Effect of Chemoradiotherapy on the Survival of Resectable Gastric Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Adjuvant chemotherapy (CT) and chemoradiotherapy (CRT) after surgery are necessary to reduce the risk of metastasis and recurrence for resectable gastric cancer (GC) patients. Adjuvant CT and CRT have been proven to significantly improve the prognosis for GC patients, when compared with surgery only. However, it is still unclear whether radiotherapy offers additional survival benefits to advanced gastric cancer (AGC) patients. METHODS: PubMed, Cochrane Library, and Embase databases were systematically searched for eligible studies that compared survival benefits between CRT and CT. The endpoints of this meta-analysis were measured as HR for OS or DFS and 95% CI using fixed- or random-effect models. Additionally, side effects, completed rate, and metastatic risk, were calculated as OR. Subgroup analyses according to clinicopathological factors were presented. RESULTS: A total of 28 eligible studies involving 20,220 patients were included in our study. Of these, 17 studies evaluated the survival benefits of additional radiotherapy on overall survival (OS) of gastric cancer patients, ten reported the impact of CRT on disease-free survival (DFS), and 26 studies showed long-term survival rate. The pooled results were significant (HR for OS 0.84, 95% CI 0.71-0.99; HR for DFS 0.76, 95% CI 0.66-0.89). The subgroup analysis showed that adjuvant CRT increased OS for patients without preoperative treatment; showed similar nausea/vomiting, but an increased risk of neutropenia; reduced the risk of locoregional recurrence; failed to improve OS for lymph node (LN)-positive GC patients; and significantly improved prognosis for R1-treated patients. Of note, DFS was improved in all the subgroups via decreasing the locoregional recurrence. CONCLUSION: Compared with CT, adjuvant CRT can improve survival for advanced gastric cancer patients, with similar nausea/vomiting, but increased risk of neutropenia. Patients without preoperative treatment or with positive surgical margins should be strongly recommended to undergo CRT. Treatment regimens should be carefully decided by doctors based on patients' tolerance, physical status, and reaction to treatment. Moreover, CRT improves the DFS for patients regardless of subgroups, because it significantly reduced the risk of locoregional recurrence.

LMOD1, an oncogene associated with Lauren classification, regulates the metastasis of gastric cancer cells through the FAK-AKT/mTOR pathway.

BACKGROUND: The Lauren classification of gastric tumors strongly correlates with prognosis. The purpose of this study was to explore the specific molecular mechanism of Lauren classification of gastric cancer and provide a possible theoretical basis for the treatment of gastric cancer. METHODS: We standardized the gene expression data of five Gene Expression Omnibus gastric cancer databases and constructed a Weighted Co-expression Network Analysis (WGCNA) model based on clinicopathological information. The overall survival (OS) and disease-free survival (DFS) curves were extracted from the Cancer Genome Atlas (TCGA) and GSE62254 databases. Western blotting was used to measure protein expression in cells and tissues. Scratch and transwell experiments were used to test the migration ability of tumor cells. Immunohistochemistry was used to measure tissue protein expression in clinical tissue samples to correlate to survival data. RESULTS: The WGCNA model demonstrated that blue cyan was highly correlated with the Lauren classification of the tumor (r = 0.24, P = 7 × 1016). A protein-protein interaction network was used to visualize the genes in the blue cyan module. The OS and PFS TCGA analysis revealed that LMOD1 was a gene of interest. The proportion of diffuse gastric cancer patients with high expression of LMOD1 was significantly higher than that of intestinal type patients. LMOD1 promoted the migration of gastric cancer cells by regulating the FAK-Akt/mTOR pathway in vitro. Additionally, a Gene Set Enrichment Analysis using the TCGA and GSE62254 databases, and western blot data, showed that LMOD1 could promote an epithelial-mesenchymal transition (EMT), thus potentially affecting the occurrence of peritoneal metastasis of gastric cancer. Immunohistochemistry showed that LMOD1 was highly expressed in cancer tissues, and the prognosis of patients with high LMOD1 expression was poor. CONCLUSION: LMOD1 is an oncogene associated with diffuse gastric cancer and can affect the occurrence and development of EMT by regulating the FAK-Akt/mTOR pathway. LMOD1 can therefore promote peritoneal metastasis of gastric cancer cells and can be used as a novel therapeutic target for gastric cancer.

Efficacy and safety of anti-PD-1/PD-L1 therapy in the treatment of advanced colorectal cancer: a meta-analysis.

