[Effect of splenectomy on the risk of hepatocellular carcinoma development among patients with liver cirrhosis and portal hypertension: a multi-institutional cohort study].

Objective: To identify whether splenectomy for treatment of hypersplenism has any impact on development of hepatocellular carcinoma(HCC) among patients with liver cirrhosis and hepatitis. Methods: Patients who underwent splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension between January 2008 and December 2012 were included from seven hospitals in China, whereas patients receiving medication treatments for liver cirrhosis and portal hypertension (non-splenectomy) at the same time period among the seven hospitals were included as control groups. In the splenectomy group, all the patients received open or laparoscopic splenectomy with or without pericardial devascularization. In contrast, patients in the control group were treated conservatively for liver cirrhosis and portal hypertension with medicines (non-splenectomy) with no invasive treatments, such as transjugular intrahepatic portosystemic shunt, splenectomy or liver transplantation before HCC development. All the patients were routinely screened for HCC development with abdominal ultrasound, liver function and alpha-fetoprotein every 3 to 6 months. To minimize the selection bias, propensity score matching (PSM) was used to match the baseline data of patients among splenectomy versus non-splenectomy groups. The Kaplan-Meier method was used to calculate the overall survival and cumulative incidence of HCC development, and the Log-rank test was used to compare the survival or disease rates between the two groups. Univariate and Cox proportional hazard regression models were used to analyze the potential risk factors associated with development of HCC. Results: A total of 871 patients with liver cirrhosis and hypertension were included synchronously from 7 tertiary hospitals. Among them, 407 patients had a history of splenectomy for hypersplenism (splenectomy group), whereas 464 patients who received medical treatment but not splenectomy (non-splenectomy group). After PSM,233 pairs of patients were matched in adjusted cohorts. The cumulative incidence of HCC diagnosis at 1,3,5 and 7 years were 1%,6%,7% and 15% in the splenectomy group, which was significantly lower than 1%,6%,15% and 23% in the non-splenectomy group (HR=0.53,95%CI:0.31 to 0.91,P=0.028). On multivariable analysis, splenectomy was independently associated with decreased risk of HCC development (HR=0.55,95%CI:0.32 to 0.95,P=0.031). The cumulative survival rates of all the patients at 1,3,5,and 7 years were 100%,97%,91%,86% in the splenectomy group,which was similar with that of 100%,97%,92%,84% in the non-splenectomy group (P=0.899). In total,49 patients (12.0%) among splenectomy group and 75 patients (16.2%) in non-splenectomy group developed HCC during the study period, respectively. Compared to patients in non-splenectomy group, patients who developed HCC after splenectomy were unlikely to receive curative resection for HCC (12.2% vs. 33.3%,χ²=7.029, P=0.008). Conclusion: Splenectomy for treatment of hypersplenism may decrease the risk of HCC development among patients with liver cirrhosis and portal hypertension.

[Is the discipline associated with self-confidence in handling rational antibiotic prescription? : Results from the MR2 study in German hospitals]. / Ist die Fachrichtung assoziiert mit der Selbstsicherheit im Umgang mit rationaler Antibiotikaverordnung? : Ergebnisse der MR2-Studien an deutschen Kliniken.

BACKGROUND: Besides public awareness and specialist knowledge and training of physicians, their self-confidence plays a key role for clinical decision-making in the respective area. OBJECTIVE: This exploratory study investigated the influence of the discipline on differences in self-confidence in dealing with antibiotics and in the self-rated knowledge. METHODS: In 2015 the multi-institutional reconnaissance of practice with multiresistant bacteria (MR2) questionnaire containing items on antibiotic prescription and multiresistant pathogens was sent out to 1061 physicians working in departments for internal medicine, general surgery, gynecology and obstetrics and urology. In 2017 a similar MR2 survey was sent to 1268 specialist and assistant physicians in anesthesiology in Germany. Besides demographic data 4 items on self-confidence in the use of antibiotic treatment and 11 items concerning self-rated knowledge about rational antibiotic therapy and multiresistant pathogens were included in the present analysis. Logistic regression analysis, the χ2-test and the Kruskal-Wallis test were used for statistical analysis of the influence of the discipline on these items. RESULTS: The response rates were 43% (456 out of 1061) from the non-anesthetists and 56% (705 out of 1268) from the anesthetists. Of the non-anesthetists 44% and 57% of the anesthetists had had no advanced training on antibiotic stewardship during the year before the study. In the overall analysis anesthetists (mean±SD: 2.53±0.54) were significantly less self-confident about antibiotics than colleagues from other departments (internal medicine: 3.10±0.50, general surgery: 2.97±0.44, gynecology and obstetrics: 3.12±0.42 and urology: 3.15±0.44) in the unadjusted (all p<0.001) and adjusted comparison. The analysis of self-rated knowledge about rational antibiotic prescription showed similar results. Senior consultant status and advanced training in infectiology were significantly associated with self-confidence and self-rated knowledge about antibiotics. CONCLUSION: Anesthetists showed significantly less self-confidence in dealing with antibiotics than colleagues from other disciplines. Advanced training on a rational prescription of antibiotics was associated with a greater self-confidence, so that the implementation of compulsory courses on rational antibiotic stewardship in the respective residency curriculum needs to be considered.

