[Parkinson's disease. Perioperative management and anesthesia]. / Morbus Parkinson. Perioperatives Management und Anästhesie.

Approximately 10,000-15,000 Parkinson's disease (PD) patients per year undergo surgery in Germany. The demographic developments along with further surgical progress and procedural refinements will lead to increasing numbers of PD patients in the operating theatre (OR). There are several perioperative risk factors for PD patients, they more often require prolonged intensive care treatment and warrant particular anesthesiological attention with regard to the choice of drugs and equipment. Careful evaluation of concomitant diseases, maintenance of oral Parkinson therapeutic drugs up to the time of surgery and continuous perioperative dopaminergic therapy are key factors for reducing postoperative morbidity in PD patients undergoing surgery.

[Cost-effectiveness of hernia repair : IPOM versus open sublay mesh technique]. / Kosten- und Risikoanalyse der Hernienreparation : Laparoskopische IPOM- vs. offene Sublay-Technik.

In comparison to the conventional technique of incisional or umbilical hernia repair with sublay mesh augmentation, incisional hernias in obese patients can be surgically treated with minor surgical trauma by laparoscopic intraperitoneal onlay mesh (IPOM) repair. However, although shortened operation time, hospital stay and faster postoperative reconvalescence might be possible with IPOM repair, the economic calculation including mesh costs is significantly higher. In this study the two operation techniques were compared and the perioperative advantages and disadvantages of both methods were analyzed based on the German diagnosis-related groups (DRG) system.

[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.

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.

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.

[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.

Inhibition of neuropilin-1 by RNA-interference and its angiostatic potential in the treatment of hepatocellular carcinoma.

Neuropilin-1 (Nrp1) was recently described as a novel receptor for the pro-angiogenic molecule vascular endothelial growth factor (VEGF), indicating a role in tumor angiogenesis and tumor progression. Recent data confirm this assumption by demonstrating that some tumor and endothelial cells express Nrp1. Therefore, we wanted to investigate the potential role of Nrp1-knockdown on hepatoma and endothelial cell function in vitro and tumor growth in vivo. Nrp1 knockdown in SVEC4 - 10 and Hepa129 cells and its influence on signal transduction (MAPK pP38, pAKT, pERK1 / 2) was analyzed by Western blot. Effects on endothelial tube formation were assayed in an in vitro and in vivo matrigel assay. In vivo, effects of siRNA-Nrp1 were analyzed in a subcutaneous hepatoma model. To verify effects on endothelial and tumor cells in vivo, immunohistochemistry for proliferation, apoptosis and endothelial vessels was performed. LightCycler and Western blot analysis showed efficient inhibition of gene expression in SVEC4 - 10 and Hepa129 cells following siRNA-Nrp1 transfection. Signal transduction pathways were not influenced after siRNA-Nrp1 treatment compared to the controls. Endothelial tube formation was reduced by 59 % and 94 % in vitro and in vivo compared to controls, corresponding to reduced VCAM expression. Subcutaneous tumor growth was not influenced after siRNA treatment. Intratumoral proliferation was not altered after treatment with siRNA-Nrp1, whereas microvessel density and apoptosis were reduced after treatment with siRNA-Nrp1 compared to siRNA-Ctrl. In conclusion, inhibition of Nrp1 expression led to strong anti-endothelial effects, whereas tumor cells and tumor growth were not affected.

Postresection survival outcomes of pancreatic cancer according to demographic factors and socio-economic status.

