Development and validation of an individualized nomogram to identify occult peritoneal metastasis in patients with advanced gastric cancer.

BACKGROUND: Occult peritoneal metastasis (PM) in advanced gastric cancer (AGC) patients is highly possible to be missed on computed tomography (CT) images. Patients with occult PMs are subject to late detection or even improper surgical treatment. We therefore aimed to develop a radiomic nomogram to preoperatively identify occult PMs in AGC patients. PATIENTS AND METHODS: A total of 554 AGC patients from 4 centers were divided into 1 training, 1 internal validation, and 2 external validation cohorts. All patients' PM status was firstly diagnosed as negative by CT, but later confirmed by laparoscopy (PM-positive n = 122, PM-negative n = 432). Radiomic signatures reflecting phenotypes of the primary tumor (RS1) and peritoneum region (RS2) were built as predictors of PM from 266 quantitative image features. Individualized nomograms of PM status incorporating RS1, RS2, or clinical factors were developed and evaluated regarding prediction ability. RESULTS: RS1, RS2, and Lauren type were significant predictors of occult PM (all P < 0.05). A nomogram of these three factors demonstrated better diagnostic accuracy than the model with RS1, RS2, or clinical factors alone (all net reclassification improvement P < 0.05). The area under curve yielded was 0.958 [95% confidence interval (CI) 0.923-0.993], 0.941 (95% CI 0.904-0.977), 0.928 (95% CI 0.886-0.971), and 0.920 (95% CI 0.862-0.978) for the training, internal, and two external validation cohorts, respectively. Stratification analysis showed that this nomogram had potential generalization ability. CONCLUSION: CT phenotypes of both primary tumor and nearby peritoneum are significantly associated with occult PM status. A nomogram of these CT phenotypes and Lauren type has an excellent prediction ability of occult PM, and may have significant clinical implications on early detection of occult PM for AGC.

[Clinicopathological and molecular characteristics of Epstein-Barr virus associated gastric cancer: a single center large sample case investigation].

OBJECTIVE: Epstein-Barr virus associated gastric cancer (EBVaGC) is different from the traditional gastric cancer (Epstein-Barr virus non-associated gastric cancer, EBVnGC), and has unique clinicopathological features. This study investigated the largest single center cancer series so as to establish the clinicopathological and molecular characteristics of EBVaGC in China. METHODS: A retrospective analysis was conducted on EBVaGC and EBVnGC patients diagnosed at Peking University Cancer Hospital from 2003 to 2018 by comparing their clinicopathological features and prognosis. The gastric cancer (GC) dataset of public database was analyzed to obtain differentially expressed genes. The expression of important genes and their association with prognosis of GC were verified in GC tissues from our hospital. RESULTS: In this study, 3 241 GC patients were included, and a total of 163 EBVaGC (5.0%) patients were identified. Compared with EBVnGC, EBVaGC was higher in male and younger patients, and positively associated with remnant GC, poorly differentiated adenocarcinoma, and mixed type GC. EBVaGC was inversely related to lymph node metastasis. The 5-year survival rate of EBVnGC and EBVaGC was 59.6% and 63.2% respectively (P<0.05). In order to explore molecular features of EBVaGC, the Cancer Genome Atlas (TCGA) dataset was analyzed (n=240), and 7 404 significant differentially expressed genes were obtained, involving cell proliferation, apoptosis, invasion and metastasis. The down-regulated invasion/metastasis gene SALL4 and the up-regulated immune checkpoint gene PD-L1 were important molecular features of EBVaGC. Validation of these two genes in large GC series showed that the majority of the EBVaGC was SALL4 negative (1/92, 1.1%, lower than EBVnGC, 303/1 727, 17.5%), and that PD-L1 was mostly positive in EBVaGC (81/110, 73.6%, higher than EBVnGC, 649/2 350, 27.6%). GC patients with SALL4 negative and PD-L1 positive were often associated with better prognosis. CONCLUSION: EBVaGC is a unique subtype of GC with less metastasis and a good prognosis. It also has a distinct molecular background. The down-regulation of invasion/metastasis gene SALL4 and up-regulation of immune checkpoint gene PD-L1 are important molecular features.