BACKGROUND: Immune checkpoint inhibitors have shown promise in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) advanced colorectal cancer (CRC) immunotherapy, and many clinical trials have been conducted. OBJECTIVE: To evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in advanced CRC. METHOD: PubMed, Web of Science, Embase, and The Cochrane Library were searched for relevant studies up to September 2021. A retrospective cross-sectional data analysis was performed and Stata 16 software was used for analyses. RESULTS: Sixteen studies including 1503 patients were analyzed. The objective response rate (ORR) of anti-PD-1/PD-L1 was 23% (95% CI 0.14, 0.31); the overall 1-year survival rate (OSR) was 57% (95% CI 0.42, 0.73). The ORR of MSI-H/dMMR advanced CRC was 37% (95% CI 0.25, 0.48) and that of microsatellite stable/mismatch repair proficient (MSS/pMMR) disease was 11% (95% CI 0.06, 0.16). The ORR was 42% in the BRAF mutant subgroup and 19% in the RAS mutant group. The ORR was 14% in the PD-L1 ( +) subgroup and 32% in the PD-L1(-) subgroup. The rate of adverse effects was 85% (95% CI 0.80, 0.91). CONCLUSION: Anti-PD-1/PD-L1 therapy in MSI-H/dMMR advanced CRC was associated with improved survival. Anti PD-1/PD-L1 combined with antiangiogenic drugs, targeted agents, or chemotherapy might be effective in MSS mCRC. Immunotherapy was effective for the BRAF mutant and KRAS/NRAS(RAS) mutant CRC. Low expression of PD-L1 was a potential predictive marker for positive response and outcome. The high incidence of adverse events at 85% was worthy of further investigation. Further analysis with a higher number of high-quality studies is needed to verify the conclusions.

A retrospective analysis of transanal surgical management of 291 cases with rectal foreign bodies.

BACKGROUND: Rectal foreign bodies (RFB) are quite uncommon except in very busy hospitals. Because of their rarity, it is seldom that the treating physicians have a standard approach to the diagnosis, technique of extraction, and post-extraction evaluation. This can be further complicated by the rather extreme variability of size, shape, and texture of the foreign bodies, as well as the potential extent of trauma to the rectum or distal colon. AIM: The objectives of this study were to delineate the demographics, classification of cause, and injury patterns of RFB and to present the results of the transanal surgical management of a large series of RFB. METHODS: We retrospectively collected extensive data from the hospital medical records of the 291 patients who presented with RFB to the emergency department of Shenyang Proctological Hospital (Shenyang, China) from 2012 July to 2020 December. Specifically, demographics, origins and circumstance of the RFB, complications, injuries, anesthesia method, and the results of the transanal surgical management were recorded and analyzed. RESULTS: Of the 291 RFB cases, 225 (77.3%) were male and 66 (22.7%) were female, with a mean age of 53.8 ± 15.5 years (range, 1 ~ 88 years). The circumstances of the RFB were categorized as swallowed, 199 cases (68.4%); self-inserted, 87 (29.9%); and iatrogenic, 5 (1.7%). The proportion of males in the self-inserted RFB group was significantly greater than the swallowed RFB group (t = 31.114, p = 0.000). In the swallowed RFB group, the most common anorectal injuries and pathological changes were the following: penetration into the mucosa (75 cases, 37.7%), perianal or submucosal abscess (27 cases, 13.6%), and penetration into the anal canal (18 cases, 9.0%). In the self-inserted RFB group, 64 (73.6%) of the 87 cases had an intact rectum, whereas 8 (9.2%) had rectal mucosal ulcers and bleeding, and 7 (8%) had rectal lacerations. In the iatrogenic RFB group, 3 cases (60%) had rectal mucosal ulcers and bleeding, and 2 cases (40%) had inflammation of the rectal mucosa. Regarding extraction procedures, in the swallowed group, 187(187/199; 94%) patients underwent a transanal surgical procedure, and all were successful. In the self-inserted group, 82 patients underwent the transanal surgical procedure, and 74 (74/82; 90.2%) were successful whereas it was unsuccessful in the remaining 8 patients (8/82, 9.8%). Three (3/4, 75%) patients with iatrogenic RFB were resolved by the transanal surgical procedure. CONCLUSION: Men were markedly more likely than women to have swallowed RFBs and self-inserted RFBs. No serious damage to the rectum and anus was found in cases of swallowed RFB. Moreover, most surgical operations to remove foreign bodies via the anus were successful in this category of RFB. In contrast, rectal injury was more severe in patients with self-inserted RFB, such as rectal laceration, rectal mucosal ulcer, and bleeding. Moreover, the transanal removal operation in patients with self-inserted RFB had a failure rate of nearly 10%. Thick, long, hard foreign bodies did present a great challenge to the operator. Therefore, if necessary, patients with foreign bodies may need to be promptly referred for transabdominal removal.

Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial.

BACKGROUND: The optimal perioperative chemotherapeutic regimen for locally advanced gastric cancer remains undefined. We evaluated the efficacy and safety of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in patients with locally advanced gastric cancer undergoing D2 gastrectomy. METHODS: We did this open-label, phase 3, superiority and non-inferiority, randomised trial at 27 hospitals in China. We recruited antitumour treatment-naive patients aged 18 years or older with historically confirmed cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma, with Karnofsky performance score of 70 or more. Patients undergoing D2 gastrectomy were randomly assigned (1:1:1) via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral capecitabine 1000 mg/m2 twice a day), adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral S-1 40-60 mg twice a day), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day one of each 21 day plus oral S-1 40-60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy). The primary endpoint, assessed in the modified intention-to-treat population, 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-SOX and the non-inferiority (hazard ratio non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx. Safety analysis were done in patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT01534546. FINDINGS: Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were screened and 1022 (93%) were included in the modified intention-to-treat population, of whom 345 (34%) patients were assigned to the adjuvant-CapOx, 340 (33%) patients to the adjuvant-SOX group, and 337 (33%) patients to the perioperative-SOX group. 3-year disease-free survival was 51·1% (95% CI 45·5-56·3) in the adjuvant-CapOx group, 56·5% (51·0-61·7) in the adjuvant-SOX group, and 59·4% (53·8-64·6) in the perioperative-SOX group. The hazard ratio (HR) was 0·77 (95% CI 0·61-0·97; Wald p=0·028) for the perioperative-SOX group compared with the adjuvant-CapOx group and 0·86 (0·68-1·07; Wald p=0·17) for the adjuvant-SOX group compared with the adjuvant-CapOx group. The most common grade 3-4 adverse events was neutropenia (32 [12%] of 258 patients in the adjuvant-CapOx group, 21 [8%] of 249 patients in the adjuvant-SOX group, and 30 [10%] of 310 patients in the perioperative-SOX group). Serious adverse events were reported in seven (3%) of 258 patients in adjuvant-CapOx group, two of which were related to treatment; eight (3%) of 249 patients in adjuvant-SOX group, two of which were related to treatment; and seven (2%) of 310 patients in perioperative-SOX group, four of which were related to treatment. No treatment-related deaths were reported. INTERPRETATION: Perioperative-SOX showed a clinically meaningful improvement compared with adjuvant-CapOx in patients with locally advanced gastric cancer who had D2 gastrectomy; adjuvant-SOX was non-inferior to adjuvant-CapOx in these patients. Perioperative-SOX could be considered a new treatment option for patients with locally advanced gastric cancer. FUNDING: National Key Research and Development Program of China, Beijing Scholars Program 2018-2024, Peking University Clinical Scientist Program, Taiho, Sanofi-Aventis, and Hengrui Pharmaceutical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Central lymph node metastasis is predictive of survival in advanced gastric cancer patients treated with D2 lymphadenectomy.

BACKGROUND: The number of positive lymph nodes, which was defined as "N stage", is mostly used to predict the survival of D2-resected gastric cancer patients, not the location. A "central lymph node" (CnLN) was defined by Ikoma et al., included common hepatic, celiac and proximal splenic artery LNs. CnLNs located in the extraperigastric area are included in the D2 LN station for gastric cancer. We speculate that CnLNs can be regarded as a predictor of survival. METHODS: Eligible advanced gastric cancer patients who underwent curative resection and D2 lymph node dissection between 2004 and 2012 at our institution were identified. The frequency of CnLN metastases and risk factors affecting DFS were examined. Survival differences were assessed by log-rank tests and Kaplan-Meier curves. RESULTS: The study identified 1178 patients who underwent curative surgery or D2 or more extensive lymphadenectomy. A total of 342 patients had been proven to have CnLN metastasis. Larger tumor size (P < 0.001), more frequent lymphatic vessel invasion (P < 0.001), signet ring cell histology (P = 0.014), and more advanced pathological T stage (P = 0.013) were significantly related to CnLNs metastasis. The patients with CnLN metastasis had a poor prognosis (HR for DFS of 1.366, 95%CI = 1.138-1.640, P = 0.001). For the pN2/3 patients, CnLN metastasis was associated with shorter 5-year DFS (for pN2 patients: 25.9% vs 39.3%, P = 0.017; for pN3 patients: 11.5% vs 23.4%, P = 0.005). CONCLUSION: Gastric cancer patients with CnLN metastasis who underwent D2 resection had a poor prognosis. With the same N stage, the patients with positive CnLNs had shorter survival. CnLNs metastasis could be a supplement to N stage and a predictor of survival in gastric cancer patients. Large sample, multicenter, randomized clinical trials are still needed in the future.

