Granulocyte Colony-Stimulating Factor–Producing Cholangiocellular Carcinoma

A 61-year-old female was admitted to our hospital with epigastric pain and fever. The laboratory data showed severe inflammatory reactions. Computed tomography revealed an irregular tumor in the left hepatic lobe and swelling of lymph nodes. ¹⁸F-fluorodeoxy-glucose positron emission tomography (FDG-PET) showed high uptake by the tumor, with diffuse uptake in the spine. Based on the elevated leukocyte count and FDG-PET findings, the patient was diagnosed with a granulocyte colony-stimulating factor (G-CSF)-producing tumor (G-CSF, 213 pg/mL). We performed left trisegmentectomy of the liver, bile duct resection, and lymph node dissection. Histologically, the tumor was a poorly differentiated adenocarcinoma with some lymph nodes metastasis. Immunohistochemical staining of the tumor cells was positive for G-CSF. Therefore, the tumor was diagnosed as G-CSF–producing cholangiocellular carcinoma. The inflammatory reactions and serum G-CSF level transiently improved immediately after surgery. However, 1 month later, the leukocyte count and serum G-CSF level increased again, and recurrence was observed in the remnant liver. The patient died 3 months after the operation. G-CSF–producing cholangiocellular carcinoma is rare. This tumor progresses rapidly, and surgical treatment for advanced condition should be carefully selected.Key words: Granulocyte colony-stimulating factor, Cholangiocellular carcinoma, FDG-PET, Immunohistochemistry, LeukocytosisGranulocyte colony-stimulating factor (G-CSF)-producing tumors were first reported in 1977.¹ G-CSF-producing cholangiocellular carcinomas (CCCs) are rare, with only 5 other reported cases. We herein report a surgical case of G-CSF–producing CCC with early recurrence and include bibliographic comments.     

Granulocyte-Colony Stimulating Factor–Producing Gallbladder Carcinoma

A 78-year-old man was admitted to our hospital with right upper abdominal pain and fever. His general condition was poor. The laboratory data showed severe inflammatory reactions. Computed tomography revealed an irregular tumor in the gallbladder. ¹⁸F-fluorodeoxy-glucose positron emission tomography (FDG-PET) showed high uptake by the tumor, with diffuse uptake in the spine. Based on the elevated leukocyte count and FDG-PET findings, a granulocyte-colony stimulating factor (G-CSF)–producing tumor was diagnosed (G-CSF 120 pg/mL). We performed cholecystectomy with central bisegmentectomy of the liver, lymph node dissection and right hemicolectomy. Histologically, the tumor was an adenosquamous cell carcinoma of the gallbladder. Immunohistochemical staining of the tumor cells was positive for G-CSF. Postoperatively, the general condition of the patient was improved. The fever subsided, the leukocyte count and serum G-CSF level normalized, and FDG-PET showed no uptake in the spine postoperatively. The patient showed no signs of recurrence at 27 months after undergoing surgery. FDG-PET is a useful method for diagnosing G-CSF–producing gallbladder carcinoma. Aggressive curative resection for G-CSF–producing gallbladder carcinoma may improve patients'' general condition and prognosis.Key words: Granulocyte-colony stimulating factor, Gallbladder carcinoma, FDG-PET, Immunohistochemistry, LeukocytosisGranulocyte-colony stimulating factor (G-CSF)–producing tumors were first reported in 1977.¹ G-CSF–producing gallbladder carcinomas are rare, with only 22 other reported cases. We herein report a case of G-CSF–producing gallbladder carcinoma and include bibliographic comments.     

Contrasting Prognostic Implications of Platelet-Derived Growth Factor Receptor-β and Vascular Endothelial Growth Factor Receptor-2 in Patients with Angiosarcoma

Background  

Angiosarcoma is an extremely rare tumor among sarcomas and comprises a heterogeneous group of high-grade vascular malignancies. Our study aimed to examine the correlations between 6 immunohistochemical biomarkers—stem cell factor receptor (KIT), platelet-derived growth factor receptor (PDGFR)-α, PDGFR-β, vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, and VEGFR-3—and overall survival (OS) in patients with angiosarcomas.     

Seminal Factor VIII and von Willebrand Factor: a possible role of the conventional clotting system in human semen?

