Impact of CCR7 on the gastrointestinal field effect.

Standardized intestinal manipulation (IM) leads to local bowel wall inflammation subsequently spreading over the entire gastrointestinal tract. Previously, we demonstrated that this so-called gastrointestinal field effect (FE) is immune mediated. This study aimed to investigate the role of CCR7 in IM-induced FE. Since CCR7 is expressed on activated dendritic cells and T cells and is well known to control their migration, we hypothesized that lack of CCR7 reduces or abolishes FE. Small bowel muscularis and colonic muscularis from CCR7(-/-) and wild-type (WT) mice were obtained after IM of the jejunum or sham operation. FE was analyzed by measuring gastrointestinal transit time of orally given fluorescent dextran (geometric center), colonic transit time, infiltration of MPO-positive cells, and circular smooth muscle contractility. Furthermore, mRNA levels of the inflammatory cytokine IL-6 were determined by RT-PCR. The number of dendritic cells and CD3+CD25+ T cells separately isolated from jejunum and colon was determined in mice after IM and sham operation. There was no significant difference in IL-6 mRNA upregulation in colonic muscularis between sham-operated WT and CCR7(-/-) mice after IM. Contractility of circular muscularis strips of the colon was significantly improved in CCR7(-/-) animals following IM and did not vary significantly from sham-operated animals. Additionally, inflammation of the colon determined by the number of MPO-positive cells and colonic transit time was significantly reduced in CCR7(-/-) mice. In contrast, jejunal contractility and jejunal inflammation of transgenic mice did not differ significantly from WT mice after IM. These data are supported by a significant increase of CD3+CD25+ T cells in the colonic muscularis of WT mice after IM, which could not be observed in CCR7(-/-) mice. These data demonstrate that CCR7 is required for FE and postoperative ileus. CCR7 indirectly affects FE by inhibiting migration of activated dendritic cells and of T cells from the jejunum to the colon. These findings support the critical role of the adaptive immune system in FE.

[Inadequate reimbursement for surgical patients with Parkinson's disease according to diagnosis-related grouping]. / Inadäquate DRG-Vergütung chirurgischer Patienten mit Morbus Parkinson.

BACKGROUND: Parkinson's disease (PD) is a progressive degenerative disease of the human central nervous system with a demographical increase in surgical patients. Comorbidities are known to increase the perioperative risk profile and therefore amplify treatment expenses. AIM: The aim of this study was to analyse whether the reimbursement of additional costs due to PD in surgical patients was sufficiently considered by diagnosis-related grouping (DRG). PATIENTS AND METHODS: Over a period of 13 years, 50 patients suffering from MP treated in the Department of Surgery were retrospectively compared using matched-pair analysis with controls not affected by PD. Both groups of patients were assessed regarding hospital stay and mortality and morbidity with an emphasis on reimbursement by the National Ordinance on Hospital Rates (Bundespflegesatzverordung, BPflV) from 2004 (last year of employment) compared to DRG in 2007. RESULTS: Extra reimbursement for PD patients in comparison to controls diminished from 20 % according to BPflV (2004) to 2 % according to DRG (2007). Within the DRG System of 2007, total compensation for PD and control patients was significantly lower (47 vs. 35 %) compared to the BPflV of 2004. CONCLUSION: Compensation of surgical therapy in PD patients has significantly decreased within the DRG system, not considering the increased perioperative risk profile of these patients. In times of rising economic pressure, inadequate reimbursement of treatment costs bears the risk of rejection or restriction for patients with concomitant PD in spite of medical indications.

Influence of immunosuppression on alloresponse, inflammation and contractile function of graft after intestinal transplantation.

