[Cost assessment for endoscopic procedures in the German diagnosis-related-group (DRG) system - 5 year cost data analysis of the German Society of Gastroenterology project]. / Kosten endoskopischer Leistungen der Gastroenterologie im deutschen DRG-System ­ 5-Jahres-Kostendatenanalyse des DGVS-Projekts.

Background In the German hospital reimbursement system (G-DRG) endoscopic procedures are listed in cost center 8. For reimbursement between hospital departments and external providers outdated or incomplete catalogues (e. g. DKG-NT, GOÄ) have remained in use. We have assessed the cost for endoscopic procedures in the G-DRG-system. Methods To assess the cost of endoscopic procedures 74 hospitals, annual providers of cost-data to the Institute for the Hospital Remuneration System (InEK) made their data (2011 - 2015; §â€Š21 KHEntgG) available to the German-Society-of-Gastroenterology (DGVS) in anonymized form (4873 809 case-data-sets). Using cases with exactly one endoscopic procedure (n = 274 186) average costs over 5 years were calculated for 46 endoscopic procedure-tiers. Results Robust mean endoscopy costs ranged from 230.56 € for gastroscopy (144 666 cases), 276.23 € (n = 32 294) for a simple colonoscopy, to 844.07 € (n = 10 150) for ERCP with papillotomy and plastic stent insertion and 1602.37 € (n = 967) for ERCP with a self-expanding metal stent. Higher costs, specifically for complex procedures, were identified for University Hospitals. Discussion For the first time this catalogue for endoscopic procedure-tiers, based on §â€Š21 KHEntgG data-sets from 74 InEK-calculating hospitals, permits a realistic assessment of endoscopy costs in German hospitals. The higher costs in university hospitals are likely due to referral bias for complex cases and emergency interventions. For 46 endoscopic procedure-tiers an objective cost-allocation within the G-DRG system is now possible. By international comparison the costs of endoscopic procedures in Germany are low, due to either greater efficiency, lower personnel allocation or incomplete documentation of the real expenses.

Rejection quantity in kidney transplant recipients is associated with increasing intracellular interleukin-2 in CD8+ T-cells.

BACKGROUND: CD8+ T-cells and interleukin-2 play an important role during organ rejection in kidney transplant recipients. Numerous studies showed increased interleukin-2 levels during acute rejection. The aim of our study is to show an association between intracellular interleukin-2 in CD8+ T-cells and the incidence of those who underwent organ rejection in kidney transplant recipients. METHODS: 407 transplant recipients were included into this study. The rejection incidence was investigated from the patient records. White blood cells from recipients were separated using a ficoll gradient. The cells were double-gated (CD3+ and CD8+) for the analysis of cellular percentage for intracellular interleukin-2 with a flow cytometer. RESULTS: The percentage of CD8+ cells with detectable intracellular interleukin-2 was significantly higher in renal transplant recipients with a documented rejection compared to recipients without any history of rejection (9.06±0.50, N=133 vs. 4.28±0.24, N=274, p<0.0001, t-test). Further, there was a significant increase in patients with one (8.02±0.54, N=80, p<0.0001, t-test), two (10.40±1.17, N=33, p<0.0001, t-test) or three (11.82±1.58, N=18, p<0.0001, t-test) rejection events. CONCLUSIONS: Past studies showed, that during acute organ rejection intracellular interleukin-2 is increased in cytotoxic T-cells, supposed to be a marker for this event. We were able to show, that intracellular interleukin-2 in CD8+ T-cells is also increased after organ rejection. Furthermore it seems to depend on the quantity of rejection events. Further studies in recipients with increased intracellular interleukin-2 in cytotoxic CD8+ T-cells and documented history of organ rejection are needed to identify this as a possible risk factor for further rejection events.

Ursodeoxycholic acid for treatment of cholestasis in patients with hepatic amyloidosis.

BACKGROUND: Amyloidosis represents a group of different diseases characterized by extracellular accumulation of pathologic fibrillar proteins in various tissues and organs. Severe amyloid deposition in the liver parenchyma has extrahepatic involvement predominantly in the kidney or heart. We evaluated the effect of ursodeoxycholic acid, in four patients with severe hepatic amyloidosis of different etiologies, who presented with increased alkaline phosphatase and gamma-glutamyl transferase. CASE REPORT: The study included four patients who presented with amyloidosis-associated intrahepatic cholestasis. Three of them had renal amyloidosis which developed 1-3 years before cholestasis occurred, the remaining one having intrahepatic cholestasis as the primary sign of the disease. Amyloidosis was identified from liver biopsies in all patients by its specific binding to Congo red and green birefringence in polarized light. The biochemical nature and the class of amyloid deposits were identified immunohistochemically. In addition to their regular treatment, the patients received 750 mg ursodeoxycholic acid per day. After 2-4 weeks all patients had a significant decrease of serum alkaline phosphatase and gamma-glutamyl transferase, and their general status significantly improved. CONCLUSION: Treatment with ursodeoxycholic acid may be beneficial in patients with hepatic amyloidosis, and do extend indications for the use of ursodeoxycholic acid in amyloidotic cholestatic liver disease.

