Ni‐rich layered LiNixCoyMn1−x−yO2 (LNCM) with Ni content over >90% is considered as a promising lithium ion battery (LIB) cathode, attributed by its low cost and high practical capacity. However, ...Ni‐rich LNCM inevitably suffers rapid capacity fading at a high state of charge due to the mechanochemical breakdown; in particular, the microcrack formation has been regarded as one of the main culprits for Ni‐rich layered cathode failure. To address these issues, Ni‐rich layered cathodes with a textured microstructure are developed by phosphorous and boron doping. Attributed by the textured morphology, both phosphorous‐ and boron‐doped cathodes suppress microcrack formation and show enhanced cycle stability compared to the undoped cathode. However, there exists a meaningful capacity retention difference between the doped cathodes. By adapting the various analysis techniques, it is shown that the boron‐doped Ni‐rich layered cathode displays better cycle stability not only by its ability to suppress microcracks during cycling but also by its primary particle morphology that is reluctant to oxygen evolution. The present work reveals that not only restraint of particle cracks but also suppression of oxygen release by developing the oxygen stable facets is important for further improvements in state‐of‐the‐art Li ion battery Ni‐rich layered cathode materials.
Herein, the effect of boron doping on oxygen stability in LiNi0.92Co0.04Mn0.04O2 (LNCM) lithium ion battery cathodes is systematically investigated using various measurements. The boron‐doped LNCM produces the textured microstructure with more oxygen stabilized facets, thus not only aiding in restraining the particle cracks but also effectively suppressing the oxygen evolution to improve the cycle stability.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Adjuvant chemotherapy after surgery improves survival of patients with stage II–III, resectable gastric cancer. However, the overall survival benefit observed after adjuvant chemotherapy is moderate, ...suggesting that not all patients with resectable gastric cancer treated with adjuvant chemotherapy benefit from it. We aimed to develop and validate a predictive test for adjuvant chemotherapy response in patients with resectable, stage II–III gastric cancer.
In this multi-cohort, retrospective study, we developed through a multi-step strategy a predictive test consisting of two rule-based classifier algorithms with predictive value for adjuvant chemotherapy response and prognosis. Exploratory bioinformatics analyses identified biologically relevant candidate genes in gastric cancer transcriptome datasets. In the discovery analysis, a four-gene, real-time RT-PCR assay was developed and analytically validated in formalin-fixed, paraffin-embedded (FFPE) tumour tissues from an internal cohort of 307 patients with stage II–III gastric cancer treated at the Yonsei Cancer Center with D2 gastrectomy plus adjuvant fluorouracil-based chemotherapy (n=193) or surgery alone (n=114). The same internal cohort was used to evaluate the prognostic and chemotherapy response predictive value of the single patient classifier genes using associations with 5-year overall survival. The results were validated with a subset (n=625) of FFPE tumour samples from an independent cohort of patients treated in the CLASSIC trial (NCT00411229), who received D2 gastrectomy plus capecitabine and oxaliplatin chemotherapy (n=323) or surgery alone (n=302). The primary endpoint was 5-year overall survival.
We identified four classifier genes related to relevant gastric cancer features (GZMB, WARS, SFRP4, and CDX1) that formed the single patient classifier assay. In the validation cohort, the prognostic single patient classifier (based on the expression of GZMB, WARS, and SFRP4) identified 79 (13%) of 625 patients as low risk, 296 (47%) as intermediate risk, and 250 (40%) as high risk, and 5-year overall survival for these groups was 83·2% (95% CI 75·2–92·0), 74·8% (69·9–80·1), and 66·0% (60·1–72·4), respectively (p=0·012). The predictive single patient classifier (based on the expression of GZMB, WARS, and CDX1) assigned 281 (45%) of 625 patients in the validation cohort to the chemotherapy-benefit group and 344 (55%) to the no-benefit group. In the predicted chemotherapy-benefit group, 5-year overall survival was significantly improved in those patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (80% 95% CI 73·5–87·1 vs 64·5% 56·8–73·3; univariate hazard ratio 0·47 95% CI 0·30–0·75, p=0·0015), whereas no such improvement in 5-year overall survival was observed in the no-benefit group (72·9% 66·5–79·9 in patients who received chemotherapy plus surgery vs 72·5% 65·8–79·9 in patients who only had surgery; 0·93 0·62–1·38, p=0·71). The predictive single patient classifier groups (chemotherapy benefit vs no-benefit) could predict adjuvant chemotherapy benefit in terms of 5-year overall survival in the validation cohort (pinteraction=0·036 in univariate analysis). Similar results were obtained in the internal evaluation cohort.
