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1.
Systematic review and meta-analysis of docetaxel perioperative chemotherapy regimens in gastric and esophagogastric tumors.
Uson Junior, PLS, Santos, VM, Bugano, DDG, Victor, EDS, Rother, ET, Maluf, FC
Scientific reports. 2019;(1):15806
Abstract
FLOT regimen became the standard perioperative treatment in several centers around the world for esophagogastric tumors despite concerns about toxicity. In addition, FLOT has never been compared with other docetaxel-based regimens. To address this question, we conducted a systematic review of PubMed, Embase and Web of Science including prospective or retrospective studies of docetaxel based perioperative regimen in gastric and esophagogastric tumors. Data regarding chemotherapy regimens, efficacy and toxicity were extracted. Outcomes were compared using a random effects model. Of 548 abstracts, 16 were considered eligible. Comparing the studies with meta-analysis we can see that the regimens are similar in terms of pathological complete response, resection rate, progression free survival and overall survival in one year, without significant heterogeneity. The meta-regression of docetaxel dose failed to show any association with dose ranging between 120-450 mg/m². Regarding the toxicity of the regimens it is noted that the regimens are quite toxic (up to 50-70% of grade 3-4 neutropenia). The results of this meta-analysis with a combined sample size of more than 1,000 patients suggest that docetaxel perioperative regimens are equivalent in outcomes. Prospective trials addressing modified regimens should be performed to provide less toxic strategies and be applicable to all patients.
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2.
The Difficult Esophageal Conduit.
Kumar, R, Wei, B
The Surgical clinics of North America. 2019;(3):471-478
Abstract
A variety of esophageal diseases are treated with esophagectomy, from benign to esophageal cancer. Careful attention must be given to management of the difficult conduit, including patients who have had prior gastric surgery and other procedures, patients with conditions such as diabetic gastroparesis, which can affect the stomach as a future usable conduit, and patients who have an absent or unusable stomach. In these situations, consideration should be raised for the use of alternative conduits, including jejunal and colonic interposition conduits. The esophageal surgeon should also be adept at management of intraoperative difficulties with the conduit.
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3.
Treatment of Patients with Advanced Gastroesophageal Adenocarcinoma: Does Age Matter?
Lorenzen, S, Hofheinz, RD
Drugs & aging. 2019;(5):403-409
Abstract
Gastroesophageal cancer is the fourth most frequent malignant disease and, despite significant advances in chemotherapy, the prognosis of unresectable or recurrent gastroesophageal cancer is poor. The majority of patients, nearly two-thirds, are over the age of 65 years at diagnosis. Elderly patients are a heterogeneous population and aging occurs at different rates in different individuals. The chronological age of a patient does not necessarily reflect the physiological age. However, elderly patients are more likely to have a number of concomitant diseases and impaired organ function, which should be considered when making treatment decisions. Therefore, treatment in older adults requires particular caution, and physiologic age rather than chronologic age should be considered when deciding for or against systemic therapy. Older patients are generally underrepresented in clinical trials and many elderly patients do not receive effective combination therapies due to concerns with tolerability. Age itself is not a negative predictive factor and treatment should not be omitted just on the basis of chronological age. Older patients who fulfill the standard inclusion criteria of clinical trials seem to have a similar advantage from palliative chemotherapy for gastroesophageal adenocarcinoma as younger patients; however, large prospective trials in the elderly population are needed to guide clinicians in making evidence-based decisions.
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4.
Advances in the diagnosis and surveillance of Barrett's esophagus (with videos).
, , Trindade, AJ, Navaneethan, U, Aslanian, HR, Bhutani, MS, Krishnan, K, Lichtenstein, DR, Melson, J, Pannala, R, Parsi, MA, et al
Gastrointestinal endoscopy. 2019;(3):325-334
Abstract
BACKGROUND AND AIMS Most patients diagnosed with esophageal adenocarcinoma do not carry a known diagnosis of Barrett's esophagus (BE), suggesting that an improved approach to screening may potentially be of benefit. The use of dysplasia as a biomarker and random biopsy protocols for its detection has limitations. In addition, detecting and appropriately classifying dysplasia in patients with known BE can be difficult. METHODS This document reviews several technologies with a recently established or potential role in the diagnosis and/or surveillance of BE as well as risk stratification for progression to esophageal adenocarcinoma. RESULTS Two technologies were reviewed for imaging or tissue sampling: (1) wide-area transepithelial sampling and (2) volumetric laser endomicroscopy. Four technologies were reviewed for molecular and biomarker technologies for diagnosis and risk stratification: (1) Cytosponge, (2) mutational load, (3) fluorescence in situ hybridization, and (4) immunohistochemistry. CONCLUSION Several technologies discussed in this document may improve dysplasia detection in BE in a wide-field manner. Moreover, the addition of different biomarkers may aid in enhanced risk stratification to optimize approaches to surveillance or treatment for patients with BE.
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5.
Perioperative enteral supplementation with glutamine, fiber, and oligosaccharide reduces early postoperative surgical stress following esophagectomy for esophageal cancer.
