Subtotal gastrectomy combined with chemotherapy: An effective therapy for patients with circumscribed Borrmann type IV gastric cancer.

BACKGROUND: Although Borrmann type IV (B-4) gastric cancer has a higher mortality rate and presents distant metastasis easily, especially peritoneal metastasis, when diagnosed, some B-4 patients were found to have no distant metastasis by preoperative detection and underwent curative surgery, which was defined as circumscribed B-4 in our study. In this study, we focused on the circumscribed B-4 patients without distant metastasis during surgery to identify factors related to prognosis and postoperative peritoneal cavity metastasis (PPCM), which is important for selecting an appropriate therapeutic strategy. AIM: To identify factors related to the prognosis and PPCM of B-4 patients. METHODS: A total of 117 B-4 patients who underwent gastrectomy between January 2005 and December 2012 were included in this study. Survival analysis was performed using Kaplan-Meier analysis and Cox multivariate models. Pearson correlation analyses were performed to identify the factors related to PPCM. All statistical analyses were performed using SPSS 20.0. RESULTS: Lymph node status, gastrectomy type, and postoperative chemotherapy were independent prognostic factors in 117 circumscribed B-4 patients. Subtotal gastrectomy combined with chemotherapy could significantly improve the long-term survival time. Six patients who were diagnosed with pN0 and received the combination therapy had a 3-year survival rate of 100% and a median survival of 77.7 mo. Even for patients with metastatic lymph nodes (n = 13), the combination therapy also increased the 3-year overall survival rate to 57.1%. In addition, positive lymph node status was the only factor (P = 0.005) correlated with PPCM in certain B-4 patients, and chemotherapy was useful for suppressing PPCM in patients with subtotal gastrectomy but not in those with total gastrectomy. CONCLUSION: Lymph node status is an independent prognostic factor for circumscribed B-4 patients. In addition, subtotal gastrectomy and postoperative chemotherapy could effectively improve prognosis and even suppress PPCM.

Prognostic significance of KIF23 expression in gastric cancer.

BACKGROUND: Kinesin super family 23 (KIF23) is a member of the KIF family, and it plays an important role in mitosis and cytokinesis. Loss of expression can cause mitotic arrest. The Oncomine database is one of the largest oncogene chip databases in the world, and is an integrated data mining platform for cancer gene information. By querying the database, differences in expression between tumor tissue and normal tissue can be determined. AIM: To study the expression and prognostic significance of KIF23 in gastric cancer (GC). METHODS: We used immunohistochemistry to compare the expression of KIF23 in GC and normal gastric tissues. We mined the data on the expression and prognosis of KIF23 in GC using Oncomine and Kaplan-Meier plotter database. RESULTS: Compared with normal gastric tissues, KIF23 expression was increased in GC tissues, and correlated with T, N, and tumor-node-metastasis stages. Survival analysis showed that patients with high expression of KIF23 had a poor overall survival. There were five studies in the Oncomine database in which expression of KIF23 was significantly higher in GC tissues than in normal gastric tissues (P < 0.05). Kaplan-Meier plotter database analysis showed that recurrence-free survival, overall survival, distant metastasis free survival, and post progression survival of patients with high expression of KIF23 were lower than those of patients with low expression. Further stratified analysis found that prognostic survival indicators worsened in patients with T2 and T3 poorly differentiated adenocarcinoma with high expression of KIF23. CONCLUSION: KIF23 is highly expressed in GC and is associated with a poor prognosis of patients. It may be of great significance in the diagnosis, treatment, and prognostic evaluation of GC.

Reduced microRNA-451 expression in eutopic endometrium contributes to the pathogenesis of endometriosis.

