Background Additional surgery is recommended after non-curative endoscopic submucosal dissection for early gastric cancer. However, it is not easy to recommend for tumors located in the upper third ...of the stomach, because it would be a total or proximal gastrectomy. This study aimed to evaluate the actual risks and benefits of additional gastrectomy for upper third tumors. Methods We reviewed the clinicopathological data of patients who underwent total or proximal gastrectomy for early gastric cancer in the upper third of the stomach between March 2002 and January 2021. The incidence of lymph node metastasis and postoperative complications were calculated, and risk factors for lymph node metastasis were identified using logistic regression analysis. Survival rates were analyzed using the Kaplan-Meier method and log-rank test. Results A total of 523 patients underwent total or proximal gastrectomy for early gastric cancer; 379 of them had tumors meeting the non-curative resection criteria for endoscopic submucosal dissection. The overall lymph node metastasis rate was 9.5%, and lymphovascular invasion was the only significant risk factor for lymph node metastasis (p < 0.001). The most common sites of lymph node metastasis were stations 1, 3, and 7, with their rates being 3.2%, 3.7%, and 3.2%, respectively. Overall and severe (Clavien-Dindo grade III or higher) postoperative complication rates were 21.1% and 14.0%, respectively, while postoperative mortality was 0.5% (2/379). The 5-year overall survival rates for patients with and without lymph node metastasis were 96.1% and 81.1%, respectively (p = 0.076). Conclusions Before planning an additional gastrectomy after non-curative endoscopic resection for the upper third tumor, we should consider both the benefit of the 9.5% curability for lymph node metastasis and the risks of the 21% postoperative complications and 0.5% mortality. Keywords: Proximal gastric cancer, Non-curative endoscopic resection, Additional gastrectomy, Lymph node metastasis
Greater lymph node retrieval in gastric cancer improves staging accuracy and may improve survival from increased clearance of nodal micrometastasis. This retrospective cohort study investigated if ...more lymph nodes removed in gastric cancer increases survival and if such effect is stage-specific due to differential risks of nodal micrometastasis and systemic disease.
The prospectively collected database of curatively resected gastric cancer patients in National Cancer Center, South Korea between 2000 and 2009 was reviewed. Disease-free survival (DFS) and overall survival (OS) for all patients and for each stage according to number of lymph nodes examined (1-30, 31-45, > 45) were analyzed.
Of 4049 patients, 96.6% and 98.4% underwent D2 (perigastric and extragastric) lymphadenectomy and had ≥ 15 lymph nodes examined. Mean number of nodes examined was 43. Five-year OS & DFS rates were 83.3% and 80.7%. Patients with > 45 nodes examined had significantly lower DFS (p = 0.002) and OS (p = 0.007) compared to those with 1-30 and 31-45 nodes. However, proportion of patients with > 45 nodes examined increased with stage (p = 0.0005). Per stage, there was no significant difference in DFS and OS according to number of nodes examined except for stage IIIA favoring more nodes (p = 0.018 and p = 0.044, respectively). Similar trend was seen in stage IIB. Number of examined nodes positively correlated with number of pathologic nodes for all patients (r = 0.144, p < .001) but not for stage IIB and IIIA. Number of nodes examined was a significant survival predictor in stage IIIA.
Greater lymph node harvest showed improved survival in intermediate-stage gastric cancer.
