Radiation therapy of breast cancer in the Nahe Breast Center: first results of an analysis in the context of health services research.

BACKGROUND: The first evaluation of radiotherapy results in patients with breast cancer treated as part of a multimodal oncologic therapy in the Nahe Breast Center is presented. Analysis of the results was performed using an in-practice registry. PATIENTS AND METHODS: From September 2016 to December 2017, 138 patients (median age 62.5 years; range 36-94 years) with breast cancer (right side, n = 67; left side, n = 71) received adjuvant radiation therapy. Of these, 103 patients received gyneco-oncologic care at the Nahe Breast Center, and 35 were referred from outside breast centers. The distribution into stages was as follows: stage I, n = 48; stage II, n = 68; stage III, n = 19; stage IV, n = 3. Neoadjuvant chemotherapy was given to 19 and adjuvant chemotherapy to 50 patients. Endocrine treatment was given to 120 patients. Both 3D conformal (n = 103) and intensity-modulated (n = 35) radiotherapy were performed with a modern linear accelerator. RESULTS: With a median follow-up of 60 months (1-67), local recurrence occurred in 4/138 (2.9%) and distant metastasis in 8/138 (5.8%) patients; 7/138 (5.1%) patients died of their tumors during the follow-up period. The actuarial 5­year local recurrence-free survival of all patients was 97.1%, and the actuarial 5­year overall survival of all patients was 94.9%. We observed no grade 3 or 4 radiogenic side effects. CONCLUSION: The results of radiotherapy for breast carcinoma at the Nahe Breast Center are comparable to published national and international results. In particular, the local recurrence rates in our study, determined absolutely and actuarially, are excellent, and demonstrate the usefulness of radiotherapy.

Counseling on Complementary Methods in the Treatment of Side Effects of Oncological Therapies: A Project of the Breast and Bowel Center Nahe at the Hospital Sankt Marienwoerth Bad Kreuznach.

BACKGROUND: Increasingly, patients with cancer are asking for additional, complementary therapy options for treating the side effects of oncological therapy. Thus, the members of the Breast and Bowel Center Nahe at the Sankt Marienwörth Hospital Bad Kreuznach decided to define the content of this type of counseling for patients before treatment. METHODS: In 2018, a team of internal oncologists, gynecological oncologists, radio-oncologists, nutritionists, psycho-oncologists, and study nurses met several times to define the content of counseling. To inform the team, an intensive literature review was conducted. RESULTS: Counseling content was determined for complementary treatment options for the most frequent side effects of oncological therapies. Counseling sessions were formulated as frontal lectures (slide presentations), given at regular intervals for patients and relatives. These lectures were highly appreciated by patients. CONCLUSION: These counseling sessions increased patient understanding of both useful complementary measures and harmful measures they should not use.

[Postoperative dumping-syndrome with relevant impairment of glucose homeostasis - relief by continuous glucose monitoring and individual therapy with GLP-1 receptor agonists]. / Postoperatives Dumping-Syndrom mit nachhaltiger Störung der Glukosehomöostase ­ Linderung durch Flash-Glukosemessung und individuelle Indikationsstellung für Glucagon-like-Peptide-1(GLP-1)-Rezeptoragonisten.

Dumping syndromes are a common side effect after partial or total gastric resection. The symptoms may be diverse, with vasomotoric reactions, collapse tendencies and digestive disorders (early dumping) as well as blood sugar derailment as a result of too fast absorption of glucose (late dumping).Entrenched therapy concepts, including personalized nutritional concepts and the use of medication as octreotide or diazoxide, will not always lead to the desired results. It is then, that individual therapy concepts have to be found to restore the patient's quality of life, as shown in this case study.

Urinary Biomarkers α-GST and π-GST for Evaluation and Monitoring in Living and Deceased Donor Kidney Grafts.

