Adaptive changes in pancreas post Roux-en-Y gastric bypass induced weight loss.

BACKGROUND: Obesity has been shown to trigger adaptive increases in pancreas parenchymal and fat volume. Consecutively, pancreatic steatosis may lead to beta-cell dysfunction. However, it is not known whether the pancreatic tissue components decrease with weight loss and pancreatic steatosis is reversible following Roux-en-Y gastric bypass (RYGB). Therefore, the objective of the study was to investigate the effects of RYGB-induced weight loss on pancreatic volume and glucose homeostasis. METHODS: Eleven patients were recruited in the Obesity Centre of the University Medical Centre Hamburg-Eppendorf. Before and 6 months after RYGB, total GLP-1 levels were measured during oral glucose tolerance test. To assess changes in visceral adipose tissue and pancreatic volume, MRI was performed. Measures of glucose homeostasis and insulin indices were assessed. Fractional beta-cell area was estimated by correlation with the C-peptide-to-glucose ratio; beta-cell mass was calculated by the product of beta-cell area and pancreas parenchymal weight. RESULTS: Pancreas volume decreased from 83.8 (75.7-92.0) to 70.5 (58.8-82.3) cm3 (mean [95% CI], P = .001). The decrease in total volume was associated with a significant decrease in fat volume. Fasting insulin and C-peptide were lower post RYGB. HOMA-IR levels decreased, whereas insulin sensitivity increased (P = .03). This was consistent with a reduction in the estimated beta-cell area and mass. CONCLUSIONS: Following RYGB, pancreatic volume and steatosis adaptively decreased to "normal" levels with accompanying improvement in glucose homeostasis. Moreover, obesity-driven beta-cell expansion seems to be reversible; however, future studies must define a method to more accurately estimate functional beta-cell mass to increase our understanding of glucose homeostasis after RYGB.

Intraoperative Ventilation of Morbidly Obese Patients Guided by Transpulmonary Pressure.

BACKGROUND: Bariatric surgery has proven a successful approach in the treatment of morbid obesity and its concomitant diseases such as diabetes mellitus and arterial hypertension. Aiming for optimal management of this challenging patient cohort, tailored concepts directly guided by individual patient physiology may outperform standardized care. Implying esophageal pressure measurement and electrical impedance tomography-increasingly applied monitoring approaches to individually adjust mechanical ventilation in challenging circumstances like acute respiratory distress syndrome (ARDS) and intraabdominal hypertension-we compared our institutions standard ventilator regimen with an individually adjusted positive end expiratory pressure (PEEP) level aiming for a positive transpulmonary pressure (P L) throughout the respiratory cycle. METHODS: After obtaining written informed consent, 37 patients scheduled for elective bariatric surgery were studied during mechanical ventilation in reverse Trendelenburg position. Before and after installation of capnoperitoneum, PEEP levels were gradually raised from a standard value of 10 cm H2O until a P L of 0 +/- 1 cm H2O was reached. Changes in ventilation were monitored by electrical impedance tomography (EIT) and arterial blood gases (ABGs) were obtained at the end of surgery and 5 and 60 min after extubation, respectively. RESULTS: To achieve the goal of a transpulmonary pressure (P L) of 0 cm H2O at end expiration, PEEP levels of 16.7 cm H2O (95% KI 15.6-18.1) before and 23.8 cm H2O (95% KI 19.6-40.4) during capnoperitoneum were necessary. EIT measurements confirmed an optimal PEEP level between 10 and 15 cm H2O before and 20 and 25 cm H2O during capnoperitoneum, respectively. Intra- and postoperative oxygenation did not change significantly. CONCLUSION: Patients during laparoscopic bariatric surgery require high levels of PEEP to maintain a positive transpulmonary pressure throughout the respiratory cycle. EIT monitoring allows for non-invasive monitoring of increasing PEEP demand during capnoperitoneum. Individually adjusted PEEP levels did not result in improved postoperative oxygenation.

Endoscopic ultrasound-guided drainage of abdominal fluid collections after pancreatic surgery: Efficacy and long-term follow-up.

