Search PubMed⌕ Search

Biomedical subjects

B Gloor

Publications and source records attributed to B Gloor.

At least 19 recordsLinked to original sources

Cellular differentiation determines the expression of the hypoxia-inducible protein NDRG1 in pancreatic cancer.

N-myc downstream-regulated gene-1 (NDRG1) is a recently described hypoxia-inducible protein that is upregulated in various human cancers. Pancreatic ductal adenocarcinoma, called pancreatic cancer, is a highly aggressive cancer that is characterised by its avascular structure, which results in a severe hypoxic environment. In this study, we investigated whether NDRG1 is upregulated in these tumours, thus providing a novel marker for malignant cells in the pancreas. By immunohistochemistry, we observed that NDRG1 was highly expressed in well-differentiated cells of pancreatic cancer, whereas the poorly differentiated tumour cells were negative. In addition, hyperplastic islets and ducts of nonquiescent pancreatic tissue were positive. To further explore its selective expression in tumours, two well-established pancreatic cancer cell lines of unequal differentiation status were exposed to 2% oxygen. NDRG1 mRNA and protein were upregulated by hypoxia in the moderately differentiated Capan-1 cells; however, its levels remained unchanged in the poorly differentiated Panc-1 cell line. Taken together, our data suggest that NDRG1 will not serve as a reliable marker of tumour cells in the pancreas, but may serve as a marker of differentiation. Furthermore, we present the novel finding that cellular differentiation may be an important factor that determines the hypoxia-induced regulation of NDRG1.

Biomarkers, Tumor↗

Laparoscopic ventral hernia repair is safe and cost effective.

BACKGROUND: Ventral hernia repair is increasingly performed by laparoscopic means since the introduction of dual-layer meshes. This study aimed to compare the early complications and cost effectiveness of open hernia repair with those associated with laparoscopic repair. METHODS: Open ventral hernia repair was performed for 92 consecutive patients using a Vypro mesh, followed by laparoscopic repair for 49 consecutive patients using a Parietene composite mesh. RESULTS: The rate of surgical-site infections was significantly higher with open ventral hernia repair (13 vs 1; p = 0.03). The median length of hospital stay was significantly shorter with laparoscopic surgery (7 vs 6 days; p = 0.02). For laparoscopic repair, the direct operative costs were higher (2,314 vs 2,853 euros; p = 0.03), and the overall hospital costs were lower (9,787 vs 7,654 euros; p = 0.02). CONCLUSIONS: Laparoscopic ventral hernia repair leads to fewer surgical-site infections and a shorter hospital stay than open repair. Despite increased operative costs, overall hospital costs are lowered by laparoscopic ventral hernia repair.

Adult↗

[Preserving vision in the elderly: a survey to start a quality development program in general practice].

The study examined the rate of patients, who do not follow recommendations for routine screening, do not visit physicians for eye-symptoms and when suffering from diabetes or glaucoma do not adhere to follow-up. To what extent can primary care physicians impact on these deficits of ophthalmologic care? 4918 consecutive, > or = 40 old patients of 107 primary care physicians of 9 networks participated. Of these patients 15% had never, 43% not within the last 3 years, consulted an ophthalmologist. 16% were diabetics, 7% had glaucoma and 46% had observed subjective eye symptoms. A quarter of these patients turn to their primary care physician, when having eye problems. Primary care physicians do not frequently suggest routine ophthalmologic controls nor do they use diagnostic tools like the Amsler-grid or the Swinging-Flash-Light Test.

Adult↗

[Technique of pancreatic anastomosis].

Postoperative morbidity after pancreatic resection is primarily due to leakage of the pancreatic anastomosis. The duct-to-mucosa pancreatico-jejunostomy either as an end-to-end or end-to-side anastomosis is the preferred technique in our hands. The use of a temporarily catheter to drain the main pancreatic duct is optimal. The pancreatic leakage rate depends in many series on the consistence of the pancreatic parenchyma, the diameter of the major pancreatic duct and the local perfusion. A meticulous, standardized technique, the possibility to adapt the technique in case of unexpected findings and the operative routine of the surgeon are of paramount importance for achieving a low leakage rate. In so called "high volume" centers the pancreatic fistula rate today is in the range of 3 to 13% and the mortality of pancreatic head resection varies between 0.5 and 3%.