The aim of this study was to analyze the value of urine α- and π-GST in monitoring and predicting kidney graft function following transplantation. In addition, urine samples from corresponding organ donors was analyzed and compared with graft function after organ donation from brain-dead and living donors. Urine samples from brain-dead (n = 30) and living related (n = 50) donors and their corresponding recipients were analyzed before and after kidney transplantation. Urine α- and π-GST values were measured. Kidney recipients were grouped into patients with acute graft rejection (AGR), calcineurin inhibitor toxicity (CNI), and delayed graft function (DGF), and compared to those with unimpaired graft function. Urinary π-GST revealed significant differences in deceased kidney donor recipients with episodes of AGR or DGF at day one after transplantation (p = 0.0023 and p = 0.036, respectively). High π-GST values at postoperative day 1 (cutoff: >21.4 ng/mg urine creatinine (uCrea) or >18.3 ng/mg uCrea for AGR or DGF, respectively) distinguished between rejection and no rejection (sensitivity, 100%; specificity, 66.6%) as well as between DGF and normal-functioning grafts (sensitivity, 100%; specificity, 62.6%). In living donor recipients, urine levels of α- and π-GST were about 10 times lower than in deceased donor recipients. In deceased donors with impaired graft function in corresponding recipients, urinary α- and π-GST were elevated. α-GST values >33.97 ng/mg uCrea were indicative of AGR with a sensitivity and specificity of 77.7% and 100%, respectively. In deceased donor kidney transplantation, evaluation of urinary α- and π-GST seems to predict different events that deteriorate graft function. To elucidate the potential advantages of such biomarkers, further analysis is warranted.

Delayed gastric emptying following pancreatoduodenectomy with alimentary reconstruction according to Roux-en-Y or Billroth-II.

BACKGROUND: Delayed gastric emptying (DGE) remains the most frequent complication following pancreatoduodenectomy (PD) with published incidences as high as 61%. The present study investigates the impact of bowel reconstruction techniques on DGE following classic PD (Whipple-Kausch procedure) with pancreatogastrostomy (PG). METHODS: We included 168 consecutive patients who underwent PD with PG with either Billroth II type (BII, n = 78) or Roux-en-Y type reconstruction (ReY, n = 90) between 2004 and 2015. Excluded were patients with conventional single loop reconstruction after pylorus preserving procedures. DGE was classified according to the 2007 International Study Group of Pancreatic Surgery definition. Patients were analyzed regarding severity of DGE, morbidity and mortality, length of hospital stay and demographic factors. RESULTS: No difference was observed between BII and ReY regarding frequency of DGE. Overall rate for clinically relevant DGE was 30% (ReY) and 26% (BII). BII and ReY did not differ in terms of demographics, morbidity or mortality. DGE significantly prolongs ICU (four vs. two days) and hospital stay (20.5 vs. 14.5 days). Risk factors for DGE development are advanced age, retrocolic reconstruction, postoperative hemorrhage and major complications. CONCLUSIONS: The occurrence of DGE can not be influenced by the type of alimentary reconstruction (ReY vs. BII) following classic PD with PG. Old age and major complications could be identified as important risk factors in multivariate analysis. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00011860 . Registered 14 March 2017.

Gender Matches in Liver Transplant Allocation: Matched and Mismatched Male-Female Donor-Recipient Combinations; Long-term Follow-up of More Than 2000 Patients at a Single Center.

OBJECTIVES: The influence of donor-recipient sex mismatches on long-term graft survival after liver transplant is controversial. In this study, our aim was to characterize the differences in long-term graft outcome after liver transplant in more than 2000 cases with special regard to sex match and mismatch. MATERIALS AND METHODS: In this retrospective, single center study of 2144 adult primary liver transplant recipients (median follow-up of 92 months), we analyzed specific long-term graft survival and the effect of different donor and recipient sex combinations (Kaplan-Meier, multivariate regression). RESULTS: In the 15-year follow-up, female recipients (58.6%) had significantly better graft survival than male recipients did (51.6%, P = .031). Matched and mismatched male-female combinations revealed significant differences (P = .003): a male donor-female recipient combination showed the best 15-year graft survival (61.1%), and a female donor-male recipient combination showed the worst graft survival (48.6%), whereas male-male (53.3%) and female-female combinations (55.6%) were not significantly different (P = .967). Donor age (P ≤ .0001), body mass index (P = .021), female sex (P = .015), Eurotransplant Donor Risk Index > 1.4 (P ≤ .001), recipients' age (P < .0001), indication for liver transplant (P < .0001), and kidney function (P = .003) significantly affected graft survival. In the multivariate analysis model, a Eurotransplant Donor Risk Index > 1.4 and impaired kidney function at liver transplant again emerged as significant negative predictors. Female donors and male recipients showed significantly more unfavorable characteristics concerning long-term graft survival. CONCLUSIONS: The impressive long-term graft survival benefit of male donor-female recipient versus female donor-male recipient and of male donor-female recipient versus matched groups (male-male, female-female) in liver transplant may be caused by significant differences in donor quality and recipient characteristics and may not be related to sex itself.