Vasopressor support vs. liberal fluid administration in deep inferior epigastric perforator (DIEP) free flap breast reconstruction - a randomized controlled trial.

BACKGROUND: Perioperatively, patients' hemodynamics are modulated predominantly by intravenous fluid administration and vasoactive pharmacological support. Vasopressor agents are suspected to be detrimental on free flap survival by the cause of vasoconstriction of the pedicle with consecutive reduced overall flap perfusion and by aggravation of flap dissection. OBJECTIVE: A novel, standardized fluid restrictive perioperative hemodynamic management was assessed for its feasibility in clinical practice in free flap patients undergoing breast reconstruction. METHODS: Patients were randomized to two perioperative regimens with different fluid and vasopressor limits. The primary endpoint regarded flap survival. Secondary endpoints included surgery times, time of patient ambulation and length of hospital stay. RESULTS: There was one total flap failure with liberal fluid administration (LFA). No total or partial flap failure was noted in the fluid restrictive regimen with norepinephrine administration up to 0.04µg/kg/min (FRV). No delay regarding operation time (p = 0.217), patient mobilization (p = 0.550) or hospital discharge (p = 0.662) was registered in the FRV study subpopulation compared to LFA. CONCLUSIONS: The results of this prospective interventional trial could not detect any negative impact of vasopressors, neither for the primary endpoint of flap survival nor for the overall patient outcome. The fear of vasopressor associated flap complications has led to a traditional liberal fluid administration, which failed to demonstrate any benefits when compared to a fluid restrictive vasopressor strategy.

A new approach for fat removal in a discontinuous autotransfusion device-concept and evaluation.

BACKGROUND: Fat present during blood salvage in orthopaedic or cardiac surgery can pose a risk of fat embolism and should be eliminated before transfusion. Based on observations of central fat accumulation at the bottom of Latham bowls, a fat reduction program was developed using two volume displacements, where blood temporarily is removed and respun in the bowl to force the fat through the RBC sediment. MATERIALS AND METHODS: Pooled ABO-matched RBC and FFP were adjusted to a haematocrit of 10%, and human fat tissue added to a concentration of 1·25 vol%. In six experiments, blood was processed with the new-generation cell salvage device CS Elite in a newly developed fat reduction program in bowls of three sizes. Volumetric quantification of fat was performed after centrifugation of blood samples in Pasteur pipettes. From volumes, haematocrits and the concentrations of fat, RBC recovery and fat elimination rates were calculated. RESULTS: Fat removal rates of 93·2 ± 2·8, 97·0 ± 2·1 and 99·6 ± 0·3% were observed with a 70-ml, 125-ml and 225-ml bowl, respectively, and even higher rates when removal rates were calculated one cycle. At the same time, high RBC recovery and plasma elimination rates were maintained, not significantly different to the default program mode. CONCLUSION: Modifications in process parameters and sequence led to a fat reduction program that significantly improves fat removal with the Cell Saver Elite from 77·4 ± 5·1% in the default mode to an average of 98·6 ± 1·1%, yielding results equivalent to the continuous cell salvage system (C.A.T.S).

The renin-angiotensin system and its vasoactive metabolite angiotensin-(1-7) in the mechanism of the healing of preexisting gastric ulcers. The involvement of Mas receptors, nitric oxide, prostaglandins and proinflammatory cytokines.

