Andrés Sánchez-Pernaute

Effects of Weight Loss after Bariatric Surgery for Morbid Obesity on Vascular Endothelial Growth Factor-A, Adipocytokines, and Insulin

BACKGROUND Adipocytes regulate blood vessel formation, and in turn endothelial cells promote preadipocyte differentiation through the expression of proangiogenic factors, such as vascular endothelial growth factor (VEGF)-A. Some adipocytokines and hormones also have an effect on vascular development. OBJECTIVES Our objectives were to analyze the relationship between weight and circulating VEGF-A in morbidly obese subjects before and after bariatric surgery, and investigate the relationship between circulating VEGF-A and certain adipocytokines and hormones regulating adipocytes. METHODS A total of 45 morbidly obese women and nine lean females were included in the study. Patients underwent bariatric surgery: vertical banded gastroplasty (n=17), gastric bypass (n=17), and biliopancreatic diversion (n=11). Serum samples for VEGF-A, adiponectin, leptin, ghrelin, and insulin were obtained preoperatively and 9-12 months after surgery. RESULTS Obese patients showed significantly higher VEGF-A levels than controls (306.3+/-170.3 vs. 187.6+/-91.9 pg/ml; P=0.04), decreasing to 246.1+/-160.4 after surgery (P<0.001), with no differences among surgical procedures. In controls there was an inverse correlation between VEGF-A and ghrelin (r=-0.85; P<.01), but not in obese patients. Leptin and insulin concentrations were increased in obese patients, with a significant decrease shown after weight loss with surgery. Conversely, adiponectin concentrations were lower in obese patients, with a significant increase shown after weight loss with surgery. Ghrelin was higher in controls than obese patients, decreasing after gastric bypass and biliopancreatic diversion, but not after vertical banded gastroplasty. CONCLUSION Serum VEGF-A levels are significantly higher in obese patients than in lean controls, decreasing after weight loss with bariatric surgery, behaving similarly to other hormones related to adipose mass like leptin and insulin.

Correlations of telomere length, telomerase activity, and telomeric-repeat binding factor 1 expression in colorectal carcinoma

Telomere maintenance has been proposed as an essential step for tumor cell immortalization. The objectives of the current study were to investigate the mechanisms implicated in telomere length in colorectal carcinoma (CRC) and to evaluate the prognostic impact of telomere status.

Single-anastomosis duodenoileal bypass with sleeve gastrectomy: metabolic improvement and weight loss in first 100 patients

BACKGROUND Single-anastomosis duodenoileal bypass with sleeve gastrectomy is a simplified 1-loop duodenal switch with a 200-250 common channel. Our objective was to analyze the weight loss and metabolic results of the technique on a series of 100 consecutively operated patients at a tertiary center university hospital. METHODS A total of 100 patients consecutively underwent surgery. The criteria of inclusion were morbid obesity or metabolic disease. In the first 50 cases, the common/efferent limb measured 200 cm. The length was changed to 250 cm to reduce the hypoproteinemia rate. RESULTS No mortality and no severe complications developed. The mean excess weight loss was >95% maintained during the follow-up period. More than 90% of the patients experimented complete remission of type 2 diabetes mellitus. Two conversions to a standard duodenal switch with a longer alimentary channel were required because of recurrent hypoproteinemia. Hypertension was controlled in 98% of the patients, with a 58% remission rate. The mean number of bowel movements was 2.5/d. CONCLUSION Single-anastomosis duodenoileal bypass with sleeve gastrectomy is a simplified duodenal switch procedure that is safe and quicker to perform and offers good results for the treatment of both morbid obesity and its metabolic complications.

