Recent progress and future prospects of treatment for peritoneal metastasis in gastric cancer / 中华胃肠外科杂志

Peritoneal metastasis is one of the most frequent patterns of metastasis in gastric cancer, and remains a major unmet clinical problem. Thus, systemic chemotherapy remains the mainstay of treatment for gastric cancer with peritoneal metastasis. In well-selected patients, the reasonable combination of cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and neoadjuvant intraperitoneal chemotherapy with systemic chemotherapy will bring significant survival benefits to patients with gastric cancer peritoneal metastasis. In patients with high-risk factors, prophylactic therapy may reduce the risk of peritoneal recurrence, and improves survival after radical gastrectomy. However, high-quality randomized controlled trials will be needed to determine which modality is better. The safety and efficacy of intraoperative extensive intraperitoneal lavage as a preventive measure has not been proven. The safety of HIPEC also requires further evaluation. HIPEC and neoadjuvant intraperitoneal and systemic chemotherapy have achieved good results in conversion therapy, and it is necessary to find more efficient and low-toxicity therapeutic modalities and screen out the potential benefit population. The efficacy of CRS combined with HIPEC on peritoneal metastasis in gastric cancer has been preliminarily validated, and with the completion of clinical studies such as PERISCOPE II, more evidence will be available.

Standardized implementation of minimally invasive surgery for Siewert Ⅱ esophagogastric junction adenocarcinoma / 中华胃肠外科杂志

The incidence of Siewert type II adenocarcinoma of the esophagogastric junction (AEG) is increasing year by year. Due to its special anatomical location and biological behavior, the treatment of AEG is still controversial in terms of lymph node dissection, the esophageal resection margin, range of gastrectomy, and the choice of reconstruction modality for postoperative gastrointestinal tract. The advent of the minimally invasive era has brought the treatment of Siewert type II AEG to a stage of gradual improvement and standardization. Experts of China are also actively exploring the value of minimally invasive surgery in the treatment of AEG through multicenter trials (CLASS-10, etc.). It is believed that based on the active development of many clinical studies, basic experimental studies and large prospective clinical studies, the strengthening of communication and cooperation among various disciplines and the innovative application of new technologies can bring greater survival benefits to patients.

Circ_0049447 acts as a tumor suppressor in gastric cancer through reducing proliferation, migration, invasion, and epithelial-mesenchymal transition / 中华医学杂志(英文版)

BACKGROUND@#Although increasing abnormal expression of circular RNAs (circRNAs) has been revealed in various cancers, there were a small number of studies about circRNAs in gastric cancer (GC). Here, we explored the expression and function of a novel circRNA, circ_0049447, in GC.@*METHODS@#A total of 80 GC tissues and non-tumorous tissues were collected from the First Affiliated Hospital of China Medical University. And all cells were cultured with 10% fetal bovine serum and incubated at 37°C and 5% CO2. The expression of circ_0049447 was quantified by real-time polymerase chain reaction. The biological function of circ_0049447 on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) was evaluated by cell counting kit-8 (CCK-8), colony formation assay, transwell migration and invasion assay, and Western blotting. Luciferase report assay was used to verify the direct binding between circ_0049447 and predicted microRNA (miRNA). Furthermore, a xenograft mouse model was used to validate the function of circ_0049447 in vivo.@*RESULTS@#We demonstrated that circ_0049447 was downregulated in GC (P < 0.001). The area under the receiver operating characteristic curve reached 0.838, while sensitivity was 82.3% and specificity was 77.2%. CCK-8 and colony formation assay showed that overexpression of circ_0049447 could inhibit the proliferation (P < 0.05). Transwell migration and invasion assay showed upregulated circ_0049447 could impede migration in GC cells (P < 0.05). In addition, overexpression of circ_0049447 could impede GC cell EMT. Upregulation of miR-324-5p in GC specimens and direct binding between miR-324-5p with circ_0049447 proven by luciferase reporter assay indicated that circ_0049447 may inhibit GC by sponging certain miRNA.@*CONCLUSION@#Circ_0049447 acts as a tumor suppressor in GC through reducing proliferation, migration, invasion, and EMT, and it is a promising biomarker for diagnosis.

Assessment of circulating tumor DNA in cerebrospinal fluid by whole exome sequencing to detect genomic alterations of glioblastoma / 中华医学杂志(英文版)

BACKGROUND@#Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma.@*METHODS@#CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared.@*RESULTS@#Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF compared with the corresponding tumor tissue samples (3.56 ± 0.75 vs. 2.22 ± 0.32, P = 0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.1% ± 6.0% vs. 73.8% ± 6.0%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3 histone, family 3A (H3F3A) which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF.@*CONCLUSION@#Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.

Clinicopathological characteristics and prognostic factors in patients with stage III gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics and prognostic factors of stage III gastric cancer.</p><p><b>METHODS</b>A retrospectively study of 1007 patients with Stage III gastric cancer in a single institute in China was performed. The patients underwent surgical resection from January 1991 to December 2005. Univariate and multivariate analyses were performed using log-rank test and Cox proportional hazards model to access the prognostic factors in stage III gastric cancer patients who received curative (R0) gastric resection.</p><p><b>RESULTS</b>The mean age of the 1007 patients was 58.7 years and the male-to-female ratio was 2.6:1.0. There were 242 patients with stage IIIA disease, 403 patients with stage IIIB, and 362 patients with stage IIIC. R0, R1, and R2 resection were performed in 754 patients (74.9%), 56 patients (5.5%), and 197 patients (19.6%), respectively. The 5-year survival rate (37.8%) of patients who received R0 resection was significant higher than that of patients who received R1(21.2%) and R2(8.9%) resection (P<0.05). Multivariate analysis revealed that pN stage, pT stage, and Borrmann type were independent prognostic factors (all P<0.01).</p><p><b>CONCLUSIONS</b>Stage III gastric cancer patients have certain clinicopathological characteristics and R0 resection should be performed if possible. Lymph node count, depth of tumor invasion, and Borrmann type are independent prognostic factors in stage III gastric cancer patients undergoing R0 resection.</p>