Intestinal-type gastric cancer often results from
infection through intestinal metaplasia, a transdifferentiated premalignant phenotype. Because
virulence factor CagA has been associated with ...aberrant expression of the transcription factor CDX1, which regulates intestinal differentiation, we explored its relationship with
infection and function during gastric carcinogenesis in normal gastric epithelial cells and gastric cancer cell lines. Infection of HFE 145 cells with CagA
increased expression of CDX1, as well as the epithelial-to-mesenchymal transition (EMT) markers Snail and Slug, increased invasion and migration, but those effects were not found in HFE 145 cells infected with CagA-deficient
. CDX1 overexpression increased expression of the intestinal markers Villin, sucrose isomaltase (SI), and MUC2, induced spheroid formation, and enhanced expression of the stem cell markers CD44, SOX2, Oct4, and Nanog, while CDX1 knockdown inhibited proliferation and intestinal stemness. Treatment of CDX1-expressing cells with metformin, an antidiabetic drug known to decrease the risk of gastric cancer, decreased expression of EMT and stemness markers, and reduced spheroid formation. In a murine xenograft model, combining metformin or shCDX1 with cisplatin reduced tumor growth, increased caspase-3 cleavage, and reduced expression of CD44 and MMP-9 to a greater degree than cisplatin alone. Patients with more advanced intestinal metaplasia staging exhibited higher CDX1 expression than those with earlier intestinal metaplasia staging (
= 0.039), and those with
tended to have more CDX1 expression than noninfected patients (
= 0.061). Finally, human tissue samples with higher CDX1 levels showed prominent CD44/SOX2 expression. Our findings indicate CagA
-induced CDX1 expression may enhance gastric cancer tumorigenesis and progression, and support therapeutic targeting of CDX1 in gastric cancer. IMPLICATIONS: This study shows that CDX1 contributes to the tumorigenesis and progression of gastric cancer and suggests the potential of targeting CDX1 to treat this malignancy.
With the development of advanced and minimally invasive surgical techniques, and in view of the functional and cosmetic aspects, the need for rapid and accurate diagnosis during surgery is ...increasing. This study was conducted to develop a tissue diagnosis method using confocal microscopy after simple tissue staining that does not require freezing and slicing. At present, fluorescence staining with confocal microscopy is not generalized for real‐time diagnosis during surgery. In this paper, we propose a fluorescence staining method using Hoechst 33342 and Eosin that does not require tissue freezing and slicing. The proposed method can be used as part of a rapid tissue diagnosis method that is suitable for use in the operating room, although further research is required before it can be applied in clinical practice.
A tissue diagnosis method using confocal microscopy after simple tissue staining without requiring freezing and slicing is proposed.
The proposed method can be used as part of a rapid tissue diagnosis method that is suitable for operating room use.
Worldwide, gastric cancer (GC) is the fourth most common malignancy and the most common cancer in East Asia. Development of targeted therapies for this disease has focused on a few known oncogenes ...but has had limited effects.
To determine oncogenic mechanisms and novel therapeutic targets specific for GC by identifying commonly dysregulated genes from the tumours of both Asian-Pacific and Caucasian patients.
We generated transcriptomic profiles of 22 Caucasian GC tumours and their matched non-cancerous samples and performed an integrative analysis across different GC gene expression datasets. We examined the inhibition of commonly overexpressed oncogenes and their constituent signalling pathways by RNAi and/or pharmacological inhibition.
Hepatocyte nuclear factor-4α (HNF4α) upregulation was a key signalling event in gastric tumours from both Caucasian and Asian patients, and HNF4α antagonism was antineoplastic. Perturbation experiments in GC tumour cell lines and xenograft models further demonstrated that HNF4α is downregulated by AMPKα signalling and the AMPK agonist metformin; blockade of HNF4α activity resulted in cyclin downregulation, cell cycle arrest and tumour growth inhibition. HNF4α also regulated WNT signalling through its target gene WNT5A, a potential prognostic marker of diffuse type gastric tumours.
Our results indicate that HNF4α is a targetable oncoprotein in GC, is regulated by AMPK signalling through AMPKα and resides upstream of WNT signalling. HNF4α may regulate 'metabolic switch' characteristic of a general malignant phenotype and its target WNT5A has potential prognostic values. The AMPKα-HNF4α-WNT5A signalling cascade represents a potentially targetable pathway for drug development.
Background
During sentinel node navigation surgery in patients with gastric cancer, intraoperative pathologic examination of sentinel nodes is crucial in determining the extent of surgery. In this ...study, we evaluated the feasibility and accuracy of intraoperative pathologic protocols using data from a prospective, multicenter, randomized trial.
