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Σάββατο, 27 Απριλίου 2019

Gastric Cancer

Clinical significance of intratumoral HER2 heterogeneity on trastuzumab efficacy using endoscopic biopsy specimens in patients with advanced HER2 positive gastric cancer

In the original publication of this article, Table 4 was published incorrectly. The correct Table 4 is given below.



Correction to: The search, coagulation, and clipping (SCC) method prevents delayed bleeding after gastric endoscopic submucosal dissection

The article "The search, coagulation, and clipping (SCC) method prevents delayed bleeding after gastric endoscopic submucosal dissection", written by Motoi Azumi, Manabu Takeuchi, Youhei Koseki, Masaru Kumagai, Yoko Kobayashi, Masafumi Takatsuna, Aiko Yoshioka, Seiichi Yoshikawa, Tsutomu Miura, and Shuji Terai, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 28 September 2018 without open access.



Correction to: Body composition assessment and sarcopenia in patients with gastric cancer: a systematic review and meta-analysis

In the original publication of this article, most of the reference citations in Tables 1 and 2 were published incorrectly. The corrected tables are given in this correction.



Synergistic triad epistasis of epigenetic H3K27me modifier genes, EZH2, KDM6A , and KDM6B , in gastric cancer susceptibility

Abstract

Background

For an epigenetic regulation of human genome, three enzymes write or erase methylation of lysine-27 residue on histone H3 (H3K27me). This methylation is catalyzed by EZH2 (KMT6A) methyltransferase and reversed by KDM6A (UTX) or KDM6B (JMJD3) demethylase. Genetic cancer risk association has been reported on EZH2, but not on KDM6A or KDM6B yet.

Methods

A total of 23 tag single-nucleotide polymorphisms (SNPs) of the three genes were genotyped in 2349 Korean participants, and their gastric cancer risk associations and epistases were statistically examined by comparing the SNP genotypes of 1100 gastric cancer patients and 1249 healthy controls.

Results

All three genes are individually associated with gastric cancer susceptibility, as evident with the genotypes of KDM6A SNP rs5952279 (P = 0.00010) and rs144974719 (P = 0.00024), KDM6B rs78633955 (P = 0.0019) and rs11657063 (P = 0.0036), and EZH2 rs67648693 (P = 0.0028) and rs1061037 (P = 0.023). Furthermore, when odds ratio of interaction (ORint) is calculated for all intergenic SNP pairs, synergistic epistasis is evident among the three genes. Specifically, the interaction is synergistic between EZH2 rs58579167 and KDM6A rs5952279 (ORint = 3.2, P = 0.00066), between KDM6A rs2230018 and KDM6B rs78633955 (ORint = 1.9, P = 0.044), and between KDM6B rs78633955 and EZH2 rs73158295 (ORint = 1.7, P = 0.00030). These inter-SNP interactions together constitute a synergistic triad epistasis of ring-type topology.

Conclusions

All three H3K27me modifier genes are individually associated with gastric cancer susceptibility with synergistic triad interaction. Not only two enzymes with the same function (KDM6A and KDM6B), but also those with opposite functions (EZH2 versus KDM6A or KDM6B) synergistically affect H3K27me consequences such as gastric cancer susceptibility.



Clinical significance of intratumoral HER2 heterogeneity on trastuzumab efficacy using endoscopic biopsy specimens in patients with advanced HER2 positive gastric cancer

Abstract

Background

We recently reported the clinical significance of intratumoral HER2 heterogeneity on trastuzumab efficacy using surgical specimens; patients with homogeneously HER2 positive gastric cancer benefitted more from trastuzumab. However, the majority of patients are diagnosed by endoscopic biopsy, and surgical specimens are not available in these patients. The aim of this study is to verify clinical significance of HER2 heterogeneity on trastuzumab efficacy using biopsy specimens.

Methods

Eighty-seven patients, who received trastuzumab-based chemotherapy and whose endoscopic biopsy specimens were available for HER2 assessment, were consecutively enrolled. When all tumor cells in all biopsy specimens overexpressed HER2 protein, it was defined as homogeneously HER2 (homo-HER2) positive group, and the others were defined as heterogeneously HER2 (hetero-HER2) positive group. Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) were evaluated.

Results

Thirty-four patients (39%) were diagnosed as the homo-HER2 group and 53 patients (61%) were the hetero-HER2 group. After the median follow-up period of 17.8 months, the median PFS and OS were 7.6 and 17.8 months, respectively. Significant survival differences were shown between the two groups; the homo-HER2 group showed significantly longer PFS (10.8 vs. 6.1 months, HR 0.469 95% CI 0.29–0.77, p = 0.003) and OS (29.3 vs. 14.4 months, HR 0.352 95% CI 0.20–0.61, p < 0.001). ORR was 68.6% in this cohort. Higher response rate (85.2% vs 58.1%, p = 0.020) and deeper response (− 49.0% vs − 40.0%, p = 0.018) were also found in the homo-HER2 group.

