Treatment Of Early Stage Gastric Cancer Research Articles

Characteristics of early gastric tumors with different differentiation and predictors of long-term outcomes after endoscopic submucosal dissection

BACKGROUND Gastric cancer is a common malignant tumor of the digestive tract, and endoscopic submucosal dissection (ESD) is the preferred treatment for early-stage gastric cancer. The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD. AIM To analyze the features of gastric mucosal tumors at different differentiation levels, and to explore the prognostic factors of ESD. METHODS We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021, according to the latest Japanese guidelines (sixth edition), and divided them into low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and differentiated and undifferentiated early carcinoma. They are followed up by endoscopy, chest and abdominal computed tomography at 3, 6 and 12 months after ESD. We compared clinicopathologic characteristics, ESD efficacy, and complications with different degrees of differentiation, and analyzed the related factors associated with ESD. RESULTS HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients (P < 0.001) and accounted for more 0-IIc (P < 0.001), atrophic gastritis was common (P < 0.001), and irregular microvascular patterns (IMVPs) and demarcation lines (DLs) were more obvious (P < 0.001). There was more infiltration in the undifferentiated carcinoma tissue (P < 0.001), more abnormal folds and poorer mucosal peristalsis (P < 0.001), and more obvious IMVPs, irregular microsurface patterns and DLs (P < 0.05) than in the LGIN and HGIN tissues. The disease-free survival rates at 2, 5, and 8 years after ESD were 95.0%, 90.1%, and 86.9%, respectively. Undifferentiated lesions (HR 5.066), white moss (HR 7.187), incomplete resection (HR 3.658), and multiple primary cancers (HR 2.462) were significantly associated with poor prognosis. CONCLUSION Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics, which are closely related to the safety and efficacy of ESD.

Endoluminal and next generation robotics in colorectal surgery

Innovative approaches leverage cutting-edge technologies to advance the field of minimally invasive colorectal surgery. The implementation of complex endoluminal and transluminal procedures is challenging and requires extensive training. Recent technological advances not only enable improved detection of colorectal neoplasms with the support of computer science, but also enhanced surgical treatment with robotic instrumentation. Early diagnosis will revolutionize colorectal cancer treatment by avoiding surgery, as has been demonstrated in the treatment of early-stage gastric cancer using third-space endoscopy. Automated colorectal cancer screening with polyp detection and classification can change the therapeutic strategy and orient towards resection during endoscopy, including full-thickness resection, with endoscopic bimanual suturing to close the defect. Several therapeutic flexible endoscopic robotic systems are expected to provide surgery-like dexterity for endo- and transluminal approaches by enabling tissue triangulation while lowering the technical hurdles for endoscopic submucosal dissection and other highly sophisticated procedures such as endoscopic creation or revision of anastomoses. In the curvilinear anatomy of the colon and rectum, navigation assistance for improved spatio-temporal orientation will aid in the detection and documentation of lesions and facilitate their localization for excision and follow-up. Flexible robotic systems encourage surgeons as well as gastroenterologists to perform advanced intra- and transluminal resections.

Accelerating ESD-induced gastric ulcer healing using a pH-responsive polyurethane/small intestinal submucosa hydrogel delivered by endoscopic catheter.

Endoscopic submucosal dissection (ESD) is the standard treatment for early-stage gastric cancer, but the large post-operative ulcers caused by ESD often lead to serious side effects. Post-ESD mucosal repair materials provide a new option for the treatment of post-ESD ulcers. In this study, we developed a polyurethane/small intestinal submucosa (PU/SIS) hydrogel and investigated its efficacy for accelerating ESD-induced ulcer healing in a canine model. PU/SIS hydrogel possessed great biocompatibility and distinctive pH-sensitive swelling properties and protected GES-1 cells from acid attack through forming a dense film in acidic conditions in vitro. Besides, PU/SIS gels present a strong bio-adhesion to gastric tissues under acidic conditions, thus ensuring the retention time of PU/SIS gels in vivo. In a canine model, PU/SIS hydrogel was easily delivered via endoscopy and adhered to the ulcer sites. PU/SIS hydrogel accelerated gastric ulcer healing at an early stage with more epithelium regeneration and slight inflammation. Our findings reveal PU/SIS hydrogel is a promising and attractive candidate for ESD-induced ulcer repair.