The single patient classifiers validated in this study provide clinically important prognostic information independent of standard risk-stratification methods and predicted chemotherapy response after surgery in two independent cohorts of patients with resectable, stage II–III gastric cancer. The single patient classifiers could complement TNM staging to optimise decision making in patients with resectable gastric cancer who are eligible for adjuvant chemotherapy after surgery. Further validation of these results in prospective studies is warranted.
Ministry of ICT and Future Planning; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
It is unclear whether laparoscopic distal gastrectomy for locally advanced gastric cancer is oncologically equivalent to open distal gastrectomy. The noninferiority of laparoscopic subtotal ...gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer compared with open surgery in terms of 3-year relapse-free survival rate was evaluated.
A phase III, open-label, randomized controlled trial was conducted for patients with histologically proven locally advanced gastric adenocarcinoma suitable for distal subtotal gastrectomy. The primary end point was the 3-year relapse-free survival rate; the upper limit of the hazard ratio (HR) for noninferiority was 1.43 between the laparoscopic and open distal gastrectomy groups.
From November 2011 to April 2015, 1,050 patients were randomly assigned to laparoscopy (n = 524) or open surgery (n = 526). After exclusions, 492 patients underwent laparoscopic surgery and 482 underwent open surgery and were included in the analysis. The laparoscopy group, compared with the open surgery group, suffered fewer early complications (15.7%
23.4%, respectively;
= .0027) and late complications (4.7%
9.5%, respectively;
= .0038), particularly intestinal obstruction (2.0%
4.4%, respectively;
= .0447). The 3-year relapse-free survival rate was 80.3% (95% CI, 76.0% to 85.0%) for the laparoscopy group and 81.3% (95% CI, 77.0% to 85.0%; log-rank
= .726) for the open group. Cox regression analysis after stratification by the surgeon revealed an HR of 1.035 (95% CI, 0.762 to 1.406; log-rank
= .827;
for noninferiority = .039). When stratified by pathologic stage, the HR was 1.020 (95% CI, 0.751 to 1.385; log-rank
= .900;
for noninferiority = .030).
Laparoscopic distal gastrectomy with D2 lymphadenectomy was comparable to open surgery in terms of relapse-free survival for patients with locally advanced gastric cancer. Laparoscopic distal gastrectomy with D2 lymphadenectomy could be a potential standard treatment option for locally advanced gastric cancer.
Background
It remains controversial whether propofol‐based total intravenous anesthesia (TIVA) or inhalation anesthesia is associated with better outcomes after cancer surgery. We investigated ...whether there is a difference in the 1‐year overall or cancer‐related mortality between propofol‐based TIVA and inhalation anesthesia in patients who underwent gastric cancer surgery.
Methods
This retrospective cohort study was based on medical records of ll patients aged ≥18 years who underwent elective gastric cancer surgery with curative intent between January 2005 and December 2015 at a single tertiary academic hospital. Propensity score (PS) matching and Cox proportional hazard models were used for analyses.
Results
After PS matching, 1538 patients (769 patients in each group) were included in the final analysis. The 1‐year overall mortality risk was not significantly different between the TIVA and inhalation groups in either the PS‐matched analysis hazard ratio (HR): 0.92, 95% confidence interval (CI): 0.52‐1.64; P = 0.774 or entire cohorts (HR: 0.82 95% CI: 0.52‐1.33; P = 0.417) after multivariable adjustment. The 1‐year cancer‐related mortality risk was similar between the groups in both the PS‐matched cohort (HR: 0.91, 95% CI: 0.50‐1.67; P = 0.764) and the entire cohort after multivariable adjustment (HR: 0.82, 95% CI: 0.50‐1.33; P = 0.406).
Conclusions
We show that propofol‐based TIVA was not significantly associated with a decrease in the 1‐year overall or cancer‐related mortality after gastric cancer surgery, as compared with inhalation anesthesia. Further studies are required to ascertain the optimal anesthetic choice for gastric cancer surgery.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background
The current AJCC staging system for gastric cancer (AJCC7) incorporated several major revisions to the previous edition. The T and N categories and the stage groups were newly defined, and ...adenocarcinoma of the esophagogastric junction (EGJ) was reclassified and staged according to the esophageal system. Studies to validate these changes showed inconsistent results. The International Gastric Cancer Association (IGCA) launched a project to support evidence-based revisions to the next edition of the AJCC staging system.
