Gastric cancer is classified into intestinal and diffuse types, the latter including a highly malignant form, linitis plastica. A two-stage genome-wide association study (stage 1: 85,576 SNPs on 188 ...cases and 752 references; stage 2: 2,753 SNPs on 749 cases and 750 controls) in Japan identified a significant association between an intronic SNP (rs2976392) in PSCA (prostate stem cell antigen) and diffuse-type gastric cancer (allele-specific odds ratio (OR) = 1.62, 95% CI = 1.38-1.89, P = 1.11 x 10(-9)). The association was far less significant in intestinal-type gastric cancer. We found that PSCA is expressed in differentiating gastric epithelial cells, has a cell-proliferation inhibition activity in vitro and is frequently silenced in gastric cancer. Substitution of the C allele with the risk allele T at a SNP in the first exon (rs2294008, which has r(2) = 0.995, D' = 0.999 with rs2976392) reduces transcriptional activity of an upstream fragment of the gene. The same risk allele was also significantly associated with diffuse-type gastric cancer in 457 cases and 390 controls in Korea (allele-specific OR = 1.90, 95% CI = 1.56-2.33, P = 8.01 x 10(-11)). The polymorphism of the PSCA gene, which is possibly involved in regulating gastric epithelial-cell proliferation, influences susceptibility to diffuse-type gastric cancer.
Response to immunotherapy in gastric cancer is associated with microsatellite instability (or mismatch repair deficiency) and Epstein-Barr virus (EBV) positivity. We therefore aimed to develop and ...validate deep learning-based classifiers to detect microsatellite instability and EBV status from routine histology slides.
In this retrospective, multicentre study, we collected tissue samples from ten cohorts of patients with gastric cancer from seven countries (South Korea, Switzerland, Japan, Italy, Germany, the UK and the USA). We trained a deep learning-based classifier to detect microsatellite instability and EBV positivity from digitised, haematoxylin and eosin stained resection slides without annotating tumour containing regions. The performance of the classifier was assessed by within-cohort cross-validation in all ten cohorts and by external validation, for which we split the cohorts into a five-cohort training dataset and a five-cohort test dataset. We measured the area under the receiver operating curve (AUROC) for detection of microsatellite instability and EBV status. Microsatellite instability and EBV status were determined to be detectable if the lower bound of the 95% CI for the AUROC was above 0·5.
Across the ten cohorts, our analysis included 2823 patients with known microsatellite instability status and 2685 patients with known EBV status. In the within-cohort cross-validation, the deep learning-based classifier could detect microsatellite instability status in nine of ten cohorts, with AUROCs ranging from 0·597 (95% CI 0·522–0·737) to 0·836 (0·795–0·880) and EBV status in five of eight cohorts, with AUROCs ranging from 0·819 (0·752–0·841) to 0·897 (0·513–0·966). Training a classifier on the pooled training dataset and testing it on the five remaining cohorts resulted in high classification performance with AUROCs ranging from 0·723 (95% CI 0·676–0·794) to 0·863 (0·747–0·969) for detection of microsatellite instability and from 0·672 (0·403–0·989) to 0·859 (0·823–0·919) for detection of EBV status.
Classifiers became increasingly robust when trained on pooled cohorts. After prospective validation, this deep learning-based tissue classification system could be used as an inexpensive predictive biomarker for immunotherapy in gastric cancer.
German Cancer Aid and German Federal Ministry of Health.
Background
Early gastric cancers (EGCs) within the mucosal layer of the gastric wall have a small risk of lymph node (LN) metastasis.
Methods
We reviewed clinicopathology data for patients who ...underwent surgery for EGC between 2001 and 2013 at the National Cancer Center, Korea. Poisson regression analyses were performed to compare the risk of LN metastasis according to the depth of tumor invasion in patients with mucosal EGCs.
Results
Among the 1776 EGC patients included, 580 (32.7 %) had tumors confined to the lamina propria (LP; LP group) and 1196 (67.3 %) had tumors invading the muscularis mucosae (MM; MM group). Seventy-one patients (4.0 %) had LN metastasis, and the MM group had a significantly higher rate of LN metastasis (59 patients, 4.9 %) than the LP group (12 patients, 2.1 %;
P
= 0.004). A multivariate analysis showed that tumors invading the MM (adjusted risk ratio 1.95;
P
= 0.045) were significantly associated with LN metastasis in addition to well-known risk factors, including tumor size greater than 3 cm, presence of ulceration, undifferentiated histologic type, and lymphovascular invasion. The incidence of LN metastasis was 1.87 % (95 % confidence interval 0.23–6.59 %) within tumors invading the MM that met the expanded criterion for endoscopic resection of differentiated histologic type of size 3 cm or smaller with ulceration. LN metastasis was not found in tumors meeting the absolute criteria for endoscopic resection.