Superiority of log odds of positive lymph nodes (LODDS) for prognostic prediction after gastric cancer surgery: a multi-institutional analysis of 7620 patients in China.

PURPOSE: To compare the 8th pN system with ratio-based and Log odds of positive lymph nodes (LODDS) staging systems for predicting the overall survival (OS) of gastric cancer (GC) patients after curative gastric resection. METHODS: We analyzed, retrospectively, clinicopathologic and prognostic data from three Chinese medical centers, on 7620 patients who underwent curative surgery for GC. We established a hypothetical tumor-LODDS-metastasis (TLM) and tumor-ratio-metastasis (TRM) staging system. The relative discriminative abilities of the different staging systems were assessed using Akaike's Information Criterion (AIC), a linear trend chi-square test, and a likelihood ratio chi-square test. RESULTS: The cut-off points of the LODDS were set as: ≤ - 1.5, - 1.5 to - 1.0, - 1.0 to - 0.5, - 0.5 to 0, and > 0. There were significant differences in the survival of patients in different LODDS classifications for each pN or LNR group. When stratified by the LODDS classification, the prognosis was more homologous according to the pN or lymph-node ratio (LNR) classifications. The modified TLM staging system had better discriminatory ability and better optimistic prognostic stratification than the 8th TNM or the TRM staging systems for predicting the prognosis of patients with GC. CONCLUSIONS: The LODDS staging system was superior to other lymph-node classifications for predicting the prognosis of patients undergoing gastrectomy GC. LODDS may be incorporated into a GC staging system if these results are confirmed by other studies.

A research of STEAP1 regulated gastric cancer cell proliferation, migration and invasion in vitro and in vivos.

Six-Transmembrane Epithelial Antigene of the Prostate 1 (STEAP1) is associated with the occurrence and development of cancer. This study aimed to clarify the role of STEAP1 in gastric cancer tumour growth and metastasis, as well as its molecular mechanism of action.Statistical methods were used for clinical data analysis. Protein expression was detected using immunohistochemistry(IHC). The mRNA and protein expression in the cell cultures were detected using reverse transcription-polymerase chain reaction(RT-PCR) and western blot analysis. Overexpression and silencing models were constructed using plasmid and lentivirus transfection. To detect cell proliferation in vitro, Cell Counting Kit-8(CCK-8), flow cytometry and colony formation assays were used; transwell and wound healing assays were used to detect cell migration and invasion;For in vivo experiments, nude BALB/c mice were used for detecting subcutaneous tumorigenesis and intraperitoneal implantation. In the results,we found STEAP1 was overexpressed in gastric cancer tissues and cell lines. Single-factor and Cox analyses showed that STEAP1 gene expression level correlated with poor prognosis. Up-regulation of STEAP1 increased cell proliferation, migration and invasion, which decreased after STEAP1 was knocked down. These changes were achieved via the activation of the AKT/FoxO1 pathway and epithelial-mesenchymal transformation (EMT). The in vivo animal experiments showed that STEAP1 knock down, resulted in a decrease in the subcutaneous tumour and peritoneal tumour formation.

Benefits of Surgery After Neoadjuvant Intraperitoneal and Systemic Chemotherapy for Gastric Cancer Patients With Peritoneal Metastasis: A Meta-Analysis.

BACKGROUND: Conversion therapy is intended to allow achieving R0 resection after chemotherapy for tumors initially considered unresectable or partially resectable. Neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) is the current conversion therapy for gastric cancer (GC) patients with peritoneal metastasis. This meta-analysis evaluated the effectiveness and safety of NIPS-combined surgery for GC patients with peritoneal metastasis. METHODS: Standard methods were used to select and analyze studies that included GC patients with peritoneal metastasis assigned to two groups, either NIPS-combined surgery or a NIPS-only control. Publications were retrieved from PubMed, EMBASE, Medline, and the Cochrane Central Register. Overall survival, conversion therapy success and R0 resection rates, and adverse events were analyzed using Stata 11.0. RESULTS: Eight of the 14 studies that were evaluated after screening the titles and abstracts of 327 retrieved publications met the selection criteria. The eight retrospective studies included 373 patients with GC and peritoneal metastasis included 265 with NIPS-combined surgery and 109 with NIPS only. Survival was significantly better with NIPS-combined surgery than with NIPS only (hazard ratio = 0.440, 95% confidence interval [CI]: 0.274-0.704; P = 0.0001; odds ratio = 1.960; 95% CI: 1.247-3.083; P = 0.004). Subgroup analysis revealed significantly better survival with S-1 Joint intravenous paclitaxel and intraperitoneal paclitaxel compared with other NIPS regimens. NIPS regimens had a higher conversion rate (effect size [ES] = 0.656; 95% CI: 0.495-0.817; P < 0.05), higher percentage of patients with R0 surgery (ES = 0.633; 95% CI: 0.568-0.699; P < 0.05), less severe adverse reactions to chemotherapy (ES = 0.030; 95% CI: 0.020-0.040; P < 0.05), and fewer postoperative complications (ES = 0.040; 95% CI: 0.020-0.050; P < 0.05). CONCLUSIONS: NIPS-combined surgical treatment was effective and safe for treating GC with peritoneal metastasis. Higher quality trials, better patient selection, and multicenter randomized controlled trials are needed to support standard treatment guidelines.