Methods
Clinical and pathological data on patients who underwent curative gastrectomy at 59 institutions in 15 countries between 2000 and 2004 were retrospectively collected. Patients lost to follow-up within 5 years of surgery were excluded. Patients treated with neoadjuvant therapy were excluded. The data were analyzed in total, and separately by region of treatment.
Results
Of 25,411 eligible cases, 84.8 % were submitted from 24 institutions of Japan and Korea, 6.4 % from other Asian countries, and 8.8 % from 29 Western institutions. The T and N categories of AJCC7 clearly stratified the patient survival. Patients with pN3a and pN3b showed distinct prognosis in all regions, and by introducing pN3a and pN3b into a cluster analysis, we established a new stage grouping with better stratification than AJCC7, especially among stage III subgroups. Survival of Siewert type 2 and 3 EGJ tumors was better stratified by this IGCA stage grouping than by either esophageal or gastric scheme of AJCC7.
Conclusions
For the next revision of AJCC classification, we propose a new stage grouping based on a large, worldwide data collection.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
There are few data on the clinical implications of immunosuppressive protein expression in tumors and immune cell infiltration within the tumor microenvironment in patients with gastric ...cancer (GC).
Methods
In this study, 243 patients with curatively resected GC were included. The levels of immunosuppressive protein expression programmed cell death 1 ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO) in tumors and the densities of immune cells CD3(+), CD4(+), CD8(+), or PD-1(+) cells within the tumor microenvironment were measured using immunohistochemical analysis.
Results
Positive PD-L1, CTLA-4, and IDO expression was observed in 43.6, 65.8, and 47.7 % of the patients, respectively. Expression of PD-L1, CTLA-4, and IDO was related to less advanced stage, intestinal type, and well/moderately differentiated adenocarcinoma (
P
< 0.05). PD-L1 expression was related to better disease-free survival (DFS) and overall survival (OS) in GC PD-L1(+) vs. PD-L1(−) tumors: 5-year DFS rate, 82.6 vs. 66.9 %; 5-year OS rate, 83.0 vs. 69.1 % (
P
values <0.05). Survival outcomes were also better in patients with a higher density of CD3(+) cells within the tumor microenvironment than in those with a lower density of CD3(+) cells 5-year DFS rate, 80.9 vs. 67.0 %; 5-year OS rate, 82.5 vs. 68.0 % (
P
values <0.05). In multivariate analysis, these two immune markers had a prognostic impact on survival, independent of other clinical variables.
Conclusions
GC patients with immunosuppressive protein expression (PD-L1, CTLA-4, or IDO) had distinct clinicopathological characteristics. PD-L1(+) expression and a high-CD3 tumor microenvironment are favorable prognostic markers in GC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary Background The CLASSIC trial was done to compare adjuvant capecitabine plus oxaliplatin versus observation after D2 gastrectomy for patients with stage II or III gastric cancer. The planned ...interim analysis of CLASSIC (median follow-up 34 months) showed that adjuvant capecitabine plus oxaliplatin significantly improved disease-free survival, the primary endpoint, compared with observation after D2 gastrectomy. We report the 5-year follow-up data from the trial. Methods CLASSIC was a phase 3, randomised, open-label study done at 35 cancer centres, medical centres, and hospitals in China, South Korea, and Taiwan. Patients with stage II–IIIB gastric cancer who underwent curative D2 gastrectomy were randomly assigned (1:1) after surgery to receive adjuvant chemotherapy with capecitabine and oxaliplatin (eight 3-week cycles of oral capecitabine 1000 mg/m2 twice daily on days 1–14 plus intravenous oxaliplatin 130 mg/m2 on day 1) for 6 months or observation alone. Randomisation was stratified by country and disease stage with a permuted block (size four) design. Neither patients nor investigators were masked to treatment assignment. The primary outcome was 3-year disease-free survival in the intention-to-treat population. This analysis presents the final preplanned assessment of outcomes after 5 years. The study is registered with ClinicalTrials.gov , NCT00411229. Findings We enrolled 1035 patients: 520 were randomly assigned to adjuvant capecitabine and oxaliplatin, and 515 to observation. Median follow-up for this analysis in the intention-to-treat population was 62·4 months (IQR 54–70). 