Leptin and ghrelin in relation to Helicobacter pylori status in adult males

CONTEXT: Leptin and ghrelin, hormones involved in human energy homeostasis, are both produced in the stomach. OBJECTIVE: We sought to determine whether the presence of Helicobacter pylori affects gastric and systemic levels of leptin and ghrelin. DESIGN, SETTING, AND PATIENTS: We consecutively enrolled 256 patients referred for upper endoscopy at a Veterans Affairs outpatient endoscopy center. OUTCOMES: We obtained fasting serum, fundic and antral biopsies, and gastric juice. Based on histological, biochemical, and serological assays, patients were categorized as H. pylori+ or H. pylori-. Leptin and total ghrelin levels in serum, gastric biopsies, and gastric juice were determined by specific ELISAs. RESULTS: Of the 256 subjects, 120 were H. pylori+ and 96 were H. pylori-; 40 patients of indeterminate status were excluded. Serum and fundic leptin levels correlated with body mass index in the H. pylori+ (r = 0.35; P < 0.0001 and r = 0.35; P < 0.0001, respectively) and H. pylori- (r = 0.65; P < 0.0001 and r = 0.41; P < 0.0001, respectively) groups, but H. pylori+ subjects had significantly lower serum leptin levels [median 2.2 ng/ml (interquartile range 0.9-4.6) vs. 4.0 ng/ml (1.7-7.2); P = 0.0003]. Serum ghrelin levels were similar in the H. pylori+ and H. pylori- groups [median 1651 pg/ml (interquartile range 845-2247) vs. 1629 pg/ml (992-2886); P = 0.23]. H. pylori status did not significantly affect gastric biopsy leptin and ghrelin levels. Ghrelin levels in gastric juice varied over 4 log(10) (<80-776,000 pg/ml) and correlated with gastric juice pH in the H. pylori+ group (r = 0.68; P < 0.0001). CONCLUSIONS: These findings provide evidence that H. pylori status affects leptin and ghrelin homeostasis, presumably via intragastric interactions.     

Leptin is an endothelial-independent vasodilator in humans with coronary artery disease: Evidence for tissue specificity of leptin resistance.

AIMS: We sought to define the mechanisms and correlates of leptin's vascular actions in humans with coronary artery disease. METHODS AND RESULTS: In 131 patients (age 65.7+/-0.7 years mean+/-SEM), ex vivo vascular reactivity to leptin (10(-13)-10(-7) M) was assessed in saphenous vein (SV) rings. Leptin led to SV relaxation (maximal relaxation 24.5+/-1.6%). In separate experiments, relaxation to leptin was unaffected by L-NMMA (17.4+/-3.4 vs.17.8+/-3.3%, P = 0.9) or endothelial denudation (17.4+/-4.4 vs. 22.5+/-3.0%, P = 0.4). We explored the possibility that leptin's vascular effects are mediated via smooth muscle hyperpolarization. In the presence of KCl (30 mmol/L) to inhibit hyperpolarization, the vasodilator effect of leptin was completely blocked (0.08+/-4.1%, P < 0.001 vs. control). Similar results were demonstrated in internal mammary artery rings. The only independent correlate of leptin-mediated vasodilatation was plasma TNF-alpha (r = 0.25, P < 0.05). Neither body mass index nor waist circumference correlated with leptin-mediated vasorelaxation. This lack of a correlation with markers of total body fat/fat distribution suggests that leptin resistance may not extend to the vasculature. CONCLUSION: Leptin is a vasoactive peptide in human SV and internal mammary artery. Its action is not nitric oxide or endothelial-dependent. Markers of body fat did not correlate with leptin-mediated vasodilatation, raising the intriguing possibility of selective resistance to leptin's actions.     

Laparoscopic Appendectomy Outcomes on the Weekend and During the Week are no Different: A National Study of 151,774 Patients

Background

The “weekend effect” is defined as increased morbidity and mortality for patients admitted on weekends compared with weekdays. It has been observed for several diseases, including myocardial infarction and renal insufficiency; however, it has not yet been investigated for laparoscopic appendectomy in acute appendicitis—one of the most prevalent surgical diagnoses.

