Background
The aim of the study was to evaluate the safety and effectiveness of a novel closed-loop gastric electric stimulation device (abiliti
®
system) featuring a transgastric sensor to detect ...food intake and an accelerometer to record physical activity to induce and maintain lifestyle changes to treat obesity.
Methods
In a prospective, multi-center study, 34 obese subjects (BMI of 42.1 ± 5.3 kg/m
2
) who passed an eligibility evaluation were implanted with the abiliti system. Safety evaluation included an endoscopic exam to assess the intragastric electrode healing. Efficacy evaluation at 1 year of therapy included weight loss, improvements in eating, and exercise behavior and quality of life.
Results
The transgastric implant controlled by endoscopy was stable for all participants. At 12 months (12 M) the mean excess weight loss (EWL) was 28.7 % (95%CI, 34.5 to 22.5 %), and mean reduction in BMI was 4.8 ± 3.2 kg/m
2
. At 27 months (27 M), the EWL was 27.5 % (95 % CI, 21.3 % to 33.7 %). Eating behavior, evaluated by the “Three Factor Eating Questionnaire”, showed a significant increase in the cognition factor and decrease in the disinhibition and hunger factors at 12 M in comparison to baseline (
p
< 0.001). Participants significantly increased their weekly physical activity (
p
< 0.001). Quality of life was improved in 55.2 % of the patients.
Conclusions
Gastric electrical stimulation with abiliti system in obese participants is well tolerated and leads to significant 12 M weight loss, which was stable to 27 M. We suggest that weight loss is achieved due to the assessed alteration of eating behavior in particular the reduction in disinhibition and hunger, and the measured increase in physical activity.
Backround
Diabetes surgery in nonobese or moderately obese patients is an emerging topic. The identification of preoperative factors predicting diabetes outcome following bariatric surgery, ...especially for metabolic nonresponders, is imperative.
Methods
Between 2005 and 2011, 235 patients underwent bariatric surgery for morbid obesity. Eighty-two of 235 patients had type 2 diabetes mellitus (T2DM). Data from this subgroup were investigated with univariate and multivariate analyses to identify predictors for metabolic nonresponse after surgery.
Results
Diabetes did not improve in 17/82 patients within 3 months after surgery. No correlation between excess body weight loss and metabolic response was detected. In univariate analysis, preoperative duration of diabetes was significantly longer in the nonresponder group (9.146 vs. 6.270 years; *
p
= 0.016), preoperative HbA1c levels were significantly higher among the nonresponders than among the responders (8.341 vs. 7.781 %; *
p
= 0.033), and more patients in the nonresponder group were reliant on a multi-drug approach preoperatively (*
p
= 0.045). In multivariate analysis, age, preoperative doses of insulin, and preoperative oral antidiabetics showed positive correlation to metabolic nonresponse after surgery (*
p
= 0.04; *
p
= 0.021; *
p
= 0.021). Metabolic failure rate was lower after Roux-en-Y gastric bypass compared to other bariatric procedures (**
p
= 0.008).
Conclusions
A long history of preoperative T2DM, high preoperative HbA1c levels, and a preoperative therapy consisting of diverse approaches to diabetes treatment may be factors predicting failure of diabetes improvement in the early postoperative course after bariatric surgery. Age, preoperative insulin, and oral antidiabetic medication can be regarded as independent, significant predictors for metabolic outcome after bariatric surgery.