Interleukin-2 in CD8+ T cells correlates with Banff score during organ rejection in liver transplant recipients.

The aim of this study is to compare the histological grading of acute organ rejection according to the Banff score with intracellular interleukin-2 (IL-2) concentrations in cytotoxic CD8+ T cells from peripheral blood samples. 66 recipients after liver transplantation and 20 healthy controls were included into this study. Blood samples of liver transplant recipients were collected beside routine visits or, in case of suspected organ rejection, with additional liver biopsy. For cytometry, the blood cells were stained with CD3, CD8 and intracellular-IL-2. The percentage of cells with detectable intracellular IL-2 was significantly increased in patients with acute rejection (n = 7, P < 0.001, t Test) compared to recipients without rejection. The percentage of cells with detectable intracellular IL-2 (mean +/- SEM) was 7.6 +/- 0.9% in rejection patients, 2.3 +/- 0.22% in stable liver transplant recipients, and 14 +/- 2.99% in healthy controls. Intracellular IL-2 correlates to the Banff score in rejection patients (Spearmans-rho = 0.81, P < 0.05). This cytometric method shows a good sensitivity (71%) with a cut-off based on a high specificity of 95% for histological proven organ rejection in our study cohort. Measurement of intracellular IL-2 in cytotoxic CD8+ T-lymphocytes by flow cytometry correlates very well to the histological grading according to the Banff score and shows a good sensitivity and excellent specificity in acute organ rejection.

Liver biochemistry profile, significance and endoscopic management of biliary tract complications post orthotopic liver transplantation.

AIM: To correlate the significance of liver biochemical tests in diagnosing post orthotopic liver transplantation (OLT) biliary complications and to study their profile before and after endoscopic therapy. METHODS: Patients who developed biliary complications were analysed in detail for the clinical information, laboratory tests, treatment offered, response to it, follow up and outcomes. The profile of liver enzymes was determined. The safety, efficacy and outcomes of endoscopic retrograde cholangiography (ERC) were also analysed. RESULTS: 40 patients required ERC for 70 biliary complications. GGT was found to be > 3 times (388.1 +/- 70.9 U/mL vs 168.5 +/- 34.2 U/L, P=0.007) and SAP > 2 times (345.1 +/- 59.1 U/L vs 152.7 +/- 21.4 U/L, P=0.003) the immediate post OLT values. Most frequent complication was isolated anastomotic strictures in 28 (40%). Sustained success was achieved in 26 (81%) patients. CONCLUSION: Biliary complications still remain an important problem post OLT. SAP and GGT can be used as early, non-invasive markers for diagnosis and also to assess the adequacy of therapy. Endoscopic management is usually effective in treating the majority of these biliary complications.

Determinants of fasting total serum homocysteine levels in liver transplant recipients.

OBJECTIVES: Homocysteine (HCY) is a sulfur-containing amino acid considered to be a marker for a relative folate deficiency. Hyperhomocysteinemia is a known risk factor for development of cardiovascular disease, vascular dementia, depression, and possibly some carcinogeneses. Liver transplant recipients have an increased risk for cardiovascular disease because of a high incidence of obesity, arterial hypertension, diabetes mellitus, and hyperlipidemia. The aim of this study is to elucidate the determinants for hyperhomocysteinemia as an additional risk factor in these patients. MATERIALS AND METHODS: Seventy stable liver transplant recipients, 48 men (mean age, 50+/-11 years) and 22 women (mean age, 52+/-13 years) had their serum homocysteine levels tested after orthotopic liver transplantation. For mainstay immunosuppression, 53 patients were treated with tacrolimus, 10 with cyclosporine, 3 with mycophenolate mofetil, and 4 with sirolimus. Fasting blood samples were obtained and analyzed immediately (within 1 hour) for total serum homocysteine by high-performance liquid chromatography. RESULTS: In all patients, mean homocysteine levels were 22.7+/-14 micromol/L (normal range, 9-15 micromol/L). Forty-six patients were found to have homocysteine levels>15 micromol/L, and all 70 recipients had homocysteine levels>9 micromol/mL. In our patients, increased homocysteine levels correlated well with body mass index and renal function. Homocysteine levels in patients receiving cyclosporine were higher than those in patients receiving tacrolimus (22.3+/-6 vs 17.9+/-12 micromol/L, P<.05). CONCLUSIONS: Overall, homocysteine levels are significantly increased in liver transplant recipients. Homocysteine levels correlate well with obesity, renal function, and the particular immunosuppressant protocol. Therefore, a specific treatment for patients after liver transplantation (eg, one with folates) might reduce the risk of complications resulting from hyperhomocysteinemia.