In small bowel transplantation (SBTx), graft manipulation, ischemia/reperfusion injury and acute rejection initiate a severe cellular and molecular inflammatory response in the muscularis propria leading to impaired motility of the graft. This study examined and compared the effect of tacrolimus and sirolimus on inflammation in graft muscularis. After allogeneic orthotopic SBTx, recipient rats were treated with tacrolimus or sirolimus. Tacrolimus and sirolimus attenuated neutrophilic, macrophage and T-cell infiltration in graft muscularis, which was associated with reduced apoptotic cell death. Nonspecific inflammatory mediators (IL-6, MCP-1) and T-cell activation markers (IL-2, IFN-gamma) were highly upregulated in allogeneic control graft muscularis 24 h and 7 days after SBTx, and tacrolimus and sirolimus significantly suppressed upregulation of these mediators. In vitro organ bath method demonstrated a severe decrease in graft smooth muscle contractility in allogeneic control (22% of normal control). Correlating with attenuated upregulation of iNOS, tacrolimus and sirolimus treatment significantly improved contractility (64% and 72%, respectively). Although sirolimus reduced cellular and molecular inflammatory response more efficiently after 24 h, contrary tacrolimus prevented acute rejection more efficiently. In conclusion, tacrolimus and sirolimus attenuate cellular and molecular inflammatory response in graft muscularis and subsequent dysmotility of the graft after allogeneic SBTx.

Perioperative infliximab application ameliorates acute rejection associated inflammation after intestinal transplantation.

As we have shown in the past, acute rejection-related TNF-α upregulation in resident macrophages in the tunica muscularis after small bowel transplantation (SBTx) results in local amplification of inflammation, decisively contributing to graft dysmotility. Therefore, the aim of this study is to investigate the effectiveness of the chimeric-monoclonal-anti-TNF-α antibody infliximab as perioperative single shot treatment addressing inflammatory processes during acute rejection early after transplantation. Orthotopic, isogenic and allogenic SBTx was performed in rats (BN-Lewis/BN-BN) with infliximab treatment. Vehicle and IV-immunoglobulin-treated animals served as controls. Animals were sacrificed after 24 and 168 h. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry, mediator mRNA expression by Real-Time-RT-PCR, apoptosis by TUNEL and smooth muscle contractility in a standard organ bath. Both, infliximab and Sandoglobulin® revealed antiinflammatory effects. Infliximab resulted in significantly less leukocyte infiltration compared to allogenic controls and IV-immunoglobulin, which was accompanied by lower gene expression of MCP-1 (24 h), IFN-γ (168 h) and infiltration of CD8-positive cells. Smooth muscle contractility improved significantly after 24 h compared to all controls in infliximab treated animals accompanied by lower iNOS expression. Perioperative treatment with infliximab is a possible pharmaceutical approach to overcome graft dysmotility early after SBTx.

Case-control comparison of profundaplasty and femoropopliteal supragenicular bypass for peripheral arterial disease.

BACKGROUND: The aim of this study was to compare preoperative and postoperative findings, and clinical progress in patients with peripheral arterial occlusive disease undergoing femoropopliteal supragenicular bypass or profundaplasty in a case-control study. METHODS: Between January 2001 and June 2004, 171 patients with occlusion of the superficial femoral artery underwent surgery. A retrospective analysis of 28 matched patient pairs was performed. Endpoints were bypass occlusion, surgical revision, amputation and death. Mean length of follow-up was 36 months. RESULTS: At 3 years after surgery there was no statistically significant difference in outcome between femoropopliteal bypass surgery and profundaplasty. There was a trend towards improved results in patients who had bypass surgery for critical leg ischaemia. Preoperative patency of the crural outflow arteries was an independent prognostic factor in multivariable analysis. CONCLUSION: There were no significant outcome differences between supragenicular bypass surgery or profundaplasty in patients who had surgery for intermittent claudication or ischaemic rest pain. Patients with a single patent tibial artery and gangrene or ulceration appeared to benefit more from bypass surgery.

Cellular uptake, subcellular distribution and toxicity of arsenic compounds in methylating and non-methylating cells.

