Long-term results after laparoscopic adjustable gastric banding in adolescent patients: follow-up of the Austrian experience.

BACKGROUND: During the last 30 years a threefold increase in the number of overweight children has been reported in Western countries. More than 15% of adolescents have a body mass index (BMI) higher than the 95th percentile. The use of surgical strategies in adolescent patients is still controversial due to the impact on the continuing maturing process. Laparoscopic adjustable gastric banding (LAGB) is considered a minimal invasive procedure that does not alter the physiological behavior of the bowel and has already shown promising results in short-term studies. METHODS: Between 1998 and 2004, 50 adolescent patients above the 99.5th age- and gender-adjusted growing percentile were treated with LAGB. The surgical procedure was performed at three highly experienced centers for bariatric surgery. Mean age was 17.1 ± 2.2 years (range = 9-19 years) at the time of surgery. Follow-up investigations were performed in the outpatient clinic of the treating hospitals. Psychological changes were analyzed using the BAROS questionnaire. RESULTS: The mean BMI decreased from 45.2 ± 7.6 kg/m(2) at the time of surgery to 38.3 ± 6.2 kg/m(2) 1 year after surgery, 31.5 ± 6.6 kg/m(2) after 3 years, and 27.3 ± 5.3 kg/m(2) after 5 years. Mean excessive weight loss was 49.7 ± 29.2, 76.8 ± 27.5, and 92.6 ± 24.5% at 1, 3, and 5 years after surgery. Quality of life showed a further significant improvement between 3 and 5 years after surgery (BAROS: 5.5 ± 1.9 increased to 6.3 ± 2.2, p = 0.01). All preoperative comorbidities resolved in patients with a functional band after 5 years of follow-up. CONCLUSION: LAGB shows promising results in the long-term follow-up with continuous weight loss in patients with a functional band. Nevertheless, most of the weight loss is within the first 3 years after surgery. Thereafter, further weight reduction is about 10% over the following 2 years. Perioperative comorbidities resolve within the first 5 years after treatment.

Recurrent abscess after primary successful endo-sponge treatment of anastomotic leakage following rectal surgery.

AIM: To assess long-term efficacy of initially successful endo-sponge assisted therapy. METHODS: Between 2006 and 2009, consecutive patients who had undergone primary successful endo-sponge treatment of anastomotic leakage following rectal cancer surgery were enrolled in the study. Patients were recruited from 6 surgical departments in Vienna. Clinical and oncologic outcomes were assessed through routine endoscopic and radiologic follow-up examination. RESULTS: Twenty patients (7 female, 13 male) were included. The indications for endo-sponge treatment were anastomotic leakage (n = 17) and insufficiency of a rectal stump after Hartmann's procedure (n = 3). All patients were primarily operated for rectal cancer. The overall mortality rate was 25%. The median follow-up duration was 17 mo (range 1.5-29.8 mo). Five patients (25%) developed a recurrent abscess. Median time between last day of endo-sponge therapy and occurrence of recurrent abscess was 255 d (range 21-733 d). One of these patients was treated by computed tomography-guided drainage and in 3 patients Hartmann's procedure had to be performed. Two patients (10%) developed a local tumor recurrence and subsequently died. CONCLUSION: Despite successful primary outcome, patients who receive endo-sponge therapy should be closely monitored in the first 2 years, since recurrence might occur.

Correlated downregulation of estrogen receptor beta and the circadian clock gene Per1 in human colorectal cancer.

There is a growing body of evidence that disturbed circadian clock gene expression is associated with tumor development and tumor progression. Based on our initial experiments demonstrating decreased period 1 (Per1) expression in colon cancer, we evaluated clock gene and estrogen receptor (ER) alpha/beta expression in colon cancer cells of primary colorectal tumors and adjacent normal colon mucosa (NM) by real-time RT-PCR. Analysis of gene expression in G(2) and G(3) colorectal tumors revealed a decrease of Per1 mRNA compared with paired NM (G(2): 0.52-fold; P = n.s. and G(3): 0.48-fold; P = 0.03). A significant gender specific difference of Per1 expression was observed in G(2) tumors as compared with NM (female: 0.38-fold; P = 0.004 vs. male: 0.73-fold; P = n.s.). Expression of CLOCK was significantly elevated in G(2) tumors of male patients (1.63-fold, P = 0.01). The expression of ER-beta was significantly decreased in G(2) and G(3) tumors (G(2): 0.32-fold; P = 0.003 and 0.27; P = 0.001). No significant gender specific differences of ER-beta reduction in tumors were observed. A significant correlation between the decrease of Per1 and ER-beta in colorectal tumors (r = 0.61; P < 0.001) was found. No changes in gene expression were detected for ER-alpha and Per2. Our data demonstrate a correlated decrease of Per1 and ER-beta in colorectal tumors, mediated probably by epigenetic mechanisms. The observed gender differences in the expression of CLOCK and Per1 in G(2) tumors might suggest a gender-specific, distinctive role of the cellular clock in colorectal tumorigenesis.

