[Relevance of MRSA on a Visceral Surgical Intensive Care Unit]. / Relevanz von MRSA auf einer viszeralchirurgischen Intensivstation.

Background: Resistance to antibiotics is a worldwide increasing problem. A well-known example is methicillin resistant Staphylococcus aureus, MRSA. What is the relevance of MRSA on a surgical ICU? Patients/Material and Methods: On a 20 bed academic SICU/intermediate care ward 14,976 patients were treated in a seven-year period. We identified only 98 MRSA-positive patients. 56 (57 %) of them were merely colonised, 42 (43 %) suffered from an MRSA infection. A control group comprised 56 similar patients without MRSA detection. Results: Patients with MRSA infection had a higher mortality rate (OR 4.18; p = 0.002), but only 4 out of 20 patients died due to the MRSA infection. APACHE 2 score of more than 20 was predictive for being colonised with MRSA (OR 3.08; p = 0.04), but it was not a risk factor for developing an MRSA infection (OR 1.03; p = 0.95). Patients with MRSA colonisation did not have a higher mortality rate than patients without. Conclusion: Outcome depended on severity of the disease, but not on the MRSA colonisation status. Patients with MRSA infection were more likely to die, but the reason of death rarely was MRSA.

CpG-island methylation of the ER promoter in colorectal cancer: analysis of micrometastases in lymph nodes from UICC stage I and II patients.

Patients with UICC stage II colorectal cancer (CRC) have a risk of approximately 20% to develop disease recurrence after tumour resection. The presence and significance of micrometastases for locoregional recurrence in these patients lacking histopathological lymph node involvement on routine stained HE sections is undefined. Oestrogen receptor (ER) promoter methylation has earlier been identified in CRC. Therefore, we evaluated the methylation status of the ER promoter in lymph nodes from 49 patients with CRC UICC stage I and II as a molecular marker of micrometastases and predictor of local recurrence. DNA from 574 paraffin-embedded lymph nodes was isolated and treated with bisulphite. For the detection of methylated ER promoter sequences, quantitative real-time methylation-specific PCR was used. Of the 49 patients tested, 15 (31%) had ER methylation-positive lymph nodes. Thirteen of those (86%) remained disease free and two (14%) developed local recurrence. In the resected lymph nodes of 34 of the 49 patients (69%), no ER promoter methylation could be detected and none of these patients experienced a local relapse. The methylation status of the ER promoter in lymph nodes of UICC stage I and II CRC patients may be a useful marker for the identification of patients at a high risk for local recurrence.

Transanal endoscopic tube decompression of acute colonic obstruction: experience with 51 cases.

BACKGROUND: Acute colorectal obstruction is a potentially life-threatening emergency that requires immediate surgical treatment. To avoid major postoperative complications, most surgeons advocate two-step surgery despite the increase in patient discomfort and cost. Various methods for performing one-step surgery have been reported including intraoperative colonic lavage, decompression with self-expandable metal stents, and transanal tube decompression. METHODS: The authors present their experience performing transanal colonic decompression for 51 patients. RESULTS: Endoscopic tube placement was successful for 43 (84%) of the 51 patients. The emergency clinical situation could be converted to semielective treatment in 37 cases (73%) (30 operations and 6 nonoperative interventions), and to an elective operation in 1 case. After successful colonic decompression, the rate of one-stage operations was 93% (28/30), as compared with 40% (4/10) if the decompression failed. CONCLUSION: Endoscopic tube decompression of acute colonic obstruction is an easy and cost-effective possibility for avoiding emergency operations with all their sequelae. Emergency surgery can be converted to semielective or elective surgery, markedly reducing the rate of staged operations.

Circadian variation in restless legs syndrome.

Restless legs syndrome (RLS) is a clinical disorder that currently is not characterized by a uniform pathophysiologiocal definition. The diagnosis of RLS requires circadian variation in symptoms, although no pathophysiological basis has been verified. Clinical observations and research studies confirm the variation in symptoms, of both sensory and motor components, over the course of the day. This contribution reviews the current literature on circadian variation in RLS and discusses potential intrinsic and extrinsic causes.

Intracerebral Bleeding and Massive Pericardial Effusion as Presenting Symptoms of Myxedema Crisis.

The endocrinological emergency of a fully blown myxedema crisis can present as a multicolored clinical picture. This can obscure the underlying pathology and easily lead to mistakes in clinical diagnosis, work-up, and treatment. We present a case of an unconscious 39-year-old patient with a medical history of weakness, lethargy, and findings of hyponatremia, intracerebral bleeding, and massive pericardial effusion. Finally, myxedema crisis was diagnosed as underlying cause. Replacement therapy of thyroid hormone and conservative management of the intracerebral bleeding resulted in patient's survival without significant neurological impairment. However, diagnostic pericardiocentesis resulted in life-threatening pericardial tamponade. It is of tremendous importance to diagnose myxoedema crisis early to avoid adverse health outcomes.