Anastomosis, Surgical↗

Predictive value of complement activation fragments C3a and sC5b-9 for development of severe disease in patients with acute pancreatitis.

BACKGROUND: Complement activation has been shown to occur in patients with acute pancreatitis. However, the diagnostic potential of complement activation products in plasma for predicting severe disease remains unclear to date. METHODS: The daily levels of the complement anaphylatoxin C3a and the soluble terminal complement complex sC5b-9 were determined by ELISA in plasma of patients with mild (n = 16) or severe (n = 14) acute pancreatitis during the first week after onset of symptoms, and in healthy control subjects (n = 14). RESULTS: Both C3a and sC5b-9 were significantly elevated during the first 7 days in plasma of patients with severe acute pancreatitis (C3a: 459.3 +/- 407.5 ng/mL (mean +/- s); sC5b-9: 617.9 +/- 297.7 ng/mL), as compared to patients with mild disease (C3a: 172 +/- 149.5 ng/mL; sC5b-9: 306.7 +/- 167.3 ng/mL) or controls (C3a: 102.3 +/- 19.7 ng/mL; sC5b-9: 40.64 +/- 19.7 ng/mL; P < 0.001, repeated measures ANOVA). The analysis of both parameters in combination during the first week after onset of symptoms revealed a high sensitivity (0.93) and specificity (0.88) as well as high negative and positive predictive values (0.93 and 0.87, respectively) with an odds ratio of 91.0 for the development of pancreatic necrosis (P < 0.0001, Fisher exact test). CONCLUSION: In patients with acute pancreatitis, the plasma levels of complement C3a and sC5b-9 measured daily during the first week after onset of symptoms represent highly specific and sensitive parameters for the prediction of severe acute pancreatitis.

Acute Disease↗

Therapeutic concept for acute leg and pelvic venous thrombosis.

Combination treatment in acute deep venous thrombosis essentially consists of a highly dosed locoregional thrombolysis of the valve-carrying crurofemoral axis and a mechanical thrombectomy of the valveless pelvic axis by Fogarty catheter. The success of this method is due to the fact that it largely eliminates the disadvantages of systemic thrombolysis, as well as those at conventional surgical thrombectomy, whilst retaining the advantages. Using combination treatment in acute leg and pelvic venous thrombosis within the first 7 days can result in restitutio ad integrum, i.e. complete desobliteration with maintained valve function in more than 80% of the cases.

Fibrinolytic Agents↗

Pancreatic stellate cells contribute to regeneration early after acute necrotising pancreatitis in humans.

BACKGROUND AND AIM: The aim of this study was to systematically analyse the pattern of regeneration in human acute pancreatitis by testing whether pancreatic stellate cells, their myofibroblastic offspring, and pancreatic ductules are involved in the regenerative process. PATIENTS AND METHODS: Between January 1994 and November 2000, 24 necrosectomy specimens containing vital tissue were obtained for pathological examination. Formalin fixed tissue samples were routinely processed and immunostained for cytokeratins 7 and 19, smooth muscle actin, desmin, Ki-67, and CD68. Pancreatic tissue from organ donors served as normal controls. RESULTS: Necrosectomy specimens were obtained between 11 and 41 days after the onset of symptoms. In vital areas of necrosectomy samples, spherical hypercellular spheres consisting of loose vascular connective tissue occurred, in part showing duct-like profiles which sprouted from remnant exocrine tissue almost perpendicular to the periphery of the spheres. In normal tissue, only a few stellate cells and myofibroblasts were present around ducts and ductules. In contrast, numerous stellate cells and myofibroblasts were detected in the hypercellular regenerative spheres after acute pancreatitis, both being situated within the loose tissue and forming compact periductular sheaths. Stellate cells/myofibroblasts and ductule cells exhibited increased proliferative activity. CONCLUSIONS: Pancreatic stellate cells and their activated myofibroblastic offspring may participate in regeneration after acute necrotising pancreatitis in humans. Time course studies are needed to further strengthen this regeneration concept.