Ghrelin and obestatin levels in severely obese women before and after weight loss after Roux-en-Y gastric bypass surgery.

BACKGROUND: Ghrelin and obestatin are derived from the same gene but have different effects: Ghrelin stimulates appetite, and previous-albeit inconsistent-data show that obestatin may be involved in satiety. The present study was designed to test the hypothesis that Roux-en-Y gastric bypass (RYGB) surgery and/or the weight loss that reliably results from this procedure would alter levels of ghrelin and obestatin and ghrelin/obestatin ratios in a cohort of morbidly obese women. METHODS: This is a longitudinal follow-up study in 18 morbidly obese women (mean weight 131.2 kg, mean body mass index [BMI] 47.4). Clinical parameters and fasting serum concentrations of ghrelin, obestatin, triglycerides, low-density lipoprotein cholesterol, glucose, and insulin were measured before and 2 years after RYGB surgery, which was associated with body weight reductions of 41.5 +/- 11.6 kg (mean 62.5% excess weight loss). RESULTS: Ghrelin concentrations (-12%, p = 0.022) and ghrelin/obestatin ratios (-14%, p = 0.017) were lower after surgery than before, while obestatin levels did not change. Changes in ghrelin concentrations correlated with changes in insulin levels (r = 0.45, p = 0.011). Most cardiovascular risk factors studied improved postsurgically (p < 0.01). CONCLUSION: In contrast to previous weight loss studies involving gastric banding, ghrelin levels decreased and obestatin levels remained stable after massive weight loss in long-term follow-up. The favorable gastrointestinal hormone profiles observed are likely to contribute to the long-term weight loss success rate attributed to RYGB.

Increase of osteopontin plasma concentrations after bariatric surgery independent from inflammation and insulin resistance.

BACKGROUND: Osteopontin (OPN) is a multifunctional matrix glycoprotein associated with bone metabolism and has been linked to chronic inflammation, insulin resistance, and atherosclerosis. Diet-induced weight loss decreases elevated OPN concentrations in obese patients. The aim of the current study was to investigate the role of OPN after bariatric surgery, where not only improvements of chronic inflammation, insulin resistance and comorbidities, but also malabsorption and altered bone metabolism have been reported. METHODS: OPN plasma concentrations were determined in 31 morbidly obese patients (5 men, 26 women, BMI 46.2+/-7.1 kg/m2, age 41+/-11 years; mean+/-SD) before and 18 months after bariatric surgery, together with parameters of bone metabolism and inflammation. RESULTS: OPN concentrations increased by +20.3+/-26.6 ng/ml (mean+/-SD, p<0.01), concomitant to a weight loss of -38+/-22 kg, and a decrease in BMI by -13.1+/-7.7 kg/m2 (both p<0.01). HOMA-index improved from 5.2+/-3.4 to 1.5+/-1.0 (p<0.01). Calcium concentrations slightly decreased, and phosphate increased (-0.06+/-0.13 mmol/l and +0.08+/-0.16 mmol/l, respectively; both p<0.05), while 25-OH-Vitamin D3 remained unchanged and PTH tended to increase (+5.1+/-14.0 pg/ml, p=0.054). Monocyte chemoattractant protein 1 and interleukin 18 were significantly decreased and associated with HOMA both before and after bariatric surgery. DeltaOPN was correlated with DeltaPTH, but not with other parameters. CONCLUSIONS: OPN plasma concentrations increased concomitant to weight loss after bariatric surgery, which was independent from an improvement of insulin sensitivity and a decrease of inflammatory markers. Further studies are needed to differentiate whether these changes in bone metabolism after bariatric surgery are secondary to calcium deficiency or an adaptation to weight loss.

Peptide YY and glucagon-like peptide-1 in morbidly obese patients before and after surgically induced weight loss.