Factor (F) VIII circulates in blood complexed with von Willebrand Factor (vWF). Deficiency or defect accounts for haemophilia A and vWF disease. In blood, FVIII functions as a co-factor for FIXa in the activation of FX. Human semen coagulates and liquefies in a process that resembles and has some links with the conventional haemostatic process. A study elsewhere has detected traces, but not measurable levels, of FVIII coagulant activity (FVIII:C). In the present study we have assessed FVIII antigen (FVIII:Ag), FVIII:C and vWF antigen (vWF:Ag) levels in 159 semen specimens obtained from sub-fertile (n = 21), normally fertile (n = 38), fertile donors (n = 32), and vasectomized men (n = 57). Seminal FVIII:Ag levels were also measured in a group defined by several parameters derived from the World Health Organization (WHO) fertility criteria, termed "pooled normal semen parameters" (PNSP). Factor VIII:Ag levels were compared with conventional fertility parameters. In addition, both FVIII:C and vWF:Ag were assessed in a separate group of normal individuals (n = 11). Factor VIII:Ag, FVIII:C and vWF were present and quantifiable in human semen. Factor VIII:Ag levels were significantly lower in vasectomy subjects compared with donors (p = 0.01) or PNSP group (p = 0.01). Several trends taken together suggest an associations between FVIII:Ag and semen quality. Parallel investigations demonstrate FV, FVII, FVIIa, FIX, FIXa, FXa, FXI, FXII, tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in semen. The present report therefore provides further evidence for the presence of a functioning clotting system in human semen.     

Transforming Growth Factor-β1-Antisense Modulates the Expression of Hepatocyte Growth Factor/Scatter Factor in Keloid Fibroblast Cell Culture

Abnormal wound healing processes can result in hypertrophic scars and keloids. Transforming growth factor-β1 (TGF-β1) and hepatocyte growth factor/scatter factor (HGF/SF) are biphasic growth factor cytokines in physiologic and pathophysiologic conditions. Findings have shown TGF-β1 to be pivotal in the formation of keloid tissue. Therefore, neutralizing antibodies may allow wound healing without keloid formation. As reported, TGF-β1 is antagonized by HGF/SF. Some authors have reported that exogenous administration of HGF/SF prevented scar formation. Hence, this study targeted TGF-β1 and determined the levels of HGF/SF in fibroblast cell culture. Keloid tissue was taken from seven patients. Another seven patients with mature nonhypertrophic scar served as controls. All tissues were cultured, and fibroblast cultures were used for further experiments. The TGF-β1 antisense was administered at 3 and 6 μmol/ml, and HGF/SF levels were determined after 16, 24, and 48 h of incubation. The levels of HGF/SF showed significant differences after incubation with antisense oligonucleotides. The increasing antisense levels resulted in increased HGF/SF levels (up to 87.66 pg/ml after 48 h of incubation). In conclusion, targeting TGF-β1 resulted in significantly increased levels of HGF/SF. The clinical relevance could include the use of locally administered HGF/SF in protein or gene form to minimize formation of keloids. Nevertheless, wound healing is the result of many interacting cytokines, so neutralizing or targeting one protein could result in no significant effect.     

Is Ventilator-associated Pneumonia an Independent Risk Factor for Death?

Background: Ventilator-associated pneumonia (VAP) has been implicitly accused of increasing mortality. However, it is not certain that pneumonia is responsible for death or whether fatal outcome is caused by other risk factors for death that exist before the onset of pneumonia. The aim of this study was to evaluate the attributable mortality caused by VAP by performing a matched-paired, case-control study between patients who died and patients who were discharged from the intensive care unit after more than 48 h of mechanical ventilation.

Methods: During the study period, 135 consecutive deaths were included in the case group. Case-control matching criteria were as follows: (1) diagnosis on admission that corresponded to 1 of 11 predefined diagnostic groups; (2) age difference within 10 yr; (3) sex; (4) admission within 1 yr; (5) APACHE II score within 7 points; (6) ventilation of control patients for at least as long as the cases. Precise clinical, radiologic, and microbiologic definitions were used to identify VAP.

Results: Analysis was performed on 108 pairs that were matched with 91% of success. There were 39 patients (36.1%) who developed VAP in each group. Multivariate analysis showed that renal failure, bone marrow failure, and treatment with corticosteroids but not VAP were independent risk factors for death. There was no difference observed between cases and controls concerning the clinical and microbiologic diagnostic criteria for pneumonia.     

How Do Vascular Surgeons Perceive Atherosclerotic Risk Factor Management?

The specific objectives of this report were to determine (1) the usual practice of vascular surgeons with respect to risk factor inquiry and intervention, (2) which risk factors are endorsed by vascular surgeons as being very important in the management of patients with PAD, and, finally, (3) which risk factors vascular surgeons are confident in managing.     

