Comparative effects of gastric bypass and sleeve gastrectomy on plasma osteopontin concentrations in humans

Background

Bariatric surgery (BS) has proven to be an effective treatment for morbid obesity. Osteopontin (OPN) is a proinflammatory cytokine involved in the development of obesity. The aim of our study was to determine the effect of weight loss following BS on circulating levels of OPN in humans.

Methods

Body composition and circulating concentrations of OPN and markers of bone metabolism were determined in obese patients who underwent Roux-en-Y gastric bypass (RYGB; n = 40) or sleeve gastrectomy (SG; n = 11).

Results

Patients who underwent RYGB or SG showed decreased body weight (P < 0.001) and body fat percentage (P < 0.001) as well as lower insulin resistance. However, plasma OPN levels were significantly increased after RYGB (P < 0.001) but remained unchanged following SG (P = 0.152). Patients who underwent RYGB also showed significantly increased C-terminal telopeptide of type-I collagen (ICTP) (P < 0.01) and osteocalcin (P < 0.001) while bone mineral density tended to decrease (P = 0.086). Moreover, OPN concentrations were positively correlated with the bone resorption marker ICTP after surgery. On the other hand, patients who underwent SG showed significantly increased ICTP levels (P < 0.05), and the change in OPN was positively correlated with the change in ICTP and negatively with the change in vitamin D after surgery (P < 0.05).

Conclusions

RYGB increased circulating OPN levels, while they remained unaltered after SG. The increase in OPN levels after RYGB could be related to the increased bone resorption in relation to its well-known effects on bone of this malabsorptive procedure in comparison to the merely restrictive SG.     

Sleeve Gastrectomy Induces Weight Loss in Diet-Induced Obese Rats Even if High-Fat Feeding Is Continued

Background

Sleeve gastrectomy (SG) has been used for the surgical treatment of morbid obesity as a first or definitive procedure with satisfactory results. The objective of this study in rats was to establish the effects of SG on weight loss depending on the post-surgical type of diet followed.

Methods

Thirty male Wistar rats were fed ad libitum during 3 months on a high-fat diet (HFD) to induce obesity. After this first phase, rats were subdivided in three groups of ten rats each and underwent a sham intervention, an SG, or no surgery but were pair-fed to the amount of food eaten by the animals of the SG group. At this time point, half of the animals in each group continued to be fed on the HFD, while the other half was switched to a normal chow diet (ND). Thus, the following subgroups were established: sham-ND, sleeve-ND, pair-fed-ND as well as sham-HFD, sleeve-HFD, and pair-fed-HFD. Body weight and food intake were recorded daily for 4 weeks. The feed efficiency rate (FER) was determined from weekly weight gains and caloric consumption during this period.

Results

Statistically significant (P?<?0.05) differences in body weight were observed between the six experimental groups after 4 weeks of the interventions with rats in the sleeve-ND group experimenting the highest weight loss (?78.2?±?10.3 g) and animals in the pair-fed-HFD group exhibiting the lowest weight reduction (?4.0?±?0.1 g). Interestingly, the FER value of rats that underwent the SG and continued to be fed on a HFD was significantly (P?<?0.05) lower than that of sham operated and pair-fed animals on the same diet.

Conclusion

The positive effects of SG on weight reduction are observed in obese rats submitted to the intervention and subsequently following an ND or even an HFD.     

Liver Injury Due to Chemotherapy-induced Sinusoidal Obstruction Syndrome Is Associated with Sinusoidal Capillarization

Background

Indocyanine green (ICG) retention is a validated test of hepatic function in patients with chronic liver disease. The underlying mechanism for the impairment of ICG retention in patients undergoing chemotherapy for colorectal liver metastases (CLM) remains unclear. We sought to elucidate the mechanism for impairment of ICG retention in patients with CLM.

Methods

Clinicopathologic data of 98 patients with CLM undergoing hepatectomy were analyzed. The archived nontumoral liver parenchyma bearing no CLM were immunostained with CD34 antibody to determine the sinusoidal capillarization.