Actins↗

Role of laparoscopy in hepatic cyst surgery.

BACKGROUND: Hepatic cysts are detected incidentally in 2.5-5% of the population. Only about 15% of such cysts are symptomatic. Since laparoscopic deroofing for liver cysts was first described in 1991 there have been a number of reports of successful laparoscopic management of hepatic cysts, including the laparoscopic management of complex and parasitic cysts. METHODS: A systematic review of English-language articles on the subject appearing in journals through May 2002 was conducted using the Medline database. RESULTS: Only a minority of cystic liver lesions need treatment, and the therapeutic approach is guided by the type of cyst. Laparoscopic deroofing (combined with omentoplasty and/or oversewing) of uncomplicated liver cysts is associated with a recurrence rate of 10-25%, with less morbidity and mortality as compared to open surgery. On the other hand, treatment of complex liver cysts and hydatid cysts by laparoscopy is not considered a standard approach. CONCLUSION: The laparoscopic approach in uncomplicated but symptomatic liver cysts is effective, with low morbidity and mortality. Additional omentoplasty or oversewing appears to reduce the recurrence rate.

Cysts↗

Pancreatic infection in severe pancreatitis: the role of fungus and multiresistant organisms.

HYPOTHESIS: Recent controlled clinical studies suggest a positive effect of early antibiotic treatment on late morbidity and mortality in severe acute pancreatitis. However, widespread use of antibiotics may lead to an increased number of fungal infections and multiresistant bacteria, thereby worsening the outcome of the disease. DESIGN: Single-center prospective study. SETTING: University hospital, gastrointestinal surgical service. PATIENTS: One hundred three patients with necrotizing pancreatitis seen consecutively in our service. INTERVENTIONS: In addition to standard treatment, patients with proven necrotizing pancreatitis received a prophylactic intravenous antibiotic treatment. Pancreatic infection was regarded as an indication for surgery. MAIN OUTCOME MEASURES: Pancreatic infection, microbiological findings, drug resistance, fungal infections. RESULTS: Thirty-three patients (32%) had infected necrosis. Gram-negative organisms were isolated from 19 patients (58%), Gram-positive organisms were isolated from 18 patients (55%), fungal organisms were isolated from 8 patients (24%), and multiresistant organisms were isolated from 3 patients (9%). In 7 patients (21%), the organisms cultured from the pancreatic tissue were resistant to the antibiotics given in for prophylaxis. Infection with multiresistant organisms or organisms resistant to the antibiotic used for prophylaxis, but not with fungal infection or Gram-positive or Gram-negative infection, was correlated with a negative outcome. CONCLUSIONS: Fungal infection under adequate treatment is not associated with a negative outcome. The occurrence of multiresistant organisms seems to be a rare finding (3 of 103 patients). Antibiotic prophylaxis is effective in preventing infection in necrotizing pancreatitis, but optimal choice and duration of administration of the antibiotic agent(s) need to be carefully determined to avoid the sequelae of multiresistant organisms.

Adult↗

Platelet activating factor antagonism reduces the systemic inflammatory response in a murine model of acute pancreatitis.

BACKGROUND: The platelet activating factor (PAF) antagonist, Lexipafant, has been used in experimental models and clinical trials to treat severe acute pancreatitis (AP). The purpose of this study was to determine whether Lexipafant reduces the local and systemic components of AP in a murine model of mild, edematous AP. MATERIALS AND METHODS: Forty-eight female Swiss-Webster mice were divided into four groups. Group 1 received 50 microl of saline ip every hour for 6 h (sham). Group 2 received saline treatment, plus Lexipafant (25 mg/kg dose ip, every 3 h starting 1 h after the first saline injection) (sham/Lex). Group 3 received cerulein (50 microg/kg dose ip, every hour for 6 h) (AP). Group 4 received AP, plus therapeutic treatment with Lexipafant (AP/Lex). Animals were sacrificed 3 h after the last injection. Serum cytokine levels were determined by ELISA. Standard assays were performed for serum amylase activity and lung myeloperoxidase activity (MPO). Histology was scored by two blinded investigators. RESULTS: Serum cytokines (TNFalpha, IL-1beta), lung MPO, and serum amylase activity were reduced by PAF antagonism. Histology showed a trend toward improvement with Lexipafant, but did not reach statistical significance. CONCLUSION: The PAF antagonism reduces the severity of systemic inflammation when given after the induction of mild AP in mice. These results suggest that Lexipafant may be useful in the treatment of mild pancreatitis after its clinical onset.