Conclusions
EGCs invading the MM had a higher rate of lymph node metastasis than those confined to the LP. Further study is needed to evaluate whether different curative treatment criteria are needed for LP-confined and MM-invading EGCs.
Lymphatic invasion (LI) is a potent risk factor for lymph node metastasis (LNM) in early gastric cancer (EGC) after endoscopic submucosal dissection (ESD). However, there are also other risk factors ...for LNM. Hence, to identify the need for additional surgery in some case of EGC without LI, the present study aimed to identify the risk factors for LNM in patients with EGC without LI.
Data from 2284 patients diagnosed with EGC who underwent curative surgery at National Cancer Center in Korea from January 2012 to May 2019 were collected. The clinicopathological characteristics of patients with EGC without LI were compared on the basis of LNM status.
There were 339 (17.1%) and 1648 (82.9%) patients with and without LI respectively. Among these patients with and without LI, 118 (34.8%) and 91 (5.5%) patients presented with LNM, respectively. In patients with EGC without LI, tumor size larger than 3 cm (OR = 2.12, 95% CI = 1.22–3.68; p = 0.007), submucosal invasion (OR = 4.14, 95% CI = 2.57–6.65; p < 0.001), and undifferentiated histologic type (OR = 2.33, 95% CI = 1.45–3.76; p < 0.001) were significant risk factors for LNM. Rates of LNM in patients meeting absolute, expanded, and beyond expanded criteria without LI were 0%, 1.5% (OR = 3.27, 95% CI = 0.18–59.41; p = 0.423), and 7.3% respectively. When the expanded criteria were divided into four subtypes patients with EGC, without LI within each subtype did not show significant risk of incidence of LNM compared to the absolute criteria.
The current expanded criteria for endoscopic resection (ER) are tolerable in cases without LI, even though minimal risk LNM exists. Therefore, additional surgery may not be needed for patients meeting expanded criteria for ER.
Recently, nonexposure simple suturing endoscopic full-thickness resection (NESS-EFTR) method was developed to avoid tumor exposure to the peritoneal cavity. The aim of this study is to compare the ...short-term outcomes of the NESS-EFTR method with those of laparoscopic and endoscopic cooperative surgery (LECS) for gastric subepithelial tumors (SETs). A prospective single-center trial of LECS for gastric SETs was performed from March 2012 to October 2013 with a separate prospective trial of NESS-EFTR performed from August 2015 to June 2017, enrolling 15 patients each. Among the 30 enrolled patients, 14 who underwent LECS and 11 who underwent NESS-EFTR were finally included in the analysis. The rate of complete resection and successful closure was 100% in both groups. The operating time was longer for NESS-EFTR group than for LECS (110 vs. 189 min;
< 0.0001). There were no postoperative complications except one case of transient fever in the NESS-EFTR group. One patient in the LECS group had peritoneal seeding of gastrointestinal stromal tumor at 17 months postoperatively, and there was no other recurrence. Although NESS-EFTR had long operating and procedure times, it was feasible for patients with gastric SETs requiring a nonexposure technique.
Only a subset of gastric cancer (GC) patients with stage II-III benefits from chemotherapy after surgery. Tumour infiltrating lymphocytes per area (TIL density) has been suggested as a potential ...predictive biomarker of chemotherapy benefit.
We quantified TIL density in digital images of haematoxylin-eosin (HE) stained tissue using deep learning in 307 GC patients of the Yonsei Cancer Center (YCC) (193 surgery+adjuvant chemotherapy S + C, 114 surgery alone S) and 629 CLASSIC trial GC patients (325 S + C and 304 S). The relationship between TIL density, disease-free survival (DFS) and clinicopathological variables was analysed.
YCC S patients and CLASSIC S patients with high TIL density had longer DFS than S patients with low TIL density (P = 0.007 and P = 0.013, respectively). Furthermore, CLASSIC patients with low TIL density had longer DFS if treated with S + C compared to S (P = 0.003). No significant relationship of TIL density with other clinicopathological variables was found.
This is the first study to suggest TIL density automatically quantified in routine HE stained tissue sections as a novel, clinically useful biomarker to identify stage II-III GC patients deriving benefit from adjuvant chemotherapy. Validation of our results in a prospective study is warranted.