Results

Of 98 patients, 80 received preoperative chemotherapy. Sinusoidal obstruction syndrome (SOS) occurred in 39 patients (39.8%). The development of SOS in patients receiving oxaliplatin-based chemotherapy was significantly higher compared to those receiving non-oxaliplatin-based chemotherapy (P?=?0.003). SOS was independently associated with abnormal ICG retention rate at 15 minutes (ICG-R15) (odds ratio 3.45, 95% confidence interval 1.31?C9.04, P?=?0.012) and CD 34 overexpression (odds ratio 18.76, 95% confidence interval 4.58?C76.81, P?r?=?0.707, P?r?=?0.423, P?r?=?0.629, P?r?=?0.522, P?Conclusions These results suggest that the deterioration of hepatic functional reserve due to SOS is associated with sinusoidal capillarization, indicated by CD34 overexpression within nontumoral liver parenchyma adjacent to SOS.     

Biliopancreatic Diversion-Duodenal Switch: Independent Contributions of Sleeve Resection and Duodenal Exclusion

Background

The choice of first-stage operation in bilio-pancreatic diversion with duodenal switch (BPD-DS) is controversial. There are no published long-term comparisons of one- and two-stage BPD-DS outcomes.

Methods

During 2001–2009, among 1,762 patients scheduled for BPD-DS 48 had duodenal switch (DS) and 53 sleeve gastrectomy (SG) as first-stage procedures. We compared prospectively updated outcomes of 42 DS (100 % open) and 49 SG (88 % laparoscopic), 13 of whom completed their second stage, to a control group of 91 patients with open one-stage BPD-DS.

Results

One-year mean percent excess weight loss (%EWL) was greater after SG than DS (47?±?19 vs. 39?±?13 SD; p?=?0.01) with earlier nadir (16?±?10 vs. 45?±?30 months; p?p?p?p?p?p?Dyslipidemia was cured in 41, 82, and 100 %, respectively. Systolic and diastolic blood pressure decreased only after DS (12 %; p?p?=?0.04).

Conclusions

SG and DS independently contribute to beneficial metabolic outcomes after BPD-DS. Long-term weight loss and correction of metabolic abnormalities were better after DS favoring its use as first stage in BPD-DS; one-stage BPD-DS outcomes were superior to two-staged.     

Osteopontin regulates anabolic effect in human menopausal osteoporosis with intermittent parathyroid hormone treatment

Summary

In this pilot study, we demonstrated that women with osteopontin (OPN) over-expression show less resistance to postmenopausal osteoporosis than women with normal OPN levels. We hypothesized that the levels of plasma OPN could be used as a treatment indicator for intermittent parathyroid hormone (PTH)-treated menopausal osteoporosis. We demonstrated that plasma OPN levels could be used as a biomarker for early treatment response.

Introduction

Animal studies indicate that OPN-deficient mice are resistant to ovariectomy induced osteoporosis. Our pilot study also demonstrated women with OPN over expression may show less resistance to postmenopausal osteoporosis. The role of plasma OPN in PTH1-34-treated osteoporosis remains unclear.

Methods

From September 2005 to September 2006, 31 menopausal women over 45?years of age with severe osteoporosis were enrolled in our study. Subjects were treated with PTH1-34 subcutaneously at a dose of 20???g/day. Plasma OPN levels and BMD of the lumbar spine and hip were measured using ELISA and dual-energy X-ray absorptiometry at baseline, 3, 6, and 9?months. Response to the treatment was assessed by the sequential change in bone mineral density and OPN expression using a general linear mixed model.

Results

The plasma OPN decreased sequentially and significantly throughout the 9-month treatment course from 20.75?±?5.36 to 11.2?±?4.37?ng/ml (p?<?0.001). The sequential improvement in the T-score and Z-score was significant in the lumbar spine but not in the hip area. In the lumbar spine, when the plasma OPN decreased by 1?ng/ml the T-score increased by 0.0406 and the Z-score increased by 0.0572 of lumbar spine.

Conclusion

OPN levels are related to the anabolic effect of PTH in human postmenopausal osteoporosis. Plasma OPN levels could be used as a biomarker for early treatment response.     

Inhibition of osteopontin reduces liver metastasis of human pancreatic cancer xenografts injected into the spleen in a mouse model

Purpose

Pancreatic cancer is associated with the poorest prognosis of any digestive cancer due to the high incidence of liver metastasis. This study evaluated the possibility that osteopontin (OPN) RNA interference (RNAi) and anti-OPN antibody (Ab) could have antimetastatic effects.