Does Helicobacter pylori Eradication Reduce the Incidence of Metachronous Gastric Cancer After Curative Endoscopic Resection of Early Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Whether Helicobacter pylori eradication could reduce the risk of metachronous gastric cancer remain controversial. In the present study, we performed a systematic review and meta-analysis to evaluate the preventive effect of H. pylori eradication on the occurrence of metachronous gastric cancer after curative endoscopic resection of early gastric cancer. METHODS: The related studies were identified by searching PubMed and Embase databases. According to the H. pylori infection status and subsequent treatment, all patients were classified into H. pylori negative group, H. pylori eradication group and noneradication group. The relevant data were extracted and pooled effect size was assessed using a fixed effect model or a random effect model. RESULTS: A total of 11 retrospective cohort studies and 3 randomized controlled trials were included in this meta-analysis. The results based on the cohort studies indicated that the risk of metachronous gastric cancer was significantly lower in H. pylori eradication group than in noneradication group (hazard ratios: 0.65, 95% confidence interval: 0.50-0.86, P=0.002; I=0%). The pooled result of 2 randomized controlled trials demonstrated that the patients receiving anti-H. pylori treatment had a lower risk of metachronous gastric cancer than those who did not receive H. pylori eradication treatment (hazard ratios: 0.43, 95% confidence interval: 0.26-0.70, P=0.001; I=0%). In addition, the occurrence of metachronous gastric cancer in H. pylori eradication group was not significantly different from that in H. pylori negative group. CONCLUSIONS: Successful H. pylori eradication may be useful for the prevention of metachronous gastric cancer after curative endoscopic resection of early gastric cancer. Thus, anti-H. pylori treatment should be considered for those patients with H. pylori infection after curative endoscopic resection.

Efficacy and safety of modified endoscopic mucosal resection for rectal neuroendocrine tumors: a meta-analysis.

PURPOSE: Rectal neuroendocrine tumors are rare with good prognosis. Several endoscopic methods such as endoscopic polypectomy, endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), and modified endoscopic mucosal resection (m-EMR) are used in the treatment of rectal neuroendocrine tumors. Although m-EMR is derived from traditional EMR, it has not been widely used in clinical practice. In this study, we compared the efficacy and safety of EMR and m-EMR in the treatment of rectal neuroendocrine tumors by performing a meta-analysis. MATERIALS AND METHODS: We searched PubMed, Web of Science, and EMBASE index up to the end of January 2017 for all published literature about EMR and m-EMR in the treatment of rectal neuroendocrine tumors. RESULTS: A total of 11 studies involving 811 patients were included. The pooled data suggested that there was a significantly higher rate of histologic complete resection and endoscopic complete resection among patients treated with m-EMR than those treated with EMR (histologic complete resection: OR = 0.23, 95 % CI = 0.10-0.51, p < 0.01; endoscopic complete resection: OR = 0.13, 95 % CI = 0.02-0.74, p = 0.02). The procedure time of EMR was longer than m-EMR (MD = 2.40, 95 % CI = 0.33-4.46, p = 0.02). There was a significantly higher rate of vertical margin involvement among patients treated with EMR than those treated with m-EMR; whereas, there was no significant difference of lateral margin involvement between the m-EMR and EMR groups (vertical margin involvement: OR = 5.00, 95 % CI = 2.67-9.33, p < 0.01; lateral margin involvement: OR = 1.44, 95 % CI = 0.48-4.37, p = 0.52). There was no significant difference in mean tumor size among patients treated with m-EMR versus those treated with EMR (MD = -0.30, 95 % CI = -0.75-0.14, p = 0.18); further, there was no significant difference in endoscopic mean sizes of the tumor and pathological mean sizes of the tumor between the m-EMR and EMR groups (endoscopic mean sizes of the tumor: MD = 0.20, 95 % CI = -0.44-0.84, p = 0.43; pathological mean sizes of the tumor: MD = 0.62, 95 % CI = -0.68-1.92, p = 0.05). No significant differences were detected among the treatment groups with regard to complications (bleeding: OR = 0.87, 95 % CI = 0.39-1.95, p = 0.73; complications (bleeding and perforation): OR = 0.87, 95 % CI = 0.40-1.88, p = 0.73). CONCLUSION: The efficacy of m-EMR are better than EMR among patients undergoing endoscopic treatment of rectal neuroendocrine tumors, and the safety of m-EMR is equivalent to EMR treatment.