Eurotransplant donor-risk-index and recipient factors: influence on long-term outcome after liver transplantation - A large single-center experience.

The organ shortage has led to increased use of marginal organs. The Eurotransplant Donor-Risk-Index (ET-DRI) was established to estimate outcome after Liver Transplantation (LT). Currently, data on impact of ET-DRI on long-term outcome for different indications and recipient conditions are missing. Retrospective, single-center analysis of long-term graft survival (GS) of 1767 adult primary LTs according to indication, labMELDcategory (1: ≤18; 2: >18-25; 3: >25-35; 4: >35), and ET-DRI. Mean ET-DRI in our cohort was 1.63 (±0.43). One-, 10, and 15-yr GS was 83.5%, 63.3%, and 54.8%. Long-term GS was significantly influenced by ET-DRI. Accordingly, four ET-DRI categories were defined and analyzed with respect to underlying disease. Significant impact of these categories was observed for: Alcohol, cholestatic/autoimmune diseases (CD/AIH), and HCV, but not for HCC, HBV, cryptogenic cirrhosis, and acute liver failure. labMELD categories showed no significant influence on graft, but on patient survival. Matching ET-DRI categories with labMELD revealed significant differences in long-term GS for labMELDcategories 1, 2, and 3, but not 4. In multivariate analysis, HCV combined with ET-DRI > 2 and labMELDcategory 3 combined with ET-DRI > 2 emerged as negative predictors. To achieve excellent long-term graft survival, higher risk organs (ET-DRI > 1.4) should be used restrictively for patients with CD/AIH or HCV. Organs with ET-DRI > 2 should be avoided in patients with a labMELD of >25-35.

Colonoscopy detects significantly more flat adenomas than 3-tesla magnetic resonance colonography: a pilot trial.

BACKGROUND AND STUDY AIMS: Colorectal cancer (CRC) is one of the most common cancers worldwide, and several efforts have been made to reduce its occurrence or severity. Although colonoscopy is considered the gold standard in CRC prevention, it has its disadvantages: missed lesions, bleeding, and perforation. Furthermore, a high number of patients undergo this procedure even though no polyps are detected. Therefore, an initial screening examination may be warranted. Our aim was to compare the adenoma detection rate of magnetic resonance colonography (MRC) with that of optical colonoscopy. PATIENTS AND METHODS: A total of 25 patients with an intermediate risk for CRC (17 men, 8 women; mean age 57.6, standard deviation 11) underwent MRC with a 3.0-tesla magnet, followed by colonoscopy. The endoscopist was initially blinded to the results of MRC and unblinded immediately after examining the distal rectum. Following endoscopic excision, the size, anatomical localization, and appearance of all polyps were described according to the Paris classification. RESULTS: A total of 93 lesions were detected during colonoscopy. These included a malignant infiltration of the transverse colon due to gastric cancer in 1 patient, 28 adenomas in 10 patients, 19 hyperplastic polyps in 9 patients, and 45 non-neoplastic lesions. In 5 patients, no lesion was detected. MRC detected significantly fewer lesions: 1 adenoma (P = 0.001) and 1 hyperplastic polyp (P = 0.004). The malignant infiltration was seen with both modalities. Of the 28 adenomas, 23 (82 %) were 5 mm or smaller; only 4 adenomas 10 mm or larger (14 %) were detected. CONCLUSION: MRC does not detect adenomas sufficiently independently of the location of the lesion. Even advanced lesions were missed. Therefore, colonoscopy should still be considered the current gold standard, even for diagnostic purposes.