Methods

The differential gene expression was measured in a parental cell line, HPC-3, and an established highly liver metastatic cell line, HPC-3H4. This study investigated the effect of OPN RNAi and anti-OPN Ab on the metastatic ability of HPC-3H4 to the liver. An OPN RNAi-expressing vector was introduced into HPC-3H4 cells (HPC-3H4/miOPN), in which OPN production was reduced to the level of the parental HPC-3 cells. Finally, the ability of anti-OPN Ab to suppress liver metastasis was investigated.

Results

Osteopontin was upregulated 11.1-fold in HPC-3H4 in comparison to HPC-3. The metastatic rate of HPC-3H4/miOPN was significantly reduced to 25% in comparison to the 100% metastatic rate of HPC-3H4 and control HPC-3H4/miNeg cells (P < 0.01). The metastatic rate of the group given anti-OPN Ab was 50%.

Conclusion

OPN RNAi and anti-OPN Ab had remarkable inhibitory effects against liver metastasis by the pancreatic cancer cell line.     

Combination of Haptoglobin and Osteopontin Could Predict Colorectal Cancer Hepatic Metastasis

Purpose

This study aimed to identify novel molecular markers for the early detection of colorectal cancer liver metastasis.

Methods

Genes related to hepatic metastasis were screened from the Oncomine database. The candidate markers were tested by immunohistochemistry, and their predictive accuracy was assessed by the cross-validation method and an independent test set.

Results

We got three datasets containing 2,973 genes that were highly expressed in primary colon cancer tissues compared with non-metastatic colon cancer tissues and identified 7 candidate molecules for immunohistochemical validation. A total of 213 colorectal cancer samples were randomly divided into a training set (113 cases) and a blind testing set (100 cases). In the training set, immunohistochemical analysis showed that HP, OPN, and PTGIS expression were significantly higher in the hepatic metastasis group than in the non-metastasis group. Logistic regression analysis showed that HP and OPN levels in primary tumors and lymph node metastasis status were the only significant (P?Conclusions Our results suggest that combined HP and OPN expression levels are significantly related to liver metastasis and prognosis, and, if this is validated, they could be used as accurate predictors of liver metastasis in colorectal cancer.     

Comparable early changes in gastrointestinal hormones after sleeve gastrectomy and Roux-En-Y gastric bypass surgery for morbidly obese type 2 diabetic subjects

Background

Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) are associated with similar type 2 diabetes mellitus (T2DM) resolution rates for morbidly obese subjects. However, the mechanisms underlying the resolution of T2DM after SG have not been clarified to date. This study aimed to compare the early changes in gastrointestinal hormones involved in insulin and glucagon secretion in morbidly obese T2DM subjects undergoing SG or RYGBP.

Methods

This prospective study investigated 12 subjects with T2DM who had undergone SG (n?=?6) or RYGBP (n?=?6). Five body mass index (BMI)-matched obese non-diabetic subjects and five BMI-matched obese diabetic subjects served as control subjects. Glucose, insulin, glucagon, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and GLP-2 were determined after a standardized mixed liquid meal before surgery and 6?weeks afterward.

Results

After 6?weeks, five of the six subjects in each surgical group presented with T2DM remission, although the area under the curve (AUC)_0–120 of glucose was greater than that of the non-diabetic control subjects (P?0–120 of GLP-1 (P?P?P?Conclusions The data show that in a cohort of morbidly obese T2DM subjects, SG and RYGBP are associated with an early improvement in glucose tolerance, similar changes in insulin and glucagon secretion, and a similar GLP-1, GIP, and GLP-2 response to a standardized mixed liquid meal.     

A Prospective Randomized Controlled Trial of the Metabolic Effects of Sleeve Gastrectomy with Transit Bipartition

Purpose

To compare the effects of the sleeve gastrectomy with transit bipartition (SG?+?TB) procedure with standard medical therapy (SMT) in mildly obese patients with type II diabetes (T2D).

Methods

This is a prospective, randomized, controlled trial. Twenty male adults, ≤?65 years old, with T2D, body mass index (BMI)?>?28 kg/m² and <?35 kg/m², and HbA1c level?>?8% were randomized to SG?+?TB or to SMT. Outcomes were the remission in the metabolic and cardiovascular risk variables up to 24 months.