Acute Disease↗

Prophylactic antibiotics and pancreatic necrosis.

Recent controlled clinical studies suggest a positive effect of early antibiotic treatment on late morbidity and mortality in severe acute pancreatitis. In contrast, widespread use of antibiotics may lead to an increased number of fungal infections and multiresistant bacteria. Optimal choice, duration, and route of administration of the antibiotic agent(s) are far from being established. The additional administration of an antifungal agent with prophylactic intention cannot be supported by the currently available data.

Animals↗

Hydrocortisone treatment of early SIRS in acute experimental pancreatitis.

This work studied the effects of hydrocortisone treatment in experimental acute pancreatitis on cytokines, phospholipase A2, and breakdown products of arachidonic acid and survival. Edematous and necrotizing pancreatitis were induced in Wistar rats by cerulein hyperstimulation and retrograde intraductal infusion of sodium taurocholate, respectively. Hydrocortisone (10 mg/kg) was administered intravenously 10 minutes after induction of acute pancreatitis. Serum was assayed for phospholipase A2; interleukin (IL) 1beta, IL-6, IL-10, thromboxane B2; Prostaglandin E2; and leukotriene B4 at five different time points. A significant release of inflammatory mediators was seen only in the severe model. Hydrocortisone powerfully suppressed arachidonic acid breakdown products and only mildly attenuated the systemic increase of phospholipase A2 and pro- and antiinflammatory cytokines. The mortality rate after 72 hr in the severe model was 86%. Hydrocortisone treatment reduced mortality to 13% (P = 0.001; Fisher's exact test). Hydrocortisone seems to be effective in the treatment of the early systemic inflammatory response syndrome associated with severe acute pancreatitis.

Acute Disease↗

Late mortality in patients with severe acute pancreatitis.

BACKGROUND: Mortality due to severe or necrotizing acute pancreatitis most often results from multiorgan dysfunction syndrome (MODS) occurring either early (within the first 14 days) or 2 weeks or more after the onset of symptoms due to septic complications. The aim of this study was to analyse the course of the disease in patients who died from severe acute pancreatitis. METHODS: Between January 1994 and August 2000 details of 263 consecutive patients with acute pancreatitis were entered prospectively into a database. All patients were treated in an intermediate or intensive care unit. RESULTS: The overall mortality rate was 4 per cent (ten of 263 patients). The mortality rate was 9 per cent (ten of 106) in patients with necrotizing disease. No patient died within the first 2 weeks of disease onset. The median day of death was 91 (range 15-209). Six patients died from septic MODS. Ranson score, Acute Physiology and Chronic Health Evaluation (APACHE) II score during the first week of disease, pre-existing co-morbidity, body mass index, infection and extent of necrosis were significantly associated with death (P < 0.01 for all parameters). However, only infection of the necrotic pancreas was an independent risk factor in the multivariate analysis. CONCLUSION: Early deaths in patients with severe acute pancreatitis are rare, mainly as a result of modern intensive care treatment. Nine of the ten deaths occurred more than 3 weeks after disease onset. Infection of pancreatic necrosis was the main risk factor for death.

APACHE↗

Intrathecal levels of complement-derived soluble membrane attack complex (sC5b-9) correlate with blood-brain barrier dysfunction in patients with traumatic brain injury.