The inhibition of angiotensin-converting enzyme (ACE) or the blockade of angiotensin (Ang) AT-1 receptors affords protection against acute gastric mucosal injury, but whether the major metabolite of renin-angiotensin system (RAS), Ang-(1-7), accelerates the healing process of preexisting gastric ulcers remains unknown. Previous studies documented that Ang-(1-7) acting via its own Mas receptor exerts vascular responses opposing those of Ang II. We studied the effects of the Ang-(1-7)/Mas receptor axis on the healing rate of acetic-acid-induced gastric ulcers with or without the blockade of Mas receptors by A 779 and compared it with the effects of activation and blockade of the AT-1 receptor by the treatment with Ang II and losartan, respectively, the inhibition of ACE by lisinopril, the NO/cNOS inhibition by L-NAME and inhibition of prostaglandin/COX system by indomethacin in the presence of Ang-(1-7). Additionally, ex vivo metabolism of Ang I in gastric tissue was assessed by LC/MS method. At day 9 after ulcer induction, the area of these ulcers and the accompanying changes in total gastric blood flow (GBF) were determined as were gastric mucosal blood flow (GMBF) at ulcer margin and gastric oxygen uptake (GVO2). The gastric mucosal expression of mRNAs for constitutive nitric oxide synthase (cNOS), superoxide dismutase (SOD), and pro-inflammatory cytokines interleukin 1ß (IL-1ß) and tumor necrosis factor alpha (TNF-α) and plasma level of both cytokines were determined by RT-PCR and ELISA. The 9 days treatment with Ang II dose-dependently increased the area of gastric ulcers and this effect was accompanied by a significant fall in the GBF, GVO2 and GMBF at ulcer margin. In contrast, treatment with Ang-(1-7) which produced a significant rise in the luminal content of NO significantly reduced the area of gastric ulcer and significantly increased the GBF, GVO2 and the GMBF at ulcer margin. Similar GMBF changes and significant reduction the area of gastric ulcer was observed in rats with gastric ulcers treated with the agonist of Mas receptor, AVE 0991. These effects of Ang-(1-7) and AVE 0991 were eliminated by blockade of the Mas receptor with A779. Similarly to Ang-(1-7), treatment with losartan or lisinopril significantly reduced the area of gastric ulcers and the accompanying increase in the GMBF at ulcer margin and these effects were significantly attenuated by a concomitant administration of L-NAME and indomethacin. The rate of healing of ulcers was associated with a decrease in ex vivo Ang-(1-7) formation and this effect was attenuated by lisinopril. The treatment with Ang-(1- 7) or AVE 0991 increased the expression of mRNA for cNOS and SOD and downregulated that of IL-1ß and TNF-α followed by the decrease in the plasma IL-1ß and TNF-α levels. We conclude that the Ang-(1-7)/Mas receptor system accelerates the healing of preexisting gastric ulcers via an increase in the gastric macro- and microcirculations, and an increase in gastric tissue oxygenation. These effects are mediated by PG and NO derived from overexpression of cNOS, an increase in the expression of antioxidizing enzyme SOD 2 and an anti-inflammatory action involving the inhibition of expression and release of pro-inflammatory cytokines IL-1ß and TNF-α. Our results seem to underlie the importance of the Ang-(1-7), AT-1 and Mas receptors in the regulation of local vascular and metabolic effects associated with mechanism of gastric ulcer healing.

Preoperative anemia is associated with adverse outcome in patients with urothelial carcinoma of the bladder following radical cystectomy.

PURPOSE: Radical cystectomy (RC) can be associated with significant blood loss, whereas many patients are presenting with anemia preoperatively. To date, there is a lack of data addressing the impact of preoperative anemia (PA) on survival of patients undergoing RC for urothelial carcinoma of the bladder (UCB). METHODS: This retrospective multicenter study includes 684 patients with UCB undergoing RC with pelvic lymph node dissection. The median follow-up was 50 (IQR 29,78) months. Anemia was defined in line with the WHO classification (hemoglobin (Hb): male ≤13 g/dL, female ≤12 g/dL) and based on contemporary gender- and age-adjusted classification (Hb: white male aged <60 years: ≤13.7 g/dL; ≥60 years: ≤13.2 g/dL; white female of all ages ≤12.2 g/dL). Univariable and multivariable Cox regression analyses were used to assess the effects of PA on oncological outcomes. RESULTS: A total of 269 (39.3 %) and 302 (44.2 %) patients were anemic according to the WHO classification versus contemporary classification. Age, increased ECOG performance status, advanced tumor stages, lymph node metastasis, positive surgical margin and anemia were associated with disease recurrence (DR), cancer-specific mortality (CSM) and all-cause mortality (ACM). In multivariable analysis, anemia was an independent predictor of DR, CSM and ACM (WHO and/or contemporary classification). Blood transfusion was significantly associated with ACM in both classifications of anemia. CONCLUSIONS: PA is significantly associated with worse oncological outcome in patients undergoing RC. Based on the additional unfavorable influence of blood transfusion, this emphasizes the importance of early diagnosis and correction of anemia and implementation of alternative methods of blood volume management.

The effect of intra- and postoperative allogenic blood transfusion on patients' survival undergoing radical cystectomy for urothelial carcinoma of the bladder.