Single-anastomosis duodenoileal bypass with sleeve gastrectomy (SADI-S) for obese diabetic patients

BACKGROUND Bariatric operations achieve a high remission rate of type 2 diabetes in patients with morbid obesity. Malabsorptive operations usually are followed by a higher rate of metabolic improvement, though complications and secondary effects of these operations are usually higher. OBJECTIVES Analyze the results of a simplified duodenal switch, the single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) on patients with obesity and type 2 diabetes mellitus (T2 DM). SETTING University Hospital, Madrid, Spain. METHODS Ninety-seven T2 DM patients with a mean body mass index (BMI) of 44.3 kg/m(2) were included. Mean preoperative glycated hemoglobin was 7.6%, and mean duration of the disease was 8.5 years. Forty patients were under insulin treatment. SADI-S was completed with a sleeve gastrectomy performed over a 54 French bougie and a 200 cm common limb in 28 cases and 250 cm in 69. RESULTS Follow up was possible for 86 patients (95.5%) in the first postoperative year, 74 (92.5%) in the second, 66 (91.6%) in the third, 46 (86.7%) in the fourth and 25 out of 32 (78%) in the fifht postoperative year. Mean glycemia and glycated hemoglobin decreased immediately. Control of the disease, with HbA1c below 6%, was obtained in 70 to 84% in the long term, depending on the initial antidiabetic therapy. Most patients abandoned antidiabetic therapy after the operation. Absolute remission rate was higher for patients under oral therapy than for those under initial insulin therapy, 92.5% versus 47% in the first postoperative year, 96.4% versus 56% in the third and 75% versus 38.4% in the fifth. A short diabetes history and no need for insulin were related to a higher remission rate. Three patients had to be reoperated for recurrent hypoproteinemia. CONCLUSION SADI-S is an effective therapeutic option for obese patients with diabetes mellitus.

Cooperative role of telomerase activity and p16 expression in the prognosis of non-small-cell lung cancer.

PURPOSE: Telomerase activity and p16 expression can be considered two of the most important molecular markers implicated in tumorigenesis. Our main aim was to study the cooperative role of both molecular alterations in the prognosis of patients surgically resected for non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We have determined telomerase activity and p16 expression in a series of 98 prospectively collected NSCLC specimens obtained from patients who had undergone surgery without other treatment. Telomerase activity was investigated by a telomeric repeat amplification protocol enzyme-linked immunosorbent assay–based procedure, and p16 expression was examined by Western blot. Associations with survival were evaluated. RESULTS: Positive results for telomerase activity were found in 82% of the cases, and this variable correlated with poor differentiation and recurrence of tumors. Lack of p16 expression was observed in 61% of tumors, and a significant association with tumor recurrence was also ...

Heterotopic gastric mucosa in the upper esophagus ("inlet patch") : a rare cause of esophageal perforation

We report the case of a 21-yr-old woman who presented with a perforation of an upper esophageal ulcer on a patch of gastric-type mucosa. Despite surgical closure of the perforation and reinforcement with a pleuro-muscular flap the patient developed an esophageal leakage and died in the postoperative period. Heterotopic gastric mucosa in the upper esophagus is usually an asymptomatic abnormality, discovered incidentally during endoscopic studies carried out for some other reason; however, complications secondary to the inlet patch acid secreting capacity can arise, and this has to be kept in mind to elude life-threatening conditions.

Single-anastomosis duodenoileal bypass as a second step after sleeve gastrectomy.

BACKGROUND After sleeve gastrectomy, many surgical options are available in patients with insufficient weight loss. Duodenal switch is typically considered the operation that results in higher weight loss, although it is, perhaps unjustly, considered technically difficult and may be accompanied by severe side effects. Single-anastomosis duodenoileal bypass with sleeve gastrectomy is a simplification of the duodenal switch that may behave as a standard biliopancreatic diversion but is easier and quicker to perform. Given its effectiveness as a primary surgery we hypothesized that it would be successful as a second-step operation. The objective of this study was to analyze the weight loss and co-morbidities resolution after a single-anastomosis duodenoileal bypass (SADI) performed as a second step after sleeve gastrectomy. METHODS Sixteen patients with an initial body mass index of 56.4 kg/m(2) and a mean excess weight loss of 39.5% after a sleeve gastrectomy were submitted to a single-anastomosis duodenoileal bypass with a 250-cm common channel. RESULTS There were no postoperative complications. The mean excess weight loss was 72% 2 years after the second-step surgery. The complete remission rate was 88% for diabetes, 60% for hypertension, and 40% for dyslipidemia. The mean number of daily bowel movements was 2.1. One patient suffered an isolated episode of clinical hypoalbuminemia. CONCLUSION SADI is a safe operation that offers a satisfactory weight loss for patients subjected to a previous sleeve gastrectomy. The side effects are well tolerated, and complications are minimal.