It has become evident in recent years that intracranial inflammation after traumatic brain injury (TBI) is, at least in part, mediated by activation of the complement system. However, most conclusions have been drawn from experimental studies, and the intrathecal activation of the complement cascade after TBI has not yet been demonstrated in humans. In the present study, we analyzed the levels of the soluble terminal complement complex sC5b-9 by ELISA in ventricular cerebrospinal fluid (CSF) of patients with severe TBI (n = 11) for up to 10 days after trauma. The mean sC5b-9 levels in CSF were significantly elevated in 10 of 11 TBI patients compared to control CSF from subjects without trauma or inflammatory neurological disease (n = 12; p < 0.001). In some patients, the maximal sC5b-9 concentrations were up to 1,800-fold higher than in control CSF. The analysis of the extent of posttraumatic blood-brain barrier (BBB) dysfunction, as determined by CSF/serum albumin quotient (Q(A)), revealed that patients with a moderate to severe BBB impairment (mean Q(A) > 0.01) had significantly higher intrathecal sC5b-9 levels as compared to patients with normal BBB function (mean Q(A) < 0.007; p < 0.0001). In addition, a significant correlation between the individual daily Q(A) values and the corresponding sC5b-9 CSF levels was detected in 8 of 11 patients (r = 0.72-0.998; p < 0.05). These data demonstrate for the first time that terminal pathway complement activation occurs after head injury and suggest a possible pathophysiological role of complement with regard to posttraumatic BBB dysfunction.

Adolescent↗

A modified technique of the Beger and Frey procedure in patients with chronic pancreatitis.

BACKGROUND: Resection of the pancreas requires control of tributaries of the superior mesenteric vein (SMV) inferior to the head of the pancreas as well as separation of the posterior surface of the pancreas from the SMV and from eventually existing collateral veins. This usually is the most tedious part when performing a resection of the pancreatic head, in particular if there are signs of portal hypertension. Portal vein pathology contributes to intra- and postoperative morbidity in pancreatic surgery. OPERATIVE TECHNIQUE: Instead of dissecting the pancreas along the anterior surface of the SMV our proposed technique allows resection of the head of the pancreas without division of the gland. This approach combines elements of Beger's duodenum-preserving pancreatic head resection and of Frey's limited local pancreatic head excision combined with a longitudinal pancreaticojejunostomy. This modified technique avoids the risk of a bleeding complication which is increased in the presence of portal hypertension and dilation. SUMMARY: The advantages of this modified technique over standard Beger and Frey procedures are: (1) the minimized risk of a bleeding complication in case of portal hypertension because pancreatic transsection does not need to be done, and (2) the considerably more radical excision as compared to local excision. Also, it represents the most minimal surgical trauma for resecting the head of the pancreas as compared to other commonly used techniques.

Anastomosis, Surgical↗

[Combination therapy of venous thrombosis with local thrombolysis and surgical thrombectomy].

Combination therapy in acute deep venous thrombosis essentially consists of a highly dosed locoregional thrombolysis of the valve carrying crurofemoral axis and a mechanical thrombectomy of the valveless pelvic axis by Fogarty catheter. The success of this method is due to the fact that it largely eliminates the disadvantages of systemic thrombolysis as well as conventional surgical thrombectomy whilst retaining the advantages. Using combination therapy within the first 7 days in acute leg and pelvic venous thrombosis can result in restutio ad integrum, i.e. complete desobliteration with maintained valve function (more than 80% of cases).

Combined Modality Therapy↗

Primary duodenal adenocarcinoma: a 40-year experience.

HYPOTHESIS: In patients with duodenal adenocarcinoma, certain pathologic features of the tumor will have prognostic significance. DESIGN: Retrospective case series. PATIENTS: Forty-nine patients diagnosed with duodenal adenocarcinoma between 1957 and 1998. RESULTS: The tumors of 31 (63%) of the 49 patients underwent resection, 18 (37%) had surgical palliation or underwent biopsy. Mean (+/- SEM) survival for all patients was 49 +/- 9 months. The patients whose tumors were resected had longer survival than those who underwent palliation (mean +/- SEM, 66 +/- 13 months vs 18 +/- 6 months, P =.02). Multivariate analysis revealed large tumor size (P =.01), transmural invasion (P =.004), and moderate to poor tumor grade (P =.03) were negatively correlated with survival. Lymph node status did not influence survival. CONCLUSIONS: Our 40-year experience with duodenal adenocarcinoma demonstrates that large tumor size, advanced histological grade, and transmural invasion are associated with decreased survival. These results underscore the importance of early diagnosis, and suggest the presence of nodal spread is not a contraindication to resection.

Adenocarcinoma↗