[Procedure-specific postoperative gastrointestinal hemorrhage]. / Verfahrensspezifische postoperative gastrointestinale Blutungen.

Gastrointestinal bleeding (GIB) can occur as a complicating issue in the postoperative course after visceral surgery. It can be of varying clinical extent ranging from mild anemia to fatal hemorrhagic shock. Symptomatic manifestations of a GIB are hematemesis, melena and hematochezia. The GIB are fundamentally differentiated into upper and lower GIB. While upper GIB is defined as the occurrence of endoluminal hemorrhage above the ligament of Treitz, correspondingly the definition of lower GIB is intraluminal bleeding distal to the duodenojejunal flexure. Knowledge of their procedure-related incidence during the postoperative course enables a better assessment of the necessary intervention.

[Endoscopic management of complications after laparoscopic sleeve gastrectomy]. / Endoskopisches Komplikationsmanagement nach Schlauchmagenbildung.

Laparoscopic sleeve gastrectomy (SG) is currently the most commonly performed standalone bariatric procedure worldwide. Gastric staple line leakage is the feared immanent complication of the operation, which is difficult to treat and often persists. This article presents the endoscopic treatment options for complications after laparoscopic SG, particularly the treatment of gastric staple line leakage. Most important for a successful treatment is the understanding of the underlying pathophysiological causes, the exact surgical comprehension of the procedure and advanced endoscopic skills. The choice of endoscopic intervention depends on the available strategies as well as on the skills of the executing endoscopist. Currently, internal drainage seems to be the most expedient method.

[Bariatric surgery: Expectations and therapeutic goals-a contradiction?] / Bariatrische Chirurgie: Erwartungshaltung und Therapieziele ­ ein Gegensatz?

In the majority of patients with morbid obesity, metabolic/bariatric surgery leads to relevant and sustained weight loss and improves obesity-related comorbidities, quality of life and functionality. Moreover, the associated reduction of risk factors for cardiovascular events and cancerous diseases has been shown to improve life expectations. Due to its excellent antidiabetic effect, the currently valid national S3 guidelines now recommend metabolic/bariatric surgery in patients who have a body mass index (BMI) ≥30 kg/m2 with poorly controlled diabetes. The Edmonton staging system enables a multidimensional consideration of the severity grade of obesity for each individual patient independent of the BMI. Patients with relevant obesity-related metabolic comorbidities should be prioritized for treatment and if possible before the occurrence of end-organ damage that is at least in some cases irreversible and which also increases the perioperative risk. Therapeutic goals for each individual patient should be carefully defined preoperatively in order to mediate realistic expectations. Unrealistic expectations, such as "surgery solves my problems", "surgery makes me more beautiful", "surgery eliminates stigma", and "surgery guarantees success", are common in bariatric surgery patients. These unrealistic expectations can lead to frustration and to severe psychological decompensation and need to be addressed as early as possible by an interdisciplinary team. Redundancies, conclusive and empathic communication in the team improve therapy adherence, the expectations and therefore the overall outcome.

[Anastomosis and suture insufficiency after interventions for bariatric and metabolic surgery]. / Anastomosen- und Nahtinsuffizienzen nach Eingriffen in der Adipositas- und metabolischen Chirurgie.

BACKROUND: Metabolic surgery is internationally well-established for the treatment of obesity and its comorbidities. The numbers of procedures performed is steadily increasing. The results of surgery are superior in comparison to conservative treatment options regarding weight loss and resolution of comorbidities. The insufficiency of suture lines is a well-known and feared complication in the stapling procedures and is associated with an increased morbidity as well as mortality, especially in super obese patients. MATERIAL AND METHODS: The current literature was reviewed and the results are reported within the context of own experience. RESULTS: The most severe complications are staple line leakage after sleeve gastrectomy, leakage of anastomoses after bypass procedures and duodenal stump insufficiency. For the treatment of sleeve leakage various endoscopic procedures, such as over the scope (OTS) clips, stents and endoluminal vacuum therapy are available. Surgical revision, such as oversuturing, drainage and redo surgery are well-established. The management of all other complications is mainly by surgical intervention. Intraoperative standardization of procedures and knowledge of the physical foundations are essential for the prevention of leakage. Several preventive methods are available but randomized controlled trials are missing. CONCLUSION: The therapy of leakages in the field of bariatric surgery is an interdisciplinary approach and dependent on the available resources in the treating hospital. The data reported show good results but the different reports published are inconsistent. Leakages often do not occur in the immediate postoperative period but in the sense of a long-term complication; therefore standardization of procedures and follow-up as well as complication management is mandatory. Randomized controlled studies must be promoted.