A polymorphism within the mismatch repair gene predicts prognosis and adjuvant chemotherapy benefit in gastric cancer patients.

3025 Background: Radical surgery with subsequent adjuvant chemotherapy was effective treatment for early-stage gastric cancer (GC) patients. Unfortunately, after optimal multimodality therapy, up to 30% to 40% of patients undergoing resection will relapse within 5 years. There are no validated prognostic and predictive biomarkers for GC patients who receive adjuvant chemotherapy, and current patient selection is based mainly on postoperative pathological staging. Defective mismatch repair (MMR) or microsatellite instability (MSI) may affect GC outcome. Polymorphisms of MMR genes with a low-penetrant effect can cause heterogeneous MMR capability among individuals. It is not known about the impact of these polymorphisms on GC outcome. Methods: The polymorphisms rs1800734 in MLH1, rs2303428 and rs3732183 in MSH2, rs735943 in EXO1, and rs11797 in TREX1 were selected and analyzed in independent discovery and validation sets that included 167 and 593 patients, respectively. MSI was determined. Results: In the discovery set, both the rs2303428 TC+CC and the rs11797 GA+AA genotypes significantly correlated with poor overall survival (OS; P < 0.05). In the validation set, we confirmed the prognostic association for the rs2303428 TC+CC genotype (P = 0.036) but not for the rs11797 GA+AA genotype (P = 0.737). Furthermore, the prognostic role of the rs2303428 TC+CC genotype was observed in non-cardia (P = 0.005) but not in cardia GC (P = 0.934). The multivariate model showed that the rs2303428 TC+CC genotype was an independent predictor for OS in non-cardia patients (HR = 1.54; 95% CI: 1.02-2.32; P = 0.040). Moreover, fluoropyrimidines-based adjuvant chemotherapy significantly improved OS (HR = 0.29; 95% CI: 0.15-0.58; P < 0.001) for non-cardia patients with the rs2303428 TC+CC genotype but not for those with the rs2303428 TT genotype. The rs2303428 genotypes were not associated with MSI frequency. Conclusions: The rs2303428 TC+CC genotype may predict prognosis and adjuvant chemotherapy benefit in non-cardia GC patients independent of MSI. To our knowledge, our study is the first to report the prognostic and predictive roles of MMR genotype in GC. Although prospective validation is necessary, our findings have the potential to improve patient selection for adjuvant chemotherapy and spare large numbers of GC patients’ unnecessary therapy.

Surgical management for early stage gastric cancer

In the last decade the implementation of the new technique of endoscopic submucosal dissection (ESD) and the rapid progression of laparoscopic gastric cancer (LAG) resection with an adequate lymphadenectomy (LAD) have played an increasing role in the treatment of patients with early stage gastric cancer (EGC). A systematic review of the currently available data in the literature was carried out to evaluate the contemporary surgical management for treatment of EGC. Endoscopic resection (ER) of mucosal T1 gastric cancer (T1m) in accordance with the German guidelines on resection criteria is awidely accepted treatment option, if adefinitive R0 resection can be achieved. Excellent en bloc and R0 results in more than 90% of these cases have been shown particularly for ESD. In contrast to T1m gastric carcinomas with a low risk of lymph node metastases (approximately 3%), nodal involvement reaches more than 20% for submucosal infiltrated EGC (T1sm). For this reason, asurgical resection with adequate LAD is further recommended in all cases of non-curative ER or any T1sm gastric cancer. In seven randomized controlled trials and aseries of meta-analyses including high-quality non-randomized trials, significant benefits in short-term postoperative outcome have been demonstrated for LAG in comparison to open gastrectomy (OG) in the treatment of EGC. The general morbidity was also significantly lower in LAG than in OG. The 30-day mortality and long-term survival outcome were comparable between the two groups. The use of ESD should be the standard treatment for T1m EGC within the guidelines criteria. For non-curative ESD and T1sm gastric cancer, surgical resection with LAD is recommended. The LAG is atechnically safe, feasible, and favorable approach in terms of faster recovery compared to OG. The long-term survival outcome is comparable between LAG and OG for EGC.

