HLA antigens are candidate markers for prediction of lymph node metastasis in gastric cancer

We investigated the association between human leucocyte antigen (HLA) antigens and lymph node metastasis in 724 gastric cancer patients. Among patients who had poorly differentiated adenocarcinoma with or without HLA-DR4 antigen, lymph node metastasis was detected in 80.8 and 54.9%, respectively (relative risk (RR)=3.5, P = 0.0005, corrected P = 0.0285). It was more common in patients with a family history of cancer death (RR = 7.7). Among signet ring cell carcinoma patients with or without HLA-1152 antigen, lymph node metastasis was detected in 57.7 and 19.7%, respectively (RR =5.6, P=0.0001, corrected P=0.0086). It was more common in patients who were smokers (RR = 8.3). Our findings suggest that HLA-DR4 and HLA-1152 antigens are associated with lymph node metastasis in gastric cancer.     

Detection of the Epstein-Barr virus in primary gastric lymphoma by in situ hybridization

The Epstein-Barr virus (EBV) has been shown to be associated with numerous human malignancies including Burktt's lymphoma and nasopharyngeal lymphoepithelioma. In addition, some typical gastric adenocarcinomas were also recently reported to demonstrate EBV relevance. The present study was designed to detect EBV in primary gastric lymphoma, using the in situ hybridization (ISH) method, in which oligo-nucleotide probes for the EBERl RNA and the EBV DNA W region have been used. Of the 49 cases of primary gastric lymphoma studied, which all showed B cell immunopheno-type, EBER1 sequences could only be found in four cases, including two low-grade cases and two high-grade cases of histological subtypes while the number of positive cells was less than 50% of the tumor cells. In one case of low-grade mucosa associated lymphoid tissue (MALT) lymphoma, the EBER1 -positive neoplastic cells were found in the regional lymph node, but the primary site of the stomach showed no positive signals. The EBV presence was further confirmed by the EBV DNA ISH. Using the ISH method, rare or occasional positive lymphoid cells (probably non-tumorous bystander cells) could be detected in 10 other cases including all histological subtypes. The present study shows that only a small proportion of primary gastric lymphoma is associated with EBV, and such positive cases could be found in both high- and low-grade histological subtypes. It is also suggested that the EBV presence in the neoplastic cells of some cases of primary gastric lymphoma is most likely a secondary phenomenon.     

葛花、枳椇子及其配伍对小鼠急性酒精性胃黏膜损伤的保护作用及机制

目的 探讨葛花、枳椇子及其配伍对急性酒精性胃黏膜损伤的改善作用,为进一步开展葛花、枳椇子及其配伍防治酒精致多脏器损伤奠定基础。方法 采用多次灌胃给予56%红星二锅头白酒（15 mL·kg^-1）建立小鼠急性酒精性胃黏膜损伤模型,将120只ICR雄性小鼠随机分为空白组、模型组、奥美拉唑组（0.026 g·kg^-1）、葛花-枳椇子（配伍）高、中、低剂量组（29.2、14.6、7.3 g·kg^-1）、葛花组（19.5 g·kg^-1）、枳椇子组（19.5 g·kg^-1）共8个组,每组15只,动物适应性喂养1周后,按10 mL·kg^-1预给相应药物3 d,从第4天开始,给药1 h后按15 mL·kg^-1灌胃二锅头白酒,空白组给予相同体积去离子水,记录小鼠醉酒和醒酒时间,连续给药给酒3 d,末次给药1 h后摘眼球处死;气相色谱仪测定各组小鼠血清中乙醇体积分数,紫外-可见分光光度计检测各组小鼠胃黏膜中乙醇脱氢酶（ADH）活性;苏木素-伊红（HE）染色观察胃黏膜病理变化;酶联免疫吸附测定法（ELISA）检测各组小鼠血清中炎症因子含量;实时荧光定量聚合酶链式反应（Real-time PCR）检测核转录因子-κB（NF-κB）p65和NF-κB抑制蛋白α（IκBα）mRNA表达。结果 与正常组比较,模型组血清中白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）含量升高（P<0.05）,胃黏膜组织NF-κB p65 mRNA表达升高（P<0.01）,IκBα mRNA表达降低（P<0.01）;与模型组比较,奥美拉唑组、配伍高、中剂量组、葛花组醉酒时间延长（P<0.05）,配伍高、中剂量组醒酒时间缩短（P<0.05）,配伍高剂量组血清中乙醇体积分数降低（P<0.05）,奥美拉唑组、配伍高、中剂量组胃黏膜中ADH活性升高（P<0.05）,配伍各剂量组、葛花组肉眼损伤评分降低（P<0.05）,奥美拉唑组、配伍各剂量组、葛花组病理损伤评分降低（P<0.01）,各给药组血清中IL-6表达降低（P<0.05）,奥美拉唑组、配伍各剂量组、枳椇子组血清中IL-1β表达降低（P<0.05）,配伍高、中剂量组血清中TNF-α表达降低（P<0.05）,各给药组胃黏膜组织NF-κB p65 mRNA表达降低（P<0.05）,奥美拉唑组、配伍各剂量组胃黏膜组织IκBα mRNA表达增加（P<0.05）;与高剂量组比较,配伍低剂量组与枳椇子组醉酒时间缩短（P<0.01）,葛花、枳椇子组醒酒时间延长（P<0.01）,配伍中、低剂量组、葛花组、枳椇子组血清中乙醇体积分数升高（P<0.05）,配伍中、低剂量组、枳椇子组肉眼损伤积分增加（P<0.05）,配伍中、低剂量组、葛花组、枳椇子组病理损伤积分增加（P<0.01）,配伍低剂量组、葛花组、枳椇子组血清中IL-1β含量升高（P<0.01）,葛花组与枳椇子组胃黏膜组织IκBα mRNA表达量降低（P<0.05）;与配伍中剂量组比较,枳椇子组醉酒时间缩短（P<0.05）,葛花组醒酒时间延长（P<0.05）,葛花组、枳椇子组病理损伤积分增加（P<0.01）,配伍低剂量组、葛花组、枳椇子组血清中IL-1β含量升高（P<0.05）;与配伍低剂量组比较,枳椇子组病理损伤积分增加（P<0.05）。结论 葛花、枳椇子及其配伍能起到对小鼠急性酒精性胃黏膜损伤的防治作用,可能与抑制胃黏膜NF-κB信号通路的表达有关,且配伍高剂量组药效最佳。     