Effects of metastasectomy and other factors on survival of patients with ovarian metastases from gastric cancer: a systematic review and meta-analysis.

Ovarian metastasis from gastric cancer (Krukenberg tumor [KT]) has no consensus treatment and the role of surgical treatment is still controversial. Identifying prognostic factors for KT could help guide the management of this tumor. We used a meta-analysis to evaluate the prognostic value of metastasectomy and other factors in patients with KT to develop a treatment plan. We searched literature in PubMed, Cochrane library and EMBASE. We analyzed hazard ratios (HR) and 95% confidence intervals (CI) with respect to overall survival (OS). The meta-analysis included 12 cohort studies with 1,031 patients associated with longer OS following metastasectomy (HR = 0.41; 95% CI = 0.32-0.53; P < 0.001), R0 resection (HR = 0.37; 95% CI = 0.26-0.53; P < 0.001), metachronous ovarian metastasis (HR = 0.74; 95% CI = 0.58-0.93; P = 0.012), size of KT (<5 cm) (HR = 0.74; 95% CI = 0.58-0.95; P = 0.019), ECOG PS (Eastern Cooperative Oncology Group performance status) 0 to 1 (HR = 0.48; 95% CI = 0.29-0.80; P = 0.004), tumor confined to ovary (HR = 0.40; 95% CI = 0.16-0.99; P = 0.047), and tumor confined to pelvic cavity (HR = 0.36; 95% CI = 0.14-0.92; P = 0.033). Shorter OS was associated with peritoneal carcinomatosis (HR = 2.00; 95% CI = 1.25-3.21; P = 0.004), ascites (HR = 1.66; 95% CI = 1.19-2.31; P = 0.003) and positive CEA (HR = 1.41; 95% CI = 1.10-1.82; P = 0.007). Gastrectomy led to a slight improvement in OS, but without statistical significance (HR = 0.69; 95% CI = 0.47-1.02; P = 0.061). No significant difference in OS was observed in patients with signet-ring cells (HR = 1.17; 95% CI = 0.91-1.51; P = 0.226), bilateral ovarian metastasis (HR = 0.87; 95% CI = 0.70-1.08; P = 0.212), age ≥ 50 years (HR = 0.93; 95% CI = 0.71-1.22; P = 0.619), positive CA19-9 (HR = 1.01; 95% CI = 0.75-1.35; P = 0.960), and positive CA-125 (HR = 0.98; 95% CI = 0.73-1.33; P = 0.915). Various factors affect OS in patients with KT.

Smoking status and subsequent gastric cancer risk in men compared with women: a meta-analysis of prospective observational studies.

BACKGROUND: Smoking is one of the well-established risk factors for gastric cancer incidence, yet whether men are more or equally susceptible to gastric cancer due to smoking compared with women is a matter of controversy. The aim of this study was to investigate and compare the effect of sex on gastric cancer risk associated with smoking. METHODS: We conducted a systemic literature search in MEDLINE, EMBASE, and the Cochrane CENTRAL databases to identify studies published from inception to December 2018. We included prospective observational studies which reported effect estimates with 95% confidence intervals (CIs) for associations of current or former smokers with the incidence of gastric cancer by sex. We calculated the ratio of relative risk (RRR) with corresponding 95% CI based on sex-specific effect estimates for current or former smokers versus non-smokers on the risk of gastric cancer. RESULTS: We included 10 prospective studies with 3,381,345 participants in our analysis. Overall, the summary RRR (male to female) for gastric cancer risk in current smokers was significantly increased compared with non-smokers (RRR: 1.30; 95% CI: 1.05-1.63; P = 0.019). Furthermore, there was no significant sex difference for the association between former smokers and gastric cancer risk (RRR: 1.20; 95% CI: 0.92-1.55; P = 0.178). However, the result of sensitivity analysis indicated the pooled result was not stable, which was altered by excluding a nested case-control study (RRR: 1.31; 95% CI: 1.10-1.57; P = 0.002). CONCLUSION: This systematic review showed a potential sex difference association between current smokers and the risk of gastric cancer. The sex differential in smokers can give important clues for the etiology of gastric cancers and should be examined in further studies.