BACKGROUND/PURPOSE: Endoscopic ultrasound-guided drainage (EUS-GD) of postoperative abdominal fluid collections (POFC) following pancreatic surgery is used as an alternative or complement to percutaneous drainage (PD) procedure. The present single-center retrospective study evaluates its efficacy and safety. METHOD: We included consecutive cases with POFC treated by EUS-GD between September 2009 and November 2014 in our department. Technical success, long-term clinical success, recurrence rate and need for surgery were analyzed. RESULTS: 24 procedures in 20 patients (95 % after pancreatic resection) were assessed. Indications for surgery included tumors/lesions located in the pancreas (15/20), chronic pancreatitis (3/20) and duodenal adenoma not completely resectable endoscopically (2/20). EUS-GD was performed within a median of 30 days (IQR: 8.25) for a median fluid collection size of 72.5 mm (IQR: 46.25), requiring a mean of 1.2 sessions with placement of a mean of 2.1 plastic stents (7 Fr/10 Fr) per patient for a mean of 89 days (IQR: 127). Microbiology of aspirated fluid revealed positive cultures in 13 patients, mostly polymicrobial, isolated positive for fungal and 3 multidrug-resistant gram negative (MRGN) in 4 cases. An additional transpapillary drainage was inserted in 1/20 patients. 4/20 patients received PD, mostly before EUS-GD. Technical and clinical success was achieved in 20/20 (100 %) and 18/20 (90 %) patients, respectively, while 2 patients required re-operation. During follow-up (median 630 days after stent removal, range: 45 - 2160), recurrence occurred in 1/18 (5.5 %) patient that was referred for surgery. No death or severe adverse events were noted. CONCLUSION: EUS-GD is an effective, minimally invasive and safe method for therapy of POFC after pancreatic surgery offering long-term remission in about 95 % of cases.

[Indications for laparoscopic pancreas operations: results of a consensus conference and the previous laparoscopic pancreas register]. / Indikation zur laparoskopischen Pankreasoperation: Ergebnisse einer Konsensuskonferenz und des bisherigen laparoskopischen Pankreasregisters.

Laparoscopic pancreatic surgery is not common practice in Germany and is only carried out in approximately 20 clinics but with an increasing trend. The reasons for this are manifold, such as the current selection of patients and both skills in laparoscopic and pancreatic surgery are necessary to perform this operation safely. In 2008 a registry called "Laparoscopic pancreatic surgery" was implemented to collect enough data in Germany to find out whether the resection is safe, feasible and beneficial for the patient.For further development of new laparoscopic techniques new data is needed. A group of experts performing laparoscopic pancreatic surgery in Germany supplied their data for the German registry for laparoscopic pancreatic resection and a consensus conference about the indications became necessary. This consensus conference discussed in particular the indications for laparoscopic pancreatic resection. A consensus was found by all members of the conference utilizing currently available evidence-based data.It was suggested that all data of laparoscopic pancreatic surgery should be evaluated in the German Registry. A consensus was made which diseases were either suitable for laparoscopic resection or not suitable or suitable in selected cases.

Near-surface structure of a bicontinuous microemulsion with a transition region.

The lamellar ordering of bicontinuous microemulsions adjacent to a planar hydrophilic wall is investigated experimentally by grazing-incidence small-angle neutron scattering and theoretically by computer simulations. It is shown that precise depth information in neutron scattering can be obtained by tuning the scattering length density of the overall microemulsion. Neutron reflectometry completes the characterization. The nucleation of a lamellar phase at the wall is observed, and a perforated lamellar transition region is identified at the lamellar-microemulsion interface. The thickness of the lamellar region is about 400 Å, which corresponds to two bilayers.

Compression of random coils due to macromolecular crowding: scaling effects.

The addition of a macromolecular crowding agent to a dilute solution of polymer exerts a compressive force that tends to reduce the size of the chain. We study here the effect of changing the size ratio between the random coil and the crowding agent. The compression occurs at lower crowding agent concentration, Φ when polymer molecular weight increases. The Flory exponent ν(Φ) decreases from ν(0)≃0.48 in water down to 0.3 with macromolecular crowding. The effective polymer-polymer interactions change from repulsive to strongly attractive inducing aggregation of the chains. This effect changes drastically for larger polymer sizes, being much more pronounced at high molecular weights.