Conclusions

Similar to surgical specimens, we verified clinical significance of HER2 heterogeneity on trastuzumab efficacy using endoscopic biopsy specimens.



Enhanced recovery versus conventional care in gastric cancer surgery: a meta-analysis of randomized and non-randomized controlled trials

Abstract

Introduction

Enhanced recovery after surgery (ERAS) protocols have been successfully integrated into peri-operative management of different cancer surgeries such as colorectal cancer. Their value for gastric cancer surgery, however, remains uncertain.

Methods

A search for randomized and observational studies comparing ERAS versus conventional care in gastric cancer surgery was performed according to PRISMA guidelines. Random-effects meta-analyses with inverse variance weighting were conducted, and quality of included studies was assessed using the Cochrane risk-of-bias tool and Newcastle-Ottawa scale (PROSPERO: CRD42017080888).

Results

Twenty-three studies involving 2686 patients were included. ERAS was associated with reduced length of hospital stay (WMD—2.47 days, 95% CI − 3.06 to − 1.89, P < 0.00001), time to flatus (WMD—0.70 days, 95% CI − 1.02 to − 0.37, P < 0.0001), and hospitalization costs (WMD—USD$ 4400, 95% CI − USD$ 5580 to − USD$ 3210, P < 0.00001), with consistent results across open and laparoscopic surgery. Postoperative morbidity and 30-day mortality were similar, although a higher rate of readmission was observed in the ERAS group (RR = 1.95, 95% CI 1.03–3.67, P = 0.04). Patients in the ERAS arm had significantly attenuated C-reactive protein levels on days 3/4 and 7, interleukin-6 levels on days 1, and 3/4, and tumor necrosis factor-α levels on days 3/4 postoperatively.

Conclusion

Compared to conventional care, ERAS reduces hospital stay, costs, surgical stress response and time to return of gut function, without increasing post-operative morbidity in gastric cancer surgery. However, precaution is necessary to reduce the increased risk of hospital readmission when adopting ERAS.



Combined detection of serum autoantibodies as diagnostic biomarkers in esophagogastric junction adenocarcinoma

Abstract

Background

We previously found that autoantibodies against a panel of six tumor-associated antigens (p53, NY-ESO-1, MMP-7, Hsp70, PRDX6 and Bmi-1) may aid in early detection of esophageal squamous cell carcinoma. Here we aimed to evaluate the diagnostic value of this autoantibody panel in esophagogastric junction adenocarcinoma (EJA) patients.

Methods

Serum autoantibody levels were measured by enzyme-linked immunosorbent assay in a training cohort and a validation cohort. We used receiver-operating characteristics (ROC) to calculate diagnostic accuracy.

Results

We recruited 169 normal controls and 122 EJA patients to the training cohort, and 80 normal controls and 70 EJA patients to the validation cohort. Detection of the autoantibody panel demonstrated an area under the curve (AUC) of 0.818, sensitivity 59.0% and specificity 90.5% in training cohort, and AUC 0.815, sensitivity 61.4% and specificity 90.0% in validation cohort in the diagnosis of EJA. Measurement of the autoantibody panel could distinguish early stage EJA patients from normal controls (AUC 0.786 and 0.786, sensitivity 50.0% and 56.0%, and specificity 90.5% and 90.0%, for training and validation cohorts, respectively). Moreover, a restricted panel consisting of autoantibodies against p53, NY-ESO-1 and Bmi-1 exhibited similar diagnostic performance for EJA (AUC 0.814 and 0.823, sensitivity 53.5% and 60.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively) and early stage EJA (AUC 0.744 and 0.773, sensitivity 55.6% and 52.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively).

Conclusions

Autoantibodies against an optimized TAA panel as serum biomarkers appear to help identify the present of early stage EJA.



Equivalent feasibility and safety of perioperative care by ERAS in open and laparoscopy-assisted distal gastrectomy for gastric cancer: a single-institution ancillary study using the patient cohort enrolled in the JCOG0912 phase III trial

Abstract

Background

Laparoscopy-assisted distal gastrectomy (LADG) has an advantage of earlier recovery after surgery due to having lower invasiveness and wound pain than open distal gastrectomy (ODG). However, whether the same enhanced recovery after surgery (ERAS) program for LADG is equally feasible and safe for ODG remains unclear.