The role of EGFR mutation as a prognostic factor in survival after diagnosis of brain metastasis in non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: The brain is a common site for metastasis in non-small-cell lung cancer (NSCLC). This study was designed to evaluate the relationship between the mutational of the epidermal growth factor receptor (EGFR) and overall survival (OS) in NSCLC patients with brain metastases. METHODS: Searches were performed in PubMed, EmBase, and the Cochrane Library to identify studies evaluating the association of EGFR mutation with OS in NSCLC patients through September 2017. RESULTS: 4373 NSCLC patients with brain metastases in 18 studies were involved. Mutated EGFR associated with significantly improved OS compared with wild type. Subgroup analyses suggested that this relationship persisted in studies conducted in Eastern, with retrospective design, with sample size ≥500, mean age of patients ≥65.0 years, percentage male < 50.0%, percentage of patients receiving tyrosine kinase inhibitor ≥30.0%. Finally, although significant publication bias was observed using the Egger test, the results were not changed after adjustment using the trim and fill method. CONCLUSIONS: This meta-analysis suggests that EGFR mutation is an important predictive factor linked to improved OS for NSCLC patients with brain metastases. It can serve as a useful index in the prognostic assessment of NSCLC patients with brain metastases.

Does adjuvant chemotherapy improve the prognosis of patients after resection of pulmonary metastasis from colorectal cancer? A systematic review and meta-analysis.

BACKGROUND: It remains controversial whether patients benefit from adjuvant chemotherapy (ACT) after resection of pulmonary metastasis (PM) from colorectal cancer (CRC). This meta-analysis was intended to evaluate the efficacy of ACT in patients after resection of PM from CRC. METHODS: We systematically retrieved articles from PMC, PubMed, Cochrane Library, and Embase (up to March 5, 2019). Survival data, including overall survival (OS) and disease-free survival (DFS), were tested by hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We included 18 cohort studies with a total of 3885 patients. The meta-analysis showed that ACT had no significant effect on OS (HR = 0.78; 95% CI = 0.60-1.03; P = 0.077) and DFS (HR = 0.91; 95% CI = 0.74-1.11; P = 0.339) in patients after resection of PM from CRC. There was no significant difference in OS (HR = 0.79; 95% CI = 0.42-1.50; P = 0.474) in patients after resection of PM from CRC treated with bevacizumab (BV). Subgroup analysis showed that ACT did not improve OS (HR = 0.86; 95% CI = 0.57-1.29; P = 0.461) in patients who had undergone previous resection of extra PM. ACT did not improve OS in patients who had positive hilar/mediastinal lymph node metastasis (HR = 0.80; 95% CI = 0.57-1.14; P = 0.22). CONCLUSION: In conclusion, ACT does not provide survival benefits for patients after resection of PM from CRC. ACT and targeted agents (BV) are not suggested for these patients.

Clinicopathologic factors associated with recurrence and long-term survival in node-negative advanced gastric cancer patients.

BACKGROUND: despite a better prognosis in node-negative advanced gastric cancer (GC), a proportion of patients have a tumor recurrence within five years and eventually die due to cancer-related causes. The present study aimed to evaluate the predictive factors of tumor recurrence and long-term survival in node-negative advanced GC. METHODS: a total of 646 node-negative advanced GC patients who underwent a curative gastrectomy in our institution were included in the study. The impact of different clinicopathologic factors on tumor recurrence and overall survival were analyzed. RESULTS: tumor recurrences were observed in 181 patients and the cumulative recurrence rate at two-years and five-years were 50.8% and 86.2%, respectively. Lymphovascular invasion, advanced T stage (T3-T4) and an inadequate number of retrieved lymph nodes (LNs) were independent predictive factors of tumor recurrence in node-negative advanced GC. Older age, an upper 1/3 tumor, lymphovascular invasion, infiltration growth pattern (INFγ) and the depth of tumor invasion (T4 stage) were independently associated with long-term survival. With regard to node-negative patients with ≥ 15 retrieved LNs, infiltration growth pattern (INFγ) and advanced T stage (T3-T4) were independent risk factors for both tumor recurrence and long-term survival. CONCLUSION: in addition to lymphovascular invasion, inadequate RLNs and advanced T stage, the prognostic significance of infiltration growth pattern in node-negative advanced GC was especially emphasized. These risk factors should be considered when selecting candidates for adjuvant chemotherapy and postoperative surveillance.