Rehabilitation Programs for Cystic Fibrosis - View from a CF Center.

BACKGROUND: Rehabilitation programs are comprehensive interventions which effectively improve the health status and reduce costs in chronic respiratory illnesses. Because patients with cystic fibrosis have been discouraged to participate for concerns of microbial cross infection, the efficacy of systematic rehabilitation is unknown for this group. METHODS: We retrospectively studied 142 cystic fibrosis patients aged 2-46 years who participated in rehabilitation programs taking place in Germany/Switzerland and in Israel, focusing on changes in lung function and weight. RESULTS: During 172 stays in 97 patients in Israel and 68 stays in 45 patients rehabilitating in Germany/Switzerland, overall lung function and weight improved. Outcome did not differ between Israel and German/Swiss sites. Interestingly, lung function improved during the initial phase of the stay, whereas weight gain was sustained throughout. The study uncovered gaps in reporting sufficient individual outcome information back to the admitting centre. CONCLUSIONS: Rehabilitation programs specified for cystic fibrosis patients need to be assessed prospectively to optimize treatment of this life limiting condition.

Association of antidiabetic therapies to glycemic control and to body weight in type 2 diabetes: a German multicenter analysis on 9294 patients.

Glycemic and body weight control are two outstanding goals in the treatment of patients with type 2 diabetes that often are not appropriately achieved. This observational study evaluates whether treatment by quality controlled diabetes centers generates an improvement in this regard and focuses on associations with different therapies. Data of 9.294 type 2 diabetic patients (mean age 66.9±11.6 years, mean diabetes duration 12.4±9.2 years) from 103 German diabetes centers were assessed by a standardized, prospective, computer-based diabetes care and outcome documentation system (DPV-Wiss-database). Therapeutic concepts included lifestyle intervention (n=1.813), oral antidiabetics (OAD, n=1.536), insulin (n=4.504) and insulin plus OAD (n=1.441). HbA1c and body weight were compared before and after a stable therapeutical period of 1.07±0.3 years. Change in HbA1c (%): all patients 7.4±1.6-7.0±1.3, lifestyle intervention 7.5±1.9-6.9±1.5, OAD 6.7±1.1-6.5±1.0, insulin 7.6±1.6-7.2±1.4, insulin plus OAD 7.5±1.5-7.2±1.3; each p≤0.05. Change in body weight (kg): all patients +0.08±0.07, n. s.; lifestyle intervention -0.28±0.20, OAD -0.56±0.13, each p<0.05 [metfomin -0.77±0.21, sulfonylurea drugs -0.75±0.34, each p<0.05; glitazones +0.62±0.70, α-glucosidase inhibitors -0.22±0.76, each n. s.], insulin +0.27±0.10, insulin plus OAD +0.63±0.14, each n. s. In summary, lifestyle, metformin or sulfonylurea drug treatment resulted in HbA1c-values below 7.0% plus a significant weight reduction. Insulin treatment-associated concepts resulted in HbA1c-values slightly above 7.0% without body weight alterations. These "real life" data underline that a specialised and quality controlled diabetes care is able to achieve significant treatment results even in patients with disease progression and a high proportion of insulin therapies.

[Operative technique and outcome in metabolic surgery: conventional and banded gastric bypass]. / Operative Technik und deren Outcome in der metabolischen Chirurgie: Konventioneller und Banded Gastric Bypass.

BACKGROUND: The prevalence of morbid obesity and its sequelae is increasing in Germany, Europe and worldwide. Bariatric surgery is thus gaining in importance for the treatment of patients with malignant obesity. Creation of a gastric bypass is one of the most frequently performed procedures for obesity. DISCUSSION: The gastric bypass has been used -since 1966 as a surgical means of weight reduction in obese patients. In the mean time various modifications have been developed. Thus, for example, the laparoscopic procedure represents the current standard. After the operation most patients experience an excess weight loss (EWL) of between 61 and 83 %. The comorbidities of obesity are also markedly improved and in a high percentage even cured after the operation. It is worthy of note that diabetes mellitus type II improves shortly after the operation even before any weight loss has occurred. The suggests that the operation induces more than "just" a loss of weight. CONCLUSION: For decades the gastric bypass has been a well known standard operation of overweight and, in addition to the reduction in weight, is also a therapy for diabetes mellitus -type II.