Iloprost donor treatment reduces ischemia-reperfusion injury in an isolated extracorporeal pig liver perfusion model.

OBJECTIVES: Iloprost has the potential to protect the liver transplant graft before and during cold ischemia. We studied iloprost administration during organ procurement and reperfusion in an extracorporeal pig liver perfusion model. MATERIALS AND METHODS: German Landrace pigs (n = 7/group; 22-26 kg each) were used as donors. Preservation was performed by aortic perfusion with 2 L Bretschneiders' Histidine-Tryptophan-Ketoglutarate solution HTK and cold ischemia time (4°C) 20 hours followed by normothermic extracorporeal perfusion for 8 hours. Untreated controls (1) were compared to iloprost (2) donor bolus-treatment (1 µg/kg body weight), (3) addition of iloprost to Bretschneiders' Histidine-Tryptophan-Ketoglutarate solution HTK (0.0125 µg/mL), (4) continuous infusion during reperfusion (2 ng/kg/min), and (5) combined treatment (2) and (4). RESULTS: Iloprost donor treatment led to significantly higher bile production. Addition of iloprost to the preservation solution significantly improved hepatic artery perfusion and was accompanied by improvements of microcirculation and bile production. Iloprost reperfusion treatment alone significantly improved bile production. Enzyme levels were positively affected by all treatment regimens. Combined use of iloprost before and after ischemia improved hepatic artery flow and microcirculation and showed significantly lower hypoxia staining versus controls. CONCLUSIONS: Iloprost donor treatment and use of iloprost in the preservation solution significantly improved graft perfusion and function. The effects of graft treatment seemed greater before than after reperfusion. Combined treatment did not reveal a synergistic advantage.

Cardiovascular risk and events after liver transplantation. Experiences from 313 consecutive transplants with a follow-up of 20 years.

Cardiovascular diseases (CVD) are the third leading cause of late death after liver transplantation (LT). The old PROCAM score was described in males (aged 35-65 yr) to estimate cardiovascular events after LT. New PROCAM is now available to estimate risks for cardiovascular events in both genders and for a wider age range (25-75 yr). We tested old and new PROCAM in long-term follow-up (10 and 20 yr) and described CVD risk factors, kidney function, and immunosuppression over two decades. A retrospective study of 313 consecutive LTs was conducted. At 10 (T2) and 20 (T3) yr, patients were screened for cardiovascular events, and for T1 (0.5 yr) and T2, CVD risk factors were recorded and old and new PROCAM calculated. PROCAM estimates were compared with observed events. CVD risk factors increased significantly over time and kidney function decreased. Between T1 and T2 in males, fewer events were observed (o) than estimated (e) (males: o: 3 vs. e: 6.05-9.88; females o: 2 vs. e: 1.35-4.21). For both genders, new PROCAM was appropriate between T2 and T3 (males o: 8; e: 4.5-8.57; females o: 2; e: 1.2-4.46). New PROCAM sufficiently estimates cardiovascular risk after LT, while overestimation in T1-T2 may be due to strict surveillance.

Response to preoperative chemotherapy predicts survival in patients undergoing hepatectomy for liver metastases from gastric and esophageal cancer.