Review article: The nutritional and pharmacological consequences of obesity surgery.

BACKGROUND: Obesity surgery is acknowledged as a highly effective therapy for morbidly obese patients. Beneficial short-term effects on common comorbidities are practically undisputed, but a growing data pool from long-term follow-up reveals increasing evidence of potentially severe nutritional and pharmacological consequences. AIMS: To assess the prevalence, causes and symptoms of complications after obesity surgery, to elucidate and compare therapy recommendations for macro- and micronutrient deficiencies, and to explore surgically-induced effects on drug absorption and bioavailability, discussing ramifications for long-term therapy and prophylaxis. METHODS: PubMed, Embase and MEDLINE were searched using terms including, but not limited to, bariatric surgery, gastric bypass, obesity surgery and Roux-en-Y, coupled with secondary search terms, e.g. anaemia, micronutrients, vitamin deficiency, bacterial overgrowth, drug absorption, pharmacokinetics, undernutrition. All studies in English, French or German published January 1980 through March 2014 were included. RESULTS: Macro- and micronutrient deficiencies are common after obesity surgery. The most critical, depending on surgical technique, are hypoalbuminemia (3-18%) and deficiencies of vitamins B1 (≤49%), B12 (19-35%) and D (25-73%), iron (17-45%) and zinc (12-91%). Many drugs commonly administered to obese patients (e.g. anti-depressants, anti-microbials, metformin) are subject to post-operative and/or PPI-associated changes affecting bioavailability and absorption. CONCLUSIONS: Complications are associated with pre-operative and/or post-operative malnutrition or procedure-related changes in intake, absorption and drug bioavailability. The high prevalence of nutrient deficiencies after obesity surgery makes life-long nutritional monitoring and supplementation essential. Post-operative changes to drug absorption and bioavailability in bariatric patients cast doubt on the validity of standard drug dosage and administration recommendations.

[Long-term results of the anatomic stem "Euroform"]. / Langzeitergebnisse des anatomischen Titanhüftschaftes "Euroform"

PURPOSE: To date there is a lack of long-term results of anatomic hip stems in the literature. In this context we present our 10-year results with the hip stem "Euroform". METHODS: In a retrospective cohort study 90% of the 51 stems implanted in our institute in the years 1993/94 51 stems were reexamined. Of them 39 were implanted cement-free while 11 were cemented. RESULTS: After 10 to 12 years no revision surgery of the cement-free stems was necessary or performed because of stem problems, in one case of a cemented stem revision was done because of cup problems. The survival rate for the complete prostheses was 97.5% after 10 years and 92% after 12 years. The revision surgery was done for cup problems. The satisfaction rate was "1.9" (according to the German school ranking system), the Merle d'Aubigné score was "good" (>10 points). However, one problem was the high rate of PE deterioration which depended on the inclination. CONCLUSION: Both the cemented and the cement-free forms of the "Euroform" stem gives good long-term results. The longevity of the prostheses is limited by polyethylene wear.

Inhibition of NOS enhances pulmonary vascular changes in stroke-prone spontaneously hypertensive rats.

To determine the effects of chronic nitric oxide (NO) blockade on the pulmonary vasculature, 58-day-old spontaneously hypertensive rats of the stroke-prone substrain (SHRSP) and Wistar-Kyoto rats (WKY) received N(omega)-nitro-L-arginine (L-NNA; 15 mg. kg(-1). day(-1) orally for 8 days). Relaxation to acetylcholine (ACh) in hilar pulmonary arteries (PAs), the ratio of right ventricular (RV) to body weight (RV/BW) to assess RV hypertrophy (RVH), and the percent medial wall thickness (WT) of resistance PAs were examined. L-NNA did not alter the PA relaxation, RV/BW, or WT in WKY. Although the PA relaxation and RV/BW in control SHRSP were comparable to those in WKY, the WT was increased (31 +/- 2 vs. 19 +/- 1%). L-NNA-treated SHRSP showed two patterns: in one group, the relaxation, RV/BW, and WT were comparable to those in the control SHRSP; in the other, impaired relaxation (36 +/- 7 vs. 88 +/- 4% for WKY) was associated with an increase in WT (37 +/- 1%) and RV/BW (0. 76 +/- 0.05). Thus the abnormal pulmonary vasculature in SHRSP at <10 wk of age is not accompanied by impaired relaxation in PAs or RVH; however, impaired relaxation is associated with increased WT and RVH.