Metastatic patterns and surgical methods for lymph nodes No. 5 and No. 6 in proximal gastric cancer.

OBJECTIVE: The current surgical treatment guidelines for early proximal gastric cancer (PGC) still lack agreement. Lymphadenectomy of lymph nodes No. 5 and No. 6 is the major difference between total and proximal gastrectomy. We elucidated the appropriate surgical procedure for PGC by investigating the pathological characteristics and prognostic significance of lymph nodes No. 5 and No. 6. METHODS: In total, 333 PGC patients who underwent total gastrectomy were enrolled in this study. We investigated their clinicopathological characteristics and the metastatic patterns of the lymph nodes. Patients with metastasis in lymph nodes No. 5 and No. 6 were combined into one group and we compared the difference in survival between those with and without metastasis in lymph nodes No. 5, 6 (lymph nodes No. 5 and No. 6 in any group of metastasis) for different subgroups. RESULTS: The metastatic rates for lymph nodes No. 5 and No. 6 in PGC were 9.91% and 16.11%, respectively. The metastatic rate for both lymph nodes No. 5, 6 was 20.42%. Multivariate analysis showed that positive metastasis in lymph node No. 4, depth of invasion, and tumor size were independently correlated with the presence of metastasis in lymph nodes No. 5, 6. CONCLUSIONS: When lymph node No. 4 is positive (intraoperative pathology) or tumor size ≥5 cm or T4 stage, lymphadenectomy should be performed for lymph nodes No. 5 and No. 6, and total gastrectomy is recommended.

Conditional survival of patients with gastric cancer who undergo curative resection: A multi-institutional analysis in China.

BACKGROUND: Conditional survival estimates, which take into consideration the changing risk with increasing survival time, provide a dynamic survival probability and more accurate survival information for clinician decision making. The objective of the current study was to evaluate the conditional disease-specific survival (DSS) for patients with gastric cancer who underwent curative surgery in China. METHODS: In total, 7658 patients with gastric cancer from a multi-institutional cohort in China were included in the analyses. Actuarial DSS was estimated using the Kaplan-Meier method. Three-year conditional DSS (CDS3 ) of patients who had already survived for x years was estimated as CDS3 = DSS(x + 3)/DSS(x). Cox proportional hazards regression analyses were used to identify the factors related to DSS. RESULTS: The 1-year, 3-year, and 5-year actuarial DSS rates were 88.2%, 64.5%, and 54.6%, respectively. By using CDS estimates, the probabilities that patients would remain alive for an additional 3 years given that they had already survived for 1, 3, and 5 years were 66.6%, 80.2%, and 88.3%, respectively. Patients who had unfavorable tumor characteristics diagnosed initially at surgery had the greatest improvement in CDS and the largest survival gap between actuarial DSS and CDS. CONCLUSIONS: The current results indicate that CDS estimates for Chinese patients with gastric cancer who underwent surgery were dynamic and increased with time elapsed. Patients who had unfavorable tumor characteristics had the greatest improvement in CDS. This valuable information could provide more a precise evaluation of long-term prognosis and may serve as an important prognostic index in clinical practice. Cancer 2018;124:916-24. © 2017 American Cancer Society.

Effect of neoadjuvant chemotherapy in patients with gastric cancer: a PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is extensively used in the treatment of patients with gastric cancer (GC), particularly in high risk, advanced gastric cancer. Previous trials testing the efficacy of NAC have reported inconsistent results. METHODS: This study compares the combined use of NAC and surgery with surgery alone for GC by using a meta-analytic approach. We performed an electronic search of PubMed, EmBase, and the Cochrane Library to identify randomized controlled trials (RCTs) on NAC published before Oct 2015. The primary outcome of the studies was data on survival rates for patients with GC. The summary results were pooled using the random-effects model. We included 12 prospective RCTs reporting data on 1538 GC patients. RESULTS: Patients who received NAC were associated with significant improvement of OS (P = 0.001) and PFS (P < 0.001). Furthermore, NAC therapy significantly increased the incidence of 1-year survival rate (SR) (P = 0.020), 3-year SR (P = 0.011), and 4-year SR (P = 0.001). Similarly, NAC therapy was associated with a lower incidence of 1-year (P < 0.001), 2-year (P < 0.001), 3-year (P < 0.001), 4-year (P = 0.001), and 5-year recurrence rate (P = 0.002). Conversely, patients who received NAC also experienced a significantly increased risk of lymphocytopenia (P = 0.003), and hemoglobinopathy (P = 0.021). CONCLUSIONS: The findings of this study suggested that NAC is associated with significant improvement in the outcomes of survival and disease progression for GC patients while also increasing some toxicity.