Gastric Sensory and Motor Functions and Energy Intake in Health and Obesity—Therapeutic Implications

Sensory and motor functions of the stomach, including gastric emptying and accommodation, have significant effects on energy consumption and appetite. Obesity is characterized by energy imbalance; altered gastric functions, such as rapid gastric emptying and large fasting gastric volume in obesity, may result in increased food intake prior to reaching usual fullness and increased appetite. Thus, many different interventions for obesity, including different diets, anti-obesity medications, bariatric endoscopy, and surgery, alter gastric functions and gastrointestinal motility. In this review, we focus on the role of the gastric and intestinal functions in food intake, pathophysiology of obesity, and obesity management.     

The Effect of Continuous Intake of Lactobacillus gasseri OLL2716 on Mild to Moderate Delayed Gastric Emptying: A Randomized Controlled Study

Probiotics have been suggested to be effective for functional dyspepsia, but their effect on gastric motility is not clear. We evaluated the effect of Lactobacillus gasseri OLL2716 (LG21 strain) on mild to moderate delayed gastric emptying by a double-blind, parallel-group, placebo-controlled, randomized trial. Participants (n = 28) were randomly assigned to ingest LG21 strain-containing yogurt (LG21 strain group) or LG21 strain-free yogurt (placebo group) for 12 weeks. The ¹³C gastric emptying breath test was performed to measure the gastric emptying rate over time following ingestion of a liquid meal, and the time to reach the peak (Tmax) was used as an indicator of gastric emptying. We also measured the salivary amylase concentration, an indicator of autonomic dysfunction under stress. The per-protocol population (n = 27, male n = 4, female n = 23) was evaluated for efficacy. When a ≥30% reduction in the difference between participant’s Tmax and the Japanese mean Tmax was defined as an improvement, the odds ratio of improvement in delayed gastric emptying compared to placebo after 12 weeks was 4.1 (95% confidence interval, 0.8 to 20.2). Moreover, salivary amylase concentrations were significantly lower than in the placebo group, indicating an improvement in autonomic function. The present data were not enough to support the beneficial effects of the LG21 strain on delayed gastric emptying. However, if we define the odds ratio in further study investigated with a larger number of participants, LG21 strain might be expected to have some impact on delayed gastric emptying.     

Postbariatric hypoglycemia: symptom patterns and associated risk factors in the Longitudinal Assessment of Bariatric Surgery study

BackgroundPostbariatric hypoglycemia (PBH) can be a devastating complication for which current therapies are often incompletely effective. More information is needed regarding frequency, incidence, and risk factors for PBH.ObjectivesTo examine hypoglycemia symptoms following Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) and baseline and in-study risk factors.SettingMulticenter, at 10 US hospitals in 6 geographically diverse clinical centers.MethodsA prospective, longitudinal cohort study of adults undergoing RYGB or LAGB as part of clinical care between 2006 and 2009 were recruited and followed until January 31, 2015, with baseline and annual postoperative research assessments. We analyzed baseline prevalence and post-operative incidence and frequency of self-reported hypoglycemia symptoms as well as potential preoperative risk factors.ResultsIn all groups, postoperative prevalence of hypoglycemia symptoms was 38.5%. Symptom prevalence increased postoperatively from 2.8%–36.4% after RYGB in patients without preoperative diabetes (T2D), with similar patterns in prediabetes (4.9%–29.1%). Individuals with T2D had higher baseline hypoglycemia symptoms (28.9%), increasing after RYGB (57.9%). Hypoglycemia symptoms were lower after LAGB, with 39.1% reported hypoglycemia symptoms at only 1 postoperative visit with few (4.0%) having persistent symptoms at 6 or more annual visits. Timing of symptoms was not restricted to the postprandial state. Symptoms of severe hypoglycemia were reported in 2.6–3.6% after RYGB. The dominant risk factor for postoperative symptoms was preoperative symptoms; additionally, baseline selective serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitor use was also associated with increased risk in multivariable analysis. Weight loss and regain were not related to hypoglycemia symptom reporting.ConclusionHypoglycemia symptoms increase over time after RYGB, particularly in patients without diabetes. In a small percentage, symptoms can be persistent or severe and require hospitalization. Preoperative hypoglycemia symptoms and SSRI/SNRI use in RYGB patients without diabetes is associated with increased risk of symptoms.     