Results

At 24 months, SG?+?TB group showed a significant decrease in HbaA1c values (9.3?±?2.1 versus 5.5?±?1.1%, P?=?<?0.05) whereas SMT group maintained similar levels from baseline (8.0?±?1.5 versus 8.3?±?1.1%, P?=?NS). BMI values were lower in the SG?+?TB group (25.3?±?2.8 kg/m² versus 30.9?±?2.5 kg/m²; P?=?<?0.001). At 24 months, none patient in SG?+?TB group needed medications for hyperlipidemia/hypertension. HDL-cholesterol levels increased in the SG?+?TB group (33?±?8 to 45?±?15 mg/dL, P?<?0.001). After 24 months, the area under the curve (AUC) of GLP1 increased and in the SG?+?TB group and the AUC of the GIP concentrations was lower in the SG?+?TB group than in the SMT. At 3 months, SG?+?TB group showed a marked increase in FGF19 levels (74.1?±?45.8 to 237.3?±?234 pg/mL; P?=?0.001).

Conclusions

SG?+?TB is superior to SMT and was associated with a better metabolic and cardiovascular profile.

     

Relationship between serum cystatin C and serum adiponectin level in type 2 diabetic patients

Background

To investigate the relationship between serum levels of cystatin C and adiponectin in patients with type 2 diabetes.

Methods

We examined serum cystatin C and adiponectin levels in 234 patients with type 2 diabetes who visited our hospital.

Results

The serum level of cystatin C was positively correlated with age (P?P?=?0.013), serum creatinine (P?P?P?P?Conclusions Serum adiponectin level was correlated with serum cystatin C level on simple and multiple regression analyses in patients with type 2 diabetes. Although circulating adiponectin is increased in advanced kidney disease, it might be biologically inactive due to binding to cystatin C and thus not display an anti-arteriosclerotic effect.     

Short- and Long-Term Changes in Gastric Morphology and Histopathology Following Sleeve Gastrectomy in Diet-Induced Obese Rats

Background

Sleeve gastrectomy (SG) has been used as a multipurpose surgical procedure for the treatment of morbid obesity. The aim of the study was to analyze gastric morphology and histology at two different time points after SG in rats.

Methods

Thirty-five male Wistar rats were fed ad libitum during 3?months on a high-fat diet to induce obesity. Subsequently, 25 diet-induced obese rats underwent either SG (n?=?12) or a sham operation (n?=?13). The remaining ten obese animals encompassed the nonoperated control group (Co). Four weeks postoperatively, 15 rats (n?=?5 rats/experimental group) were sacrificed, while the remaining 20 rats were sacrificed after 16?weeks (animals/group; Co?=?5, sham?=?8, SG?=?7) to compare the gastric morphological and histopathological changes over time. Body weight and food intake were regularly recorded.

Results

For both time periods, the Co groups exhibited the highest body weight, while the rats undergoing the SG showed the lowest weight gain (P?P?Conclusion After SG gastric macro- and microscopic changes with functional implications in both the short and long term take place.     

Effects of sleeve gastrectomy in high fat diet-induced obese mice: respective role of reduced caloric intake,white adipose tissue inflammation and changes in adipose tissue and ectopic fat depots

Background

Sleeve gastrectomy (SG) has become a popular bariatric procedure. The mechanisms responsible for weight loss and improvement of metabolic disturbances have still not been completely elucidated. We investigated the effect of SG on body weight, adipose tissue depots, glucose tolerance, and liver steatosis independent of reduced caloric intake in high-fat-diet-induced obese mice.

Methods

C57BI/6 J mice fed a high fat diet (45 %) for 33 weeks were divided into three groups: sleeve gastrectomy (SG, 13 mice), sham-operated ad libitum fed (SALF, 13 mice) and sham-operated pair fed (PFS, 13 mice). The animals were humanely killed 23 days after surgery.