Arsenic is a known human carcinogen, inducing tumors of the skin, urinary bladder, liver and lung. Inorganic arsenic, existing in highly toxic trivalent and significantly less toxic pentavalent forms, is methylated to mono- and di-methylated species mainly in the liver. Due to the low toxicity of pentavalent methylated species, methylation has been regarded as a detoxification process for many years; however, recent findings of a high toxicity of trivalent methylated species have indicated the contrary. In order to elucidate the role of speciation and methylation for the toxicity and carcinogenicity of arsenic, systematic studies were conducted comparing cellular uptake, subcellular distribution as well as toxic and genotoxic effects of organic and inorganic pentavalent and trivalent arsenic species in both non-methylating (urothelial cells and fibroblasts) and methylating cells (hepatocytes). The membrane permeability was found to be dependent upon both the arsenic species and the cell type. Uptake rates of trivalent methylated species were highest and exceeded those of their pentavalent counterparts by several orders of magnitude. Non-methylating cells (urothelial cells and fibroblasts) seem to accumulate higher amounts of arsenic within the cell than the methylating hepatocytes. Cellular uptake and extrusion seem to be faster in hepatocytes than in urothelial cells. The correlation of uptake with toxicity indicates a significant role of membrane permeability towards toxicity. Furthermore, cytotoxic effects are more distinct in hepatocytes. Differential centrifugation studies revealed that elevated concentrations of arsenic are present in the ribosomal fraction of urothelial cells and in nucleic and mitochondrial fractions of hepatic cells. Further studies are needed to define the implications of the observed enrichment of arsenic in specific cellular organelles for its carcinogenic activity. This review summarizes our recent research on cellular uptake, distribution and toxicity of arsenic compounds in methylating and non-methylating cells.

Secondary surgery subsequent to distal pancreatectomy.

BACKGROUND/AIMS: Early revision procedures after pancreatic head resection significantly increase mortality. Due to their complexity, secondary operations at a later stage rank amongst the most demanding surgical procedures. We sought to critically analyze indications and outcome from early revision and subsequent redo procedures following distal pancreatic resection (DPR). METHODOLOGY: During a 5-year period 53 subsequent patients undergoing DPR were identified from a pancreatic resection database and analyzed regarding indication for and outcome of early revision and late redo procedures. RESULTS: Six patients (11%) underwent early revision procedures during the same hospital stay. Indications were peritonitis (n = 3), intraabdominal hemorrhage (n = 2) and oncologic re-resection (n = 1). Four patients (7.6%) were readmitted after 192 days (d) on average (range 53 - 538d) and underwent subsequent redo surgery due to occurrence of metastases in 2 cases, and insufficiency of an ascendo-rectostomy and adhesive ileus. Hospital stay and mortality were significantly increased after early revision surgery (40d vs. 18d; 33% vs. 0%). Splenectomy during DPR was carried out in all patients requiring early operative reintervention, compared to 63% in patients without secondary surgery (p < 0.07). CONCLUSIONS: Early revision surgery following DPR increases postoperative mortality and length of hospital stay. Risk factors were complex injuries (e.g. gun shot wound), concomitant portal hypertension with collateral circulation and splenectomy. Subsequent redo surgery following DPR was performed on average within 7 month following the index operation without mortality and with comparable morbidity. Indications were recurrent malignant disease and complications of the intestine.

[Heterozygous alpha-1-antitrypsin deficiency (PiMZ): risk factor in the development of primary liver carcinoma in non-cirrhotic liver?]. / Heterozygoter Alpha-1-Antitrypsin-Mangel (PiMZ): Risikofaktor zur Entwicklung eines hepatozellulären Karzinoms in der nicht zirrhotischen Leber?

Here we report on a patient with a primary hepatocellular carcinoma in a non-cirrhotic liver, in whom heterozygosity for an AAT-deficiency allele was found (PiMZ). Based on this observation and the current literature, the possible mechanisms for an eventual contribution of a heterozygosity of a heterozygous AAT-deficiency for a hepatocellular carcinoma are discussed. Alpha-1-antitrypsin (AAT)-deficiency (Laurell-Eriksson syndrome) is a genetic disorder, in which individuals who are homozygous for a deficiency allele are at an increased lifetime risk for pulmonary emphysema, liver cirrhosis, and primary hepatocellular carcinoma. It has been controversially discussed whether the heterozygous form (PiMZ) is also associated with an increased risk for liver diseases. Hepatocarcinogenesis for AAT-deficiency is probably based on a series of toxic events. Precipitation of AAT aggregates in hepatocytes is the initial step. These accumulate in the endoplasmic reticulum and cannot be eliminated from all hepatocytes by proteasomal and non-proteasomal mechanisms. AAT aggregates induce proinflammatory pathways and may be a stimulus for hepatocarcinogenesis. This hypothesis is based mostly on studies of individuals homozygous for a deficiency allele (PiZZ). The mechanism may also play a role in heterozygous patients. Since not all patients with precipitates of AAT-aggregates are develop a hepatocellular carcinoma related comorbidities such as chronic hepatitis B, C, chronic alcohol abuse, or so far unknown genetic and environmental factors may be crucial.