[From standard to precision treatment: the development of surgery for gastric cancer].

Gastric cancer remains a significant health problem worldwide. The incidence of gastric cancer is the 5(th) of all the malignancies, and the mortality is the 3(rd). The type and resection area of gastric cancer surgery have changed a lot. D2 lymph node dissection is recommended for locally advanced gastric cancer. Prophylactic pancreatectomy or splenectomy is not necessary for radical resection. Indication of minimally invasive surgery is confined to early gastric cancer with distal gastrectomy. Less extensive approach of early stage cases is suitable, and application of sentinel lymph node is a potential method. Meanwhile, the development of chemotherapy, radiotherapy, targeted therapy and immunotherapy during the perioperative period also improved the prognosis of gastric cancer patients. Recently, the development of molecular biology, such as the maturity of the new generation sequencing approach, started a new era of precision treatment for gastric cancer.

Preoperative chemotherapy with a trastuzumab-containing regimen for a patient with gastric cancer and hepatic metastases.

Gastric cancer is the fourth most common cancer worldwide and the leading cause of tumor-related death in China. Gastric cancer is a heterogeneous disease and therefore requires different treatments based on the subtype. We describe a patient who had gastric cancer with liver metastases. Biopsy and tumor analysis using the HercepTest revealed a human epidermal growth factor receptor 2 (HER2)-positive adenocarcinoma as confirmed by fluorescence in situ hybridization. The patient was treated with a regimen of trastuzumab, oxaliplatin, and S-1 (six cycles). When positron emission tomography findings suggested that the metastases had resolved, the patient underwent surgery. Histopathologically, no cancer cells were observed in the resected hepatic tissue. The patient underwent tumor resection surgery, during which the tumor and gastric lymph nodes with lesions were removed. The patient has remained disease-free for 3 months. Therefore, trastuzumab may be an effective agent in the chemotherapeutic treatment of liver metastases in patients with HER2-positive gastric adenocarcinoma.

[Neoadjuvant immunotherapy ushers in a new era of gastric cancer treatment].

Recent advances in tumor immunology have made immunotherapy a new direction for neoadjuvant treatment of gastric cancer. Multiple clinical trials have confirmed that combining immunotherapy with chemotherapy and targeted therapy in the neoadjuvant treatment of gastric cancer can effectively improve treatment response and prolong patient survival time. This article aims to comment on the application of immunotherapy in the neoadjuvant treatment of gastric cancer, exploring its mechanisms, integration strategies with traditional treatments, safety, and personalized precision therapy in the hope of providing new insights and directions for the field of gastric cancer treatment.

Prognostic value of metastatic lymph node ratio as an additional tool to the TNM stage system in gastric cancer.

BACKGROUND: Gastric cancer is one of most common malignancies in the world. Currently the prognostic prediction is entirely based on the TNM staging system. In this study, we evaluated whether metastatic lymph node ratio (rN) at the time of surgery would improve the prognostic prediction in conjunction with the TNM staging system. METHODS: This retrospective study includes 745 patients, who had been referred for surgery due to gastric cancer between 1995 and 2007 and had at least 15 lymph nodes examined at the time of surgery without preoperative treatment. Clinicopathologic features and overall survival were analyzed using univariate and multivariate modes to identify the risk factors for overall survival. RESULTS: Median overall survival of all patients analyzed is 57.8 months and 5-year overall survival is 49.5%. Tumor site, macroscopic type, pTNM stage, and rN stage are identified as independent prognostic factors. Increased positive lymph node ratio correlates with shorter survival in all patients and in each T and N stage. In stage III gastric cancer patients, rN stage shows additional prognostic value on overall survival (p < 0.001). CONCLUSIONS: rN stage is a simple and promising prognostic factor of gastric cancer after surgery in addition to the TNM stage system especially in stage III patients. But the independent prognostic value of rN stage in stage I, II and IV gastric cancer is yet to be determined.