Results

In SG mice, food intake was reduced transiently, but weight loss was significant and persistent compared to controls (SG vs. PFS, P < 0.05; PFS vs. SALF, P < 0.05). SG mice showed improved glucose tolerance and lower levels of liver steatosis compared with controls (area under the curve, SG vs. PFS, P < 0.01; PFS vs. SALF, P < 0.05) (liver steatosis, SG vs. PFS, P < 0.05; PFS vs. SALF, P < 0.01). This was associated with a decrease in the ratios of the weight of pancreas, epididymal and inguinal adipose tissues to body weight, and an increase in the ratio of brown adipose tissue weight to body weight. Epididymal adipose tissue was also infiltrated by fewer activated T cells and by more anti-inflammatory regulatory T cells. Serum levels of fasting acyl ghrelin were still significantly decreased 3 weeks after surgery in SG mice compared to PFS mice (P < 0.05).

Conclusions

Reduced white adipose tissue inflammation, modification of adipose tissue development (brown vs. white adipose tissue), and ectopic fat are potential mechanisms that may account for the reduced caloric intake independent effects of SG.     

Osteopontin Expression is Associated with Improved Survival in Patients with Pancreatic Adenocarcinoma

Background

Osteopontin (OPN) is a secreted protein of the extracellular matrix. It has been used as a marker for tumor aggressiveness and correlated with clinical outcomes in several solid tumors, such as liver, lung, and breast. We determined the OPN expression and its influence on survival in patients with resected pancreatic adenocarcinoma.

Methods

Tissue microarrays were constructed from 245 resected pancreatic adenocarcinomas. Immunohistochemical staining for OPN was undertaken and compared to normal pancreas (n?=?12). OPN expression was then correlated with patient demographics, tumor size, grade, node, and margin status. Survival curves were created by the Kaplan?CMeier method and compared by log rank analysis.

Results

In total, 181 (74?%) of pancreatic adenocarcinoma tissues expressed OPN compared to 7 (58?%) of normal controls (p?=?0.004). Expression was observed predominantly in the cytoplasm of the tumor cells. The median and 2?year overall survival was longer when OPN was expressed (17.1 vs. 11.6?months, and 38 vs. 24?%, respectively, p?=?0.04). Multivariate analysis showed OPN expression and T stage to be independent predictors of overall survival, while other histopathologic factors such as tumor grade, tumor size, and nodal status were not.

Conclusions

These results suggest that the presence of OPN expression in pancreatic adenocarcinoma may have a protective effect independent of tumor stage. This emphasizes the importance of the interaction between pancreatic cancer cells and their stromal elements.     

CD146 gene expression in clear cell renal cell carcinoma: a potential marker for prediction of early recurrence after nephrectomy

Objectives

To investigate whether CD146 gene expression could provide useful information to predict early recurrence after nephrectomy.

Methods

This study included 84 patients with clear cell renal cell carcinoma (cRCC), and 44 subjects without tumor were used as controls. Quantitative RT-PCR was used to measure the CD146 gene expression.

Results

The mean value of CD146 expression in patients with metastatic cRCC (0.0438?±?0.0024) was significantly higher than in those with localized cRCC (0.0374?±?0.0012, P?=?0.018) or in controls (0.0344?±?0.0010, P?=?0.001). Of patients with localized cRCC, those with recurrence had a significantly higher CD146 expression than those without recurrence (P?=?0.029). The univariate analysis showed that CD146 was associated with early recurrence. The recurrence-free survival curve indicated that patients with a high CD146 expression had a significantly higher recurrence rate than those with a low CD146 expression (P?=?0.018).

Conclusions

CD146 gene expression can be useful for predicting early recurrence and stratifying the patients into risk groups for possible adjuvant treatment.     

Tyrosine kinase expression profile in clear cell renal cell carcinoma

Purpose

To profile different tyrosine kinase (TK) expression patterns in clear cell renal carcinoma (ccRCC).

Methods

We analysed mRNA expression levels of 89 receptor and non-receptor TK in corresponding cancer and normal renal tissue from 5 patients with ccRCC using the TaqMan Low-Density Array technology. In order to confirm aberrant TK expressions, a subsequent analysis of 25 ccRCC and corresponding normal renal tissues was performed, applying quantitative real-time PCR. To confirm mRNA expression levels on protein level, we studied ERBB4 and HCK using immunohistochemistry.