[A sizeable chance--surgical management of profound obesity concurrent with post-traumatic osteoarthrosis]. / Dicke Chance -- die operative Behandlung der schweren Adipositas bei posttraumatischer Osteoarthrose.

In times of plentiful nutrition an environmental advantage turns into a problem - obesity. Apart from an increase in morbidity and overall mortality the development of osteoarthrosis is well documented. Pre-arthrotic conditions may arise from trauma and can lead, depending on the pattern of injury, to full-blown arthrosis. The presence of obesity can play the role of a relevant progressive factor in this setting. Here we report about the case of an obese man (BMI 53.5 kg/m(2)), who suffered a fracture of the femoral head with acetabular participation (Pipkin IV) as well as a fracture of the tibial plateau. Operative management and rehabilitation were followed by gastric bypass surgery for weight reduction. The case is discussed with regard to the present literature.

Is the frequency of self-monitoring of blood glucose related to long-term metabolic control? Multicenter analysis including 24,500 patients from 191 centers in Germany and Austria.

Blood glucose measurements are generally accepted components of a modern diabetes self-management. The value of self-monitoring of blood glucose (SMBG) is, however, discussed controversially and only a few studies addressed the efficacy of SMBG under real-life conditions so far. In order to investigate whether the frequency of SMBG is related to long-term metabolic control, data from the DPV-Wiss-database, a standardized,prospective, computer-based documentation of diabetes care and outcome, were analyzed for patients with type 1(n = 19,491) and type 2 (n = 5,009) diabetes from 191 centers in Germany and Austria. Local HbA1c reference ranges were mathematically adjusted to the DCCT reference. For each patient, data from the most recent year of diabetes care were used. On average,patients with type 1 diabetes performed 4.4 blood glucose measurements/day. Corrected for age, gender, diabetes duration,on intensified (>or=4 daily injections or CSII) therapy (HbA1c reduction of 0.32% for one additional SMBG/day) compared to patients on conventional (1-3 daily injections) therapy(HbA1c-reduction of 0.16% for one additional SMBG/day). In 2,021 patients with insulin-treated type 2 diabetes (2.7 measurements/day), more frequent SMBG was associated with better metabolic control (HbA1c-reduction of 0.16% for one additionalSMBG/day, p < 0.0001), while in 2,988 patients on OAD or diet alone (2.0 measurements/day), more frequent blood glucose measurements were associated with higher HbA1c-levels(HbA1c-increase of 0.14% for one additional SMBG/day,p < 0.0001). These data indicate that more frequent SMBG are associated with better metabolic control in both, patients with type 1 and insulin-treated type 2 diabetes. Since no benefit ofSMBG on metabolic control was found in patients with type 2 diabetes on OAD or diet alone, SMBG should primarily be recommended for those patients with suboptimal metabolic control whereas the benefit of SHBG in non-insulin-treated patients with adequate HbA1c-levels remains uncertain.insulin therapy and center difference, the SMBG frequency was associated with better metabolic control (HbA1c-reduction of0.26% for one additional SMBG/day, p < 0.0001). HbA1c-reduction with higher frequency of SMBG was more pronounced in patients Blood glucose measurements are generally accepted components of a modern diabetes self-management. The value of self-monitoring of blood glucose (SMBG) is, however, discussed controversially and only a few studies addressed the efficacy of SMBG under real-life conditions so far. In order to investigate whether the frequency of SMBG is related to long-term metabolic control, data from the DPV-Wiss-database, a standardized,prospective, computer-based documentation of diabetes care and outcome, were analyzed for patients with type 1(n = 19,491) and type 2 (n = 5,009) diabetes from 191 centers in Germany and Austria. Local HbA1c reference ranges were mathematically adjusted to the DCCT reference. For each patient, data from the most recent year of diabetes care were used. On average,patients with type 1 diabetes performed 4.4 blood glucose measurements/day. Corrected for age, gender, diabetes duration,insulin therapy and center difference, the SMBG frequency wasassociated with better metabolic control (HbA1c-reduction of 0.26% for one additional SMBG/day, p < 0.0001). HbA1c-reduction with higher frequency of SMBG was more pronounced in patients on intensified (>or= 4 daily injections or CSII) therapy (HbA1c reduction of 0.32% for one additional SMBG/day) compared to patients on conventional (1-3 daily injections) therapy(HbA1c-reduction of 0.16% for one additional SMBG/day). In 2,021 patients with insulin-treated type 2 diabetes (2.7 measurements/day), more frequent SMBG was associated with better metabolic control (HbA1c-reduction of 0.16% for one additionalSMBG/day, p < 0.0001), while in 2,988 patients on OAD or diet alone (2.0 measurements/day), more frequent blood glucose measurements were associated with higher HbA1c-levels(HbA1c-increase of 0.14% for one additional SMBG/day, p < 0.0001). These data indicate that more frequent SMBG are associated with better metabolic control in both, patients with type 1 and insulin-treated type 2 diabetes. Since no benefit of SMBG on metabolic control was found in patients with type 2 diabetes on OAD or diet alone, SMBG should primarily be recommended for those patients with suboptimal metabolic control whereas the benefit of SHBG in non-insulin-treated patients with adequate HbA1c-levels remains uncertain.

