Gastrokine-1, an anti-amyloidogenic protein secreted by the stomach, regulates diet-induced obesity

Obesity and its sequelae have a major impact on human health. The stomach contributes to obesity in ways that extend beyond its role in digestion, including through effects on the microbiome. Gastrokine-1 (GKN1) is an anti-amyloidogenic protein abundantly and specifically secreted into the stomach lumen. We examined whether GKN1 plays a role in the development of obesity and regulation of the gut microbiome. Gkn1−/− mice were resistant to diet-induced obesity and hepatic steatosis (high fat diet (HFD) fat mass (g) = 10.4 ± 3.0 (WT) versus 2.9 ± 2.3 (Gkn1−/−) p < 0.005; HFD liver mass (g) = 1.3 ± 0.11 (WT) versus 1.1 ± 0.07 (Gkn1−/−) p < 0.05). Gkn1−/− mice also exhibited increased expression of the lipid-regulating hormone ANGPTL4 in the small bowel. The microbiome of Gkn1−/− mice exhibited reduced populations of microbes implicated in obesity, namely Firmicutes of the class Erysipelotrichia. Altered metabolism consistent with use of fat as an energy source was evident in Gkn1−/− mice during the sleep period. GKN1 may contribute to the effects of the stomach on the microbiome and obesity. Inhibition of GKN1 may be a means to prevent obesity

Socioeconomic disparities and outcomes in midgut neuroendocrine tumors

Abstract only 613 Background: Demographic and socioeconomic disparities have been shown to effect cancer specific outcomes in numerous malignancies but the effect in midgut neuroendocrine tumors (mNETs) is unknown. We sought to investigate whether these factors are associated with survival in mNETs. Methods: The NCDB was queried to identify patients with mNETs between 2004 and 2015. Only patients treated at a single hospital with complete data were included. Overall Survival (OS) was compared based on demographic data, socioeconomic factors, insurance status and place of living. Results: A total of 14,083 patients were identified with a mean age of 72 years (range 18-90). The majority of patients were Caucasian (83.9%) and male (50.9%). Most patients had private insurance (50.5%) or medicare (41.3%). Patients typically lived in larger metropolitan areas (51.5%) and 60.7% lived in zip codes with median household incomes > $48,000. Only 14.7$63,000],p 20% no HSD] vs 80.7% [ 20% no HSD) (HR 1.14, 95% CI 1.02-1.26), no insurance (HR 1.66, 95% CI 1.33-2.06) and not living in proximity to a metro area (HR 1.27, 95% CI 1.10-1.47). Conclusions: Socioeconomic factors shown to have worse OS in patients with mNETs were lower median income, lower education, treatment at a community cancer center and not living in proximity to a metro area. Patient demographic and socioeconomic factors play an important role in OS for patients with mNETs and access to care must be considered in this subpopulation of cancer patients

Midgut Neuroendocrine Tumors with Liver-only Metastases: Benefit of Primary Tumor Resection

Management of metastatic midgut neuroendocrine tumors (MNET) remains controversial. The benefits of resecting the primary tumor are not clear and advocated only for select patients. This study aimed to determine whether resection of the primary MNET in patients with untreated liver-only metastases has an impact on survival. This retrospective study reviewed data of the National Cancer Database from 2004 to 2015 for patients with liver-only metastatic MNETs and compared those who received resection of their primary MNET with those who did not. Patient demographics, tumor characteristics, and clinical outcomes were compared between the groups. The primary outcome was overall survival (OS) after adjustment for patient, demographic, and tumor-related factors. The study identified 1952 patients with a median age of 63 years (range, 18-90 years). The median primary tumor size was 2.4 cm (range, 0.1-20 cm). Of these patients, 1295 (66%) underwent resection of the primary tumor and 667 (34%) did not. The patients who underwent resection were younger (median age, 63 vs 65 years; p < 0.001) and had smaller primary tumors (median, 2.3 vs 3.0 cm; p < 0.001). The patients with clinical T1 or T2 tumors were significantly less likely to undergo resection than those with stage T3 or T4 tumors (58.5% vs 89.7%; p < 0.001). The median follow-up period was 43 months (range, 1-83 months). In the entire cohort, 483 deaths occurred, with a 5-year OS of 61%. The 5-year OS rate was 49% for the patients who underwent resection and 66% for those who did not (p < 0.001). When the patients were grouped according to T stage, no OS difference between resection and no resection for stages T1 (p = 0.07) and T2 (p = 0.40) was identified. However, the 5-year OS rate was significantly better for the resected patient cohort with T3 (67.5% vs 37.2%; p < 0.001) or T4 (59.8% vs 21.5%; p < 0.001) tumors. The patients with treatment-naïve liver-only metastatic MNET had improved OS when the primary tumor was resected, particularly those with clinical stage T3 or T4 tumors. These patients may benefit from surgical resection of their primary tumor

Risk of liver-related death or transplantation according to quartiles of average BCAA intake (measured in grams of BCAA per 1000 kcal of daily energy intake).

Risk of liver-related death or transplantation according to quartiles of average BCAA intake (measured in grams of BCAA per 1000 kcal of daily energy intake).</p

Risk of liver-related death or transplantation according to quartiles of average BCAA/total protein/caloric intake (measured in grams BCAA per grams total protein per 1000 kcal).

Risk of liver-related death or transplantation according to quartiles of average BCAA/total protein/caloric intake (measured in grams BCAA per grams total protein per 1000 kcal).</p

Crude and adjusted hazard ratios of first liver related decompensations (including first event of variceal bleeding, ascites, spontaneous peritonitis or encephalopathy) according to quartiles of BCAA intake derived from average daily BCAA intake (measured in grams of BCAA per 1000 kcal of daily energy intake).

Crude and adjusted hazard ratios of first liver related decompensations (including first event of variceal bleeding, ascites, spontaneous peritonitis or encephalopathy) according to quartiles of BCAA intake derived from average daily BCAA intake (measured in grams of BCAA per 1000 kcal of daily energy intake).</p

Risk of liver-related death or transplantation according to quartiles of average daily absolute BCAA intake without accounting for total energy intake (measured in grams of BCAA).

Risk of liver-related death or transplantation according to quartiles of average daily absolute BCAA intake without accounting for total energy intake (measured in grams of BCAA).</p

Crude and adjusted hazard ratios of liver-related death or transplantation according to quartiles of BCAA intake derived from average daily energy adjusted BCAA intake (measured in grams of BCAA per 1000 kcal of daily energy intake).

Crude and adjusted hazard ratios of liver-related death or transplantation according to quartiles of BCAA intake derived from average daily energy adjusted BCAA intake (measured in grams of BCAA per 1000 kcal of daily energy intake).</p