Hyperproliferation of homocysteine-treated colon cancer cells is reversed by folate and 5-methyltetrahydrofolate.

BACKGROUND: There is an increasing evidence, stemming from epidemiological studies as well as studies performed in human biopsies and animal and cell culture models, suggesting that folate is chemopreventive in colonic carcinogenesis. Hyperhomocysteinemia is frequently associated with folate deficiency. Homocysteine, an amino acid, is metabolized to methionine in a 5-methyltetrahydrofolate (5-MTHF) dependent reaction. AIM OF THE STUDY: The aim of this study was i) to evaluate the effects of folate and its metabolites on growth and cell cycle progression in human colon cancer cells (Caco-2) in culture, and ii) to assess the effects of exogenous homocysteine on colon cancer cell proliferation. iii) Having found that homocysteine enhances colon cancer cell growth while metabolites of folate inhibit cell proliferation, we investigated the effects of simultaneous treatment in colon cancer cells. METHODS: Caco-2 cells were incubated either with homocysteine (0.1-10 microM), and/or with folic acid and its metabolites (0.625-10 microg/ml). Cell proliferation was determined after 24 h and 48 h by measuring 5- bromo-2'-desoxyuridine (BrdU) incorporation. Additionally, the cells were trypsinized and prepared for cell cycle determination using propidium iodide for DNA staining. The stained cells were analyzed using a flow cytometer. RESULTS: Folate inhibited cell proliferation moderately within 24 h. Its metabolites, dihydrofolate and 5-MTHF were more potent inhibitors of cell growth. Treatment with folate and 5-MTHF resulted in the accumulation of cells in G1-G0 phase of the cell cycle and decreased the number of cells in G2-M phase. In addition, cells treated with 5-MTHF were predominantly accumulated in the S-phase. There was no difference in cell cycle progression of Caco-2 cells treated with homocysteine in comparison to controls. In homocysteine-treated cells, both folate and 5-MTHF reversed the homocysteine-induced enhancement of growth. In contrast, folate reduced the Caco-2 cell growth rate to control values and 5-MTHF depleted growth of homocysteine-treated cells to levels significantly lower than controls. CONCLUSIONS: Our data suggest that 5-MTHF, being the key metabolite in both the folate and homocysteine metabolic pathway, is the main modulator of growth-promoting actions of homocysteine as well as antiproliferative effects of folate in colon cancer cells.

Anti-inflammatory drugs modulate C1q secretion in human peritoneal macrophages in vitro.

The complement system plays an important role in the humoral immune response. Activation of the classical complement pathway is mediated by its subcomponent, C1q, which is involved in the pathogenesis of several autoimmune disorders. Among the main C1q-synthesising tissues, macrophages have been attributed as the main source. We investigated the effects of anti-inflammatory drugs (methylprednisolone and acetylsalicylic acid (ASA)) on C1q secretion in human peritoneal macrophages in vitro. The macrophages were isolated from peritoneal lavage fluid of patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis, and were maintained in culture for up to 6 days. ASA decreased while methylprednisolone increased C1q secretion from human peritoneal macrophages in vitro, which correlated well with the percentage of CD14 positive cells after treatment. We conclude that different response of the macrophages to treatment with methylprednisolone and ASA may point out to the importance of macrophage activation after treatment, as well as an increased abundance of membrane C1q accompanied by increased phagocytosis.

Piceatannol, a natural analog of resveratrol, inhibits progression through the S phase of the cell cycle in colorectal cancer cell lines.

Piceatannol, a naturally occurring analog of resveratrol, was previously identified as the active ingredient in herbal preparations in folk medicine and as an inhibitor of p72(Syk). We studied the effects of piceatannol on growth, proliferation, differentiation and cell cycle distribution profile of the human colon carcinoma cell line Caco-2. Growth of Caco-2 and HCT-116 cells was analyzed by crystal violet assay, which demonstrated dose- and time-dependent decreases in cell numbers. Treatment of Caco-2 cells with piceatannol reduced proliferation rate. No effect on differentiation was observed. Determination of cell cycle distribution by flow cytometry revealed an accumulation of cells in the S phase. Immunoblotting demonstrated that cyclin-dependent kinases (cdk) 2 and 6, as well as cdc2 were expressed at steady-state levels, whereas cyclin D1, cyclin B1 and cdk 4 were downregulated. The abundance of p27(Kip1) was also reduced, whereas the protein level of cyclin E was enhanced. Cyclin A levels were enhanced only at concentrations up to 100 micromol/L. These changes also were observed in studies with HCT-116 cells. On the basis of our findings, piceatannol can be considered to be a promising chemopreventive or anticancer agent.