Methods
A retrospective analysis was conducted using data from the SEntinel Node ORIented Tailored Approach trials from 2013 to 2016. All sentinel lymph nodes were evaluated during surgery with hematoxylin–eosin (HE) staining using a representative section at the largest plane for lymph nodes. For permanent histologic evaluation, sentinel basin nodes were stained with HE and cytokeratin immunohistochemistry in formalin-fixed, paraffin-embedded (FFPE) sections and examined with HE for three deeper-step sections at 200-μm intervals. The failure rate of identification by frozen section and the metastasis rate in non-sentinel basins were investigated.
Results
Of the 237 patients who underwent sentinel node basin dissection, 30 had lymph node metastases on permanent pathology. Thirteen patients had macrometastasis confirmed in frozen sections as well as FFPE sections (failure rate: 0%). Patients with negative sentinel nodes in frozen sections but micrometastasis in FFPE sections had no lymph node recurrence during the follow-up period (0%, 0/6). However, in cases with tumor-positive nodes in frozen sections, metastases in non-sentinel basins were detected in the paraffin blocks (8.3%, 2/24).
Conclusions
The single-section HE staining method is sufficient for detecting macrometastasis via intraoperative pathological examination. If a negative frozen-section result is confirmed, sentinel basin dissection can be performed safely. Otherwise, standard surgery is required.
Background and Aims
The definition and incidence of gastric cancer (GC) without Helicobacter pylori (Hp) infection varies between studies. The aim of our study was to compare the characteristics of ...GC according to Hp infection status.
Methods
We evaluated the presence of Hp infection in 1833 GC patients with rapid urease tests, serology examinations, and histological evaluations. GC was classified as GC with current Hp infection (HpC‐GC), GC with past Hp infection (HpP‐GC), and GC not associated with Hp infection (HpN‐GC). HpP‐GC was defined as GC without current infection but with a positive serology test, glandular atrophy, and/or intestinal metaplasia. HpN‐GC was defined as GC with negative Hp test results and no histological changes.
Results
The numbers of HpC‐GC, HpP‐GC, and HpN‐GC were 1378 (75.2%), 412 (22.5%), and 43 (2.3%), respectively. Among GCs without current infection, 90.5% (412/455) were associated with HpP‐GC. HpP‐GCs were more common in older and male patients, had an increased incidence of synchronous cancer, and less frequently had a diffuse‐type histology than HpC‐GCs. HpN‐GCs were more common in younger, female patients; had a higher proportion of diffuse‐type cancers; and more frequently showed distant metastasis than HpP‐GCs. In the 40s, the proportion of HpP‐GCs with diffuse‐type histology (41.9%) was lower than that of HpC‐GCs (60.3%) (P = 0.016). The difference was also significant in the 50s (29.1% vs 40.1%, respectively, P = 0.004).
Conclusions
Most GCs in Korea without current Hp infection showed evidence of past Hp infection. The proportion of GCs with diffuse‐type histology decreased in patients with past infection.
Background
Smad4 and p53 mutations are the most common mutations in human colorectal cancers (CRCs). We evaluated whether and how they are synergistic in intestinal carcinogenesis using novel ...autochthonous mouse models.
Method
To recapitulate human CRCs, we generated Villin‐Cre;Smad4F/F;Trp53F/F mice. We then compared the intestinal phenotype of Villin‐Cre;Smad4F/F;Trp53F/F mice (n = 40) with Villin‐Cre;Smad4F/F (n = 30) and Villin‐Cre;Trp53F/F mice (n = 45).