[Redo procedures in patients with pancreatic left resection]. / Revisionseingriffe und Interventionen nach Pankreaslinksresektion.

BACKGROUND: Distal pancreatectomy is performed less frequently than pancreatic head resection. Secondary operations due to postoperative complications are surgically complex and demanding, hence often interdisciplinary approaches are pursued. We have analysed the indications and outcome of revision surgery and interventional procedures subsequent to pancreatic left resection. PATIENTS AND METHODS: Between 2001 and 2009 we prospectively evaluated 61 patients regarding demographic factors, hospital stay, diagnosis, closure technique, redo operations and interventions, morbidity and mortality. RESULTS: Major complications without redo procedures were observed in 4 (9 %) of 44 patients. 8 (13 %) patients underwent early (7 +/- 8 days) postoperative revision procedures. A significant in-crease in hospital stay and mortality appeared in this group. Interventional procedures (7 x CT-guided abscess drains, 1 x haemorrhage with angio-graphic coiling, 1 x transgastral stenting of a pseudocyst) were performed significantly later (22 +/- 11 days p. o., p < 0,01) in 9 (15 %) patients. CONCLUSIONS: Pancreatic fistulas and related complications represent the most common indications for revisions, but can usually be controlled by interventional procedures. In contrast to secondary surgery, interventional revisions do not significantly increase the length of hospital stay or mortality. There was no benefit of any certain closure technique of the pancreatic remnant.

Methylated bismuth, but not bismuth citrate or bismuth glutathione, induces cyto- and genotoxic effects in human cells in vitro.

Bismuth compounds are widely used in industrial processes and products. In medicine, bismuth salts have been applied in combination with antibiotics for the treatment of Helicobacter pylori infections, for the prevention of diarrhea, and in radioimmunotherapy. In the environment, bismuth ions can be biotransformed to the volatile bismuth compound trimethylbismuth (Me3Bi) by methanobacteria. Preliminary in-house studies have indicated that bismuth ions are methylated in the human colon by intestinal microflora following ingestion of bismuth-containing salts. Information concerning cyto- and genotoxicity of these biomethylated products is limited. In the present study, we investigated the cellular uptake of an organic bismuth compound [monomethylbismuth(III), MeBi(III)] and two other bismuth compounds [bismuth citrate (Bi-Cit) and bismuth glutathione (Bi-GS)] in human hepatocytes, lymphocytes, and erythrocytes using ICP-MS. We also analyzed the cyto- and genotoxic effects of these compounds to investigate their toxic potential. Our results show that the methylbismuth compound was better taken up by the cells than Bi-Cit and Bi-GS. All intracellularly detected bismuth compounds were located in the cytosol of the cells. MeBi(III) was best taken up by erythrocytes (36%), followed by lymphocytes (17%) and hepatocytes (0.04%). Erythrocytes and hepatocytes were more susceptible to MeBi(III) exposure than lymphocytes. Cytotoxic effects of MeBi(III) were detectable in erythrocytes at concentrations >4 microM, in hepatocytes at >130 microM, and in lymphocytes at >430 microM after 24 h of exposure. Cytotoxic effects for Bi-Cit and Bi-GS were much lower or not detectable in the used cell lines up to a tested concentration of 500 microM. Exposure of lymphocytes to MeBi(III) (250 microM for 1 h and 25 microM/50 microM for 24 h) resulted in significantly increased frequencies of chromosomal aberrations (CA) and sister chromatid exchanges (SCE), whereas Bi-Cit and Bi-GS induced neither CA nor SCE. Our study also showed an intracellular production of free radicals caused by MeBi(III) in hepatocytes but not in lymphocytes. These data suggest that biomethylation of bismuth ions by the intestinal microflora of the human colon leads to an increase in the toxicity of the primary bismuth salt.

Treatment of high output cardiac failure by flow-adapted hepatic artery banding (FHAB) in patients with hereditary hemorrhagic telangiectasia.