BACKGROUND: The role of hepatectomy for patients with liver metastases from gastric and esophageal cancer (GELM) is not well defined. The present study examined the morbidity, mortality, and long-term survivals after liver resection for GELM. METHODS: Clinicopathological data of patients who underwent hepatectomy for GELM between 1995 and 2012 at two European high-volume hepatobiliary centers were assessed, and predictors of overall survival (OS) were identified. In addition, the impact of preoperative chemotherapy for GELM on OS was evaluated. RESULTS: Forty-seven patients underwent hepatectomy for GELM. The primary tumor was located in the stomach, cardia, and distal esophagus in 27, 16, and 4 cases, respectively. Twenty patients received preoperative chemotherapy before hepatectomy. After a median follow-up time of 76 months, 1-, 3-, and 5-year OS rates were 70, 37, and 24%, respectively. Postoperative morbidity and mortality rates were 32 and 4%, respectively. Outcomes were comparable between the two centers. Preoperative chemotherapy for GELM (5-year OS: 45 vs 9%, P = .005) and the lack of posthepatectomy complications (5-year OS: 34 vs 0%, P < .0001) were significantly associated with improved OS in univariate and multivariate analyses. When stratifying OS by radiologic response of GELM to preoperative chemotherapy, patients with progressive disease despite preoperative treatment had significantly worse OS (5-year OS: 0 vs 70%, P = .045). CONCLUSION: For selected patients with GELM, liver resection is safe and should be regarded as a potentially curative approach. A multimodal treatment strategy including systemic therapy may provide better patient selection resulting in prolonged survival in patients with GELM undergoing hepatectomy.

Different cava reconstruction techniques in liver transplantation: piggyback versus cava resection.

BACKGROUND: Originally, cava reconstruction (CR) in liver transplantation meant complete resection and reinsertion of the donor cava. Alternatively, preservation of the recipients inferior vena cava (IVC) with side-to-side anastomosis (known as "piggyback") can be performed. Here, partial clamping maintains blood flow of the IVC, which may improve cardiovascular stability, reduce blood loss and stabilize kidney function. The aim of this study was to compare both techniques with particular focus on kidney function. METHODS: A series of 414 patients who had had adult liver transplantations (2006-2009) were included. Among them, 176 (42.5%) patients had piggyback and 238 had classical CR operation, 112 (27.1%) of the patients underwent CR accompanied with veno-venous bypass (CR-B) and 126 (30.4%) without a bypass. The choice of either technique was based on the surgeons' individual preference. Kidney function [serum creatinine, calculated glomerular filtration rate (GFR), RIFLE stages] was assessed over 14 days. RESULTS: Lab-MELD scores were significantly higher in CR-B (22.5+/-11.0) than in CR (17.3+/-9.0) and piggyback (18.8+/-10.0) (P=0.008). Unexpectedly, the incidences of arterial stenoses (P=0.045) and biliary leaks (P=0.042) were significantly increased in piggyback. Preoperative serum creatinine levels were the highest in CR-B [1.45+/-1.17 vs 1.25+/-0.85 (piggyback) and 1.13+/-0.60 mg/dL (CR); P=0.033]. Although a worsening of postoperative kidney function was observed among all groups, this was most pronounced in CR-B [creatinine day 14: 1.67+/-1.40 vs 1.35+/-0.96 (piggyback) and 1.45+/-1.03 mg/dL (CR); P=0.102]. Accordingly, the proportion of patients displaying RIFLE stages ≥2 was the highest in CR/CR-B (26%/19%) when compared to piggyback (18%). CONCLUSIONS: Piggyback revealed a shorter warm ischemic time, a reduced blood loss, and a decreased risk of acute kidney failure. Thus, piggyback is a useful technique, which should be applied in standard procedures. When piggyback is unfeasible, cava replacement, which displayed a lower incidence of vascular and biliary complications in our study, remains as a safe alternative.

Plasmid transfer of plasminogen K1-5 reduces subcutaneous hepatoma growth by affecting inflammatory factors.

There is evidence that plasminogen K1-5 (PlgK1-5) directly affects tumour cells and inflammation. Therefore, we analysed if PlgK1-5 has immediate effects on hepatoma cells and inflammatory factors in vitro and in vivo. In vitro, effects of plasmid encoding PlgK1-5 (pK1-5) on Hepa129, Hepa1-6, and HuH7 cell viability, apoptosis, and proliferation as well as VEGF and TNF-alpha expression and STAT3-phosphorylation were investigated. In vivo, tumour growth, proliferation, vessel density, and effects on vascular endothelial growth factor (VEGF) and tumour necrosis factor alpha (TNF-alpha) expression were examined following treatment with pK1-5. In vivo, pK1-5 halved cell viability; cell death was increased by up to 15% compared to the corresponding controls. Proliferation was not affected. VEGF, TNF-alpha, and STAT3-phosphorylation were affected following treatment with pK1-5. In vivo, ten days after treatment initiation, pK1-5 reduced subcutaneous tumour growth by 32% and mitosis by up to 77% compared to the controls. Vessel density was reduced by 50%. TNF-alpha levels in tumour and liver tissue were increased, whereas VEGF levels in tumours and livers were reduced after pK1-5 treatment. Taken together, plasmid gene transfer of PlgK1-5 inhibits hepatoma (cell) growth not only by reducing vessel density but also by inducing apoptosis, inhibiting proliferation, and triggering inflammation.