Effect of liver regeneration after partial hepatectomy and ischemia-reperfusion on expression of growth factor receptors.

AIM: To investigate the effects of experimental partial hepatectomy and normothermic ischemia-reperfusion damage on the time course of the expression of four different growth factor receptors in liver regeneration. This is relevant due to the potential therapeutic use of growth factors in stimulating liver regeneration. METHODS: For partial hepatectomy (PH) 80% of the liver mass was resected in Sprague Dawley rats. Ischemia and reperfusion (I/R) were induced by occlusion of the portal vein and the hepatic artery for 15 min. The epidermal growth factor receptor, hepatic growth factor receptor, fibroblast growth factor receptor and tumour necrosis factor receptor-1 were analysed by immunohistochemistry up to 72 h after injury. Quantitative RT-PCR was performed at the time point of minimal receptor expression (24 h). RESULTS: In immunohistochemistry, EGFR, HGFR, FGFR and TNFR1 showed biphasic kinetics after partial hepatectomy with a peak up to 12 h, a nadir after 24 h and another weak increase up to 72 h. During liver regeneration, after ischemia and reperfusion, the receptor expression was lower; the nadir at 24 h after reperfusion was the same. To evaluate whether this nadir was caused by a lack of mRNA transcription, or due to a posttranslational regulation, RT-PCR was performed at 24 h and compared to resting liver. In every probe there was specific mRNA for the receptors. EGFR, FGFR and TNFR1 mRNA expression was equal or lower than in resting liver, HGFR expression after I/R was stronger than in the control. CONCLUSION: At least partially due to a post-transcriptional process, there is a nadir in the expression of the analysed receptors 24 h after liver injury. Therefore, a therapeutic use of growth factors to stimulate liver regeneration 24 h after the damage might be not successful.

Hepatocyte proliferation and apoptosis in rat liver after liver injury.

BACKGROUND/AIMS: In this paper the early phase of proliferate response and apoptosis of hepatocytes after partial liver resection, during reperfusion after ischemia and during sepsis is demonstrated. METHODOLOGY: Experiments were conducted in a rat model with regeneration times of 0.5-24 hours after injury. Proliferation was analyzed by Ki-67 immunohistochemistry and confirmed by double staining with CK18 in FACS. Apoptosis was analyzed by TUNEL technique. RESULTS: Periportal hepatocytes enter the cell cycle already 0.5-2 hours after injury in all three models. This early proliferative response is predominant periportally localized. During reperfusion and during sepsis there was a strict pericentral apoptosis of hepatocytes found. CONCLUSIONS: An early periportal proliferation of hepatocytes is a common reaction of the liver to injury. This proliferation takes place much earlier then the main proliferative response 24-72 h after partial resection. This predominant periportal proliferation together with the pericentral apoptosis fit to the concept of the "streaming liver" in liver regeneration.

Independence and health related quality of life in 200 onco-geriatric surgical patients within 6 months of follow-up: Who is at risk to lose?

AIMS: Comprehensive Geriatric Assessment (CGA) provides information on aspects of older patients to predict risks and benefits of interventions. METHODS: To evaluate the application of CGA (including quality of life (QOL)) for the risk prediction of postoperative dependence and QOL in elderly patients with malignant tumours, a prospective observational study including 200 patients >70 years was performed. The primary outcome was postoperative activities of daily living (ADL < 95), secondary outcome was QOL at 6 months. Multivariate regression was performed to assess the impact of associated factors (socio-demographic, clinical, functional, cognitive variables, resilience, and EORTC-QLQ-C30 QOL). RESULTS: Median age of patients was 75 (70-88) years with 69% males. The majority of operations was for colon carcinoma; morbidity was 24.8%, mortality 1.5%. Impairment in ADL (<95) affected 6.7% (13/195) pre-, and 9.7% (12/124) post-operatively. Analyzing factors predicting loss of ADL, the following reached significance: BMI (OR: 1.7; p = 0.019), ADL (OR: 0.67; p = 0.0317), and of the QLQ-C30: diarrhea (OR: 1.04; p = 0.013), emotional functioning (OR: 0.91; p = 0.0242), physical functioning (OR: 0.92; p = 0.027). QOL paralleled ADL (pre-op: 65.4 to 67 postoperatively, respectively); predictive were: Karnofsky Index (Parameter Estimate (PE): 0.55; p = 0.0003) and (QLQ-C30) emotional functioning (PE: 0.14; p = 0.0208). CONCLUSIONS: Those considered for oncologic surgery can be assured that few lose independence. CGA/QOL highlight signs of vulnerability and options for pre-habilitation. Registries including a minimal CGA data set will make pre-selections reproducible and objectify risk/benefit estimations - relevant for those withheld from potentially curative surgery.