One year's clinical experience of 18F-FDG PET with a modified SPET camera using molecular coincidence detection.

High-quality positron emission tomographic (PET) cameras are expensive and, therefore, not available in many centres. To allow access to clinical 18F-fluorodeoxyglucose (18F-FDG) PET, we began working with an ADAC Vertex camera equipped with a molecular coincidence detection (MCD) module in February 1997. Here we give a preliminary assessment of the clinical utility of our approach. To date, 109 studies have been performed in MCD-mode using standardized protocols (99 oncology cases, 10 neurology cases). Twenty-eight cardiological and 15 other studies were performed using 511 keV collimators without attenuation correction. The average dose of 18F-FDG for MCD studies was 150 MBq, thus avoiding overloading the detectors; cardiac studies required 370 MBq. The results obtained were carefully compared with computed tomography, magnetic resonance imaging, myocardial perfusion scans, coronary angiography and conventional radiology. The results were compared on a patient basis, including histology, surgical notes, autopsy reports and follow-up data. Oncological studies were performed to assess malignancy in a particular lesion (n = 22), staging of cancer (n = 57) or to evaluate whether therapy had been successful or not (n = 20). Indications for conducting studies were categorized as appropriate (Ia) or adequate (Ib). For Ia category cases, the results were: true-positive = 31, true-negative = 12 and false-positive = 2. For Ib category cases, the corresponding figures were: true-positive = 18, true-negative = 10, false-positive = 3 and false-negative = 1. False-positive studies were a result of inflammatory disease or artefacts. Six cases with temporal lobe epilepsy were correctly identified. In cardiac studies, we also found a good correlation with clinical parameters (i.e. hibernating myocardium or scarred tissue). Altogether, this cost-effective set-up allows nuclear medicine institutions to obtain valuable data in clinical practice with a system used both for single photon emission tomography and PET.

Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats.

Stroke-prone spontaneously hypertensive rats (SHRSP) on 1% NaCl drinking solution and Stroke-Prone Rodent Diet develop severe hypertension and glomerular and vascular lesions characteristic of thrombotic microangiopathy seen in malignant nephrosclerosis. We recently reported that spironolactone, a mineralocorticoid receptor antagonist, markedly reduced proteinuria and malignant nephrosclerotic lesions in these animals. This observation, together with our previous findings that angiotensin-converting enzyme inhibitors prevent the development of vascular damage, suggests that mineralocorticoids, as part of the renin-angiotensin-aldosterone system, play a pathophysiological role in this model. In the present study, we examined whether chronic (2-week) infusion of aldosterone can reverse the renal vascular protective effects of captopril in SHRSP. SHRSP received vehicle (n=8); captopril alone (50 mg. kg-1. d-1, orally) (n=10); aldosterone infusion alone (40 microg. kg-1. d-1, SC) (n=7); or captopril and aldosterone at 20 (n=6) or 40 (n=7) microg. kg-1. d-1. Systolic blood pressure was markedly elevated in all groups. Vehicle- and aldosterone-infused SHRSP developed severe proteinuria and comparable degrees of renal injury (21+/-3% and 29+/-3%, respectively) manifested as thrombotic and proliferative lesions in the arterioles and glomeruli. Captopril treatment reduced plasma aldosterone levels concomitant with marked reductions in proteinuria and the absence of histologic lesions of malignant nephrosclerosis. Aldosterone substitution at 20 or 40 microg. kg-1. d-1 in captopril-treated SHRSP resulted in the development of severe renal lesions (16+/-3% and 21+/-2%, respectively) and proteinuria comparable with that observed in SHRSP given either aldosterone or vehicle alone. These findings support a major role for aldosterone in the development of malignant nephrosclerosis in saline-drinking SHRSP, independent of the effects of blood pressure.

beta 1-Integrin expression in papillary thyroid carcinoma.

beta 1-integrins are widespread adhesion molecules which belong to a family of heterodimeric membrane glycoproteins and consist of two subunits, alpha and beta. Integrins seem to play an important role in the spreading and metastasis of malignant tumors. We investigated the expression and distribution of these adhesion molecules on papillary thyroid carcinomas by immunohistochemistry on formalin-fixed, paraffin embedded cancer tissues. We estimated the beta 1-integrin expression in cancerous areas in comparison to normal adjacent thyroid tissue. Our results revealed a highly significant difference in all investigated parameters between cancer and normal thyroid cells (p < 0.0001). Comparing our findings with the metastatic potential of the primary thyroid tumors, our results show that beta 1-integrin expression could be used as a prognostic parameter for papillary thyroid tumors.

Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats.

Chronic treatment of saline-drinking stroke-prone spontaneously hypertensive rats (SHRSP) with agents that interfere with the formation or actions of angiotensin II (Ang II) prevents the development of stroke and renal vascular damage. Ang II, in addition to its direct vascular effects, stimulates the synthesis and release of aldosterone. To assess the role of aldosterone in the development of pathologic changes in these rats, we implanted time-release pellets containing 200 mg of the mineralocorticoid receptor antagonist, spironolactone, into 14 SHRSP at 7.5 weeks of age. Eight SHRSP littermates received placebo pellets. Over the period of study (3 to 4 weeks), systolic blood pressure (SBP) was not different between the groups. Spironolactone did not enhance water and electrolyte excretion. All placebo-treated SHRSP developed marked proteinuria (150+/-6 mg/d) whereas in spironolactone-treated SHRSP, urinary protein excretion (UPE) averaged 39+/-9 mg/d (P<.0001). In a second study to assess effects on survival, 6 SHRSP received spironolactone (10 mg/kg/d) and 6 received vehicle. All but one of the control rats displayed signs of stroke and died by 16 weeks of age, while the spironolactone-treated SHRSP remained asymptomatic through 19 weeks of age (P<.03). At 16 weeks of age, spironolactone-treated SHRSP were severely hypertensive (247+/-3 mm Hg), yet UPE remained at baseline levels. In contrast, preterminal UPE averaged 136+/-13 mg/d in control rats (P<.0001). In both studies, histopathologic examination revealed a marked protective effect of spironolactone against the development of malignant nephrosclerotic and cerebrovascular lesions. These observations indicate a vascular and end organ protective effect of spironolactone in the absence of lowered blood pressure in saline-drinking SHRSP and are consistent with a major role for mineralocorticoids as hormonal mediators of vascular injury.

Regional renal nitric oxide release in stroke-prone spontaneously hypertensive rats.

Diminished nitric oxide (NO) production has been implicated in the pathogenesis of salt-sensitive hypertension. We questioned whether such a defect is responsible for the malignant hypertension and nephrosclerosis in stroke-prone spontaneously hypertensive rats (SHRSP) fed a high-salt/stroke-prone diet (S) versus a regular diet (R). NO release from 30-minute incubates of cortex and outer and inner medulla were studied in SHRSP at 10, 12, and 16 weeks of age on the S diet versus R diet. SHRSP-S (n=16) exhibited a marked age-dependent increase in NO release, especially in the cortex. Increases were only modest in SHRSP-R (n=21). At 16 weeks, cortical NO was 93+/-25 versus 6+/-1 pmol/mg tissue in SHRSP-S versus SHRSP-R (P<.001). Immunohistochemical staining increased mostly for neuronal, slightly for endothelial, and negligibly for inducible isoforms of NO synthase and was predominantly in the cortex of SHRSP-S versus SHRSP-R. Despite similar hypertension in SHRSP-S versus SHRSP-R (mean arterial pressure, 174+/-7 versus 177+/-2 mm Hg), malignant nephrosclerosis was seen only in SHRSP-S, affecting 22+/-6% of glomeruli and 23+/-4 vessels per 100 glomeruli by 16 weeks. N omega-nitro-L-arginine (15 mg/kg per day) in SHRSP-S (n=6) abrogated the increase in cortical NO but further augmented the hypertension and accelerated lesion development. Wistar-Kyoto rats at 16 weeks on the R diet (n=8) had NO levels similar to those of SHRSP-R, showed increased cortical NO to only 28+/-10 pmol/mg on the S diet (n=9) (P<.05 versus SHRSP-S), but remained normotensive and lesion-free. We conclude that hypertension and lesion development in SHRSP are not due to deficient renal NO. Accelerated onset of malignant nephrosclerosis by NO synthase inhibition suggests that NO is protective in these animals, mitigating the effects of hypertension and S diet on renal pathology.

Incidence and clinical characteristics of thyroid carcinoma after iodine prophylaxis in an endemic goiter country.