PURPOSE: Radical cystectomy (RC) can be associated with significant blood loss. Allogenic blood transfusion (ABT) may alter disease outcome because of a theoretical immunomodulatory effect. We evaluated the effects of ABT on overall survival (OS) and progression-free survival (PFS) of patients undergoing RC for urothelial carcinoma of the bladder (UCB). MATERIALS AND METHODS: This is a retrospective single-center study of 350 consecutive patients of a university health center with a median follow-up of 70.1 month. All patients underwent RC and pelvic lymph node dissection. The effect of ABT on OS and PFS was analyzed using univariable and multivariable Cox proportional hazards models. RESULTS: The overall ABT rate was 63 % (n = 219), with intraoperative blood transfusion and postoperative blood transfusion being performed in 183 patients (52 %) and 99 patients (28 %), respectively. Preoperative anemia was detected in 156 patients (45 %) with median estimated blood loss of 800 ml (IQR: 500-1,200). ABT was associated with significant decrease of OS and PFS in multivariable analyses (p < 0.001), whereas patients' prognosis worsened the more packed red blood cells (PRBC) were transfused (p < 0.001). The study is limited in part due to its retrospective design. CONCLUSIONS: We found that ABT and the number of PRBC transfused are associated with poor prognosis for UCB patients undergoing RC, whereas preoperative anemia had no influence on survival. This emphasizes the importance of surgeon's awareness for a strict indication for ABT. A prospective study will be necessary to evaluate the independent risks associated with ABT during surgical treatments.

Esophagoprotective activity of angiotensin-(1-7) in experimental model of acute reflux esophagitis. Evidence for the role of nitric oxide, sensory nerves, hypoxia-inducible factor-1alpha and proinflammatory cytokines.

Gastroesophageal reflux disease (GERD) is a global disease rapidly increasing among world population. The pathogenesis of reflux esophagitis which is considered as the early stage of GERD is complex, resulting from an imbalance between aggressive factors damaging the esophagus and a number of the natural defense mechanisms. The esophageal mucosa is in a state of continuous exposure to potentially damaging endogenous and exogenous factors. Important aggressive components of gastric refluxate include acid and pepsin and also pancreatic enzymes and bile. Among aggressive factors of exogenous origin, cigarette smoking, non-steroidal anti-inflammatory drugs (NSAID), and steroids are of the utmost importance. The basic level of esophageal defense against acid-pepsin damage consists of the anti-reflux mechanisms such as the luminal acid clearance and removal of the esophageal contents and neutralization of luminal acidity. In addition the esophageal mucosal protection includes the presence of pre-epithelial, epithelial and post-epithelial cellular and functional components. Recently, the progress have been made in the understanding of role of the heptapeptide member of the renin-angiotensin system (RAS), angiotensin-(1-7) (Ang-(1-7)) in the control of gastrointestinal functions. It has been shown that all components of local RAS including Ang-(1-7) are detectable in the gastrointestinal wall including not only the stomach but also the esophagus. Previous studies revealed that Ang-(1-7), which is an important component of the RAS, exerts vasodilatory, anti-inflammatory and antioxidant activities in the stomach. Ang-(1-7) was recently implicated in gastroprotection, but its effects on esophageal mucosa in a rodent model of reflux esophagitis and in human subjects presenting GERD symptoms have not been explored. The present study was aimed to evaluate the possible protective effects of Ang-(1-7) and Mas-receptors upon esophageal mucosal damage in acute reflux esophagitis (RE) induced in anesthetized rats by ligating the pylorus and the limiting ridge (a transitional region between the forestomach and the corpus of stomach). Consequently, the total gastric reservoir to store gastric juice was greatly diminished, resulting in the reflux of this juice into the esophagus. Because Mas receptors are functionally linked to nitric oxide (NO) formation, we also studied involvement of endogenous NO in the mediation of protective and circulatory effects of exogenous Ang-(1-7). Moreover, an attempt was made to assess the possible role of sensory neurons in the modulation of the protective effects exerted by Ang-(1-7)/Mas receptor system. Six series of rats were pretreated 30 min before induction of RE with 1) vehicle (saline), 2) Ang-(1-7) (5-50 µg/kg i.p.), 3) A779 (50 µg/kg i.p.), the selective Mas receptor antagonist applied alone, 4) Ang-(1-7) (50 µg/kg i.p.) combined with A779, 5) L-NNA (20 mg/kg i.p.) administered alone, and 6) Ang-(1-7) (50 µg/kg i.p.) combined with L-NNA. In separate group of rats, capsaicin (total dosage of 125 mg/kg within three days) was administered s.c. 2 weeks before the induction of RE to induce functional ablation of sensory nerves. Rats with intact sensory nerves and those with capsaicin-induced sensory denervation received vehicle (saline) or Ang-(1-7) (50 µg/kg i.p.) to determine whether this vasoactive metabolite of angiotensin I could be also effective in rats with capsaicin-induced impairment of the synthesis and release of sensory neuropeptides such as CGRP. Four hours after induction of RE, the mucosal damage was graded with mucosal lesion index (LI) from 0 to 6, the esophageal microcirculatory blood flow (EBF) was determined by H2-gas clearance technique and plasma level of pro-inflammatory cytokines interleukin-1b (IL-1ß), and tumor necrosis factor-α (TNF-α) was determined by ELISA. The expression of proinflammatory factors including COX-2, cytokine IL-1ß and hypoxia inducible factor 1alpha (Hif1α) was analyzed in the esophageal mucosal biopsies. In rats with RE, the esophageal LI was significantly elevated comparing its value observed in intact rats, and the EBF was significantly decreased as compared with intact mucosa. Pretreatment with Ang-(1-7) of control rats without esophagitis induced increase in EBF by about 25% without any macroscopic changes in the esophageal mucosa or in the plasma level of cytokines. In animals with RE, pretreatment with Ang-(1-7) significantly reduced gross and histological esophageal mucosal injury and significantly increased EBF in comparison to vehicle-pretreated animals. The observed gross and histologic esophagoprotective effect of Ang-(1-7) was totally abolished by A779 so in rats with combined treatment of A779 with Ang-(1-7), the LI was identical with this observed in control RE and the EBF was decreased in these animals by about 39%. Inhibition of NO synthase by L-NNA significantly reduced the LI and the rise in EBF caused by Ang-(1-7). Similarly, the capsaicin denervation also significantly attenuated the vasodilatory and the esophagoprotective effects of Ang-(1-7). The expression of proinflammatory factors COX-2, Hif1α and IL-1ß which was negligible in intact esophageal mucosa, was upregulated in esophageal mucosa of rats with RE. In contrast, the administration of Ang-(1-7) resulted in a downregulation of mRNA for COX-2, Hif1 and IL-1ß in esophageal mucosa an this effect was abolished in A779-dependent manner. The Ang-(1-7) significantly decreased the RE-induced elevation of plasma levels of IL-1ß and TNF-α, and this effect was also reversed by pretreatment with A779, and significantly attenuated by pretreatment with L-NNA and capsaicin-induced sensory denervation. The present study indicates that the protective effect of Ang-(1-7) observed in the esophageal mucosa during early acute stage of gastroesophageal reflux depends upon the enhancement of esophageal microcirculatory blood flow via the activation of Mas receptor possibly due to NO synthase/NO system activation, stimulation of sensory nerves, the inhibition of expression of pro-inflammatory factors including COX-2, Hif1α and IL-1ß and release of proinflammatory cytokines IL-1ß and TNF-α.