Abe, T, Hosoi, T, Kawai, R, Uemura, N, Higaki, E, An, B, Kawakami, J, Saito, T, Shimizu, Y
Esophagus : official journal of the Japan Esophageal Society. 2019;(1):63-70
Abstract
BACKGROUND We clarified the effects of perioperative enteral supplementation with glutamine, fiber, and oligosaccharide (GFO) after an esophagectomy on preventing surgical stress. METHODS Of 326 patients with esophageal cancer, 189 received GFO administration (GFO group) and 137 did not (control group). The propensity score matching method was used to identify 89 well-balanced pairs of patients to compare postoperative laboratory parameters and clinical and postoperative outcomes. RESULTS The duration of the systemic inflammatory response syndrome (SIRS) was significantly shorter in the GFO group compared to the control group (p = 0.002). Moreover, the lymphocyte/neutrophil ratio (L/N ratio) had significantly recovered in the GFO group on postoperative day-3, and the CRP value was significantly lower in the GFO group than that in the control group on postoperative day-2. CONCLUSIONS Perioperative use of enteral supplementation with glutamine, fiber, and oligosaccharide likely contributes to a reduction in early surgical stress after an esophagectomy. These beneficial effects can bring about early recovery from postoperative immunosuppressive conditions after radical esophagectomy.
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6.
Inhibitory Effects of (-)-Epigallocatechin-3-gallate on Esophageal Cancer.
Wang, LX, Shi, YL, Zhang, LJ, Wang, KR, Xiang, LP, Cai, ZY, Lu, JL, Ye, JH, Liang, YR, Zheng, XQ
Molecules (Basel, Switzerland). 2019;(5)
Abstract
There is epidemiological evidence showing that drinking green tea can lower the risk of esophageal cancer (EC). The effect is mainly attributed to tea polyphenols and their most abundant component, (-)-epigallocatechin-3-gallate (EGCG). The possible mechanisms of tumorigenesis inhibition of EGCG include its suppressive effects on cancer cell proliferation, angiogenesis, DNA methylation, metastasis and oxidant stress. EGCG modulates multiple signal transduction and metabolic signaling pathways involving in EC. A synergistic effect was also observed when EGCG was used in combination with other treatment methods.
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7.
Bowel obstruction associated with a feeding jejunostomy and its association to weight loss after thoracoscopic esophagectomy.
Kitagawa, H, Namikawa, T, Iwabu, J, Uemura, S, Munekage, M, Yokota, K, Kobayashi, M, Hanazaki, K
BMC gastroenterology. 2019;(1):104
Abstract
BACKGROUND Our aim was to clarify the incidence of bowel obstruction associated with a feeding jejunostomy (BOFJ) after thoracoscopic esophagectomy and its association to characteristics and postoperative change in body weight. METHODS We reviewed 100 consecutive patients who underwent thoracoscopic esophagectomy with gastric tube reconstruction and placement of a jejunostomy feeding catheter for esophageal cancer. The incidence of BOFJ was evaluated and the change in body weight after surgery was compared between patients with and without BOFJ. RESULTS BOFJ developed in 17 patients. Compared to patients without BOFJ, those with BOFJ had a higher preoperative body mass index (23.3 kg/m2 versus 20.9 kg/m2, P = 0.022), and greater postoperative body weight loss rate: 3 month, decrease to 84.2% of initial body weight versus 89.3% (P = 0.002). Patients with BOFJ had shorter distance between the jejunostomy and midline (40 mm versus 48 mm, P = 0.011) compared to patients without BOFJ. On multivariate analysis, higher preoperative body mass index (odds ratio (OR) = 9.248; 95% confidence interval (CI) = 1.344-63.609; p = 0.024), higher postoperative weight loss at 3 months (OR = 8.490; 95% CI = 1.765-40.837, p = 0.008), and shorter distance between the jejunostomy and midline (OR = 8.160; 95% CI = 1.675-39.747, p = 0.009) were independently associated with BOFJ. CONCLUSION Patients of BOFJ had greater preoperative body mass, shorter distance between jejunostomy and midline, and greater postoperative weight loss.
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8.
The Therapeutic and Preventive Efficacy of Curcumin and Its Derivatives in Esophageal Cancer.
Komal, K, Chaudhary, S, Yadav, P, Parmanik, R, Singh, M
Asian Pacific journal of cancer prevention : APJCP. 2019;(5):1329-1337
Abstract
Esophageal cancer is the eighth most common occurring cancer type worldwide and 6th most common among the cancer related deaths of which the most common type is squamous cell carcinoma which comprise about 90% of esophageal cancer cases. The standard of care for esophageal cancer is neoadjuvant concurrent chemotherapy and radiation (NACRT) followed by surgery however the prognosis remains dismal with 5 year survival a meager 10-15%. The treatment modalities for esophageal cancer is associated with both long term and short term toxicities. Curcumin has been explored as a therapeutic modality as a chemo adjuvant in different cancers due to its low toxicity profile and potent anticancer effect however despite lot of promising preclinical data it has not progressed from bench side to bed side. The primary reason that has obstructed its application in clinic has been its low bioavailability which was seen in different clinical trials but there has been tremendous progress in developing formulations of curcumin which have significantly increased its bioavailability and are being tested in clinical trials. Esophageal cancer is associated with inflammation that’s why curcumin being a natural antioxidant offer a potential avenue to reduce toxicity of current therapeutic modalities in a chemo adjuvant setting while simultaneously targeting different pro oncogenic pathways. The present review tries to cover in depth different aspects of curcumin application in treatment of esophageal cancer and progress of this potent anticancer agent in its treatment and prevention.