BACKGROUND: Endometriosis (EMs) is a chronic and recurrent, but benign, disease in women of reproductive age, and EMs patients have a high risk of developing gynecological tumors and autoimmune disorders. The etiology of EMs is not clear. Certain genetic markers in the eutopic endometrium are key in the pathogenesis of EMs. MicroRNAs (miRNAs) are implicated in several biological processes, such as cell proliferation, differentiation, and apoptosis. MiR-451 is interesting, as it acts as a tumor suppressor and is relevant to the poor prognosis of cancers. AIM: To evaluate the expression levels and role of miR-451 in the eutopic endometrium and predict possible targets of miR-451 and related signaling pathways. METHODS: Quantitative real-time polymerase chain reaction was used to evaluate miR-451 expression in cultured cell lines as well as in pathologic tissues from 40 patients with EMs and 20 donors with no history of the disease (controls). Cell Counting Kit-8 and flow cytometric assays were performed to determine cell proliferation and survival rates after transfection with miR-451 mimics and siRNAs. MiR-451 targets were predicted using miRDB and miRcode target-predicting databases. RESULTS: We observed lower miR-451 levels in eutopic endometrial tissues from patients with EMs than in control tissues, and this difference was not related to the American Society for Reproductive Medicine stage. Ectopic overexpression of miR-451 in eutopic cells induced apoptosis and inhibited cell proliferation. SiRNA-mediated miR-451 knockdown reversed these effects. Using miRDB and miRcode, we identified 12 potential miR-451 target genes. We hypothesize that the expression of YWHAZ, OSR1, TTN, and CDKN2D may be regulated by miR-451 and be involved in disease pathogenesis. CONCLUSION: Reduced miR-451 expression in the eutopic endometrium contributes to the pathogenesis of EMs by promoting cell proliferation and reducing apoptosis. Thus, miR-451 is a novel biomarker for EMs. YWHAZ, OSR1, TTN, and CDKN2D are potential target genes of miR-451 and may have key roles in this disease.

Prognostic significance of 14v-lymph node dissection to D2 dissection for lower-third gastric cancer.

BACKGROUND: Radical gastrectomy with D2 lymph node (LN) dissection is the standard surgical procedure for patients with resectable gastric cancer (GC). In the fifteenth edition of the Japanese Classification of Gastric Carcinoma, the 14v LN (LNs along the root of the superior mesenteric vein) was defined as the regional gastric LN. The efficacy of 14v LN dissection during radical distal gastrectomy for lower-third GC remains controversial. AIM: To analyze whether the addition of 14v LN dissection improved the survival of patients with lower-third GC. METHODS: The data from 65 patients who underwent 14v LN dissection and 65 patients treated without 14v LN dissection were selected using the propensity score-matched method from our institute database constructed between 2000 and 2012. Overall survival was compared between the groups. RESULTS: Overall survival was similar between patients with 14v LN metastasis and those with distant metastasis (P = 0.521). Among patients with pathological stage IIIA disease, those who were treated with 14v LN dissection had a significantly higher overall survival than those treated without it (P = 0.020). Multivariate analysis showed that age < 65 years and pT2-3 stage were independent favorable prognostic factors for prolonged overall survival in patients with pathological stage IIIA disease. Patients with No. 1, No. 6, No. 8a, or No. 11p LN metastasis were at higher risk of having 14v LN metastasis. CONCLUSION: Adding 14v LN dissection to D2 dissection during radical distal gastrectomy may improve the overall survival of patients with pathological stage IIIA lower-third GC.

Downregulation and DNA methylation of ECRG4 in gastric cancer.