Interobserver Agreement in MR Enterography for Diagnostic Assessment in Patients with Crohn's Disease.

PURPOSE: To evaluate the extent to which MRE can be used as an observer-independent, objective imaging method for the diagnosis and evaluation of CD with respect to the detection of inflammatory changes of the small bowel and lymphadenopathy as diagnostic criterion and bowel distension as a quality criterion. MATERIALS AND METHODS: MRE scans of 84 patients (42 female, median age 37 years) were evaluated independently by 4 experienced radiologists. Analysis of inflammatory changes of the bowel wall, lymphadenopathy and adequate bowel distension was conducted separately for the jejunum, ileum and terminal ileum. The Kendall's W-test was used for the statistical comparison of concordance. RESULTS: In a total of 55 patients, inflammatory activity of the bowel wall was detected and MRE was found to have a high interobserver reproducibility concerning inflammatory changes of the intestinal wall (Kendall's W 0.527 - 0.823). Concerning lymphadenopathy (31 cases, 36.9 %), a low to moderate consensus could be shown with a Kendall's W value of 0.402 - 0.505. For the assessment of adequate bowel distension, a moderate concordance between the operators could be found (Kendall's W 0.497 - 0.581). CONCLUSION: MRE has proven high interobserver agreement with respect to the diagnosis of inflammatory disease activity of the bowel as a diagnostic criterion in patients with CD. Concerning adequate bowel distension as a quality criterion of the examination itself and lymphadenopathy as a diagnostic criterion, moderate interobserver agreement could be found. This is thought to have a rather small effect on the diagnostic significance and conclusiveness of the method in the daily routine. KEY POINTS: ▶ MR enterography as observer independent diagnostic procedure in patients with Chron's Disease. ▶ Highest interobserver concordance for the criterion of inflammatory bowel wall affection. ▶ Moderate interobserver concordance for lymphadenopathy and bowel distension.

[MR enterography sequence evaluation for patients with Crohn's disease]. / Sequenz-Evaluation für die MR-Enterografie für Patienten mit Morbus Crohn.