BACKGROUND: Peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) are cosecreted in the same enteroendocrine L-cells of the gut and reported to inhibit food intake additively. However, findings in human studies regarding these peptides are controversial. The aim of this study was to analyze the relationships between fasting PYY, GLP-1, and weight status in morbidly obese patients before and after surgically induced weight loss. METHODS: Fasting GLP-1, PYY, glucose, and insulin concentrations; blood pressure; and body-mass index (BMI) were determined in 30 morbidly obese adults (mean BMI 45.8, mean age 40 years) before bariatric surgery [Roux-en-Y gastric bypass (RYGB): n = 19; gastric banding (GB): n = 11] and after weight loss (mean 50% excess weight loss) in the course of mean 2 years. RESULTS: GLP-1 concentrations decreased (mean -20 pg/ml; mean -38%; p = 0.001) and PYY concentrations increased (mean +19 pg/ml; mean +19%, p = 0.036) after bariatric surgery. The weight loss and changes of GLP-1 were significantly (p < 0.05) more pronounced after RYGB as compared to GB, whereas the changes of PYY did not differ significantly between the patients who had undergone RYGB or GB. CONCLUSIONS: In morbidly obese adults reducing their weight by bariatric surgery, fasting PYY levels increased and GLP-1 concentrations decreased independently of each other. Therefore, the relationship between PYY and GLP-1 seems more complicated than might be anticipated from animal and in vitro studies.

Regulation of genes of the circadian clock in human colon cancer: reduced period-1 and dihydropyrimidine dehydrogenase transcription correlates in high-grade tumors.

Expression of dihydropyrimidine dehydrogenase (DPD) displays a regular daily oscillation in nonmalignant cells. In colorectal cancer cells, the expression of this 5-fluorouracil-metabolizing enzyme is decreased, but the reason remains unclear. In this study, we analyzed by real-time reverse transcription-PCR (RT-PCR) the expression of DPD and of members of the cellular oscillation machinery, period 1 (Per1), period 2 (Per2), and CLOCK, in primary colorectal tumors and normal colon mucosa derived from the same patients. Analysis of tumors according to differentiation grade revealed a 0.46-fold (P = 0.005) decrease for DPD mRNA and a 0.49-fold (P = 0.004) decrease for Per1 mRNA in undifferentiated (G3) tumors compared with paired normal mucosa. In this tumor cohort, the correlation between DPD and Per1 levels was r = 0.64, P < 0.01. In moderately differentiated (G2) colon carcinomas, reduction of DPD and Per1 mRNA levels did not reach significance, but a significant correlation between the respective mRNA levels was detectable (r = 0.54; P < 0.05). The decrease and correlation of DPD and Per1 mRNA levels were even more pronounced in female (G3) patients (DPD: female, 0.35-fold, P < 0.001 versus male, 0.58-fold, P < 0.05; and Per1: female, 0.47-fold, P < 0.01 versus male, 0.52-fold, P < 0.01). The highly significant correlation of DPD mRNA with Per1 mRNA expression suggests control of DPD transcription by the endogenous cellular clock, which is more pronounced in women. Our results also revealed a disturbed transcription of Per1 during tumor progression, which might be the cause for disrupted daily oscillation of DPD in undifferentiated colon carcinoma cells.

Relationship of androgens to insulin resistance and chronic inflammation in morbidly obese premenopausal women: studies before and after vertical banded gastroplasty.

BACKGROUND: Morbid obesity is associated with insulin resistance (IR), type 2 diabetes, lipid abnormalities, and hypertension. The association of obesity with increased androgen production and low concentrations of sex hormone-binding globulin (SHBG) in women has been demonstrated as well as a strong association of androgens with markers of inflammation such as high-sensitive C-reactive protein (hsCRP). Because weight loss results in a significant decrease in cardiovascular risk factors, IR and inflammation, we questioned a possible interrelationship between androgens, IR and inflammation in a prospective study with 43 morbidly obese female patients undergoing bariatric surgery. METHODS: SHBG, dehydroepiandrosterone-sulfate (DHEA-S), and insulin were measured by ELISA, cortisol by fluorescence polarization immunoassay, androstendione by RIA, and testosterone by electrochemiluminescence immunoassay. The free androgen index (FAI) was calculated as the total testosterone/SHBG ratio. High sensitivity assays were used to obtain concentrations of fasting hsCRP, Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). RESULTS: Weight loss resulted in a significant increase in SHBG (17+/-12 vs 70+/-30 nmol/l, P<0.0001). Serum concentrations of androstendione, total testosterone, DHEA-S and the FAI decreased significantly (2.05+/-0.78 vs 1.40+/-0.54 ng/ml, P<0.0001; 1.88+/-0.84 vs 1.16+/-0.57 nmol/L, P<0.0001; 1.72+/-0.86 vs 1.49+/-0.78 microg/ml, P<0.01; 0.15+/-0.10 vs 0.02+/-0.01, P<0.0001; respectively). Preoperatively and postoperatively, no association between androgens and IR, chronic subclinical inflammation and lipid parameters could be observed. CONCLUSION: Massive weight loss induced by bariatric surgery is associated with a significant reduction of androgen concentrations but not related to the concomitant decline of chronic inflammation, IR, glucose and lipid abnormalities in premenopausal morbidly obese women.