Toxic damage increases angiogenesis and metastasis in fibrotic livers via PECAM-1.

Excessive ethanol consumption is one of the main causes of liver fibrosis. However, direct effects of ethanol exposure on endothelial cells and their contribution to fibrogenesis and metastasis were not investigated. Therefore we analysed whether ethanol directly affects endothelial cells and if this plays a role during fibrogenesis and metastasis in the liver. Murine and human endothelial cells were exposed to ethanol for up to 72 hours. In vitro, effects on VEGF, HIF-1alpha, PECAM-1, and endothelial cell functions were analysed. In vivo, effects of continuous liver damage on blood vessel formation and metastasis were analysed by PECAM-1 immunohistochemistry. Ethanol increased HIF-1alpha and VEGF levels in murine and human endothelial cells. This resulted in enhanced intracellular signal transduction, and PECAM-1 expression as well as tube formation and wound healing. In vivo, toxic liver damage increased angiogenesis during fibrogenesis. Metastasis was also enhanced in fibrotic livers and located to PECAM-1 positive blood vessels compared to nonfibrotic mice. In conclusion, ethanol had strong effects on endothelial cells, which--at least in part--led to a profibrotic and prometastatic environment mediated by PECAM-1. Blockade of increased PECAM-1 expression could be a promising tool to inhibit fibrogenesis and metastasis in the liver.

Mycophenolate mofetil enhances the negative effects of sirolimus and tacrolimus on rat kidney cell metabolism.

BACKGROUND AND PURPOSE: Mycophenolate mofetil (MMF) per se is not known to have negative effects on the kidney. MMF alone or in combination with sirolimus, can be the basis of calcineurin inhibitor (CNI)-free, kidney sparing drug protocols. However, long-term outcomes in patients on MMF/SRL seem to be inferior to those treated with regimens that include the CNI tacrolimus (TAC) due to an increased risk of allo-immune reactions. Interestingly, potential enhancement of the negative effects of SRL and TAC on the kidney by MMF has never been considered. EXPERIMENTAL APPROACH: It was our aim to study the effects of TAC, SRL and MMF alone and evaluate their interactions when combined on the rat kidney. For this purpose we used a comprehensive molecular marker approach including measurements of urinary 8-isoprostane concentrations (oxidative stress marker) and changes of urinary metabolite patterns ((1)H-NMR spectroscopy) and comparing these markers to renal function (glomerular filtration rate (GFR)) and morphologic alterations (histology). KEY RESULTS: While MMF alone did not impact GFR, its interaction with SRL and TAC led to a significant decrease of rats' renal function. The decline went in parallel with a significant increase in urinary isoprostane concentrations and an enhancement of negative effects on urinary metabolite patterns. CONCLUSIONS: In broad summary, the present study showed that MMF may enhance the negative effects of TAC on kidney function and may even display nephrotoxic properties when combined with SRL.

The conservative and interventional treatment of the complications of liver cirrhosis: Part 2 of a series on liver cirrhosis.

