Expression of EMT inducers integrin-linked kinase (ILK) and ZEB1 in phyllodes breast tumors is associated with aggressive phenotype.

Phyllodes tumors (PTs) of the breast constitute an uncommon group of mammary fibroepithelial lesions with ambiguous biologic behavior. Recent evidence suggests that epithelial mesenchymal transition (EMT), a driving force of cancer progression is implicated in PTs pathogenesis. Integrin-linked kinase (ILK), a focal adhesion kinase, has been implicated in cancer and EMT and represents a novel cancer therapeutic target. In this study, we aimed to investigate ILK and EMT markers expression in phyllodes breast tumors in relation to tumor grade. Expression of ILK and EMT markers E-cadherin, ß-catenin, Ν-cadherin, vimentin, Snail, ZEB1 and Twist was evaluated by immunohistochemistry in paraffin-embedded tissue sections from 96 human phyllodes breast tumors (48 benign, 27 borderline, 21 malignant). Cytoplasmic and nuclear immunopositivity of ILK were observed in both the epithelial and the stromal component of phyllodes breast tumors and were significantly higher with increasing tumor grade. An EMT-related expression profile consisting of decreased membranous and increased nuclear/cytoplasmic immunoreactivity of E-cadherin and ß-catenin and increased expression of N-cadherin, vimentin, Snail, ZEB1 and Twist was observed in tumor epithelial and stromal component and was significantly associated with malignant phyllodes breast tumor histopathology. Interestingly, there was a significant correlation of ILK expression with all of the EMT markers examined. Our results suggest that EMT significantly contributes to phyllodes tumor pathogenesis and originally implicate ILK and ZEB1 in phyllodes tumors malignant phenotype.

Biliopancreatic diversion with Roux-en-Y gastric bypass and long limbs: advances in surgical treatment for super-obesity.

BACKGROUND: Over the past 14 years, we have used different malabsorptive bariatric operations to treat super-obesity. We compared the efficacy and safety of our preferred procedure for the last 8 years with previous methods used in super-obese. METHODS: Our first procedure was distal Roux-en-Y gastric bypass (distal RYGBP) (gastric pouch 15 ± 5 mL, 80 cm biliopancreatic limb, 100 cm common limb [CL]). The second was distal RYGBP with short alimentary limb (distal RYGBP-sAL) (gastric pouch 15 ± 10 mL, alimentary limb [AL] 250 cm, CL 100 cm). Our preferred procedure for the past 8 years has been biliopancreatic diversion with RYGB and long limbs (BPD-RYGB-LL) (gastric pouch 40 ± 10 mL, AL 400 cm, CL 100 cm). RESULTS: Seventy-five patients underwent distal RYGBP, 44 distal RYGBP-sAL, and 841 BPD-RYGB-LL. Eight years postoperatively, the mean BMIs were 39.0, 29.4, and 29.2, respectively. The greatest reduction of 47.6% was achieved with BPD-RYGB-LL (distal RYGBP 30.6%; distal RYGBP-sAL 43.1%). Mean excess weight loss was 51.3% for distal RYGBP, 76.5% for distal RYGBP-sAL, and 80.9% for BPD-RYGB-LL. Six patients died at the early postoperative period. Sixteen patients died during the first eight postoperative years, of whom significantly more were after distal RYGBP-sAL (P = 0.0003). Complications were significantly more frequent after distal RYGBP-sAL (P = 0.001). All procedures led to rapid and sustained resolution of major comorbidities in almost all patients affected. Metabolic and nutritional deficiencies were similar and manageable. CONCLUSIONS: Our variant of biliopancreatic diversion (BPD-RYGB-LL) results in substantial and sustained weight loss in super-obese, without compromising safety.

Randomized clinical trial of laparoscopic Roux-en-Y gastric bypass versus laparoscopic sleeve gastrectomy for the management of patients with BMI < 50 kg/m2.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is currently the gold standard bariatric procedure for the treatment of morbid obesity. Laparoscopic sleeve gastrectomy (LSG) is a relatively innovative procedure which has been increasingly applied lately as a sole bariatric procedure. A randomized trial was conducted in a Greek population to evaluate perioperative safety and 3-years results. METHODS: Sixty patients with body mass index (BMI) ≤ 50 Kg/m(2) were randomized to LRYGB or LSG. Patients were monitored for 3 years postoperatively and throughout the study period weight loss, in terms of percent excess weight loss (%EWL), early and late complications, improvement of obesity related comorbidities and nutritional deficiencies were compared between groups. RESULTS: There was no death in either group and there was no significant difference in early (10% after LRYGB and 13% after LSG, P > 0.05) and late morbidity (10% in each group). Weight loss was significantly better after LSG in the first years of the study and at 3 years %EWL reached 62% after LRYGB and 68% after LSG (p = 0.13). There was no significant difference in the overall improvement of comorbidities. Nutritional deficiencies occurred at the same rate in the two groups except to vitamin B(12) deficiency which was more common after LRYGB (P = 0.05). CONCLUSION: LSG and LRYGB are equally safe and effective in the amelioration of comorbidities, while LSG is associated with fewer postoperative metabolic deficiencies, without the need of supplementation. Furthermore, LSG is a promising bariatric procedure, equally effective to LRYGB at 3 years follow up on weight reduction.

Adipokine serum levels are related to liver histology in severely obese patients undergoing bariatric surgery.