Laparoscopic adjustable gastric banding in adolescents: the Austrian experience.

BACKGROUND: Morbid obesity is a rising problem in adolescents in the industrial nations. Up to 25% of children have a body mass index (BMI) higher than the 85th age- and sex-adjusted percentile. Obesity in youth is associated with increased risk for morbidity and mortality in adulthood. In addition, these patients suffer from psychological problems and decreased quality of life. Bariatric procedures have shown effective long-term results in adults, but they are still discussed controversially in adolescent patients. METHODS: Between 1998 and 2004, 50 adolescent patients with a mean age of 17.1+/-2.2 years (range 9-19 years) underwent laparoscopic adjustable gastric banding (LAGB) in Austria. The psychological changes were analyzed by using Moorehead-Ardelt/BAROS questionnaire. RESULTS: The mean BMI decreased from 45.2+/-7.6 kg/m2 at time of surgery to 32.6+/-6.8 kg/m2 after a mean follow-up of 34.7+/-17.5 months. The mean excess weight loss was 61.4+/-35.5%. Most of the adolescents showed remarkable improvements in their quality of life. The outcome was regarded as "excellent or very good" in 32 patients, "good" in 12 patients and "fair" in 5 patients. Only one patient noticed no alterations after surgery. Two-thirds of the preoperative co-morbidities resolved, and one-third improved during follow-up. Except for one port dislocation, no peri- or postoperative complications arose. CONCLUSION: LAGB is an effective and attractive treatment option in very carefully selected obese adolescents, because of its adjustability and the preservation of the gastrointestinal passage. The majority of patients showed a remarkable improvement in their quality of life.

Effect of massive weight loss induced by bariatric surgery on serum levels of interleukin-18 and monocyte-chemoattractant-protein-1 in morbid obesity.

BACKGROUND: Morbid obesity is associated with insulin resistance (IR), chronic inflammation and premature atherosclerosis. Since vascular inflammation may contribute to the increased risk of cardiovascular morbidity and mortality of these patients, we studied circulating Interleukin-18 (L-18) and monocyte-chemoattractant-protein-1 (MCP-1) levels in 37 patients with morbid obesity before and after significant weight loss induced by bariatric surgery and their preoperative and postoperative associations with C-reactive protein (CRP) and IR-associated factors. METHODS: High sensitivity assays were used to measure concentrations of fasting CRP, IL-18 and MCP-1. Differences between patients before and after bariatric surgery were analyzed by Student's paired t-test. To investigate the associations of the observed reductions of values, delta of parameters were calculated and preoperative, postoperative and delta data were tested by univariate and multivariate linear regression. RESULTS: After a mean follow-up period of 26.5 months and a massive weight loss of 35 kg induced by bariatric surgery, circulating IL-18 levels decreased by 37% (P<0.001) and circulating MCP-1 levels by 47% (P<0.001). Multiple linear regression of delta values of IL-18 showed that only 2-hour glucose (P=0.008) remained independently and significantly associated with IL-18, whereas multiple linear regression analysis of delta values of MCP-1 revealed that only delta of HOMA-IR (P<0.001) remained independently and significantly associated with MCP-1, respectively. CONCLUSIONS: Because both biomarkers have been shown to play an important role in the development and progression of atherosclerosis, the observations presented in this study could be of clinical relevance for morbidly obese patients undergoing bariatric surgery.

25-hydroxyvitamin D3-1alpha-hydroxylase expression in normal and malignant human colon.

1,25-dihydroxyvitamin D(3) has anti-mitotic, pro-differentiating, and pro-apoptotic activity in tumor cells. We demonstrated that the secosteroid can be synthesized and degraded not only in the kidney but also extrarenally in intestinal cells. Evaluation of 1,25-dihydroxyvitamin D(3)-synthesizing CYP27B1 hydroxylase mRNA (real-time PCR) and protein (immunoblotting, immunofluorescence) showed enhanced expression in high- to medium-differentiated human colon tumors compared with tumor-adjacent normal mucosa or with colon mucosa from non-cancer patients. In high-grade undifferentiated tumor areas expression was lost. Many cells co-expressed CYP27B1 and the vitamin D receptor. We suggest that autocrine/paracrine antimitotic activity of 1,25-dihydroxyvitamin D(3) could prevent intestinal tumor formation and progression.