Methods

The present study is based on the Nationwide Inpatient Sample (NIS) from 1999 to 2008. The following outcomes were compared between patients undergoing laparoscopic appendectomy for acute appendicitis admitted on weekdays versus weekends: severity of appendicitis, intraoperative and postoperative complications, conversion rate, in-hospital mortality, and length of hospital stay. Unadjusted and risk-adjusted generalized linear regression analyses were performed.

Results

Overall, 151,774 patients were included, mean age was 39.6?years, 52.6% (n?=?79,801) were male, and 25.3% (n?=?38,317) were admitted on weekends. After risk adjustment, the conversion rate was lower [odds ratio (OR): 0.94, p?=?0.004, number needed to harm (NNH): 244], whereas pulmonary complications (OR: 1.12, p?=?0.028, NNH: 649) and reoperations (OR: 1.21, p?=?0.013, NNH: 1,028) were slightly higher on weekends than on weekdays. Overall postoperative complications (OR: 1.03, p?=?0.24), mortality (OR: 1.37, p?=?0.075) and length of hospital stay (mean on weekday: 2.00?days, weekends: 2.01?days, p?=?0.29) were not statistically different.

Conclusions

The present investigation provides evidence that no clinically significant “weekend effect” for patients undergoing laparoscopic appendectomy exists. Therefore, hospital or staffing policy changes are not justified based on the findings from this large national study.     

Changes in Bone Mineral Density in Women Following 1-Year Gastric Bypass Surgery

Background

Roux-en-Y gastric bypass (RYGB) surgery is the gold standard surgical treatment for obesity. However, unintended nutritional deficiencies following this surgery are common, including changes in bone metabolism. We assessed changes in bone mineral density (BMD), nutritional compounds, and bone resorption markers before and 1?year following RYGB surgery.

Methods

Our study included 22 female patients with class II/III obesity. A clinical questionnaire, a 24-h recall, blood and urine samples, and dual-energy X-ray absorptiometry were provided.

Results

Mean age was 37.2?±?9.6?years; 86?% were Caucasian and 77.2?% were premenopausal. Mean preoperative body mass index was 44.4?±?5.0 and 27.5?±?4.5?kg/m² at 1-year follow-up (p?p?=?0.327]. Serum N-telopeptide (16.3?±?3.4 vs. 38.2?±?7.0 nM BCE, p?p?=?0.026) increased after RYGB surgery, reflecting bone resorption. BMD decreased after RYGB surgery in the lumbar spine (1.13?±?0.11 vs. 1.04?±?0.09?g/cm², p?=?0.001), femoral neck (1.03?±?0.15 vs. 0.94?±?0.16?g/cm², p?=?0.001), and total femur (1.07?±?0.11 vs. 0.97?±?0.15?g/cm², p?=?0.003).

Conclusions

Decreased BMD in the lumbar spine, femoral neck, and total femur is detectable in women 1?year after RYGB surgery. Calcium malabsorption, caused by vitamin D deficiency and increased bone resorption, is partially responsible for these outcomes and should be targeted in future clinical trials.     

Prognostic Significance of Regulators of Cell Cycle and Apoptosis, p16INK4a, p53, and bcl-2 in Primary Mucosal Melanomas of the Head and Neck