Detection of T lymphocyte subsets in patient with glioma / 中华神经医学杂志

Objective To explore the relationship between T lymphocyte subsets and both glioma malignancy and its prognosis, and determine a clinical immunologic index for evaluating preoperative glioma malignancy and its prognosis. Methods The data of 117 inpatients with primary intracranial tumors, including glioma (n=85) and meningioma (n=32), were retrospectively analyzed. Fluorescence-activated cell sorting (FACS) analysis was performed to detect the preoperative contents of T lymphocyte subsets on 32 patients with meningioma and patients with glioma, including 45 high-grade glioma (WHO, grade Ⅲ-Ⅳ) and 40 low-grade glioma (WHO, grade Ⅰ -Ⅱ); and then the differences of their immunologic indexes were analyzed. Based on the detection result of T lymphocyte subsets, patients with glioma were divided into two groups: CD4~+CD8~+<1 and CD4~+CD8~+>1. Follow-up for 3-5 years was performed and the survival difference of these two groups was analyzed. Results Patients with high-grade glioma showed a decreased ratio of CD4~+CD8~+ and an increased value of CD8~+ with significant difference as compared with patients with low-grade glioma (P<0.05); patients with high-grade glioma showed a decreased ratio of CD4~+CD8~+, and an increased value of CD8~+ with statistical significance compared with patients with meningioma (P <0.05); patients with low-grade glioma showed a decreased ratio of CD4~+CD8~+ with statistical significance compared with the patients with meningioma (P<0.05). Patients with glioma showed a decreased ratio of CD4~+CD8~+ and CD4~+, and an increased CD8~+ with statistical significance compared with patients with meningioma (P<0.05). After follow-up for 3-5 years, 48 patients with glioma was found in the CD4~+CD8~+>1 group with 21 death (43.8%) and 31 months as a median survival time; 37 patients with glioma was found in the CD4~+CD8~+<1 group with 23 death (62.2%) and 16 months as a median survival time. The Kaplan-Meier survival curves were analyzed with statistical significance (P<0.05). Conclusion The prognosis is poor in patients with low ratio of CD4~+CD8~+. The preoperative level of T lymphocyte subsets in peripheral blood, correlated to the glioma malignancy, can be considered as an index to evaluate the glioma malignancy and the prognosis in patients with glioma.

Clinicopathologic features and prognosis of gastric cancer in young adults / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the clinicopathologic features and prognosis of young patients with gastric cancer by comparing with older patients.</p><p><b>METHOD</b>The clinicopathologic data of 157 younger adults (age, </= 40 years) with gastric cancer and 1761 cases of elder gastric cancer patients (age, > 40 years) was analyzed and compared retrospectively. All of the 1918 patients were surgically treated between January 1980 and December 2000.</p><p><b>RESULTS</b>The rates of poorly differentiation, diffusive growth, Borrmann 4 type, whole-stomach invasion were significantly higher in younger cases than those in the elder counterparts (P < 0.05), especially in young female patients. The rate of early gastric cancer was significantly higher in young patients than that in older patients (P < 0.05), especially in young male patients. There was significant difference between the survival rate of younger male cases (median survival, 35 months) and younger female cases (median survival, 19 months) (P = 0.0219), but no significant difference was found between elder male and elder female (median survival, 26 vs. 30 months). TNM stage, operative curability, gross type were independent predictive factors of survival for younger patients.</p><p><b>CONCLUSIONS</b>Younger female gastric cancer patients tends to have worse prognosis than older patients, while younger male patients have better prognosis due to higher percentage of early gastric cancer when diagnosed. Pathologic staging and operative curability are the independent predictive factors of survival for younger patients.</p>

Expression of survivin mRNA in peritoneal lavage fluid from patients with gastric carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Peritoneal dissemination is the most common pattern of metastasis in advanced gastric carcinoma with serosal invasion. In the present study, we reported the clinical relevance of a new diagnostic method involving RT-PCR, using survivin as the target gene, for the detection of free cancer cells in peritoneal washes.</p><p><b>METHODS</b>Intraoperative peritoneal washes were obtained from 48 patients who underwent surgery for gastric cancer. RT-PCR analysis with primers specific for survivin and conventional cytological examinations were both performed.</p><p><b>RESULTS</b>Survivin mRNA was not detected in any peritoneal wash samples from patients with benign disease, but was detected in 28 of 48 samples taken from patients with gastric cancer and in all metastatic nodules. Survivin expression in the peritoneal cavity significantly correlated with depth of cancer invasion, lymph node metastasis, and TNM stage. There were 92% of clinically evident peritoneal metastasis cases showed detectable survivin expression. The combination of survivin RT-PCR and cytological examination yielded positive results in 66.7% (32/48) of patients with gastric cancer, much higher than the results produced by cytological method alone.</p><p><b>CONCLUSIONS</b>Survivin mRNA detected in peritoneal lavage fluid might indicate the presence of free cancer cells in the peritoneal cavity. The high sensitivity of the RT-PCR-based survivin assay suggests that survivin serves as a molecular marker for detecting peritoneal micrometastasis. Its ubiquitous expression in peritoneal cancer cells and metastatic nodules also suggests a promising future therapeutic strategy based on survivin inhibition for cases of gastric cancer involving peritoneal metastasis.</p>