Involvement of abdominal organs in Osler's disease may lead to the development of hepatic arteriovenous shunts with a dilatation of the hepatic artery. Right and subsequent global heart failure due to cardiac valvular insufficiency, pulmonary artery hypertension, and hepatomegaly as well as increased cardiac output may result. This hyperdynamic hepatic blood flow can be reduced by ligature or banding of the hepatic artery or by orthotopic liver transplantation. We report on two female patients suffering from Osler's disease (68 and 76 years old) with severe heart insufficiency (NYHA III-IV) caused by the high hepatic shunt volumes. A gradual banding of the hepatic artery directed by intraoperative flow measurement in the hepatic artery and control of the systemic hemodynamics by Swan-Ganz or COLD catheters was performed in these patients. The banding was achieved by encasing the hepatic artery in a PTFE cuff (length, 1.0 cm). The high cardiac output could be reduced from 11.2 to 7.0 l/min and from 10.7 to 6.0 l/min, respectively. The respective hepatic artery flow was reduced from 2.0 to 0.3 l/min and from 4.0 to 0.7 l/min. An improvement of heart insufficiency, a reduction in the severity of the cardiac valvular insufficiency, and a reduction of the pulmonary arterial hypertension could be already observed intraoperatively. One patient died of right cardiac failure after an orthotopic liver transplantation 7 months later. The other one died 3 years after the banding. The banding of the hepatic artery controlled by hepatic arterial flow measurement can be considered as an effective and safe palliative procedure in intrahepatic HHT compared to therapeutic alternatives such as hepatic artery ligation or embolization.

Course and therapy of acute liver failure.

OBJECTIVES AND METHODS: Despite liver transplantation and advances in intensive care medicine fulminant hepatic failure [FHF] remains a life-threatening condition. Actual observations of the clinical course of these patients are rare. Therefore, we analyzed course of disease and survival in all patients treated for FHF at the University of Bonn between 1998 and 2004 and compared it to the patients treated for FHF during 1992-1997. RESULTS: 35 patients were treated for FHF during this period. FHF was viral induced in 13 patients (HBV n = 11, HAV n = 2), toxic in nine, cryptogenic in eleven and autoimmune and hyperthermia in one patient each. According to London- and/or Clichy criteria 16 patients were transplanted. Four of them died during the first year after transplantation due to infectious and hemorrhagic complications. Three patients died without liver-transplantation. All together, 1-year survival was 80%. When compared to patients with FHF analyzed in the period 1992-1997 numbers of patients with FHF in our centre had increased from 16 to 35 patients and 1-year survival improved from 67.5% to 80%. This improved survival was associated with a lower proportion of transplanted patients (45% versus 68%). CONCLUSIONS: These changes reflect advances in therapy of patients with FHF, which enables a greater proportion of patients to survive without the need for transplantation.

Liver transplantation for hilar cholangiocarcinoma: a German survey.

BACKGROUND: The present study reports a German survey addressing outcomes in nonselected historical series of liver transplantation (OLT) for hilar cholangiocarcinoma (HL). PATIENTS AND METHODS: We sent to all 25 German transplant centers performing OLT a survey that addressed (1) the number of OLTs for HL and the period during which they were performed; (2) the incidence of HL diagnosed prior to OLT/rate of incidental HL (for example, in primary sclerosing cholangitis); (3) tumor stages according to Union Internationale Centre le Cancer; (4) patient survival; and (5) tumor recurrence rate. RESULTS: Eighty percent of centers responded, reporting 47 patients who were transplanted for HL. Tumors were classified as pT2 (25%), pT3 (73%), or pT4 (2%). HL was diagnosed incidentally in 10% of cases. A primary diagnosis of PSC was observed in 16% of patients. Overall median survival was 35.5 months. When in-hospital mortality (n = 12) was excluded, the median survival was 45.4 months, corresponding to 3- and 5-year survival rates of 42% and 31%, versus 31% and 22% when in-hospital mortality was included. HL recurred in 34% of cases. Three- and 5-year survivals for the 15 patients transplanted since 1998 was 57% and 48%, respectively. Median survival ranged from 20 to 42 months based on the time period (P = .014). CONCLUSIONS: The acceptable overall survival, the improved results after careful patient selection since 1998, and the encouraging outcomes from recent studies all suggest that OLT may be a potential treatment for selected cases of HL. Prospective multicenter randomized studies with strict selection criteria and multimodal treatments seem necessary.