Abstract 2129: HB-EGF expression in gastric cancer promotes chemotherapy resistance and represents a promising target for molecular therapy and a novel biomarker of 5-FU resistance

Abstract The incidence of gastric cancer (GC) has been on the decline in the U.S. over the last 40 years, but remains high in Asia and Latin America. The primary treatment for early-stage GC is surgery. Many patients will also benefit from adjuvant 5-fluorouracil (5-FU) or platin-based chemotherapy. When it presents at an advanced stage, GC uniformly carries a poor prognosis, due to chemotherapy resistance. To improve the response of GC to chemotherapy, molecular-targeted therapies are needed. One of the EGFR family ligands called heparin-binding epidermal growth factor (HB-EGF) was recently found to be up-regulated in several epithelial-based malignancies, including GC. Our objective in this study was to evaluate the role of HB-EGF in GC chemotherapy resistance. We hypothesize that constitutive expression of HB-EGF is associated with chemotherapy resistance. Furthermore we propose that inhibition of HB-EGF enhances drug sensitivity and augments the apoptotic response to chemotherapy in GC. To test our hypothesis, we isolated RNA and protein from a panel of 6 GC cell lines and measured the basal HB-EGF expression compared to that of normal gastric epithelia. We similarly measured HB-EGF expression in response to 5-FU or cisplatin treatment, and then determined the response when cells were co-treated with HB-EGF or an inhibitor of HB-EGF (CRM197). We found that HB-EGF expression at both the protein and RNA levels was highly variable across the panel of GC cell lines. In addition, HB-EGF expression increased in response to drug treatment at 24 and 48 hours post-treatment. A positive correlation was observed between HB-EGF mRNA levels and chemoresistance to 5-FU. GC cell lines that are high-expressers of HB-EGF showed decreased cell growth when treated with CRM197, whereas low-expressers increased when treated with recombinant HB-EGF. The combination of CRM197 with anticancer agents increased apoptosis in high-expressers, but made no significant difference in low-expressers. Likewise, HB-EGF gene silencing using a lentiviral short-hairpin RNA significantly decreased high-expressers survival and proliferation. Similar to our findings using GC cell lines, we found that human gastric cancer tumor samples showed highly variable HB-EGF expression compared to their matching normal gastric epithelia. Our findings suggest that HB-EGF plays an important role in the proliferation and chemotherapy resistance of a subset of gastric cancers. HB-EGF may represent a promising molecular target in those select patients, in whom the gastric cancer expresses high levels of HB-EGF. Furthermore, HB-EGF expression may represent a novel biomarker for 5-FU chemoresistance in patients with gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2129. doi:10.1158/1538-7445.AM2011-2129

Laparoscopic gastric resections.

The impressive breakthrough in laparoscopic surgery has pushed surgeons to perform gastric resection through such an approach. Laparoscopy reduces the surgical stress and the postoperative pain and has a positive impact on the rehabilitation time, the hospital stay, and return to work and social activities. Laparoscopic partial gastrectomy for benign diseases and for palliation has been accepted as an effective surgical option: they are reproducible operations performed worldwide at a more and more rapid pace. Laparoscopic gastric resections and laparoscopically assisted gastric resections for malignancy deserve a word of caution. Nevertheless, the investigators report their series of laparoscopic subtotal and distal gastrectomies for cancer with medium and long-term results comparable with those of open surgery. Furthermore, new and less invasive surgical options have been recently introduced. Full and partial thickness local resections may be accomplished through intragastric procedures, for treatment of small benign tumors and early stage gastric cancer.