The search for the causes of neurodegenerative disorders is a major theme in brain research. Acquired disturbances of several aspects of cellular metabolism appear pathologically important in ...sporadic Alzheimer's disease (SDAT). Among these brain glucose utilisation is reduced in the early stages of the disease and the regulatory enzymes important for glucose metabolism are reduced. In the brain, insulin, insulin-like growth factors and their receptors regulate glucose metabolism and promote neuronal growth. To detect changes in the functional activity of the brain insulin neuromodulatory system of SDAT patients, we determined the concentrations of insulin and c-peptide as well as insulin receptor binding and IGF-I receptor binding in several regions of postmortem brain cortex during aging and Alzheimer's disease. Additionally, we performed immunohistochemical staining with antibodies against insulin in neocortical brain areas in SDAT and controls. We show for the first time that insulin and c-peptide concentration in the brain are correlated and decrease with aging, as do brain insulin receptor densities. Weak insulin-immunoreactivity could be demonstrated histochemically in pyramidal neurons of controls, whereas in SDAT a stronger insulin-immunoreactivity was found. On a biochemical level, insulin and c-peptide levels were reduced compared to middle-aged controls, but were unchanged compared to age-matched controls. Brain insulin receptor densities in SDAT were decreased compared to middle-aged controls, but increased in comparison to age-matched controls. IGF-I receptor densities were unchanged in aging and in SDAT. Tyrosine kinase activity, a signal transduction mechanism common to both receptor systems, was reduced in SDAT in comparison to middle-aged and age-matched control groups. These data are consistent with a neurotrophic role of insulin in the human brain and a disturbance of insulin signal transduction in SDAT brain and favor the hypothesis that insulin dependent functions may be of pathogenetic relevance in sporadic SDAT.
Background
The purpose of this work was to perform a single institution comparison between preoperative short-course radiotherapy (SC-RT) and long-course radiochemotherapy (LC-RCHT) for locally ...advanced rectal cancer.
Methods
A total of 225 patients with clinical stage UICC II–III rectal cancer were treated with SC-RT (29 Gy in 10 twice daily fractions followed by immediate surgery; n = 108) or LC-RCHT (54 Gy in 28 fractions with simultaneous 5-fluorouracil (5-FU) ± oxaliplatin chemotherapy followed by delayed surgery; n = 117). All patients in the LC-RCHT cohort and patients in the SC-RT with pathological UICC stage ≥ II received adjuvant chemotherapy. Before 2004, the standard of care was SC-RT with LC-RCHT reserved for patients where downstaging was considered as required for sphincter preservation or curative resection. In the later period, SC-RT was practiced only for patients unfit for radiochemotherapy.
Results
Patients in the LC-RCHT cohort had a significantly higher proportion of cT4 tumors, clinical node positivity, and lower tumor location. The 5-year local control (LC) and overall survival (OS) were 91% and 66% without differences between the SC-RT and LC-RCHT groups. Acute toxicity was increased during LC-RCHT (grade ≥ II 1% vs. 33%) and there were no differences in postoperative complications. Severe late toxicity grade ≥ III was increased after SC-RT (12% vs. 3%). Of patients aged > 80 years, 7 of 7 patients and 4 of 9 patients received curative surgery after SC-RT and LC-RCHT, respectively.
Conclusion
Despite the fact that patients with worse prognostic factors were treated with LC-RCHT, there were no significant differences in LC and OS between the SC-RT and LC-RCHT group. Age > 80 years was identified as a significant risk factor for LC-RCHT and these patients could be treated preferably with SC-RT.
Anti-EGFR targeted therapy is a potent strategy in the treatment of metastatic colorectal cancer (mCRC) but activating mutations in the KRAS gene are associated with poor response to this treatment. ...Therefore, KRAS mutation analysis is employed in the selection of patients for EGFR-targeted therapy and various studies have shown a high concordance between the mutation status in primary CRC and corresponding metastases. However, although development of therapy related resistance occurs also in the context of novel drugs such as tyrosine kinase-inhibitors the effect of the anti-EGFR treatment on the KRAS/BRAF mutation status itself in recurrent mCRC has not yet been clarified. Therefore, we analyzed 21 mCRCs before/after anti-EGFR therapy and found a pre-/posttherapeutic concordance of the KRAS/BRAF mutation status in 20 of the 21 cases examined. In the one discordant case, further analyses revealed that a tumor mosaicism or multiple primary tumors were present, indicating that anti-EGFR therapy has no influence on KRAS/BRAF mutation status in mCRC. Moreover, as the preselection of patients with a KRASwt genotype for anti-EGFR therapy has become a standard procedure, sample sets such ours might be the basis for future studies addressing the identification of potential anti-EGFR therapy induced genetic alterations apart from KRAS/BRAF mutations.