Which criteria should be used to define type 2 diabetes remission after bariatric surgery

BackgroundComparison of diabetes remission rates after bariatric surgery using two different models of criteria.MethodsRetrospective analysis of data from 110 patients with type 2 diabetes and morbid obesity who underwent bariatric surgery, preoperatively and at 18-month follow-up. Comparison of two models of remission: 1) 2009 consensus statement criteria; 2) simple criteria using ADA’s HbA1c diabetes diagnostic cut-off values.ResultsPatients’ mean ± SD preoperative characteristics were: age 53.3 ± 9.5 years, BMI 43.6 ± 5.5 kg/m2, HbA1c 7.9 ± 1.8%, duration of diabetes 7.6 ± 7.5 years. 44.5% of patients with previous insulin therapy. With 2009 consensus statement criteria: complete, partial and no remission in 50%, 12.7% and 37.3%, respectively; with HbA1c criteria: 50%, 15% and 34.5% in the analogous categories (p = 0.673).ConclusionsWe suggest a simpler approach to evaluate diabetes remission after bariatric surgery, following the rationale of the definition of diabetes itself.

Differential Wnt Pathway Gene Expression and E-Cadherin Truncation in Sporadic Colorectal Cancers with and without Microsatellite Instability

Purpose: Alterations in the Wnt pathway play a major role in colorectal cancer with high (MSI-H) or low microsatellite instability (MSS/MSI-L). However, the differential impact of the Wnt pathway components on these tumors is poorly understood. MMP-3 (stromelysin-1) promoter is a target of the mutator phenotype in sporadic colorectal cancer. Among MMP-3 targets, we investigated E-cadherin integrity status in both groups of tumors. Because beta-catenin is the main effector of the Wnt pathway, we have also investigated the differential cellular status of beta-catenin. Experimental Design: Expression profiles of 114 genes related to the Wnt pathway were analyzed by oligo microarrays in 48 tumors classified by their MSI status. In addition, we analyzed 48 sporadic colorectal cancers for E-cadherin integrity status. We performed investigation of beta-catenin and cyclin D1 by immunohistochemistry using tissue arrays containing 96 tumors. Results: Our data show that a group of genes that negatively regulate Wnt signaling are downregulated in MSS/MSI-L as compared with MSI-H colorectal tumors. E-cadherin truncation was significantly higher in MSS/MSI-L as compared with MSI-H tumors. Moreover, MSI-H tumors showed low or null beta-catenin nuclear presence, whereas the group of tumors classified as MSS or MSI-L displayed a high content of the nuclear beta-catenin location. Conclusions: Our results suggest that the differential expression of genes that negatively regulate the Wnt pathway, as well as the status of E-cadherin and beta-catenin in MSI-H or MSS/MSI-L colorectal tumors, shed some light on the different clinical behavior showed by the two groups.

Genomic organization of a novel glycosylphosphatidylinositol MAM gene expressed in human tissues and tumors

We report the genomic organization of a novel human gene mapped to chromosome 6p21, encoding a putative glycosylphosphatidylinositol (GPI) anchored protein containing a MAM (meprin, A5 antigen, protein tyrosine phosphatase μ) domain, that we have termed as GPIM (GPI and MAM) protein. GPIM gene consists of an 8.9 kb transcript composed of 17 coding exons spanning about 65.5 kb of genomic DNA. The deduced polypeptide consists of 955 amino acids and exhibits structural features found in different types of cell adhesion molecules (CAMs), such as the presence of immunoglobulin domains, the presence of a MAM domain or the capacity to anchor to the cell membrane by a GPI motif. Expression analysis in normal human tissues revealed that this gene is expressed as a 5 kb and 9.5 kb mRNA. Furthermore, the smaller transcript is highly expressed in some human cancer cell lines, as well as in different primary tumors (lung, colon, uterus, stomach and breast). Interestingly, the gene was higher expressed in several tumor tissues analysed as compared to their corresponding normal tissues. Thus, GPIM is a novel gene codifying a protein with structural features characteristics of some CAMs, which might be involved in the tumor progression.