Duodenal-Jejunal Bypass and Jejunectomy Improve Insulin Sensitivity in Goto-Kakizaki Diabetic Rats Without Changes in Incretins or Insulin Secretion

Gastric bypass surgery can dramatically improve type 2 diabetes. It has been hypothesized that by excluding duodenum and jejunum from nutrient transit, this procedure may reduce putative signals from the proximal intestine that negatively influence insulin sensitivity ( S I ). To test this hypothesis, resection or bypass of different intestinal segments were performed in diabetic Goto-Kakizaki and Wistar rats. Rats were randomly assigned to five groups: duodenal-jejunal bypass (DJB), jejunal resection (jejunectomy), ileal resection (ileectomy), pair-fed sham-operated, and nonoperated controls. Oral glucose tolerance test was performed within 2 weeks after surgery. Baseline and poststimulation levels of glucose, insulin, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured. Minimal model analysis was used to assess S I . S I improved after DJB ( S I = 1.14 ± 0.32 × 10 −4 min −1 ⋅ pM −1 ) and jejunectomy ( S I = 0.80 ± 0.14 × 10 −4 min −1 ⋅ pM −1 ), but not after ileectomy or sham operation/pair feeding in diabetic rats. Both DJB and jejunal resection normalized S I in diabetic rats as shown by S I levels equivalent to those of Wistar rats ( S I = 1.01 ± 0.06 × 10 −4 min −1 ⋅ pM −1 ; P = NS). Glucose effectiveness did not change after operations in any group. While ileectomy increased plasma GIP levels, no changes in GIP or GLP-1 were observed after DJB and jejunectomy. These findings support the hypothesis that anatomic alterations of the proximal small bowel may reduce factors associated with negative influence on S I , therefore contributing to the control of diabetes after gastric bypass surgery

Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma

Background: The aim of this multicenter trial was to prospectively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) and radiotherapy, including quality of life as outcome. Patients and methods: Eligible patients had malignant pleural mesothelioma of all histological types, World Health Organization performance status of zero to two and clinical stage T1-T3, N0-2, M0 disease considered completely resectable. Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP. Postoperative radiotherapy was considered for all patients. Results: In all, 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy. Forty-five patients (74%) underwent EPP and in 37 patients (61%) the resection was complete. Postoperative radiotherapy was initiated in 36 patients. The median survival of all patients was 19.8 months [95% confidence interval (CI) 14.6-24.5]. For the 45 patients undergoing EPP, the median survival was 23 months (95% CI 16.6-32.9). Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82% (N = 36) at baseline and 76% (N = 26) at 3 months after surgery (P = 0.5). Conclusions: The observed rate of operability is promising. A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery. This approach was not associated with an increase in psychological distres

Multicenter phase II trial of preoperative induction chemotherapy followed by chemoradiation with docetaxel and cisplatin for locally advanced esophageal carcinoma (SAKK 75/02)

Background: This multicenter phase II study investigated the efficacy and feasibility of preoperative induction chemotherapy followed by chemoradiation and surgery in patients with esophageal carcinoma. Patients and methods: Patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the esophagus received induction chemotherapy with cisplatin 75 mg/m2 and docetaxel (Taxotere) 75 mg/m2 on days 1 and 22, followed by radiotherapy of 45 Gy (25 × 1.8 Gy) and concurrent chemotherapy comprising cisplatin 25 mg/m2 and docetaxel 20 mg/m2 weekly for 5 weeks, followed by surgery. Results: Sixty-six patients were enrolled at eleven centers and 57 underwent surgery. R0 resection was achieved in 52 patients. Fifteen patients showed complete, 16 patients nearly complete and 26 patients poor pathological remission. Median overall survival was 36.5 months and median event-free survival was 22.8 months. Squamous cell carcinoma and good pathologically documented response were associated with longer survival. Eighty-two percent of all included patients completed neoadjuvant therapy and survived for 30 days after surgery. Dysphagia and mucositis grade 3/4 were infrequent (<9%) during chemoradiation. Five patients (9%) died due to surgical complications. Conclusions: This neoadjuvant, taxane-containing regimen was efficacious and feasible in patients with locally advanced esophageal cancer in a multicenter, community-based setting and represents a suitable backbone for further investigatio

Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: a randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK

Background: To determine the activity and tolerability of adding cetuximab to the oxaliplatin and capecitabine (XELOX) combination in first-line treatment of metastatic colorectal cancer (MCC). Patients and methods: In a multicenter two-arm phase II trial, patients were randomized to receive oxaliplatin 130 mg/m2 on day 1 and capecitabine 1000 mg/m2 twice daily on days 1-14 every 3 weeks alone or in combination with standard dose cetuximab. Treatment was limited to a maximum of six cycles. Results: Seventy-four patients with good performance status entered the trial. Objective partial response rates after external review and radiological confirmation were 14% and 41% in the XELOX and in the XELOX + Cetuximab arm, respectively. Stable disease has been observed in 62% and 35% of the patients, with 76% disease control in both arms. Cetuximab led to skin rash in 65% of the patients. The median overall survival was 16.5 months for arm A and 20.5 months for arm B. The median time to progression was 5.8 months for arm A and 7.2 months for arm B. Conclusion: Differences in response rates between the treatment arms indicate that cetuximab may improve outcome with XELOX. The correct place of the cetuximab, oxaliplatin and fluoropyrimidine combinations in first-line treatment of MCC has to be assessed in phase III trial