Results

A total of 12 TK were significantly upregulated in ccRCC (ABL2, FLT1, BTK, HCK, JAK3, CSF1R, MET, JAK1, MATK, PTPRC, FYN and CSK), coherently 7 TK demonstrated a down-regulation (ERBB4, PDGFRA, NRTK3, SYK, ERBB2, FGFR3 and PTK7). These findings were validated by the utilization of RT-PCR for ABL2, FLT1 BTK, HCK, JAK3, CSF1R, MET, JAK1, MATK and vice versa for ERBB4 and PDGFRA. Immunohistochemistry revealed ERBB4 expression to be significantly lower in ccRCC in comparison to papillary RCC, chromophobe RCC, renal oncocytoma and normal renal tissue (P?P?P?=?0.023), but similar to chromphobe RCC (P?=?0.470), sarcomatoid RCC (P?=?0.754) and normal renal tissue (P?=?0.083). Neither ERBB4 nor HCK were correlated (P?>?0.05) with clinical–pathological parameters.

Conclusion

TK constitute valuable targets for pharmaceutical anti-cancer therapy. ERBB4 and HCK depict significantly lower expression levels in renal cancer tissues.     

SLEEVEPASS: A randomized prospective multicenter study comparing laparoscopic sleeve gastrectomy and gastric bypass in the treatment of morbid obesity: preliminary results

Background

The long-term efficacy of laparoscopic Roux-en-Y gastric bypass (RYGB) in the treatment of morbid obesity has been demonstrated. Laparoscopic sleeve gastrectomy (SG) as a single procedure has shown promising short-term results, but the long-term efficacy of SG has not yet been demonstrated. The aim of this study was to determine the preliminary 30-day morbidity and mortality of RYGB and SG in a prospective multicenter randomized setting.

Methods

A total of 240 morbidly obese (BMI?=?35–66?kg/m2) patients evaluated by a multidisciplinary team were randomized to undergo either RYGB or SG. There were 117 patients in the RYGB group and 121 in the SG group; two patients had to be excluded after randomization. Both study groups were comparable regarding age, gender, BMI, and comorbidities.

Results

There was no 30-day mortality. The median operating time was significantly shorter in the SG group (66?min vs. 94?min, p?p?=?0.292). Nine (7.4 %) SG patients and 20 (17.1 %) RYGB patients had minor complications (p?=?0.023). The overall morbidity was 13.2 % after SG and 26.5 % after RYGB (p?=?0.010). There were three (2.5 %) early reoperations after SG and four (3.3 %) after RYGB (p?=?0.719).

Conclusions

At 30-day analysis SG is associated with a shorter operating time and fewer early minor complications compared to RYGB. There were no significant differences in major complications or early reoperations. Long-term follow-up is required to determine the effect on weight loss, resolution of obesity-related comorbidities, and improvement of quality of life.     

The Diagnostic Accuracy of Transient Elastography for the Diagnosis of Liver Fibrosis in Bariatric Surgery Candidates with Suspected NAFLD

Background

Severe obesity and metabolic syndrome have been implicated in the development of nonalcoholic fatty liver disease (NAFLD). We evaluated the diagnostic value of liver stiffness measurement (LSM), by transient elastography (FibroScan®) in bariatric surgery candidates with suspected NAFLD.

Methods

A total of 100 prospectively included consecutive severely obese subjects underwent bariatric surgery with liver needle biopsy. LSM was performed in the 15 days preceding liver biopsy.

Results

According to Kleiner’s classification, 28 patients had no fibrosis, 50 had stage F1 fibrosis, 13 had stage F2 fibrosis, and nine had stage F3 fibrosis. LSMs were higher in patients with fibrosis stage F ≥2, than in patients with a fibrosis stage below F2 (p?p?p?p?p?=?0.027) were independently correlated with LSM. Homeostasis model assessment (HOMA) index was also significantly and independently correlated with LSM (p?r?=?0.43, p?=?0.01), but not with changes in BMI or weight.

Conclusion

FibroScan® allows the early diagnosis of fibrosis in severely obese patients. Our results also suggest that FibroScan® could identify a subgroup of NAFLD patients at high risk of progressive liver disease and that LSM could be used as a surrogate marker of insulin resistance. Further studies are required to evaluate the prognostic value of FibroScan®.