Influence of thymidylate synthase and p53 protein expression on clinical outcome in patients with colorectal cancer.

AIMS: Thymidylate synthase (TS) and tumor suppressor p53 are two proteins with an influence on tumor resistance to radio-chemotherapy that is well known. For this reason we tested the effect of TS and p53 expression on clinical outcome (tumor recurrence and survival) in patients after curative tumor resection, especially in patients who received adjuvant radio-chemotherapy. PATIENTS AND METHODS: A total of 120 patients with colorectal cancer were included in the study. A curative resection was possible in 83 patients, and 30 of this group received adjuvant therapy. For the immunohistochemical staining of tumor specimens, monoclonal antibody (mAb) TS 106 against TS and mAb DO-1 against p53 protein were used. TS positivity was defined as a moderate to high staining intensity in the cytoplasma of cells and p53 positivity as nuclear staining of tumor cells in >10% of these cells. RESULTS: Thymidylate synthase immunoreactivity was found in 59% of all cases and p53 staining in 51%. No relation between clinicopathological features and p53 expression was found in contrast to TS expression, where a highly significant association of TS-positive cases with tumor invasion (pT) was observed. Curatively resected patients with a TS-positive tumor developed tumor recurrence/distant metastases significantly more often than TS negative tumors. The same result was found when comparing p53-positive with p53-negative tumors and TS+/p53+ with TS-/p53- tumors. TS expression was highly significantly associated with poor survival and was the strongest independent prognostic factor in multivariate analysis, followed by lymph node status. CONCLUSION: Thymidylate synthase expression seems to be an independent prognostic factor and a possible predictor of tumor recurrence in patients with colorectal cancer.

Quantum states and generalized observables: a simple proof of Gleason's theorem.

A quantum state can be understood in a loose sense as a map that assigns a value to every observable. Formalizing this characterization of states in terms of generalized probability distributions on the set of effects, we obtain a simple proof of the result, analogous to Gleason's theorem, that any quantum state is given by a density operator. As a corollary we obtain a von Neumann-type argument against noncontextual hidden variables. It follows that on an individual interpretation of quantum mechanics the values of effects are appropriately understood as propensities.

Objective emotional assessment of tactile hair properties and their modulation by different product worlds.

Tactile properties of cosmetic products constitute weak stimuli and thus can be expected to be easily modified by mental images. In order to enhance an intended positive-emotion-inducing effect of such a product, its experience can be embedded in a certain 'world' that generates a positive emotional imagination. The present study investigated such an influence in 12 males and 12 females, half of each being laymen and experts in sensory assessment. Two product worlds (emotional and technical) and three different hair samples, two of them treated with different shampoos and an untreated one as control, were presented to each subject in counter-balanced order of all six combinations. An objective emotional assessment using a psychophysiological technique developed in an earlier study was applied and compared with a traditional sensory assessment. Among the physiological measures, peripheral blood volume and facial muscular activity were the most sensitive in revealing effects of and interactions between the product worlds and hair samples. A multivariate evaluation of the physiological data revealed three discriminant functions that explained 78.4% of the total variance and enabled a re-classification considerably better than chance. The first discriminant function clearly separated the treated from the untreated hair samples which was not possible by subjective ratings or traditional sensory assessment. The two other discriminant functions comprised a hedonistic and a product world factor. The emotional product world exerted the largest influence in case of the weakest tactile differences between the hair samples, and its influence was larger on laymen than on experts. Gender effects were most prominent in the subjective domain. In conclusion, multivariate psychophysiological methodology is superior to traditional sensory assessment in revealing subtle differences in the tactile perception of cosmetic products.