Colchicine inhibits taurodeoxycholate transport in pericentral but not in periportal hepatocytes.

Indirect evidence for a microtubule-dependent vesicular hepatocellular transport of bile acids has accumulated. Since inhibition of this transport by colchicine can be achieved only at high but not at low bile acid infusion rates we were wondering whether this transport pathway shows a hepatic zonation or not. To answer this question we perfused isolated rat livers antegradely or retrogradely, respectively, with unlabeled and labeled taurocholate or taurodeoxycholate. Inhibition of microtubule-dependent bile acid transport was aimed at co-infusion of colchicine. Periportal cells eliminated the likewise hydrophobic taurodeoxycholate as fast as the more hydrophilic taurocholate. In contrast, pericentral cells excreted taurodeoxycholate much slower than taurocholate. Colchicine did not change the biliary taurocholate excretion profile in periportal and pericentral cells. However, colchicine reduced significantly taurodeoxycholate excretion in pericentral but not in periportal cells. It is concluded that a microtubule-dependent vesicular, colchicine-sensitive transport pathway seems to be involved in the translocation of taurodeoxycholate in pericentral but not in periportal cells. Since such a vesicular bile acid transport is regarded to be much slower than transcellular transport by diffusion, this observation may explain the much slower excretion of hydrophobic bile acids like taurodeoxycholate in pericentral than in periportal cells under physiological conditions.

Comparison of murine band 3 protein-mediated Cl- transport as measured in mouse red blood cells and in oocytes of Xenopus laevis.

Murine band 3 protein was expressed in oocytes of Xenopus laevis after microinjection of the mRNA from the spleens of anemic mice. The 36Cl- efflux from the oocytes was compared with the chloride fluxes measured in murine red cells. In both oocytes and red cells, the band 3-mediated chloride transport showed the following features: the selective inhibitor of band 3-mediated anion transport, 4,4'-dinitrostilbene-2,2'-disulfonate exerts its effects only when applied to the outside and not when applied to the inside of the membrane. The K1/2 for inhibition by external 4,4'-dinitrostilbene-2,2'-disulfonate was of the order of 1.5 to 2.0 mumol/l. Flufenamate and persantine also produce similar inhibitory effects. Decreasing the pH from 7.4 to 6.0 leads to some inhibition. It is concluded that essential features of the mode of action of murine erythroid band 3 protein in the plasma membrane of the oocyte are similar to the mode of action in the bilayer of the red blood cell of the mouse.

Chemokines in human colorectal carcinoma.

BACKGROUND: Chemokines (CKs) may promote antitumor immunity in cancer, act as tumor growth factors, influence metastatic spreading or angiogenesis. The purpose of this study was to investigate whether CK expression is altered in colorectal carcinomas compared to normal mucosa and to elucidate its possible clinico-pathological implications. MATERIALS AND METHODS: The levels of CCL2 (MCP-1), CCL4 (MIP-1beta), CCL5 (RANTES), CXCL 1 (GRO-alpha), CXCL 5 (ENA-78) and CXCL 8 (IL-8) were investigated in 10 colorectal carcinomas and their corresponding normal mucosa by the use of ELISA. RESULTS: All CK analyzed, with the exception of CCL5 (RANTES), were expressed at a significantly higher level in malignant tissue. CONCLUSION: Therapeutic studies in colon carcinomas should, therefore, focus more on the neutralization of CKs than on their application.

Dyslipemia in familial partial lipodystrophy caused by an R482W mutation in the LMNA gene.

Lipatrophic diabetes, also referred to as familial partial lipodystrophy, is a rare disease that is metabolically characterized by hypertriglyceridemia and insulin resistance. Affected patients typically present with regional loss of body fat and muscular hypertrophic appearance. Variable symptoms may comprise pancreatitis and/or eruptive xanthomas due to severe hypertriglyceridemia, acanthosis nigricans, polycystic ovaria, and carpal tunnel syndrome. Mutations within the LMNA gene on chromosome 1q21.2 were recently reported to result in the phenotype of familial partial lipodystrophy. The genetic trait is autosomal dominant. We identified a family with partial lipodystrophy carrying the R482W (Arg(482)Trp) missense mutation within LMNA. Here we present the lipoprotein characteristics in this family in detail. Clinically, the loss of sc fat and muscular hypertrophy especially of the lower extremities started as early as in childhood. Acanthosis and severe hypertriglyceridemia developed later in life, followed by diabetes. The characterization of the lipoprotein subfractions revealed that affected children present with hyperlipidemia. The presence and severity of hyperlipidemia seem to be influenced by age, apolipoprotein E genotype, and the coexistence of diabetes mellitus. In conclusion, dyslipemia is an early and prominent feature in the presented lipodystrophic family carrying the R482W mutation within LMNA.