Influence of temporary abdominal wall repair on the intestinal integrity: an experimental study in the rat.

BACKGROUND AND AIMS: The aim of this study was to analyze intestinal integrity after temporary abdominal wall repair with absorbable mesh. METHODS: Rats underwent abdominal wall repair with absorbable mesh or sham operation. Myeloperoxidase-positive cells in the intestinal muscularis were histochemically quantified. Intestinal transit was visualized 48 h after surgery. Local and systemic inflammatory response was measured with TNF-alpha and IL-6 ELISA as well as malondialdehyde (MDA) expression in serum and peritoneal fluid. RESULTS: Neutrophil count of the intestinal muscularis revealed that infiltration in the mesh-implanted and in the mesh-free animals 48 h postoperatively was similar. Gastrointestinal transit was similarly unaffected 48 h after surgery, with or without mesh implantation. TNF-alpha, IL-6 and MDA concentration in serum and peritoneal fluid showed no significant differences between the two groups. CONCLUSION: Intestinal contractility and local and systemic inflammatory response remained unaffected. Therefore, absorbable mesh augmentation is a safe and reliable method for temporary repair of the abdominal wall without affecting the intestinal integrity.

[Primary neuroendocrine carcinoma of the liver. From carcinoid tumor to small-cell hepatic carcinoma: case reports and review of the literature]. / Primäre neuroendokrine Karzinome der Leber: Vom Karzinoidtumor bis zum kleinzelligen Leberkarzinom: Fallberichte und Literaturübersicht.

Primary hepatic neuroendocrine tumors are rare neoplasms. While primary hepatic carcinoid tumors (PHCT) are well-differentiated tumors, primary hepatic small-cell carcinomas (PHSCC) represent the poorly differentiated end of the spectrum of neuroendocrine carcinomas. The first patient, suffering from PHCT, has had a follow-up for 32 years and is still alive. Within this time, the tumor relapsed 4 times with unchanged histology and immunohistochemistry features. The second patient suffered from small-cell carcinoma of the liver. There were no risk factors for a hepatocellular carcinoma. An extensive preoperative and postoperative diagnostic investigation could rule out an extrahepatic primary site. Immunohistochemically the tumor was negative for Hepar-1, AFP, TTF1 and CDX2 but reacted positively with CD56 and sporadically with the keratins 8, 18 and 20. A neuroendocrine PHSCC was diagnosed. After neoadjuvant cytostatic treatment the carcinoma was completely extirpated and 18 months after treatment the patient is healthy.PHCT and PHSCC have to be clearly separated from hepatocellular and cholangiocellular carcinomas. Exclusion of an extrahepatic primary site requires an accurate and synoptic analysis of clinical, radiologic and pathologic findings. Surgical resection is the treatment of choice.

[Unusual cause of pneumomediastinum]. / Ungewöhnliche Ursache eines Pneumomediastinums.

The 3,4-methylenedioxy-N-methylamphetamine (MDMA) also known as ecstasy is a hallucinogen prevalently used by teenagers. Known complications of its consumption are hyperpyrexia, disseminated intravasal coagulation, acute kidney failure, and rhabdomyolysis. We report about an 18-year-old patient who developed a pneumomediastinum and skin emphysema by excluded lesions of the lung and respiratory tract. We present the hypothesis of the pathogenesis of this disease. The correct therapy is observation of the patient and maximum sedation.

Gastric stump carcinoma - epidemiology and current concepts in pathogenesis and treatment.