Background The purpose of this study was to compare the clinical usefulness of the seventh Union Internationale Contre le Cancer/American Joint Committee on Cancer (AJCC/UICC) staging system vs the ...sixth AJCC/UICC staging system in patients with gastric cancer. Study Design Included were 1,799 patients who underwent surgery for gastric cancer between January 2001 and June 2005 at the National Cancer Center (South Korea). For the sixth and seventh AJCC/UICC staging systems, survival outcomes stratified by stage, by T classification, and by N classification were summarized using Kaplan-Meier curves and compared statistically using a log rank test; survival differences were quantified using hazard ratios estimated from a Cox regression model. The 2 systems were compared in terms of prognostic performances using the linear trend chi-square test, likelihood ratio chi-square test, and Akaike information criterion (AIC) in the Cox regression analysis. Results Significant survival differences between each stage were not found using the seventh staging system, especially for stages IB, IIA, and IIB (p = 0.14 and p = 0.11). The sixth staging system had higher linear trend chi-square score and likelihood ratio chi-square score, which means better discriminatory ability, monotonicity, and homogeneity, and had smaller AIC, which indicates better optimistic prognostic stratification, especially in the N classification. The modified staging system combining the T classification of the seventh AJCC/UICC system and the N classification of the sixth system showed better prognostic performance compared with each separate version (sixth or seventh) of the staging system. Conclusions The seventh AJCC/UICC staging system is not more clinically useful than the sixth system in surgically treated patients with gastric cancer because of an inappropriate N classification. A new TNM system is required with a different N classification.
Background
The Operative Link for Gastritis Assessment (OLGA) and the Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) staging systems have been suggested to provide risk assessment ...for gastric cancer. This study aimed to evaluate the distribution of OLGA and OLGIM staging by age and Helicobacter pylori status.
Materials and Methods
We studied 632 subjects who underwent esophagogastroduodenoscopy for gastric cancer screening. Helicobacter pylori status and histologic changes were assessed using the updated Sydney system. Stage III and IV OLGA or OLGIM stages were considered as high‐risk stages.
Results
The rate of H. pylori infection was 59.0% (373/632). Overall, the proportion of high OLGA and OLGIM stages was significantly increased with older age (p < .001 for both). Old age (OR = 5.17, 6.97, and 12.23 for ages in the 40's, 50's, and 60's, respectively), smoking (OR = 2.54), and H. pylori infection (OR = 8.46) were independent risk factors for high‐risk OLGA stages. These risk factors were the same for high‐risk OLGIM stages. In the H. pylori‐positive subgroup, the proportion of high‐risk OLGA stages was low (6.9%) before the age of 40, but increased to 23.0%, 29.1%, and 41.1% for those in their 40s, 50s, and 60s, respectively (p < .001). High‐risk OLGIM stages showed a similar trend of 2.8% before the age of 40 and up to 30.1% for those in their 60s. High‐risk OLGA and OLGIM stages were uncommon in the H. pylori‐negative group, with a respective prevalence of 10.3% and 3.4% even among those in their 60s.
Conclusions
Because high‐risk OLGA and OLGIM stages are uncommon under the age of 40, H. pylori treatment before that age may reduce the need for endoscopic surveillance for gastric cancer.
As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine ...tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea.
We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters.
Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET.
The incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET.
Background
Information on surgical complications of laparoscopy-assisted distal gastrectomy (LADG) and their risk factors is limited in the literature despite increasing popularity of this procedure. ...This study was performed to identify the surgical complications and their associated risk factors of LADG in early gastric cancer.
Methods
LADG was performed in 347 gastric cancer patients from January 2002 to December 2006 at the Korean National Cancer Center by four surgeons with ample experience of open gastric surgery before LADG. LADG indications for cases of gastric cancer at our institution are preoperatively diagnosed cT1N0 or cT1N1, except in cases with an absolute indication for endoscopic resection. Lymph node dissection of more than D1 + β was performed in all patients. Intraoperative and postoperative complications were reviewed and their risk factors were retrospectively analyzed by prospective database information.
Results
Forty complications occurred in 34 patients (9.8%), but there was no mortality. Intraoperative complications occurred in nine patients (2.6%), and open conversion was performed in eight (2.3%) of these patients. Early and late postoperative complications occurred in 21 (6.1%) and 10 (2.9%) patients, respectively. The most serious complication was vascular injury resulting in bleeding or organ ischemia, which occurred in seven patients. Degree of lymph node dissection and surgical inexperience were found to be risk factors of surgical complication (
P
= .023, odds ratio 2.832, 95% confidence interval 1.155–6.946 vs.
P
= .028, odds ratio 2.975, 95% confidence interval 1.127–7.854).
Conclusions
Lymph node dissection during LADG should be performed cautiously to prevent surgical complications like vascular injuries, especially during the surgeon’s early learning period.
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