BACKGROUND: Esophageal cancer-related gene 4 (ECRG4) is a novel candidate tumor suppressor gene. Our study investigated the expression and function of ECRG4 in gastric cancer and highlighted the role of DNA hypermethylation at the promoter in silencing the ECRG4 expression. METHODS: The GSE63089 data set was obtained from the Gene Expression Omnibus and analyzed for differentially expressed genes. Carcinoma and para-carcinoma tissues of 102 patients with gastric cancer were collected from January 2010 to July 2011. Immunohistochemistry, real-time polymerase chain reaction (PCR), and western blot analyses were performed to evaluate the expression of ECRG4. After measuring the change in the level of ECRG4 expression, CCK-8, Transwell, and flow cytometric cell cycle assays were performed. In addition, methylation-specific PCR was performed to detect the methylation state of ECRG4, and 5-aza-2'-deoxycytidine was used for demethylation of ECRG4. All statistical analyses were performed using the SPSS 17.0 software. RESULTS: We found that ECRG4 expression was downregulated in gastric cancer, and this was closely related to lymph node metastasis. After ECRG4 was silenced using a specific small interfering RNA, the BGC-823 cell line became highly aggressive and proliferative. In addition, we verified whether downregulation of ECRG4 was highly correlated with DNA methylation of the ECRG4 promoter and found that the demethylating agent 5-aza-2'-deoxycytidine could effectively enhance ECRG4 expression. CONCLUSION: The aberrant expression of ECRG4 is associated with hypermethylation in the promoter region and plays an important role in the malignancy of gastric cancer. Therefore, ECRG4 may be a potential biomarker for molecular diagnosis of gastric cancer, and the use of 5-Aza-dC to reverse the hypermethylation of ECRG4 may be a new approach to the treatment of gastric cancer.

Association of IL-8 gene promoter -251 A/T and IL-18 gene promoter -137 G/C polymorphisms with head and neck cancer risk: a comprehensive meta-analysis.

PURPOSE: No consensus exists on the impact of polymorphisms in cytokines (such as interleukin IL-8 and IL-18) on cancer risk; moreover, there is very little evidence regarding head and neck cancer (HNC). METHODS: Thus, a meta-analysis including 22 studies with 4731 cases and 8736 controls was conducted to evaluate this association. The summary odds ratio (OR) and corresponding 95% confidence intervals (CIs) for C-X-C motif chemokine ligand 8 (CXCL8, which encodes IL-8) and IL-18 polymorphisms and HNC risk were estimated. RESULTS: The results showed a significantly increased risk of HNC susceptibility for IL18 -137 G/C in five genetic models, but, interestingly, no significant association was found for the CXCL8 -251 A/T polymorphism. When stratified by cancer type, an increased risk of nasopharyngeal cancer was found for both -137 G/C and -251A/T. When the studies were stratified by ethnicity and genotyping method, there were significant associations between Asian populations and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) studies for -137 G/C, and African populations for -251 A/T in some genetic models. A positive association was also found between the population-based groups in some models for -137 G/C; conversely, significantly decreased risk was found among the -251 A/T hospital-based group. Meta-regression was also conducted. The publication year, control source, and cancer type contributed to CXCL8 -251 A/T heterogeneity; however, no factors were found that contributed to IL-18 -137 G/C heterogeneity. Marginal significance was found in the recessive model for IL-18 -137 G/C by Egger's test, whereas no publication bias was detected for CXCL8 -251 A/T. CONCLUSIONS: The results indicate that the IL-18 -137 G/C polymorphism is associated with HNC risk, especially nasopharyngeal cancer, in Asian populations and, when using PCR-RFLP, CXCL8 -251 A/T polymorphisms play a complex role in HNC development.

TNM-PNI: a novel prognostic scoring system for patients with gastric cancer and curative D2 resection.

PURPOSE: Gastric cancer (GC) is one of the most common malignancies and has a high mortality rate. In recent years, several nutritional or inflammatory biomarkers have been shown to effectively predict the prognosis of tumors. In this study, we intended to establish a prognostic scoring system for GC patients. PATIENTS AND METHODS: Our study included a total of 501 GC patients who were diagnosed with GC stage I-III and received curative gastrectomy with D2 lymphadenectomy between January 2011 and December 2012. Survival analysis was performed using Kaplan-Meier and log-rank tests. Two Cox multivariate models, one for continuous and one for categorical variables, were established to identify independent prognostic factors. All statistical analyses were performed using SPSS 20.0. RESULTS: Univariate and multivariate analyses revealed that tumor-node-metastasis (TNM) stage, preoperative prognostic nutritional index (PNI), and adjuvant therapy were independent prognostic factors for GC patients. We established a new composite variable, TNM-PNI, which was confirmed to be a major prognostic factor for curative D2 resection, independent of whether adjuvant therapy was administered. GC patients with higher TNM-PNI scores always had worse cancer outcomes. In addition, we found that adjuvant therapy might be beneficial for the survival of GC patients with TNM-PNI =4 or 5. CONCLUSION: Preoperative PNI plays a distinctly subsidiary role to the TNM stage when predicting patient prognosis. TNM-PNI is a novel and an effective prognostic index for GC patients with curative D2 resection and a good supplement for the National Comprehensive Cancer Network Guidelines.