139 (27%) patients had disease-free survival events in the adjuvant capecitabine and oxaliplatin group versus 203 (39%) patients in the observation group (stratified hazard ratio HR 0·58, 95% CI 0·47–0·72; p<0·0001). Estimated 5-year disease-free survival was 68% (95% CI 63–73) in the adjuvant capecitabine and oxaliplatin group versus 53% (47–58) in the observation alone group. By the clinical cutoff date, 103 patients (20%) had died in the adjuvant capecitabine and oxaliplatin group versus 141 patients (27%) in the observation group (stratified HR 0·66, 95% CI 0·51–0·85; p=0·0015). Estimated 5-year overall survival was 78% (95% CI 74–82) in the adjuvant capecitabine and oxaliplatin group versus 69% (64–73) in the observation group. Adverse event data were not collected after the primary analysis. Interpretation Adjuvant treatment with capecitabine plus oxaliplatin after D2 gastrectomy should be considered for patients with operable stage II or III gastric cancer. Funding F Hoffmann La-Roche and Sanofi.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The oncologic outcomes of laparoscopy-assisted gastrectomy for the treatment of gastric cancer have not been evaluated. The aim of this study is to validate the efficacy and safety of laparoscopic ...gastrectomy for gastric cancer in terms of long-term survival, morbidity, and mortality retrospectively.
The study group comprised 2,976 patients who were treated with curative intent either by laparoscopic gastrectomy (1,477 patients) or open gastrectomy (1,499 patients) between April 1998 and December 2005. The long-term 5-year actual survival analysis in case-control and case-matched population was conducted using the Kaplan-Meier method. The morbidity and mortality and learning curves were evaluated.
In the case-control study, the overall survival, disease-specific survival, and recurrence-free survival (median follow-up period, 70.8 months) were not statistically different at each cancer stage with the exception of an increased overall survival rate for patients with stage IA cancer treated via laparoscopy (laparoscopic group; 95.3%, open group: 90.3%; P < .001). After matching using a propensity scoring system, the overall survival, disease-specific survival, and recurrence-free survival rates were not statistically different at each stage. The morbidity of the case-matched group was 15.1% in the open group and 12.5% in the laparoscopic group, which also had no statistical significance (P = .184). The mortality rate was also not statistically significant (0.3% in the open group and 0.5% in the laparoscopic group; P = 1.000). The mean learning curve was 42.
The long-term oncologic outcomes of laparoscopic gastrectomy for patients with gastric cancer were comparable to those of open gastrectomy in a large-scale, multicenter, retrospective clinical study.
Background
The application of ERAS protocol has widely gained acceptance after gastrointestinal surgery. Well-designed, randomized, control trials are needed to evaluate fully its safety and efficacy ...in the field of gastric cancer. This study aims to compare the enhanced recovery after surgery (ERAS) protocol and the conventional perioperative care program after totally laparoscopic distal gastrectomy (TLDG) in gastric cancer.
Methods
Patients with gastric cancer indicated for TLDG were randomly assigned to either the ERAS group or the conventional group. The ERAS protocol included short fasting time, fluid restriction, early oral feeding, immediate mobilization, and use of epidural patient-controlled analgesia. Primary endpoint was recovery time, which was defined with the criteria of tolerable diet, safe ambulation, no requirement of additional analgesics, and afebrile state. Hospital stay, pain score, complications, and readmission rate were secondary endpoints.
Results
A total of 97 patients who underwent TLDG from October 2012 to August 2014 were enrolled (ERAS = 46, conventional = 51). The ERAS group had faster recovery time (111.6 ± 34.3 vs. 126.7 ± 30.7 h;
p
= 0.026) and significantly less pain through postoperative days 1–4. Possible hospital stay also was faster in the ERAS group (5.0 ± 1.9 vs. 5.7 ± 1.6 days,
p
= 0.038), but there was no difference in actual hospital stay. No difference was found in complication, and there was no mortality or readmission in both groups.
Conclusions
ERAS is safe and enhances postoperative recovery after TLDG in gastric cancer.
Trial Registration
The trial was registered in ClinicalTrials.gov (NCT01938313).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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