Results
Twenty‐week‐old Villin‐Cre;Smad4F/F;Trp53F/F mice displayed spontaneous highly proliferative intestinal tumors, and 85% of mice developed adenocarcinomas. p21 was downregulated in the intestinal mucosa in Villin‐Cre;Smad4F/F;Trp53F/F mice than in Villin‐Cre;Smad4F/F and Villin‐Cre;Trp53F/F mice. Villin‐Cre;Smad4F/F;Trp53F/F mice displayed multistep intestinal tumorigenesis and Wnt activation. Long‐term CWP232291 (small‐molecule Wnt inhibitor) treatment of Villin‐Cre;Smad4F/F;Trp53F/F mice suppressed intestinal tumorigenesis and progression. CWP232291 treatment downregulated cancer stem cell (CSC) tumor markers including CD133, Lgr‐5, and Sca‐1. CWP232291 treatment reduced the CSC frequency. Small‐molecule Wnt inhibitors reduced intestinal CSC populations and inhibited their growth, along with Bcl‐XL downregulation. Furthermore, BH3I‐1, a Bcl‐XL antagonist, increasingly inhibited intestinal CSCs than bulk tumor cells.
Conclusion
Smad4 loss and p53 loss are synergistic in autochthonous intestinal carcinogenesis, by downregulating p21 and activating Wnt/β‐catenin pathway.
Cooperation of Smad4 and p53 in constraining the intestinal tumor development and progression. Loss of Trp53 and Smad4 is synergistic in spontaneous mouse intestinal carcinogenesis and unrecognized therapeutic vulnerabilities. Wnt inhibitors and TGF‐β inhibitors provide therapeutic benefit to mice‐bearing colorectal tumors, as monotherapy or in combination with immune checkpoint inhibitors.
Countries differ in their treatment expertise and research results regarding gastric cancer; hence, treatment guidelines are diverse based on evidence and medical situations. A comprehensive and ...comparative review of each country's guidelines is imperative to understand the similarities and differences among countries. We reviewed and compared five gastric cancer treatment guidelines in terms of endoscopic, surgical, perioperative, and palliative systemic treatment based on evidence levels and recommendation grades, as well as the postoperative follow-up strategies for each guideline. The Korean, Chinese, and European guidelines provided evidence and grading of the recommendations. The United States guidelines suggested categories for evidence and consensus. The Japanese guidelines suggested evidence and recommendations only for systemic treatment. The Korean and Japanese guidelines described endoscopic treatment, surgery, and lymphadenectomy in detail. The Chinese, United States, and European guidelines more intensively considered perioperative chemotherapy. In particular, the indications for chemotherapy and the regimens recommended by each guideline differed slightly. Considering their medical situations, each guideline had some diversity in terms of adopting evidence, which resulted in heterogeneous recommendations. This review will help medical personnel to comprehensively understand the diversity in gastric cancer treatment guidelines for each country in terms of evidence and recommendations.
Purpose
Despite theoretical advantages, no clear benefit was proven for initial application of robotic surgery for gastric cancer so far. The aim of this analysis was to examine the role of robotic ...surgery regarding nodal dissection technically demanding areas compared to conventional laparoscopic surgery.
Methods
This analysis included 87 patients who underwent robot-assisted distal gastrectomy (RADG) and 288 patients who underwent laparoscopy-assisted distal gastrectomy (LADG) at the National Cancer Center, Korea, between February 2009 and September 2011. Clinicopathologic data, surgery-related data, postoperative morbidity, and pathologic data for each nodal station were analyzed.
Results
Time to flatulence was 3.5 ± 0.8 days for RADG and 3.8 ± 0.8 days for LADG (
P
= 0.01). Postoperative hospital stay was 6.7 ± 1.0 days in RADG and 7.4 ± 2.4 days in LADG (
P
< 0.001).The number of dissected lymph nodes was 37.1 ± 12.9 in the RADG group and 34.1 ± 12.1 in the LADG group (
P
= 0.044). In patients undergoing D2 gastrectomy, the number of dissected lymph nodes in the N2 area was 16.3 ± 7.7 for RADG and 13.2 ± 5.3 for LADG (
P
= 0.001). The number of dissected lymph nodes around the splenic artery area was 2.9 ± 2.9 in RADG and 2.2 ± 2.0 in LADG (
P
= 0.04). Regarding postoperative complications, there was no statistically significant difference five patients (5.7 %) in RADG and 26 patients (9 %) in LADG) (
P
= 0.330).
Conclusion
RADG could provide an advantage over LADG in the dissection of the N2 area lymph nodes, especially around the splenic artery area.
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