Predictive Value of ERCC1, ERCC2, and XRCC Expression for Patients with Locally Advanced or Metastatic Gastric Cancer Treated with Neoadjuvant mFOLFOX-4 Chemotherapy.

The dismal outcome in patients with locally advanced or metastatic gastric cancer (GC) highlights the need for effective systemic neoadjuvant chemotherapy to improve clinical results. This study evaluated the correlation between the expression of three DNA repair genes, namely the excision repair cross-complementing group 1 (ERCC1), excision repair cross-complementing group 2 (ERCC2), and X-ray repair cross-complementing protein 1 (XRCC1) and the clinical outcome of patients with locally advanced or metastatic GC treated with mFOLFOX-4 neoadjuvant chemotherapy. Fifty-eight patients with histologically confirmed locally advanced or metastatic GC following neoadjuvant mFOLFOX-4 chemotherapy were enrolled between January 2009 and January 2018. We analyzed clinicopathological features and ERCC1, ERCC2, and XRCC1 expression to identify potential predictors of clinical response. Among the 58 patients, 16 (27.6%) were categorized into the response group (partial response) and 42 into the nonresponse group (stable disease in 24 patients and progressive disease in 18 patients). A multivariate analysis showed that ERCC1 overexpression (P = 0.003), ERCC2 overexpression (P = 0.049), and either ERCC1 or ERCC2 overexpression (P = 0.002) were independent predictors of response following mFOLFOX-4 neoadjuvant chemotherapy. Additionally, ERCC1 and ERCC2 overexpression did not only predict the response but also progression-free survival (both P < 0.05) and overall survival (both P < 0.05). ERCC1 and ERCC2 overexpression are promising predictive biomarkers for patients with locally advanced or metastatic GC receiving neoadjuvant mFOLFOX-4 chemotherapy and the potential clinical implication is mandatory for further investigation.

Prospective double-blind randomized study on the efficacy and safety of an n-3 fatty acid enriched intravenous fat emulsion in postsurgical gastric and colorectal cancer patients.

BACKGROUND: A lipid emulsion composed of soybean oil (long-chain triglycerides, LCT), medium-chain triglycerides (MCT) and n-3 poly-unsaturated fatty acids (PUFAs) was evaluated for immune-modulation efficacy, safety, and tolerance in patients undergoing major surgery for gastric and colorectal cancer. METHODS: In a prospective, randomized, double-blind study, 99 patients with gastric and colorectal cancer receiving elective surgery were recruited and randomly assigned to either the study group, receiving the n-3 PUFAs enriched intravenous fat emulsion (IVFE), or the control group, receiving a lipid emulsion comprised of soybean oil and MCTs (0.8 - 1.5 g · kg-1 · day-1) as part of total parenteral nutrition (TPN) regimen from surgery (day -1) up to post-operative day 7. Safety and efficacy parameters were assessed on day -1 and post-operative visits on day 1, 3, and 7. Adverse events were documented daily and compared between the groups. RESULTS: Pro-inflammatory markers, laboratory parameters, and adverse events did not differ prominently between the 2 groups, with the exception of net changes (day 7 minus day -1) of free fatty acids (FFAs), triglyceride, and high-density lipoprotein (HDL). Net decrease of FFAs was remarkably higher in the study group, while the net increase of triglyceride and decrease of HDL was significantly lower. CONCLUSIONS: The n-3 PUFA-enriched IVFE showed improvements in lipid metabolism. In respect of efficacy, safety and tolerance both IVFE were comparable. In patients with severe stress, there is an inflammation-attenuating effect of n-3 PUFAs. Further, adequately powered clinical trials will be necessary to address this question in postsurgical GI cancer patients. TRIAL REGISTRATION: US ClinicalTrials.gov NCT00798447.

The effect of Helicobacter pylori eradication on the levels of essential trace elements.

OBJECTIVE: This study was designed to compare the effect of Helicobacter pylori (H. pylori) infection treatment on serum zinc, copper, and selenium levels. PATIENTS AND METHODS: We measured the serum zinc, copper, and selenium levels in H. pylori-positive and H. pylori-negative patients. We also evaluated the serum levels of these trace elements after H. pylori eradication. These serum copper, zinc, and selenium levels were determined by inductively coupled plasma mass spectrometry. RESULTS: Sixty-three H. pylori-positive patients and thirty H. pylori-negative patients were studied. Serum copper, zinc, and selenium levels had no significant difference between H. pylori-positive and H. pylori-negative groups. There were 49 patients with successful H. pylori eradication. The serum selenium levels were lower after successful H. pylori eradication, but not significantly (P = 0.06). There were 14 patients with failed H. pylori eradication. In this failed group, the serum selenium level after H. pylori eradication therapy was significantly lower than that before H. pylori eradication therapy (P < 0.05). The serum zinc and copper levels had no significant difference between before and after H. pylori eradication therapies. CONCLUSION: H pylori eradication regimen appears to influence the serum selenium concentration (IRB number: KMUH-IRB-20120327).

LINE-1 Methylation Status Correlates Significantly to Post-Therapeutic Recurrence in Stage III Colon Cancer Patients Receiving FOLFOX-4 Adjuvant Chemotherapy.