Upper gut heat shock proteins HSP70 and GRP78 promote insulin resistance, hyperglycemia, and non-alcoholic steatohepatitis

A high-fat diet increases the risk of insulin resistance, type-2 diabetes, and non-alcoholic steato-hepatitis. Here we identified two heat-shock proteins, Heat-Shock-Protein70 and Glucose-Regulated Protein78, which are increased in the jejunum of rats on a high-fat diet. We demonstrated a causal link between these proteins and hepatic and whole-body insulin-resistance, as well as the metabolic response to bariatric/metabolic surgery. Long-term continuous infusion of Heat-Shock-Protein70 and Glucose-Regulated Protein78 caused insulin-resistance, hyperglycemia, and non-alcoholic steato-hepatitis in rats on a chow diet, while in rats on a high-fat diet continuous infusion of monoclonal antibodies reversed these phenotypes, mimicking metabolic surgery. Infusion of these proteins or their antibodies was also associated with shifts in fecal microbiota composition. Serum levels of Heat-Shock-Protein70 and Glucose-Regulated Protein78were elevated in patients with non-alcoholic steato-hepatitis, but decreased following metabolic surgery. Understanding the intestinal regulation of metabolism may provide options to reverse metabolic diseases

Surfactant Protein D, a Marker of Lung Innate Immunity, Is Positively Associated With Insulin Sensitivity

Impaired lung function and innate immunity have both attracted growing interest as a potentially novel risk factor for glucose intolerance, insulin resistance, and type 2 diabetes. We aimed to evaluate whether surfactant protein D (SP-D), a lung-derived innate immune protein, was behind these associations

Effect of Contemporary Bariatric Surgical Procedures on Type 2 Diabetes Remission. A Population-Based Matched Cohort Study.

OBJECTIVE: The objective of the study is to evaluate the effect of gastric banding, gastric bypass and sleeve gastrectomy on medium to long-term diabetes control in obese participants with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: Matched cohort study using primary care electronic health records from the UK Clinical Practice Research Datalink. Obese participants with type 2 diabetes who received bariatric surgery from 2002 to 2014 were compared with matched control participants who did not receive BS. Remission was defined for each year of follow-up as HbA1c <6.5 % and no antidiabetic drugs prescribed. RESULTS: There were 826 obese participants with T2DM who received bariatric surgery including adjustable gastric banding (LAGB) 220; gastric bypass (GBP) 449; or sleeve gastrectomy (SG) 153; with four procedures undefined. Mean HbA1c declined from 8.0 % before BS to 6.5 % in the second postoperative year; proportion with HbA1c <6.5 % (<48 mmol/mol) increased from 17 to 47 %. The proportion of patients in remission was 30 % in the second year, being 20 % for LAGB, 34 % for GBP and 38 % for SG. The adjusted relative rate of remission over the first six postoperative years was 5.97 (4.86 to 7.33, P < 0.001) overall; for LAGB 3.32 (2.27 to 4.86); GBP 7.16 (5.64 to 9.08); and SG 6.82 (5.05 to 9.19). Rates of remission were maintained into the sixth year of follow-up. CONCLUSIONS: Remission of diabetes may continue for up to 6 years after bariatric surgical procedures. Diabetes outcomes are generally more favourable after gastric bypass or sleeve gastrectomy than LAGB

Feasibility and acceptance of electronic monitoring of symptoms and syndromes using a handheld computer in patients with advanced cancer in daily oncology practice

Purpose: We investigated the feasibility and acceptance of electronic monitoring of symptoms and syndromes in oncological outpatient clinics using a PALM (handheld computer). Methods: The assessment of a combination of symptoms and clinical benefit parameters grouped in four pairs was tested in a pilot phase in advanced cancer patients. Based on these experiences, the software E-MOSAIC was developed, consisting of patient-reported symptoms and nutritional intake and objective assessments (weight, weight loss, performance status and medication for pain, fatigue, and cachexia). E-MOSAIC was then tested in four Swiss oncology centers. In order to compare the methods, patients completed the E-MOSAIC as a paper and a PALM version. Preferences of version and completion times were collected. Assessments were compared using Wilcoxon signed-rank tests , and the test-retest reliability was evaluated. Results: The pilot phase was completed by 22 patients. Most patients and physicians perceived the assessment as useful. Sixty-two patients participated in the feasibility study. Twelve patients reported problems (understanding, optical, tactile), and five patients could not complete the assessment. The median time to complete the PALM-based assessment was 3min. Forty-nine percent of patients preferred the PALM, 23% preferred a paper version, and 28% of patients had no preference. Paper vs. PALM revealed no significant differences in symptoms, but in nutritional intake (p = 0.013). Test-retest (1h, n = 20) reliability was satisfactory (r = 073-98). Conclusion: Electronic symptom and clinical benefit monitoring is feasible in oncology outpatient clinics and perceived as useful by patients, oncology nurses, and oncologists. E-MOSAIC is tested in a prospective randomized trial

High accuracy 234U(n,f) cross section in the resonance energy region

New results are presented of the 234U neutron-induced fission cross section, obtained with high accuracy in the resonance region by means of two methods using the 235U(n,f) as reference. The recent evaluation of the 235U(n,f) obtained with SAMMY by L. C. Leal et al. (these Proceedings), based on previous n-TOF data [1], has been used to calculate the 234U(n,f) cross section through the 234U/235U ratio, being here compared with the results obtained by using the n-TOF neutron flux