Zahlreiche nationale und internationale Studien zeigen den hohen Stellenwert der Adipositaschirurgie in der Behandlung morbid adipöser Patienten mit entsprechenden metabolischen Begleiterkrankungen. ...Langzeitergebnisse weisen aber auch darauf hin, dass die alleinige operative Therapie zu kurz greift. Nur die interdisziplinäre Vernetzung konservativer und operativer Therapieansätze führt langfristig zu einem zufriedenstellenden Ergebnis.
The development of therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models generating both metastases and the dissemination ...of tumor cells.
To prove the efficiency of orthotopic implantation concerning induction of minimal residual disease (MRD) colorectal cancer tissue from 10 patients was transplanted orthotopically into nude mice. In the intraportal injection model 1 x 10(6) HT-29 human colon cancer cells were injected. We investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human colon cancer cells in bone marrow.
Following orthotopic implantation of human colon cancer tissue the lymph node and hepatic metastasis rates were low. MRD as reflected by CK-20 positivity of the bone marrow was present in 22.2%. The intraportal injection of 1 x 10(6) HT-29 human colon cancer cells produced hepatic metastases in up to 89% of all animals. The intraportal injection of 1 x 10(6) cells also generated MRD in the bone marrow in 63% of animals.
The intraportal injection model represents a biologically relevant and adequate animal model for the induction of both reproducible hepatic metastasis and MRD in the bone marrow. In this regard it seems to be superior to the orthotopic implantation model.
The review article "Operative Techniques and Outcomes in Metabolic Surgery: Sleeve Gastrectomy" by Hüttl et al. is concerned with laparoscopic sleeve stomach operations ("sleeve gastrectomy") for the ...surgical treatment of morbid obesity (Zentralblatt für Chirurgie 2009; 134: 24-31). After an analysis of the available literature and own results, the authors concluded that the laparoscopic sleeve operation is established today as an effective standard procedure in the therapy for obesity.We would like to comment on the content of this article.
Although extremely rare, the group of primary malignant tumors of the aorta (PMTA) exhibits enormous histologic heterogeneity. In most cases, diagnosis is established late in the course of the ...disease; the median survival time is only a few months. We present the case of a 75-year-old patient with an intimal angiosarcoma of the infrarenal abdominal aorta and discuss the clinical presentation, histopathologic diagnosis, and classification of primary aortic sarcomas. A critical review of the diagnostic and therapeutic management in this case revealed that the atypical aortic thrombus should have prompted a comprehensive preoperative diagnostic work-up, specifically with magnetic resonance tomography of the aorta and bone scintigraphy.
Background The aim of the study was to evaluate the safety and effectiveness of a novel closed-loop gastric electric stimulation device (abiliti^sup ^ system) featuring a transgastric sensor to ...detect food intake and an accelerometer to record physical activity to induce and maintain lifestyle changes to treat obesity. Methods In a prospective, multi-center study, 34 obese subjects (BMI of 42.1±5.3 kg/m^sup 2^) who passed an eligibility evaluation were implanted with the abiliti system. Safety evaluation included an endoscopic exam to assess the intragastric electrode healing. Efficacy evaluation at 1 year of therapy included weight loss, improvements in eating, and exercise behavior and quality of life. Results The transgastric implant controlled by endoscopy was stable for all participants. At 12 months (12 M) the mean excess weight loss (EWL) was 28.7 % (95%CI, 34.5 to 22.5 %), and mean reduction in BMI was 4.8±3.2 kg/m^sup 2^. At 27 months (27 M), the EWL was 27.5 % (95 % CI, 21.3 % to 33.7 %). Eating behavior, evaluated by the "Three Factor Eating Questionnaire", showed a significant increase in the cognition factor and decrease in the disinhibition and hunger factors at 12 M in comparison to baseline (p<0.001). Participants significantly increased their weekly physical activity (p<0.001). Quality of life was improved in 55.2 % of the patients. Conclusions Gastric electrical stimulation with abiliti system in obese participants is well tolerated and leads to significant 12 M weight loss, which was stable to 27 M. We suggest that weight loss is achieved due to the assessed alteration of eating behavior in particular the reduction in disinhibition and hunger, and the measured increase in physical activity.
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