Methods

We retrospectively extracted the clinical data of the patients enrolled in JCOG0912 from the medical record system of our hospital and compared the treatment process and short-term surgical outcomes between LADG and ODG. Our ERAS program consisted of 13 elements (4 preoperative, 4 intraoperative, and 5 postoperative elements). The morbidity was defined as complications of grade 2 or more.

Results

One hundred and sixty-three patients were entered from our hospital and randomized to undergo ODG (82 patients) or LADG (81 patients). The patient's backgrounds, surgical outcomes, and pathological outcomes were similar between the ODG and LADG groups. The rate of completing the clinical pathway was 95.1% in both groups, and the rates of completing each ERAS element were similar. However, the additional use of acetaminophen was significantly more frequent in the ODG group than in the LADG group (18.3% vs. 6.2%, p = 0.03). The median hospital stay after surgery was 9 days in both groups. Morbidity, defined as Clavien–Dindo classification > grade 2, was observed in 6.1% of the ODG group and 11.1% of the LADG group. No mortality occurred in either group.

Conclusion

This study showed that the regimen of perioperative care performed by the ERAS program for LADG was equally feasible and safe for ODG with additional pain control. Less pain observed in LADG was not so apparent advantage for completion and safety of ERAS care.



CRP/prealbumin, a novel inflammatory index for predicting recurrence after radical resection in gastric cancer patients: post hoc analysis of a randomized phase III trial

Abstract

Background

Serum prealbumin (PALB) can predict the prognosis of patients with gastric cancer (GC). However, the prognostic value of combination of C-reactive protein and PALB (CRP/PALB) remains unclear.

Methods

A total of 419 gastric cancer patients included in a clinical trial (NCT02327481) were analyzed. The present study is a substudy of the trial. Receiver operating characteristic (ROC) curves were generated, and by calculating the areas under the curve (AUC) and the C-index, the discriminative ability of each inflammatory index was compared, including CRP/PALB, C-reactive protein/albumin, Glasgow prognostic score (GPS), modified GPS, systemic immune-inflammation index, neutrophil–lymphocyte ratio, and platelet–lymphocyte ratio.

Results

Ultimately, 401 patients were included in this study. The optimal cutoff value of CRP/PALB was 17.7. According to this cutoff point, the entire sample was divided into a CRP/PALB < 17.7 (LCP) group and a CRP/PALB ≥ 17.7 (HCP) group, comprising 245 and 156 patients, respectively. There were 54 and 22 patients experienced recurrence in the HCP and LCP group, respectively, p < 0.001. Compared with traditional inflammatory indices, CRP/PALB had the highest AUC (0.707) and C-index (0.716), all p < 0.05. The post-recurrence survival (PRS) of patients in the HCP group was significantly shorter than that in the LCP group (p = 0.010), especially for pathological stage III patients (p = 0.015) or patients with distant (p = 0.018) or local (p = 0.023) recurrences.

Conclusions

The predictive value of preoperative CRP/PALB for the recurrence of GC is significantly better than traditional inflammatory indices. HCP significantly reduces the PRS, especially for pathological stage III patients or patients with distant or local recurrences.



The search, coagulation, and clipping (SCC) method prevents delayed bleeding after gastric endoscopic submucosal dissection

Abstract

Background

Delayed bleeding is an important complication after gastric endoscopic submucosal dissection (ESD). The search, coagulation, and clipping (SCC) method can be used to prevent delayed bleeding after ESD. However, its safety and efficacy are unclear. We compared the SCC method with post-ESD coagulation (PEC) to clarify the safety and efficacy of the SCC method for preventing delayed bleeding after gastric ESD.

Methods

This retrospective study included 438 patients (478 lesions) who underwent gastric ESD. Multivariate logistic regression analysis was performed to identify the significant independent factors associated with delayed bleeding and we performed propensity-score matching (PSM) to reduce the effect of procedure-selection bias of SCC method.

Results

Of the 438 patients, 216 underwent PEC and 222 underwent SCC. Delayed bleeding was significantly less common in the SCC than in the PEC (2.6% vs. 7.2%; P = 0.013). Among patients treated with antithrombotic therapy, the delayed bleeding rate was lower in the SCC group than in the PEC group; however, the difference was not significant (P = 0.15). The SCC method was found to be a significant independent factor for the prevention of delayed bleeding. PSM was performed in 156 patients in the PEC group and SCC group. There was a significant difference in the incidence of bleeding in the PEC and SCC groups (P = 0.013). No patient had perforation/bleeding associated with the SCC method.

Conclusions

Our findings suggest that the SCC method is a simple, safe, and effective approach for preventing delayed bleeding after gastric ESD.



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