Akt/PKB activation in gastric carcinomas correlates with clinicopathologic variables and prognosis

Akt/protein kinase B (PKB) plays an important role in cell survival. However, the role of Akt in the biology of gastric cancer has not been well studied. We sought to investigate the expression of Akt or phosphorylated Akt (pAkt) in human gastric carcinomas and to analyze the relationship between Akt or pAkt and the clinicopathologic parameters. The expressions of Akt and pAkt were evaluated immunohistochemically in 311 gastric carcinomas using the tissue array method. Akt expression was detected in 74% of the tumors and pAkt expression in 78%. pAkt was highly expressed in the early stage of pTNM (p=0.011). We also found an inverse association between pAkt and lymphatic invasion (p=0.01) or lymph node metastasis (p=0.008). pAkt expression was significantly correlated with a higher survival in patients with stage I carcinomas (p=0.0003). Interestingly, combined evaluation revealed that the group with pAkt-positive and lymph node-negative carcinomas showed a better prognosis than the other groups (p<0.0001). In addition, pAkt was shown to correlate positively with APC (p=0.002) and Smad4 (p<0.0001) expression. These findings suggest that pAkt expression may help to predict the clinical outcome of gastric cancer patients.     

Is there an abnormal fasting duodenogastric reflux in nonulcer dyspepsia?

A quantitatively and/or qualitatively abnormal duodenogastric reflux (DGR) could be involved in the pathogenesis of nonulcer dyspepsia (NUD). The aims of this prospective study were to look for (1) a pathological DGR profile during fasting and (2) an eventual correlation between DGR profile and clinical symptoms. Twenty-six NUD patients were investigated. Seven other operated patients with a surgical procedure facilitating DGR episodes and 27 healthy volunteers served as control groups. A clinical score was determined for each patient from a standardized questionnaire. Gastric aspiration was performed for 6 hr in fasting subjects. The aspirates were pooled into 17 samples. In each sample the concentration and the output of total bile acids was determined. If the concentration was larger than 30 mol/liter in pooled samples, the concentrations of free bile acids and the distribution of the conjugated bile acids was determined. The percentage of aliquots with a total bile acid concentration larger than 50 mol/liter (without upper limit), and the percentage with a concentration larger than 2500 mol/liter was also obtained. No significant difference was demonstrated between the healthy volunteers and NUD patients, whatever the parameter considered. However, there was a significant increase in each of the quantitative parameters for the group of operated patients in comparison with the NUD patient group. No significant correlation was found between the clinical score and the DGR profile in NUD patients. Apparently, DGR episodes do not play a primary role in the pathogenesis of NUD.Part of this work was presented at the 4th European Symposium on Gastrointestinal Motility, Krakow, Poland. September 22–24, 1988.Hepatogastroenterology, 35:178, 1988 (abstract).     

Natural killer activity and serum immunosuppressive acidic protein levels in esophageal and gastric cancers

The natural killer (NK) activity of peripheral blood mononuclear cells and serum immunosuppressive acidic protein (IAP) levels were examined in patients with esophageal or gastric cancer, before and after surgery. Patients with stage IV esophageal or stage IV gastric cancer had significantly lower NK activity (39.5±14.8% and 37±11.6%, respectively), and also higher serum IAP levels (778±264 g/mL and 633±156 g/mL, respectively), than the corresponding control values (50±5.6% and 375±26 g/mL, respectively). Patients with esophageal or gastric cancer who underwent curative resection had high NK activity (54.8±11.6% and 54.8±8.0%, respectively), and low IAP levels (471±116 g/mL and 490±42 g/mL, respectively), compared with those who underwent non-curative resection. Patients who underwent non-curative resection had lower NK activity and higher serum IAP levels than those who underwent curative resection, even 1 month after surgery. Mononuclear cells in the regional lymph nodes and tumor specimens showed significantly lower NK activity than those in the peripheral blood and spleen. Thus, NK activity and the IAP level reflected the immunocompetence, clinical course, and surgical curability of those patients. NK cells appeared not to have any significant antitumor activity in the regional lymph nodes or in the tumor itself, although they were still active in the peripheral blood.