Iodized salt prophylaxis has been performed in Austria since 1963. Through this approach, mean urinary iodine excretion has been normalized to 144+/-23.5 microg/g creatinine per day. Thus Tyrol is no longer an endemic goiter area. We have analyzed the impact of iodized salt prophylaxis on thyroid cancer (TC) comparing data from the early 1960s with those corresponding to the period 1986 to 1995, when iodine supply was normalized. The study included 439 patients from Tyrol and Southern Tyrol. The incidence of TC in Tyrol has risen during the past decades from 3.07 between in 1957 and 1970 to 7.8 between 1990 and 1994 (CR/100000/year). We observed a rise in the percentage of differentiated adenocarcinomas (56% to 91.5%) with a predominance of papillary TC (54.4%) along with a decrease of anaplastic TC. In addition to these histological features, a shift to less advanced TNM stages, eg, T1-3, N0-1a, M0, was obvious, increasing from 29% to 72.2%, whereas advanced tumors, ie, T4 or N1b or M1, decreased from 71% to 28%. These changes have significantly improved prognosis. The current 5-year survival rate is 90.7% as compared with a rate of 73% in the 1960s; the values for 7-year survival are 89% and 48%, respectively. The marked effects of age, tumor stages, and histology on prognosis were confirmed with the Kaplan-Meier method. We conclude that together with normalization of iodine supply in an endemic goiter region the epidemiological profile of TC has changed. Even though the incidence of TC has risen, prognosis has significantly improved due to a shift towards differentiated forms of TC that are diagnosed at earlier stages.

GM1 ganglioside treatment of spontaneously hypertensive stroke prone rats.

Many reports indicate that GM1 ganglioside is effective in reducing CNS ischemic injury in animal models. These models employ invasive surgery to induce ischemic damage in otherwise healthy animals. The purpose of this study was to determine if the beneficial effects of GM1 could be generalized to Spontaneously Hypertensive Rats-Stroke Prone (SHRSP). The SHRSP strain develops a pathology similar to those observed in patients with stroke. The SHRSP have "risk" factors that include hypertension, fibrinoid necrosis, and sensitivity to diet. Female SHRSP were randomly assigned to GM1- or saline-treatment conditions. Rats were fed a stroke-inducing diet. Daily body weights, weekly blood pressure, time of stroke onset, and age at death were recorded. Spontaneous activity and performance on a tail-hang test were assessed thrice weekly. The results indicate that GM1 treatment did not delay the time of stroke onset or death. GM1 did reduce hyperactivity in the initial stages of the ischemic pathology, but did not prevent the marked decline in behavioral activity observed at later time points. There were no differences in weight loss, performance on the tail-hang test, or number of CNS injury-related symptoms observed. These findings suggest that GM1 was not as effective in decreasing mortality, weight loss, or behavioral deficits in SHRSP as previously reported using other animal models of ischemia. Distinguishing between those animal models in which GM1 is more and less effective may be useful in determining under which clinical situations GM1 is likely to be most suitable.

Adenosine 3',5'-monophosphate-dependent protein kinases of myocardial non-histone nuclear proteins.

Myocardial acidic non-histone nuclear proteins (NHPs) contain endogenous protein kinase activity. Phosphocellulose chromatography of purified NHPs identifies nine separate peaks of protein kinases which can phosphorylate both endogenous and exogenous substrates to a variable degree; endogenous NHPs are the best substrates. Cyclic AMP-stimulated protein kinase induced phosphorylation of endogenous and exogenous substrates; the extent of this stimulation varied according to the protein kinase fraction and substrate used. Cyclic AMP also enhanced NHP-induced stimulation of RNA polymerase activity. This enhancement was dependent on protein kinase-induced phosphorylation of NHPs since it was prevented by alkaline phosphatase pretreatment. It is concluded that nuclear protein kinases regulate myocardial RNA synthesis by enhancing phosphorylation of NHPs and that this regulation is under cyclic AMP control.

Reactions of bis(thiosemicarbazonato) copper(II) complexes with tumor cells and mitochondria.

The respiration of Ehrlich ascites tumor cells is inhibited by 3-ethoxy-2-oxobutyraldehyde bis (thiosemicarbazanato) copper (II). State 3 oxidative phosphorylation in mitochondria from tumor cells is also inhibited, with the effect more pronounced using glutamate or pyruvate-malate as substrates than with succinate. The disruption of oxidative phosphorylation in bovine heart mitochondria is qualitatively similar. The principal site of inhibition is in coupling site one, energetically between the electron transport site chain and the locus of uncoupling by 2,4-dinitrophenol. This appears to contain thiol groups which are oxidized by the complex. For a series of bis (thiosemicarbazonato) copper complexes, the extent of inhibition of heart mitochondrial oxidative phosphorylation is correlated with the reduction potentials of the complexes and with their in vitro cytotoxic effects against Walker 256 carcinoma tumor cells.