AIM: Aim of the study was to evaluate the impact of demographic factors (DGF) and socio-economic status (SES) on survival after pancreatic cancer resection in a German setting. METHODS: Patients with pancreatic adenocarcinoma and pancreaticoduodenectomy were identified from our pancreatic resection database (1989-2008). DGF, SES, survival and tumor-related information were obtained from hospital records, a registry office questionnaire, and telephone interviews with patients, relatives and general practitioners. RESULTS: Follow-up was completed in 117 patients. Median overall survival and 5-year survival rate was 22 month and 10%, respectively. Survival significantly improved over time with a 16% 5-year survival and a median survival of 27 month for recent patients. The longest survival period with a median of 63 month was observed for patients with AJCC stage I. Tumor-related factors and treatment period, but not SES influenced survival after pancreatic cancer resection in our cohort. CONCLUSIONS: To our knowledge, this is the first study to explore survival from pancreatic cancer according to DGF and SES in a German setting. Disparities in survival among our patients depend solely on tumor-related factors and treatment period and could not be explained by SES including key factors like income or type of health insurance. The comparable postresection outcome of patients with low and high SES at our department could be in part due to the universal German multi-payer health system, based on compulsory enrolment for the majority, which seems not to support health care inequalities seen in other OECD countries.

[Technique of pancreatogastrostomy after pancreaticoduodenectomy]. / Technik der Pankreatogastrostomie nach partieller Pankreatoduodenektomie.

A broad spectrum of different techniques for anastomosing the pancreatic remnant after the Kausch-Whipple procedure has been published. Most commonly used is the pancreaticojejunostomy, preferably in an end-to-side and duct-to-mucosa fashion. Utilisation of the posterior gastric wall represents an interesting alternative, which is being increasingly discussed in the literature. Two current meta-analyses and three prospective, randomised trials have proved the comparability of the two procedures. Accordingly, our own data show corresponding results regarding mortality and morbidity using this anastomosis. We personally prefer a purse-string suture for fixation of the pancreatic remnant, which seems to be more easily and more rapidly performed than application of interrupted sutures.

[Parkinson's disease influences the perioperative risk profile in trauma patients]. / Der Einfluss des Morbus Parkinson auf das perioperative Risikoprofil unfallchirurgischer Patienten.

AIM: Parkinson's disease (PD) is one of the most common degenerative diseases of the central nervous system affecting elderly patients with increasing demographic prevalence. The aim of this study was to define the perioperative risk profile in trauma patients suffering from Parkinson's disease in order to improve treatment options in these patients. METHOD: Over a period of 13 years, 16 patients suffering from Parkinson's disease treated in the department of trauma surgery were retrospectively compared using matched-pair analysis with 16 controls not affected by PD. Both groups of patients were assessed regarding morbidity, length of treatment and rehabilitation. RESULTS: Trauma patients suffering from Parkinson's disease showed an increase in morbidity risk. Postoperative falls occurred significantly, infections of the urinary tract and pneumonia tendentiously more often in PD patients. Postoperative stay and length of treatment were significantly longer in patients with PD. These patients also tended to stay longer preoperatively and remained longer in intensive care. PD patients required on-ward rehabilitation significantly more often. CONCLUSION: Concomitant Parkinson's disease is a significant factor of perioperative morbidity in trauma patients. Perioperative morbidity in PD patients may be influenced by early diagnostic and therapeutic measures.

Early diagnosis of pancreatic cancer: neutrophil gelatinase-associated lipocalin as a marker of pancreatic intraepithelial neoplasia.