Minimally invasive percutaneous nephrolithotomy improves stone-free rates for impacted proximal ureteral stones: A systematic review and meta-analysis.

BACKGROUND: Urinary stones are common medical disorders and the treatment of impacted proximal ureteral stones (IPUS) is still a challenge for urologists. The aim of this study was to compare the efficacy and safety of minimally invasive percutaneous nephrolithotomy (MI-PCNL) and ureteroscopic lithotripsy (URL) in the treatment of IPUS via a meta-analysis. METHODS: We collected studies using PubMed, Embase, and Cochrane Library from 1978 to November 2016 and analyzed them using Stata 12.0 and RevMan 5.3. Odds ratios (ORs) and standard mean difference (SMD) were calculated for binary and continuous variables respectively, accompanied with 95% confidence intervals (CIs). All study procedures followed the PRISMA guidelines. RESULTS: Five prospective studies were included in our meta-analysis, with 242 MI-PCNL and 256 URL cases. MI-PCNL was associated with a longer postoperative hospital stay than URL (SMD, 3.14; 95% CI, 1.27 to 5.55). However, no significant difference was observed in operative time (SMD, -0.38; 95% CI, -3.15 to 2.38). In addition, MI-PCNL had higher initial (OR, 11.12; 95% CI, 5.56 to 22.24) and overall stone-free rates (OR, 8.70; 95% CI, 3.23 to 23.45) than URL, along with lower possibilities of surgical conversion (OR, 0.11; 95% CI, 0.03 to 0.49) and postoperative shock wave lithotripsy (OR, 0.06; 95% CI, 0.02 to 0.18). Regarding complications, no significant differences were observed between MI-PCNL and URL (OR, 1.39; 95% CI, 0.93 to 2.10), except for hematuria (OR, 4.80; 95% CI, 1.45 to 15.94). CONCLUSIONS: MI-PCNL is optimal and should be considered as the preferred treatment method for IPUS, as it has better efficacy and a safety profile similar to that of URL. However, further high quality studies with larger sample size are required in future.

Rare upper gastrointestinal hemorrhage of cetuximab: A case report.

RATIONALE: cetuximab, an epidermal growth factor receptor inhibitor, is a targeted therapeutic regimen of colorectal cancers. Several common adverse effects have been found, such as cutaneous or gastrointestinal toxicity. However, according to the articles had been published, upper gastrointestinal bleeding (UGIB) is considered to be rare and its mechanism remains unclear. PATIENT CONCERNS: In this report, we presented a 42-year-old male patient with advanced recto-sigmoid cancer. After palliative operation, the patient suffered from complete upper gastrointestinal (GI) obstruction, which was induced by extensive abdominal metastasis of the tumor. Considering his poor condition, we chose the targeted drug, cetuximab, as his further treatment. But after the application of cetuximab, the UGIB immediately happened twice in this patient. DIAGNOSIS: UGIB, as a rare complication of cetuximab, occured to the patient. INTERVENTIONS: We stopped the bleeding with thrombin, hemocoagulase and somatostatin and suspended the subsequent treatment plan of cetuximab. At the same time, anti-shock treatment was given immediately. OUTCOMES: He was died of respiratory and circulatory failure caused by UGIB and advanced tumor eventually. LESSONS: UGIB should be considered as a rare but severe complication of cetuximab. When cetuximab is applied for patients with advanced colon tumors, more cautions should be required if the patients are accompanied by upper gastrointestinal obstruction. In addition, for those patients who suffered from UGIB recently, cetuximab should be prohibited if the Rockall score ranged > 5 points.