PURPOSE: To evaluate a routine MR enterography (MRE) protocol for patients with Crohn's disease (CD) in order to assess and rank the subjectively most important sequences regarding diagnostic decisions. MATERIALS AND METHODS: We prospectively examined 84 patients (42 male) with known CD using a coronal T2 / T1-weighted balanced SSFP (TrueFISP), axial T2-weighted single shot TSE (HASTE) as well as an axial T1-weighted gradient-echo sequence (2D-FLASH) before intravenous contrast application and a 2D-FLASH sequence with axial and coronal orientation after intravenous contrast application. 4 experienced radiologists subjectively evaluated the sequences independently using a scale between 1 and 5 (1 = excellent; 5 = non-diagnostic) regarding their diagnostic significance for a final radiologic decision. The ranking of the different sequences was statistically tested by the Friedman analysis. RESULTS: The following ranking was found: HASTE sequences were ranked prior to contrast-enhanced axial gradient-echo (2D-FLASH). The third to fifth ranking was TrueFISP, the axial contrast-enhanced 2D-FLASH and the 2D-FLASH without contrast, respectively. Differences between the first and second rank were significant (p < 0.05), and all other differences were highly significant (p < 0.01). CONCLUSION: The stable and fast T2-weighted MR sequences without intravenous contrast represented by axial HASTE and coronal TrueFISP were ranked as number 1 and 3. The examination protocol should be completed by a coronal T1-weighted gradient-echo-sequence after contrast injection, which can be supplemented by an axial acquisition. The T1-weighted gradient-echo sequence without contrast could be omitted.

XY gonadal dysgenesis--development of a germ cell tumor: case report.

Gonadal dysgenesis (GD) is a rare congenital malformation that affects about one in 3,000 births. The authors present a case of a 17-year-old woman with primary amenorrhea and poor breast development. They conducted a laparoscopic surgery and bilaterally removed hypoplastic streak gonads. Histopathology of the ovaries revealed bilateral streak gonads with gonadoblastomas and a right-sided dysgerminoma.

Interobserver agreement in mr enterography for diagnostic assessment in patients with Crohn's disease.

PURPOSE: To evaluate the extent to which MRE can be used as an observer-independent, objective imaging method for the diagnosis and evaluation of CD with respect to the detection of inflammatory changes of the small bowel and lymphadenopathy as diagnostic criterion and bowel distension as a quality criterion. MATERIALS AND METHODS: MRE scans of 84 patients (42 female, median age 37 years) were evaluated independently by 4 experienced radiologists. Analysis of inflammatory changes of the bowel wall, lymphadenopathy and adequate bowel distension was conducted separately for the jejunum, ileum and terminal ileum. The Kendall's W-test was used for the statistical comparison of concordance. RESULTS: In a total of 55 patients, inflammatory activity of the bowel wall was detected and MRE was found to have a high interobserver reproducibility concerning inflammatory changes of the intestinal wall (Kendall's W 0.527 ­ 0.823). Concerning lymphadenopathy (31 cases, 36.9 %), a low to moderate consensus could be shown with a Kendall's W value of 0.402 ­ 0.505. For the assessment of adequate bowel distension, a moderate concordance between the operators could be found (Kendall's W 0.497 ­ 0.581). CONCLUSION: MRE has proven high interobserver agreement with respect to the diagnosis of inflammatory disease activity of the bowel as a diagnostic criterion in patients with CD. Concerning adequate bowel distension as a quality criterion of the examination itself and lymphadenopathy as a diagnostic criterion, moderate interobserver agreement could be found. This is thought to have a rather small effect on the diagnostic significance and conclusiveness of the method in the daily routine.

[Inpatient pain consultation service at a university hospital: a retrospective analysis of patient characteristics and the rate of the implementation of recommendations]. / Stationäre Schmerzkonsile einer universitären Schmerzambulanz : Eine retrospektive Analyse der Patientencharakteristika und der Umsetzungsrate der Empfehlungen.

BACKGROUND: The aim of this study was to conduct an audit of a university inpatient pain consultation service and to examine the quality and the implementation of the recommended therapeutic measures. Factors that influenced the implementation should be identified. PATIENTS AND METHODS: All inpatients treated by the consultation service in the years 2009 and 2010 were analyzed retrospectively. Demographic patient characteristics as well as quality parameters of the consultation service and pharmacological and non-pharmacological recommendations and their implementation were analyzed. RESULTS: In total 1,048 requests for the consultation service were processed of which 39.7% of the requests were for patients with acute pain, 33.8% with chronic and 19.9% with tumor-associated pain. Measures recommended most were medication, physiotherapy and psychological treatment. Recommended medications were actually prescribed in more than 80%, physiotherapy recommended in about 75% and psychological treatment recommended in 47% of the cases. Only a few influencing factors for the implementation of the recommended measures could be identified. CONCLUSION: Many different pain states are seen in an inpatient pain consultation service. The recommendations given are implemented in most cases especially concerning the medication.

Interaction between selective cyclooxygenase inhibitors and capsaicin-sensitive afferent sensory nerves in pathogenesis of stress-induced gastric lesions. Role of oxidative stress.