Precancer of the prostate.

The evolution of the malignant phenotype requires a set of genetic and epigenetic changes in sets of genes responsible for regulation of normal growth and cell death, of "social behaviour" and differentiation. The sum of these changes, not only the sequence, determines the malignancy as well as its grade. The probability of invasiveness shows a remarkable relationship to morphological changes, which in turn prove to be accompanied by a multitude of discrete molecular perturbations. Some of these can be characterized as functional, others as inductive with respect to their participation in the process. Since only the functional changes regulate malignant behaviour per se, it is an important task for future research to assemble a set of such changes, find markers for them and combine morphological and molecular indicators to achieve prognostically optimal scores. It should be emphasized, though, that rational use of such scores using biopsy samples as a source of information cannot be defined until biopsy strategies have been standardized and optimized.

Panic disorder: the overlooked problem.

The anxiety syndrome of Panic Disorder shares symptoms of numerous physical conditions and may aggravate existing physical conditions. Because many clients experiencing this disorder become isolated and homebound, the home care nurse is in a position to see patients with this disorder. This article provides assessment criteria guidelines that help the nurse identify patients with this problem.

Cellular immune response to human renal-cell carcinomas: definition of a common antigen recognized by HLA-A2-restricted cytotoxic T-lymphocyte (CTL) clones.

Cytotoxic T lymphocyte (CTL) clones directed against autologous renal-cell carcinoma (RCC) cell lines were generated by mixed lymphocyte/tumor-cell culture (MLTC) using peripheral blood lymphocytes (PBL). A CD8+, CD4- CTL clone MZ1257-CTL 5/30 with high cytolytic activity for the autologous tumor cell line MZ1257-RCC was established. No lysis of the autologous EBV-transformed B lymphocytes (EBV-B) or K562 cells was observed. A panel of HLA-A2-matched allogeneic RCC lines was recognized by CTL 5/30. Further specificity analysis showed a cross-reactivity with HLA-A2-matched allogeneic tumor cells of various origins, especially melanoma. CTL 5/30 was also cross-reactive with several HLA-A2-positive allogeneic normal kidney cells in culture. The restriction element identified for CTL 5/30 was HLA-A2, as shown by blocking of cytotoxicity using an anti-HLA-A2 monoclonal antibody (MAb) and by resistance of an HLA-A2-negative melanoma variant SK29-MEL. 1.22 against lysis by CTL 5/30. In this report we demonstrate HLA-A2-restricted recognition of a T-cell-defined antigen on autologous renal-cancer cells. This antigen is also expressed and recognized in association with HLA-A2 on normal kidney cells in culture and other HLA-A2-positive tumor cells. It may therefore be a normal differentiation antigen to which tolerance is incomplete in the renal-cell cancer system investigated.

Life quality assessment of breast cancer patients receiving adjuvant therapy using incomplete data.

Previous research on the effects of adjuvant treatment for women with operable breast cancer focused exclusively on disease-free and overall survival. In this study we evaluate life quality of premenopausal node-positive breast cancer patients receiving adjuvant chemotherapy for at least three months. For the first time, a modified latent variable model is used to assess treatment outcome in a prospective clinical trial. This poses a number of econometric problems which did not occur in the preceding studies. One of them is how to deal with patients whose records are incomplete. The data are provided by the International Breast Cancer Study Group (study VI). The results indicate that the lowest dose treatment improves life quality faster than the remaining three alternatives. At the end of the 24 months observation period no significant differences between the four treatment options remain. Although the lowest dose treatment is also the least costly no definite conclusion regarding cost-effectiveness can be drawn at this stage since survival data is not yet available.