ERBB2-positive disease. Median follow-up was 17.4 months. The ORR was 61%(95% CI, 44.5%-75.8%) (25 of 41) in the ERBB2-negative group and 85% (95% CI, 65.1%-95.6%) (22 of 26) in the ERBB2-positive group, including 1 patient with complete response. For ERBB2-negative patients, median PFS was 8.4 months and median OS was 15.5 months; for ERBB2-positive patients, median PFS was 13.8 months and median OS was 19.6 months. Fifty-six patients (84%) had dose modifications or treatment delays. The most common toxic effects were neutropenia (91%, n = 61), diarrhea (63%, n = 42), peripheral sensory neuropathy (61%, n = 41), and nausea (48%, n = 32), with no unexpected toxic effects. CONCLUSIONS AND RELEVANCE The FOLFIRINOX regimen with or without trastuzumab was associated with improved ORR and PFS in patients with advanced gastroesophageal adenocarcinoma in the first-line setting. This regimen may be a reasonable therapeutic option for patients with preserved performance status. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01928290.
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Robotic versus laparoscopic surgery for gastric cancer: an overview of systematic reviews with quality assessment of current evidence.
Hoshino, N, Murakami, K, Hida, K, Hisamori, S, Tsunoda, S, Obama, K, Sakai, Y
Updates in surgery. 2020;(3):573-582
Abstract
Many systematic reviews have been published to evaluate the clinical benefits of robotic surgery for gastric cancer. However, these reviews have investigated various outcomes and differ considerably in quality. In this overview, we summarize the findings and quality of these reviews. A comprehensive literature search was conducted using PubMed, Scopus, and the Cochrane Central Register of Controlled Trials to identify systematic reviews and meta-analyses that compared robotic surgery with laparoscopic surgery for gastric cancer. We summarized the results of the meta-analyses and evaluated the quality of the reviews using the AMSTAR-2 tool. The literature search identified 14 eligible reviews. The reviews showed that estimated blood loss was significantly less and time to resumption of oral intake was significantly shorter in patients who underwent robotic surgery than in those who underwent laparoscopic surgery. However, no significant differences in other outcomes were found between the two types of surgery. The quality of the included reviews was judged to be critically low. In conclusion, the available evidence, albeit of critically low quality, suggests that robotic surgery decreases estimated blood loss and shortens the time to resumption of oral intake in patients with gastric cancer. There is currently no high-quality evidence that robotic surgery has clinical benefits for gastric cancer patients.