BACKGROUND: It is estimated that 1 million persons in Germany suffer from hepatic cirrhosis, which is the final stage of chronic inflammation of the liver. Cirrhosis has multiple causes, all of which lead to structural changes of the liver and to portal hypertension. The main complications of cirrhosis arise in turn: These include bleeding from collateral veins, ascites, hepatocellular carcinoma, encephalopathy, and infection leading to organ failure. METHODS: We present the treatment of the main complications of liver cirrhosis with reference to the relevant literature (phase II and III trials, meta-analyses, and reviews). RESULTS: Endoscopic treatment (ligation) is used for the primary and secondary prophylaxis of variceal bleeding. Drugs to lower portal pressure (e.g., beta-blockers) are an established means of preventing initial or recurrent variceal bleeding over the long term. Vasoconstrictors such as terlipressin are mainly used to treat acute hemorrhage and type 1 hepatorenal syndrome. The main treatment of ascites is with spironolactone, in combination with a loop diuretic where indicated. A shunt (TIPS) is used to treat severe or repeat variceal hemorrhage or refractory ascites. Antibiotics play a well-established role in the treatment of acute hemorrhage, in the treatment and prevention of spontaneous bacterial peritonitis, and in the treatment of encephalopathy. The treatment of hepatocellular carcinoma depends on its extent of spread and on the degree of decompensation of cirrhosis. CONCLUSION: For most of the main complications of liver cirrhosis, there are treatments that have been well-tested in randomized trials. Liver transplantation should also be considered in every case.

Development and validation of an LC-MS/MS assay for the quantification of the trans-methylation pathway intermediates S-adenosylmethionine and S-adenosylhomocysteine in human plasma.

BACKGROUND: Although increased levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) have been implicated as markers for renal and vascular dysfunction, until now there have been no studies investigating their association with clinical post-transplant events such as organ rejection and immunosuppressant nephrotoxicity. METHODS: A newly developed and validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the quantification of SAM and SAH in human EDTA plasma was used for a clinical proof-of-concept pilot study. Retrospective analysis was performed using samples from a longitudinal clinical study following de novo kidney transplant patients for the first year (n=16). RESULTS: The ranges of reliable response were 8 to 1024 nmol/l for SAM and 16 to 1024 nmol/l for SAH. The inter-day accuracies were 96.7-103.9% and 97.9-99.3% for SAM and SAH, respectively. Inter-day imprecisions were 8.1-9.1% and 8.4-9.8%. The total assay run time was 5 min. SAM and SAH concentrations were significantly elevated in renal transplant patients preceding documented acute rejection and nephrotoxicity events when compared to healthy controls (n=8) as well as transplant patients void of allograft dysfunction (n=8). CONCLUSION: The LC-MS/MS assay will provide the basis for further large-scale clinical studies to explore these thiol metabolites as molecular markers for the management of renal transplant patients.

Association of socio-economic status and stage of pancreatic cancer at time of surgery in a German setting.

BACKGROUND/AIMS: Curative resection has been proven to be one of the most important factors determining outcome in pancreatic cancer patients. Advanced stage of pancreatic cancer at diagnosis is strongly associated with a low socioeconomic status (SES), and patients from affluent areas have better cancer survival than patients from deprived areas. We tested, in our population of pancreatic cancer patients, the hypothesis that surrogates representing a lower SES or demographic factors (DGF) linked to rural areas are associated with a more advanced disease stage at presentation. METHODOLOGY: Between 1989 and 2008, patients with pancreatic adenocarcinoma and pancreaticoduodenectomy were identified from our pancreatic resection database. DGF, SES surrogates and tumor stage were obtained from patients' files together with pathology reports, a residents' registration office questionnaire and telephone interviews with patients and family members. RESULTS: Follow-up was completed in 117 patients. There were no significant differences regarding tumor stage (local size and lymph node metastases), or the likelihood of negative resection margins in relation to the patients' DGF or any surrogate parameters for SES. Furthermore, comparison of two different treatment periods showed no significant advances regarding secondary cancer prevention within 20 years. CONCLUSIONS: Longer waiting times for appointments combined with less sensitive imaging techniques and consecutive later referral to a cancer specialist are likely to be associated with inferior quality of medical results. Therefore, a lively debate is currently underway in Germany concerning the harmonization of reimbursement modes for statutory and private health insurance. Our data with no negative correlation of low SES or unfavorable DGF and disease stage at time of presentation or the likelihood for a curative resection, do not promote the universal accusation of health care disparities solely based on economic issues in Germany.