Mutations in the NOD2/CARD15 gene in Crohn's disease are associated with ileocecal resection and are a risk factor for reoperation.

BACKGROUND: Mutations within the NOD2/CARD15 gene have recently been shown to be associated with Crohn's disease. AIMS: To investigate the clinical impact of the three common NOD2/CARD15 mutations in patients with Crohn's disease. METHODS: We investigated the prevalence of the three common NOD2/CARD15 mutations (Arg702Trp, Gly908Arg, 3020insC) in 180 patients with Crohn's disease, 70 patients with ulcerative colitis and 97 controls. In patients with Crohn's disease, prevalence of NOD2/CARD15 mutations were correlated to clinical and demographical parameters. RESULTS: In Crohn's disease patients, 35.6% carried at least one mutant allele of NOD2/CARD15 mutations compared with 14.3% of patients with ulcerative colitis (P = 0.006) and to 15.5% of controls (P = 0.0001). Genotype phenotype analyses revealed that NOD2/CARD15 mutations determined younger age at disease diagnosis (P = 0.03), ileal disease location (P = 0.01) and ileocecal resections (P = 0.0002). Interestingly, reoperation with resection of the anastomosis was significantly more frequent in patients with NOD2/CARD15 mutations (P = 0.01). CONCLUSIONS: Our investigations support the current hypothesis that NOD2/CARD15 mutations are associated with a phenotype of Crohn's disease with younger age at diagnosis, ileal involvement, ileocecal resections and a high risk of postoperative relapse and reoperation. NOD2/CARD15 mutations might therefore be used to identify high risk patients for relapse prevention strategies.

The C/C_13910 and G/G_22018 Genotypes for Adult-type Hypolactasia are not Associated with Inflammatory Bowel Disease.

BACKGROUND: Lactose intolerance with adult-onset is due to the inadequate enzymatic activity of lactase-phlorizin hydrolase (LPH). It is frequently seen in patients with Crohn disease, but the mechanism remains to be elucidated. Two DNA genotypes, C/C_13910 and G/G_22018, located upstream from the LCT locus, the gene encoding for LPH, were recently identified as representing genetic markers for lactose intolerance. We utilized these two DNA genotypes to study their role in inflammatory bowel disease. METHODS: We investigated the prevalence of these two DNA variants using specific restriction enzyme digest assays in 166 patients with Crohn disease, in 120 healthy first-degree relatives of Crohn disease patients, in 63 patients with ulcerative colitis and in 187 healthy individuals. RESULTS: The analysis revealed a frequency of 21.4% of the 2 genotypes for adult-type hypolactasia in our studied German cohort of healthy individuals, which is higher than previously reported (15%) based on the hydrogen (H2) breath test. This might indicate a higher sensitivity of genotyping, but it has to be confirmed in larger cohorts. No significant difference was detectable in the frequency of the C/C_13910 and G/G_22018 genotypes in patients with Crohn Disease (C/C_13910: 21.7%; G/G_22018: 22.3%) compared to first-degree relatives (C/C_13910: 21.7%; G/G_22018: 20.8%), patients with ulcerative colitis (C/C_13910: 20.3%; G/G_22018: 20.3%) and healthy individuals (C/C_13910: 21.4%; G/G_22018: 21.4%). CONCLUSIONS: The C/C_13910 and G/G_22018 genotype of adult-type hypolactasia is not associated with susceptibility to the pathogenesis of Crohn disease and ulcerative colitis.

Endoscopic management of pancreatic fistulas secondary to intraabdominal operation.

BACKGROUND: Pancreatic fistulas may arise secondary to several disorders of the pancreas. Although approximately 70% of pancreatic fistulas close with nonoperative management, this course of treatment usually takes several weeks or even months. To reduce this long period, closures with fibrin glue have been attempted in the past. In this study, we describe the course, management, and outcome of eight patients with postoperative external pancreatic fistulas of the pancreatic body and tail that arose after oncologic operations in the upper abdomen. METHODS: All eight cases were treated by external drainage, insertion of an endoprosthesis into the pancreatic duct, and closure of the fistula with fibrin glue. RESULTS: Immediately after this intervention, secretion from the fistulas was absent in all cases. None of the patients developed abscesses, recurrent fistulas, or complications associated with the fibrin glue. CONCLUSION: The early endoscopic management of postoperative pancreatic fistula with an approach combining internal drainage of the pancreatic duct and external occlusion of the fistula with fibrin glue is expeditious and beneficial.