Gastric microcirculation plays an important role in the maintenance of the mucosal gastric integrity and the mechanism of injury as well as providing protection to the gastric mucosa. Disturbances in the blood perfusion, through the microcapillaries within the gastric mucosa may result in the formation of mucosal damage. Acute gastric mucosal lesions constitute an important clinical problem. Originally, one of the essential component of maintaining the gastric mucosal integrity was the biosynthesis of prostaglandins (PGs), an issue that has captured the attention of numerous investigations. PGs form due to the activity of cyclooxygenase (COX), an enzyme which is divided into 2 isoforms: constitutive (COX-1) and inducible (COX-2) ones. The inhibition of COX-1 by SC-560, or COX-2 by rofecoxib, reduces gastric blood flow (GBF) and impairs gastric mucosal integrity. Another detrimental effect on the gastric mucosal barrier results from the ablation of sensory afferent nerves by neurotoxic doses of capsaicin. Functional ablation of the sensory afferent nerves by capsaicin attenuates GBF and also renders the gastric mucosa more susceptible to gastric mucosal damage induced by ethanol, aspirin and stress. However, the role of reactive oxygen species (ROS) in the interaction between COX specific inhibitors and afferent sensory nerves has not been extensively studied. The aim of our present study was to determine the participation of ROS in pathogenesis of stress-induced gastric lesions in rats administered with SC-560 or rofecoxib, with or without ablation of the sensory afferent nerves. ROS were estimated by measuring the gastric mucosal tissue level of MDA and 4-HNE, the products of lipid peroxidation by ROS as well as the SOD activity and reduced glutathione (GSH) levels, both considered to be scavengers of ROS. It was demonstrated that exposure to 3.5 h of WRS resulted in gastric lesions, causing a significant increase of MDA and 4-HNE in the gastric mucosa, accompanied by a decrease of SOD activity and mucosal GSH level. Pretreatment with COX-1 and COX-2 inhibitors (SC-560 and rofecoxib, respectively) aggravated the number of gastric lesions, decreased GBF, attenuated GSH level without further significant changes in MDA and 4-HNE tissue levels and SOD activity. Furthermore, the capsaicin--nactivation of sensory nerves resulted in exaggeration of gastric mucosal damage induced by WRS and this was further augmented by rofecoxib. We conclude that oxidative stress, as reflected by an increase of MDA and 4-HNE tissue concentrations (an index of lipid peroxidation), as well as decrease of SOD activity and the fall in GSH tissue level, may play an important role in the mechanism of interaction between the inhibition of COX activity and afferent sensory nerves releasing vasoactive neuropeptides. This is supported by the fact that the addition of specific COX-1 or COX-2 inhibitors to animals with capsaicin denervation led to exacerbation of gastric lesions, and further fall in the antioxidizing status of gastric mucosa exposed to stress.

Gastric secretion, proinflammatory cytokines and epidermal growth factor (EGF) in the delayed healing of lingual and gastric ulcerations by testosterone.

Hormonal fluctuations are known to predispose ulceration of the upper gastrointestinal tract, but to date no comparative study of their effects on the healing of pre-existing ulcers in the oral cavity and stomach has been made. We studied the effects of depletion of testosterone and of EGF on the healing of acetic acid-induced ulcers using rats having undergone bilateral orchidectomy and/or salivectomy respectively. We measured alterations in gastric acid secretion and blood flow at ulcer margins, as well as plasma levels of testosterone, gastrin and the proinflammatory cytokines IL-1 beta and TNF-alpha. Testosterone (0.01-10 mg/kg/day i. m.) dose-dependently delayed oral and gastric ulcer healing. When applied in an optimal dose of 1 mg/kg/day, this hormone significantly raised gastric acid secretion and plasma IL-1 beta and TNF-alpha levels. Attenuation of plasma testosterone levels via bilateral orchidectomy inhibited gastric acid secretion and accelerated the healing of oral and gastric ulcers, while increasing plasma gastrin levels and these effects were reversed by testosterone. Salivectomy raised plasma testosterone levels, and delayed oral and gastric ulcer healing. Treatment of salivectomised animals with testosterone further inhibited ulcer healing, and this effect was counteracted by EGF. We propose that testosterone delays ulcer healing via a fall in blood flow at the ulcer margin, a rise in plasma levels of IL-1 beta and TNF-alpha and, in the case of gastric ulcers, an increase in gastric acid secretion. EGF released from the salivary glands plays an important role in limitation of the deleterious effects of testosterone on ulcer healing.

Transcriptional upregulation of gastrin in response to peroxisome proliferator-activated receptor gamma agonist triggers cell survival pathways.