Pancreatic cancer is a highly lethal malignancy with a dismal 5-year survival of less than 5%. The scarcity of early biomarkers has considerably hindered our ability to launch preventive measures for this malignancy in a timely manner. Neutrophil gelatinase-associated lipocalin (NGAL), a 24-kDa glycoprotein, was reported to be upregulated nearly 27-fold in pancreatic cancer cells compared to normal ductal cells in a microarray analysis. Given the need for biomarkers in the early diagnosis of pancreatic cancer, we investigated the expression of NGAL in tissues with the objective of examining if NGAL immunostaining could be used to identify foci of pancreatic intraepithelial neoplasia, premalignant lesions preceding invasive cancer. To examine a possible correlation between NGAL expression and the degree of differentiation, we also analysed NGAL levels in pancreatic cancer cell lines with varying grades of differentiation. Although NGAL expression was strongly upregulated in pancreatic cancer, and moderately in pancreatitis, only a weak expression could be detected in the healthy pancreas. The average composite score for adenocarcinoma (4.26+/-2.44) was significantly higher than that for the normal pancreas (1.0) or pancreatitis (1.0) (P<0.0001). Further, although both well- and moderately differentiated pancreatic cancer were positive for NGAL, poorly differentiated adenocarcinoma was uniformly negative. Importantly, NGAL expression was detected as early as the PanIN-1 stage, suggesting that it could be a marker of the earliest premalignant changes in the pancreas. Further, we examined NGAL levels in serum samples. Serum NGAL levels were above the cutoff for healthy individuals in 94% of pancreatic cancer and 62.5% each of acute and chronic pancreatitis samples. However, the difference between NGAL levels in pancreatitis and pancreatic cancer was not significant. A ROC curve analysis revealed that ELISA for NGAL is fairly accurate in distinguishing pancreatic cancer from non-cancer cases (area under curve=0.75). In conclusion, NGAL is highly expressed in early dysplastic lesions in the pancreas, suggesting a possible role as an early diagnostic marker for pancreatic cancer. Further, serum NGAL measurement could be investigated as a possible biomarker in pancreatitis and pancreatic adenocarcinoma.

[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.

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.

[Helical computed tomography in penetrating injury to the torso. Diagnostic value in emergent use]. / Spiralcomputertomographie bei penetrierendem Rumpftrauma. Diagnostischer Wert in der Notfallsituation.

BACKGROUND: Nontherapeutic laparotomy and thoracotomy rates in penetrating torso trauma remain high. The aim of this study was to define the value of helical computed tomography (CT) in this emergency situation. MATERIAL AND METHODS: Retrospectively, we studied 11 hemodynamically stable patients with penetrating injury to the torso admitted to our trauma center over a 3-year period who underwent intravenous contrasted helical CT immediately after admission. A positive CT scan was defined as showing any evidence of intrathoracal or intra-abdominal injury necessitating immediate operation. Patients with positive CT underwent laparotomy and/or thoracotomy. Patients with negative CT were observed. RESULTS: Eleven consecutive patients were studied: nine male, two female; mean age 39 years (range 19-62). Nine stab wounds and two shotgun wounds were seen. Seven patients had positive helical CT findings, and four patients were negative. All patients with positive CT findings were operated on; those with negative scans recovered uneventfully. This imaging method accurately predicted whether thoracotomy or laparotomy was needed in 10/11 cases. CONCLUSION: In penetrating torso trauma, helical CT can clarify the need for thoracotomy or laparotomy vs nonoperative treatment.

MUC4 mucin expression in human pancreatic tumours is affected by organ environment: the possible role of TGFbeta2.

MUC4 is highly expressed in human pancreatic tumours and pancreatic tumour cell lines, but is minimally or not expressed in normal pancreas or chronic pancreatitis. Here, we investigated the aberrant regulation of MUC4 expression in vivo using clonal human pancreatic tumour cells (CD18/HPAF) grown either orthotopically in the pancreas (OT) or ectopically in subcutaneous tissue (SC) in the nude mice. Histological examination of the OT and SC tumours showed moderately differentiated and anaplastic morphology, respectively. The OT tumour cells showed metastases to distant lymph nodes and faster tumour growth (P<0.01) compared to the SC tumours. The MUC4 transcripts in OT tumours were very high compared to the undetectable levels in SC tumours. The SC tumour cells regained their ability to express MUC4 transcripts after in vitro culture. Immunohistochemical analysis using MUC4-specific polyclonal antiserum confirmed the results obtained by Northern blot analysis. Interestingly, the OT tumours showed expression of TGFbeta2 compared to no expression in SC, suggesting a possible link between MUC4 and TGFbeta2. The MUC4 expression, morphology, and metastasis of human pancreatic tumour cells are regulated by a local host microenvironment. TGFbeta2 may serve as an interim regulator of this function.

Expression of nerve growth factors in pancreatic neural tissue and pancreatic cancer.