AIM: The aim of this article is to review the aetiology, pathology and treatment of gastric stump carcinoma (GSC). GSC is an uncommon tumour; however, the incidence is not declining, so this tumour entity will be encountered in the years to come. METHODS: The electronic literature search was performed in the MEDLINE database to identify relevant studies concerning epidemiology, prognosis, treatment, aetiology and pathology of GSC. The references reported in these studies were used to complete the literature search. RESULTS: Patients subjected to distal gastric resection have a 4-7-fold increased risk of developing GSC, which is attributed mainly to gastroduodenal reflux. Denervation during partial gastrectomy may also contribute to the risk of developing GSC. Gastroduodenal ulcers were the main reason for partial gastrectomy. Both ulcer locations have an increased risk of developing GSC after 20 years. In GSC, Helicobacter pylori seems not to be an important risk factor, contrary to primary gastric cancer, because gastroduodenal reflux impairs the growth of Helicobacter pylori. CONCLUSION: The treatment of choice for GSC should be the total removal of the gastric remnant including at least D2 lymphadenectomy. The pattern of lymph node metastases in GSC may differ from primary gastric cancer, as lymph node metastases have been reported in the jejunal mesentery and the lower mediastinum. Therefore, GSC may require a modified lymphadenectomy to include all important lymph node stations. After radical remnant gastrectomy, GSC has a prognosis not different from primary proximal gastric cancer.

The cyto- and genotoxicity of organotin compounds is dependent on the cellular uptake capability.

Organotin compounds have been widely used as stabilizers and anti-fouling agents with the result that they are ubiquitously distributed in the environment. Organotins accumulate in the food chain and potential effects on human health are disquieting. It is not known as yet whether cell surface adsorption or accumulation within the cell, or indeed both is a prerequisite for the toxicity of organotin compounds. In this study, the alkylated tin derivatives monomethyltin trichloride (MMT), dimethyltin dichloride (DMT), trimethyltin chloride (TMT) and tetramethyltin (TetraMT) were investigated for cyto- and genotoxic effects in CHO-9 cells in relation to the cellular uptake. To identify genotoxic effects, induction of micronuclei (MN), chromosome aberrations (CA) and sister chromatid exchanges (SCE) were analyzed and the nuclear division index (NDI) was calculated. The cellular uptake was assessed using ICP-MS analysis. The toxicity of the tin compounds was also evaluated after forced uptake by electroporation. Our results show that uptake of the organotin compounds was generally low but dose-dependent. Only weak genotoxic effects were observed after exposure of cells to DMT and TMT. MMT and TetraMT were negative in the test systems. After forced uptake by electroporation MMT, DMT and TMT induced significant DNA damage at non-cytotoxic concentrations. The results presented here indicate a considerable toxicological potential of some organotin species but demonstrate clearly that the toxicity is modulated by the cellular uptake capability.

[The history of thymus surgery]. / Die Geschichte der Thymuschirurgie.

Thymus surgery was initially dominated by the erroneous interpretation of the organs' pathogenicity and associated thymus diseases. Misleadingly, the thymus gland was made responsible for dyspnoea in children and a transcervical ektropexia was performed in a child suffering from dyspnoea in 1896. After F. Sauerbruch's thymectomy in a patient with myasthenia gravis syndrome (MG), A. Blalock established thymectomy in the 1940s for the treatment of MG. At the same time, the drug treatment initiated by M.B. Walker increased in significance. Despite progress in surgical techniques and the molecular understanding of MG pathogenesis, randomized controlled trials, which would increase the evidence for surgical access and indications for surgery compared to immunosuppressive treatment in MG, are lacking.

[Port stapling for simplified port implantation in laparoscopic adjustable gastric banding]. / Port-Stapling zur Erleichterung der Portimplantation bei der laparoskopischen Magenbandoperation.

BACKGROUND: The purpose of this study was to evaluate the applicability of a port stapling device to simplify and improve port implantation in laparoscopic adjustable gastric banding (LAGB). METHODS: From November 2005 to September 2006, a prospective study was conducted on 23 consecutive patients who underwent LAGB with Swedish adjustable gastric banding. Patients were randomized to either conventional titanium-port implantation or port stapling using the "Velocity" device. RESULTS: No differences in age, body weight, body mass index, fascia depth or incision length were reported between the groups. Port implantation time was significantly less using port stapling (90+/-24 s) compared to conventional port implantation (521+/-138 s). Port related complaints postoperatively and at follow-up were equal in both groups. CONCLUSIONS: Port stapling is an excellent tool to facilitate port implantation, particularly in massively obese patients with a thick abdominal wall.