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9.
Effect of dietary cholesterol intake on the risk of esophageal cancer: a meta-analysis.
Jin, Y, Yang, T, Li, D, Ding, W
The Journal of international medical research. 2019;(9):4059-4068
Abstract
OBJECTIVE This systematic review aimed to explore the potential association between dietary cholesterol intake and esophageal cancer risk. METHODS A literature search was conducted using PubMed, Embase, and Web of Science databases from inception to March 2019 according to specific inclusion and exclusion criteria. Pooled estimates with odds ratio (ORs) and 95% confidence intervals (CIs) were obtained using random effects models. RESULTS Nine articles of 12 independent studies were included in the final meta-analysis. Pooled analysis suggested that dietary cholesterol intake may increase the risk of esophageal cancer (summarized OR = 1.424, 95% CI = 1.191–1.704). Consistent results were found in American (summarized OR = 1.410, 95% CI = 1.130–1.758) and European populations (summarized OR = 1.556, 95% CI = 1.021–2.373). Subgroup analysis by disease type showed that dietary cholesterol intake had a significant association with the development of esophageal adenocarcinoma and esophageal squamous cell carcinoma. CONCLUSION Our findings indicated that dietary cholesterol intake could significantly increase the risk of developing esophageal cancer in both European and American populations. Further high-quality studies are necessary to confirm the effects of cholesterol intake.
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10.
Results of a Phase 1/2 Trial of Chemoradiotherapy With Simultaneous Integrated Boost of Radiotherapy Dose in Unresectable Locally Advanced Esophageal Cancer.
Chen, D, Menon, H, Verma, V, Seyedin, SN, Ajani, JA, Hofstetter, WL, Nguyen, QN, Chang, JY, Gomez, DR, Amini, A, et al
JAMA oncology. 2019;(11):1597-1604
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Abstract
IMPORTANCE Effective treatment options for locally advanced esophageal cancer are limited, and rates of local recurrence after standard chemoradiotherapy remain high. OBJECTIVE To evaluate toxic effects, local control, and overall survival rates after chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose to the gross tumor and nodal disease for patients with unresectable locally advanced esophageal cancer. DESIGN, SETTING, AND PARTICIPANTS A phase 1/2, single-arm trial was conducted in 46 patients from April 28, 2010, to April 9, 2015 (median follow-up, 52 months [range, 2-86 months]), at a tertiary academic cancer center. Outcomes of the study patients were compared with those of 97 similar patients treated at the same institution from January 10, 2010, to December 5, 2014, as part of the interim analysis. Statistical analysis was performed from December 15, 2018, to February 12, 2019. INTERVENTIONS Chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose (50.4 Gy to subclinical areas at risk and 63.0 Gy to the gross tumor and involved nodes, all given in 28 fractions) with concurrent docetaxel and capecitabine or fluorouracil. MAIN OUTCOMES AND MEASURES Toxic effects, local (in-field) control, and overall survival rates. RESULTS All 46 patients (11 women and 35 men; median age, 65.5 years [range, 37.3-84.4 years]) received per-protocol therapy, as intensity-modulated photon therapy (39 [85%]) or intensity-modulated proton therapy (7 [15%]); 11 patients (24%) ultimately underwent resection. No patients experienced grade 4 or 5 toxic effects; the 10 acute grade 3 toxic events were esophagitis (4), dysphagia (3), and anorexia (3) and the 3 late grade 3 toxic events were all esophageal strictures. The actuarial local recurrence rates were 22% (95% CI, 11%-35%) at 6 months, 30% (95% CI, 18%-44%) at 1 year, and 33% (95% CI, 20%-46%) at 2 years. Overall, 15 patients (33%) experienced local failure, at a median interval of 5 months (range, 1-24 months). The median overall survival time was 21.5 months (range, 2.3-86.4 months). Exploratory comparison with a 97-patient contemporaneous institutional cohort receiving standard-dose (non-simultaneous integrated boost) chemoradiotherapy showed superior local control (hazard ratio, 0.49; 95% CI, 0.26-0.92; P = .03) and overall survival (hazard ratio, 0.66; 95% CI, 0.47-0.94; P = .02) in the group that received chemoradiotherapy with a simultaneous integrated boost. CONCLUSIONS AND RELEVANCE These findings suggest that chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose for locally advanced esophageal cancer is well tolerated, with encouraging local control, and thus warrants further study. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01102088.