BACKGROUND: Methylation levels of long interspersed nucleotide elements (LINE-1) are representative of genome-wide methylation status and crucial in maintaining genomic stability and expression. Their prognostic impact on colon cancer patients receiving adjuvant chemotherapy has not been well established. We evaluated the association between LINE-1 methylation status and clinicopathologic features and postoperative oncological outcomes in stage III colon cancer patients. MATERIALS AND METHODS: 129 UICC stage III colon cancer patients who had received radical resection and FOLFOX adjuvant chemotherapy were enrolled. Global methylation was estimated by analyzing tumor LINE-1 methylation status using bisulfite-polymerase chain reaction (PCR) and pyrosequencing assay. Demographics, clinicopathological data, and postoperative outcomes were recorded by trained abstractors. Outcome measurements included postoperative recurrence and disease-free survival. Univariate, multivariate, and survival analyses were conducted to identify prognostic factors of oncological outcomes. RESULTS: The LINE-1 methylation of all 129 patients was measured on a 0-100 scale (mean 63.3; median 63.7, standard deviation 7.1), LINE-1 hypomethylation was more common in patients aged 65 years and above (61.7%±7.6% vs. 64.6±6.4, p=0.019) and those with post-therapeutic recurrence (61.7±7.4 vs 64.3±6.7, p=0.041). Considering risk adjustment, LINE-1 hypomethylation was found to be an independent risk factor of post-therapeutic recurrence (Adjusted OR=14.1, p=0.012). Kaplan-Meier analysis indicated that patients in the low methylation group had shorter period of disease free survival (p=0.01). In a stratified analysis that included 48 patients with post-therapeutic recurrence, it was found that those who experienced shorter period of disease free survival (≦6 months) appeared to have lower LINE-1 methylation levels than patients who reported of recurrence after 6 months (56.68±15.75 vs. 63.55±7.57, p=0.041). CONCLUSION: There was a significantly greater risk of early postoperative recurrence and a shorter period of disease-free survival in Stage III colon cancer patients exhibiting LINE-1 hypomethylation status after being treated with radical resection and FOLFOX chemotherapy.

A double-blind randomized study comparing the efficacy and safety of a composite vs a conventional intravenous fat emulsion in postsurgical gastrointestinal tumor patients.

BACKGROUND: Composite intravenous fat emulsion, a fat emulsion composed of soybean oil, medium-chain triglycerides (MCT), olive oil, and fish oil, was evaluated for metabolic efficacy, immune modulation, clinical efficacy, safety, and tolerance in surgical gastrointestinal (GI) tumor patients. METHODS: In a prospective, randomized, double-blind study, 40 patients were randomized after elective digestive surgery to receive isonitrogenous, isoenergetic parenteral nutrition for 5 days postoperatively with either composite 20% IVFE (composed of soybean, MCT, olive, and fish oils) or a conventional long-chain triglyceride (LCT)/MCT 20% IVFE (LCT/MCT IVFE); IVFE was dosed at 1-2 g/kg body weight. Safety and efficacy parameters were assessed on operation day (day 0) and at the end of study (day 6). Adverse events were documented daily and clinical outcomes were recorded and compared between the groups. RESULTS: Metabolic parameters, laboratory parameters, proinflammatory cytokine levels, adverse events, and clinical outcomes did not differ between the 2 groups, with the exception that postoperative low-density lipoprotein levels decreased significantly in the composite IVFE group (93.2 ± 24.3 vs 110.5 ± 26.4 mg/dL, P = .038). CONCLUSIONS: composite IVFE was comparable with conventional LCT/MCT IVFE in efficacy, safety, tolerance, and clinical outcomes in surgical GI tumor patients.

Randomized, controlled study of branched chain amino acid-enriched total parenteral nutrition in malnourished patients with gastrointestinal cancer undergoing surgery.

The objective of this study was to investigate the potential benefit of branched chain amino acid (BCAA)-enriched total parenteral nutrition (TPN) for malnourished surgical patients with gastrointestinal cancer. Sixty-four malnourished patients with gastrointestinal cancer with elective surgical intervention were equally allocated into two groups to receive isonitrogenous and isocaloric TPN. All of them must have received TPN soon after surgery and were subsequently randomized and divided into either BCAA-enriched TPN (30% BCAA; intervention group) or standard TPN (24% BCAA; control group). Patient biochemical data, nutritional parameters, and clinical outcome were collected to analyze the significance of BCAA-enriched TPN. After a period of TPN, laboratory data, including white blood cell (WBC), C-reactive protein (CRP), alkaline phosphatase (ALK-P), and gamma-glutamyltransferase (gamma-GT) levels, were significantly different between these two groups (all P < 0.05). Decreasing white blood cell and C-reactive protein levels were observed in the intervention group that might partially explain the reduced numbers of infectious complications. Furthermore, elevating alkaline phosphatase and gamma-glutamyltransferase levels being also less prominent might indicate a lesser hepatic burden by using BCAA-enriched TPN. The BCAA-enriched TPN can maintain a patient's serum visceral protein (albumin and prealbumin) and positive nitrogen balance better than standard TPN (all P < 0.05). Furthermore, a prominently decreased frequency of postoperative morbidity was also found in the BCAA-enriched TPN group (P = 0.021) despite no difference regarding surgical mortality. Our observations show that BCAA-enriched TPN may be beneficial in improving the nutritional status and reducing postoperative complications for malnourished patients with gastrointestinal cancer undergoing major surgery.