Abnormalities in cell cycle regulation, tumor suppressor gene functions and apoptosis are frequent events in tumorigenesis. Their role in the pathogenesis and prognosis of primary mucosal melanomas (MM) of the upper aerodigestive tract remains unknown. Sixty-four patients (40 men, 24 women, median age 64 years) with MM were included in this study; 32 had tumors in the nasal/paranasal cavities, 28 in the oral cavity and 4 in the pharynx. Archival tissues from 47 initial mucosal tumors, 17 mucosal recurrences, and 13 nodal/distant metastases were subjected to immunohistochemistry using antibodies against p16, p53, and bcl-2. The results were correlated with histological features and survival data. Expressions of p16, p53, and bcl-2 proteins were seen in 25% (N=19/76), 21% (N=16/76), and 74% (N=56/76) of all tumors, respectively. bcl-2 expression in the initial tumors was associated with significantly longer overall and disease specific survival (3.3 vs. 1.5 years, P ≤ 0.05). Expression of p16 was increasingly lost, from 32% in initial tumors to 12% in recurrent and 15% in metastatic tumors (P=0.06). Tumors comprised of undifferentiated cells were significantly more p53 positive than epithelioid or spindle cells (80% vs. 33%, P=0.02). Expression of these markers did not correlate with necrosis, or vascular and/or deep tissue invasion. Expression of bcl-2 is associated with better survival in MM. Loss of p16 was seen with tumor progression whereas aberrant p53 expression was frequent in undifferentiated tumor cells.     

Impact of 2013 ASCO/CAP HER2 reporting guidelines in breast cancer: An assessment study from Indian oncology centre that primarily performs HER2 IHC testing with special emphasis on IHC equivocal category

The ASCO/CAP guidelines for HER2 reporting in breast cancer published in 2007 and were updated in 2013 to assure that the right patient receives the targeted therapy. The updated guidelines have lowered the threshold for HER2 positivity criteria and altered the equivocal category for both IHC and FISH. This first study from India addresses the impact of these updated guidelines in the various reporting categories at a tertiary care centre. We compared the trend of HER2 IHC reporting 1 year before (Period A) and 1 year after (Period B) the implementation of updated 2013 ASCO/CAP guidelines. All HER2 equivocal IHC cases of post 2013 guidelines were reclassified as per 2007 guidelines to detect additional number of cases that have been put into equivocal category. Reflex FISH correlation was also assessed to detect any additional cases eligible for anti HER2 therapy with implementation of these updated guidelines. With implementation of updated 2013 guidelines, there was significant decrease in the number of cases scored as 1+ (from 30.7% to 20.6%; P value: .0001) while significant increase in number of 2+ cases (from 20.2% to 27.3%; P value: .004). Post 2013 guidelines, 39% (64 cases) of tumors were additionally put into the equivocal category which would have been considered as negative (score 1+) as per 2007 guidelines. The reflex FISH testing in these equivocal cases resulted in detection of only 1.5% of additional cases eligible for anti HER2 therapy. With implementation of updated 2013 guidelines, there is no significant increase in HER2 positivity trend. However, there is appreciable increase in IHC equivocal cases which subsequently led to increased reflex FISH testing without significantly contributing to the detection of additional eligible cases for anti HER2 therapy, but resulted in delaying of definite HER2 status along with financial implications.     

Myoepithelial carcinoma of the parotid gland with a novel CTCF::NCOA2 fusion

We describe a case of a myoepithelial carcinoma of the superficial parotid gland in a 46-year-old male harboring a novel CTCF::NCOA2 gene fusion. To our knowledge, this novel gene fusion has not been described previously in myoepithelial carcinoma. A 46-year-old male patient presented with a mass involving the superficial left parotid gland with extension into the external auditory canal (EAC) and erosion of the conchal cartilage. Histologically, the neoplasm was composed of uniform spindled, epithelioid/ovoid cells arranged in cords and nests within hyalinized to myxoid stroma. On immunohistochemistry (IHC), the tumor cells demonstrated patchy and variable staining for low molecular weight cytokeratin (CAM5.2), pan-cytokeratin (OSCAR), and S-100. Overall, the morphological and immunohistochemical attributes supported a locally aggressive tumor of myoepithelial differentiation consistent with myoepithelial carcinoma. Molecular analysis using a custom 115-gene gene panel by targeted RNA sequencing, showed an in-frame CTCF::NCOA2 fusion. In addition to reporting this novel fusion in myoepithelial carcinoma, we also discuss relevant differential diagnosis, and provide a brief review of NCOA2 gene function in both normal and neoplastic contexts.