Peroxisome proliferator-activated receptor gamma (PPAR gamma) are members of the largest nuclear hormone receptor family of transcription factors (1). PPAR gamma (PPARgamma) plays an important role in adipogenesis, control of sensitivity to insulin, inflammation and atherosclerosis but recent studies also suggest that PPARgamma is involved in cell cycle withdrawal. PPARgamma can promote cell differentiation, exert an antiproliferative action and inhibit angiogenesis (2, 3). However, there are studies showing that activation of PPARgamma promotes the development of colon cancer (4). These data are in sharp contrast with studies that attribute anticancer effects to PPARgamma in gastrointestinal malignancies. Probably, the action of PPARgamma on cell cycle and proliferation depends on the cell type and presence of other stimuli that predispose cells to cancer development. Amidated and non-amidated gastrins may play an important role in the proliferation and carcinogenesis of GI cancers. It is known that gastrin peptides activate phosphorylation of Protein Kinase B (PKB/Akt) and anti-apoptotic signalling but there is little known about the link between gastrins and PPARgamma receptors in relation to apoptosis.

Diffuse nodular lymphoid hyperplasia of the gastrointestinal tract in patient with selective immunoglobulin A deficiency and sarcoid-like syndrome--case report.

Nodular lymphoid hyperplasia is uncommon in adult patients. Associated diseases are common variable immunodeficiency (CVI) and lymphoid tissue malignancies. In this case report we focus on clinical presentation and differential diagnosis of diffuse nodular lymphoid hyperplasia of the gastrointestinal tract coexisting with selective immunoglobulin A deficiency and sarcoid-like syndrome.

The role of female and male sex hormones in the healing process of preexisting lingual and gastric ulcerations.

Studies in different animal species and in humans have suggested that sex hormones influence gastric acid secretion and contribute to the integrity of the oral and gastroduodenal mucosa but the effect of male and female sex hormones on the healing of the preexisting ulcers in the oral cavity and stomach have not been studied. We compared the effects of major male hormone, testosterone, and female hormone, progesterone, on the healing of lingual and gastric ulcers induced by acetic acid technique in male rats with intact or removed testicles (testectomy) and female rats with intact or removed ovaries (ovariectomy). The gastric acid secretion was determined in rats with gastric ulcers equipped with chronic gastric fistula (GF). Rats were sacrificed at day 7 upon ulcer induction; the ulcer area was measured by planimetry and the lingual and gastric blood flow (GBF) was determined by H(2)-gas clearance method and venous blood was collected for determination of plasma gastrin and plasma proinflammatory cytokine interleukin (IL)-1 beta levels. Gastric acid output from GF rats was significantly reduced while plasma gastrin was significantly enhanced in testectomized animals as compared to those in intact control rats and these effects were reversed by supplementation of testectomized animals with testosterone. The area of lingual and gastric ulcers in placebo-control rats decreased significantly at day 7 and this effect was significantly accelerated by testectomy or ovariectomy. In contrast, testosterone significantly delayed ulcer healing while producing a significant fall in the gastric blood flow and lingual blood flow determined at the margin of these ulcers. Treatment with progesterone significantly accelerated ulcer healing and increased the gastric and lingual blood flow at margin of these ulcers. Testosterone applied alone or supplemented in testectomized animals produced the significant increment in plasma IL-1 beta levels as compared to the respective levels of this cytokine in placebo-control animals. We conclude that: 1) major male (testosterone) and female (progesterone) sex hormones exhibit opposite effect on healing of preexisting ulcers in the oral cavity and stomach because testosterone markedly delayed while progesterone significantly accelerated this healing; 2) testosterone-induced delay in ulcer healing involves the fall in the gastric microcirculation at the margin of lingual and gastric ulcers and the excessive production and release of proinflammatory cytokine IL-1 beta; and 3) testectomy improves the gastric ulcer healing due to inhibition of gastric acid secretion and the rise in plasma gastrin, which exerts gastroprotective, trophic and ulcer healing action on the gastric mucosa.

[Autologous transfusion -- from euphoria to reason: clinical practice based on scientific knowledge (Part II). Intraoperative blood salvage with blood irradiation -- from an anaesthesiological point of view]. / 3. Internationales Symposium: "Autologe Transfusion -- Von der Euphorie zur Ratio: Praktisches Handeln aus wissenschaftlicher Sicht" (Teil II).

The requirement for intraoperative blood salvage (IBS) in cancer surgery stems from the high transfusion rate, the unfavourable effects of an anaemia, and the impact of transfusion risks like immunomodulation in tumor patients. The advantages of IBS are availability, the low waste rate, and the excellent quality of this autologous, unstored blood. The only effective elimination of the risk of tumor cell dissemination after retransfusion of wound blood is achieved by blood irradiation. The combination of the established methods of IBS and blood irradiation is practical, and allows a very efficient saving of blood. For Jehovah's witnesses it may open the possibility for tumor surgery. From an anaesthesiological point of view it is part of the therapy, but any context that puts it compatible to medicolegal regulations is welcome. For him as the one responsible for the therapy of intraoperative blood loss it represents the safest and best blood for an optimal hemotherapy in tumor patients. In addition, first data indicate a better outcome of these patients.