BACKGROUND: Leptin, adiponectin, and resistin are adipokines linked to the development of insulin resistance, which plays a central role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We aimed to define adipokine serum levels in severely obese patients undergoing bariatric surgery and to correlate these with anthropometric and metabolic variables, liver function tests, and histopathological parameters of NAFLD and nonalcoholic steatohepatitis (NASH). METHODS: Surgical liver biopsies were obtained from 50 bariatric patients with no history of liver disease or significant alcohol consumption. Serum leptin, adiponectin, and resistin levels were measured, and histology was assessed using Brunt's and Kleiner's scoring systems. RESULTS: Waist/hip ratio was significantly higher in men (p = 0.0001), and leptin (p = 0.036) and adiponectin (p = 0.0001) serum levels were higher in women. Forty-one of 50 patients (82%) had histological NAFLD, including 10 (20%) with NASH. Nine patients (18%) had normal liver histology (obese control subgroup). In NAFLD patients, serum adiponectin was negatively correlated with activity grade and fibrosis stage, resistin was negatively correlated with steatosis grade (p = 0.033), while leptin was not related to histology. Leptin/adiponectin ratio showed positive association with stage (p = 0.044). In the subgroup of NASH patients, adiponectin was negatively correlated only with stage (p = 0.01), while there was no correlation between leptin, resistin, or leptin/adiponectin and histology. CONCLUSIONS: Serum adiponectin and resistin levels are related to liver histology in bariatric patients and may be indicative of the histological severity of NAFLD and the extent of hepatic steatosis, respectively. Serum leptin levels are not informative of underlying liver histology in severely obese patients.

Dissociation of thyrotropin and leptin secretion in acute surgical stress in severely obese patients.

BACKGROUND: During illness, thyroid parameters undergo acute changes, which are known as non-thyroidal illness syndrome, the cause of which has not been elucidated. In vitro and in vivo data demonstrate that leptin regulates the expression of thyrotropin-releasing hormone (TRH)-mRNA in the paraventricular nucleus as well as the secretion of thyrotropin (TSH) in response to fasting in humans and animals. Moreover, in healthy adults, TSH and leptin have almost identical circadian rhythms. Our aim was to investigate the secretion of leptin and TSH, and their probable interaction, during the acute stress that is induced by surgery. METHODS: We studied 18 severely obese but otherwise healthy men. All participants were admitted to the hospital in the morning after an overnight fast. On the following day, 14 of the participants underwent bariatric surgery at 0900. The remaining four participants did not undergo surgery and served as controls. Serum samples to measure the levels of TSH and leptin were collected from all participants, as follows: upon admission to the hospital (baseline values) and on the following day at 0900 and every 10 min, thereafter for 9 h. RESULTS: The serum TSH increased during the first hour after skin incision (si) and then decreased gradually throughout the rest of the observation period. In contrast, during the first hour after si, the leptin levels remained unaltered. The leptin levels then decreased and reached a nadir at 4 h and 10 min post si after which they remained constant for approximately 1 h. Thereafter, while TSH continued to decrease, leptin started to increase and reached baseline values at 9 h post si. In control subjects, the TSH and leptin profiles seemed parallel each other. CONCLUSIONS: During acute surgical stress, the secretion of TSH and leptin in severely obese men is asynchronous and causality could not be proven.

A global assessment of the inflammatory response elicited upon open abdominal aortic aneurysm repair.

The inflammatory response during elective open infrarenal abdominal aortic aneurysm repair and its impact on outcome is investigated. Twenty high-risk patients were enrolled, and blood samples were obtained at 8 perioperative time points. Endotoxin, cytokines (tumor necrosis factor-alpha and interleukin-1beta, and interleukin-6), CD11b expression, and nitric oxide were measured. Peak endotoxin levels occurred within 30 minutes of reperfusion and were higher among patients developing complications. Interleukin-6 levels increased during reperfusion, reaching a peak on the first postoperative day. Interleukin-6 increase correlated with aortic clamp time and morbidity. CD11b expression increased 30 minutes after reperfusion, and this effect was greater among patients who developed complications. Endotoxin may be important in the pathogenesis of multiple organ dysfunction syndrome. Activated neutrophils may have a central role in tissue injury after reperfusion. Intraoperative CD11b upregulation may be an early marker for postoperative complications after infrarenal abdominal aortic aneurysm repair.

Thyroid function in humans with morbid obesity.

Morbidly obese subjects may present with abnormal thyroid function tests but the reported data are scarce. Therefore, we studied the thyroid parameters in 144 morbidly obese patients, 110 females and 34 males, to assess the prevalence of hypothyroidism. Eleven percent (11.8%) carried the diagnosis of hypothyroidism and were undergoing levothyroxine (LT4) replacement therapy, 7.7% had newly diagnosed subclinical hypothyroidism, 0.7% had subclinical hyperthyroidism and 7.7% were euthyroid with positive antibodies (anti-thyroid peroxidase antibodies [TPOAb]). From the 144 subjects, we selected a cohort of 78 euthyroid subjects with negative TPOAb, who did not receive LT4 replacement or suppression therapy (the experimental group) and compared them to 77 normal-weight euthyroid subjects, TPOA-negative, matched for age and gender who served as controls. The experimental group had higher serum levels of triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), and thyrotropin (TSH) compared to the control group. Serum TSH concentration was associated with fasting serum insulin levels and insulin resistance but not with serum leptin levels, body mass index (BMI), fat mass, and lean body mass. In conclusion, in morbidly obese individuals, the prevalence of overt and subclinical hypothyroidism was high (19.5%). The morbidly obese subjects have higher levels of T3, FT3, T4, and TSH, probably the result of the reset of their central thyrostat at higher level.