One of the characteristics of pancreatic cancer is its tendency to invade neural tissue. We hypothesized that the affinity of cancer cells for nerve tissue is related to the presence of growth factors in neural tissue and their receptors in cancer cells. Sections of pancreatic cancer and normal pancreatic tissue were examined by immunohistochemistry for the expression of the neurotrophins NGF, BDNF, NT-3, NT-4, and their receptors TrkA, TrkB, and TrkC, as well as the low-affinity receptor, p75NTR. TrkA expression was found in duct, islet, and cancer cells; TrkB was found in the alpha-cells of the islet only. The anti-pan-Trk antibody (TrkB3), which is presumed to recognize all three receptors, immunoreacted with duct and acinar cells in normal tissue and with cancer cells. The staining with TrkC was similar to that of TrkA. The low-affinity receptor p75NTR was expressed in the neural tissue and in scattered duct cells of the normal tissue only. Duct and acinar cells, as well as neural tissue and cancer cells, showed weak to strong immunoreactivity with NGF. NT-3 expression was noted in capillary endothelia and erythrocytes. NT-4 showed specific staining for ductule cells. The expression and distribution of neurotrophins and their receptors suggest their role in the potential of pancreatic cancer cells for neural invasion.

Pacinian corpuscle in the human pancreas.

During our systematic examination of the distribution of cytochrome P450 enzymes in the normal and diseased human pancreas, we observed a Pacinian corpuscle in a serial section of a tissue from a pancreatic cancer patient. We report the histologic and immunohistochemical patterns in this corpuscle and review the literature. The Pacinian corpuscle was situated within the pancreas of a 76-year-old woman with cancer in the head of the pancreas. We could demonstrate immunoreactivity within the corpuscle for the neurofilament protein. neuron-specific enolase, S-100 Protein, and for four cytochrome P450-isozymes. The possible function of Pacinian corpuscles in the mammalian and human pancreas is discussed.

Experimental animal models in pancreatic carcinogenesis: lessons for human pancreatic cancer.

The silent course of pancreatic cancer and its explosive fatal outcome have hindered studies of tumor histogenesis and the identification of early biochemical and genetic alterations that could help to diagnose the disease at a curable stage and develop therapeutic strategies. Experimental animal models provide important tools to assess risk factors, as well as preventive and therapeutic possibilities. Although several pancreatic cancer models presently exist, only models that closely resemble human tumors in morphological, clinical, and biological aspects present useful media for preclinical studies. Because an estimated 70% of human tumors are induced by carcinogens and because a significant association has been found between cigarette smoking and pancreatic cancer, chemically induced models are of particular value. Moreover, in such models the etiology, modifying factors, effects of diets, and naturally occurring products can be studied and early diagnostic, preventive, and therapeutic possibilities sought out. Many of the existing models are described in this review, and the advantages and shortcomings of each model and their clinical implications are discussed.

Prevention of pancreatic cancer induction in hamsters by metformin.

BACKGROUND AND AIMS: Our previous study suggested that the known promotional effect of a high fat diet, which in hamsters induces peripheral insulin resistance, is related to a compensatory proliferation of islet cells. The present study was to examine whether the prevention of islet cell proliferation can inhibit the promotional effect of a high-fat diet in pancreatic carcinogenesis. METHODS: Two groups of high fat-fed hamsters were used. One group received Metformin in drinking water for life (HF+Met group), and the other group served as a control (HF group). At the time when the normalization of the plasma insulin level was expected, all hamsters were treated with the pancreatic carcinogen, N-nitrosobis-(2-oxopropyl)amine, and the experiment was terminated 42 weeks later. RESULTS: Although 50% of the hamsters in the high-fat group developed malignant lesions, none was found in the HF+Met group (P < 0.05). Also, significantly more hyperplastic and premalignant lesions, most of which were found within the islets, were detected in the high-fat group (8.6 lesions/hamster) than in the HF+Met group (1.8 lesions/hamster). CONCLUSIONS: The results lend further support on the significant role of islet cells in pancreatic carcinogenesis and may explain the association between pancreatic cancer and obesity, which is usually associated with peripheral insulin resistance.