The Insulin-Like Growth Factor–I Axis in Acute Renal Failure

We have examined the response of the renal insulin-like growth factor (IGF-I) axis to acute ischemic injury in the rat Key findings. included a de-crease in IGF-I mRNA and peptide levels, a decrease in GH receptor gene plus protein expression and a decrease in the IGF binding proteins except for IGF binding protein 1. Administration of GH to compensate for the reduced GH receptor binding corrected the IGF-I mRNA levels suggesting a relative GH deficiency. Interestingly, IGF-I receptor mRNA levels were unchanged while plasma membrane IGF-I receptor number increased two fold. This appeared to be due to a redistribution of receptors to a membrane location. IGF-I receptor autophosphorvlation and tyrosine kinase activity were intact despite severe uremia for up to 6 days. We propose that this increase of functional IGF-I receptors following acute tubular necrosis will sensitize the kidney to the administration of exogenous IGF-I.     

Cost Analysis of Carotid Endarterectomy: Is Age a Factor?

Carotid endarterectomy (CEA) has been demonstrated to be safe and effective in elderly patients. Our aim was to analyze and compare outcome and cost of CEA in both elderly and younger patient groups. A total of 125 consecutive patients who underwent CEA were examined retrospectively and grouped according to age (<80 years old, n = 95; and 80 years old, n = 30). The actual total costs and itemized costs were analyzed, and diagnosis-related group (DRG) code payor mix were identified. Patient demographics and risk factors were similar except for a greater incidence of coronary artery disease (CAD) in the 80 group than in these <80 (43.3% vs. 21.1%, p < 0.05). Patients had similar minor complication rates; however, the 80 group had higher perioperative major complications (16.7% vs. 1.1%, p < 0.01). There were no deaths and there was one perioperative stroke, which occurred in the <80 group. Mean length of stay (LOS), intensive care unit (ICU) LOS, and ICU admissions were greater in the 80 group. Cost figures were normalized to a base value of $100 to maintain proprietary data. Actual total costs of CEA were $131.50 for the 80 group and $100 for the <80 group (p < 0.001). Significant cost differences were found in ICU room costs, and costs for clinical laboratory, radiology imaging, other specialty consults, operating room, and ancillary services in the 80 group compared with the <80 group. These results show that the cost of CEA in the elderly is significantly greater than that for younger patients. This difference can be attributed to a greater number of major complications in the more elderly group, who require increased ICU stay, and thus require more clinical laboratory, radiology imaging, and specialty consult service resources. Consideration should be given for a DRG modifier code to increase hospital reimbursement for increased associated costs in elderly patients undergoing CEA.Presented at the Twenty-eighth Annual Meeting of the Peripheral Vascular Surgery Society, Chicago, IL, June 7, 2003.     

Catalase Overexpression Prevents Nuclear Factor Erythroid 2–Related Factor 2 Stimulation of Renal Angiotensinogen Gene Expression,Hypertension, and Kidney Injury in Diabetic Mice

This study investigated the impact of catalase (Cat) overexpression in renal proximal tubule cells (RPTCs) on nuclear factor erythroid 2–related factor 2 (Nrf2) stimulation of angiotensinogen (Agt) gene expression and the development of hypertension and renal injury in diabetic Akita transgenic mice. Additionally, adult male mice were treated with the Nrf2 activator oltipraz with or without the inhibitor trigonelline. Rat RPTCs, stably transfected with plasmid containing either rat Agt or Nrf2 gene promoter, were also studied. Cat overexpression normalized systolic BP, attenuated renal injury, and inhibited RPTC Nrf2, Agt, and heme oxygenase-1 (HO-1) gene expression in Akita Cat transgenic mice compared with Akita mice. In vitro, high glucose level, hydrogen peroxide, and oltipraz stimulated Nrf2 and Agt gene expression; these changes were blocked by trigonelline, small interfering RNAs of Nrf2, antioxidants, or pharmacological inhibitors of nuclear factor-κB and p38 mitogen-activated protein kinase. The deletion of Nrf2-responsive elements in the rat Agt gene promoter abolished the stimulatory effect of oltipraz. Oltipraz administration also augmented Agt, HO-1, and Nrf2 gene expression in mouse RPTCs and was reversed by trigonelline. These data identify a novel mechanism, Nrf2-mediated stimulation of intrarenal Agt gene expression and activation of the renin-angiotensin system, by which hyperglycemia induces hypertension and renal injury in diabetic mice.     

Is Contralateral Carotid Artery Occlusion a Risk Factor for Carotid Endarterectomy?

Occlusion of the contralateral internal carotid artery (ICA) is considered to have a significant impact on the outcome of carotid endarterectomy (CEA). The purpose of this study was to review one center’s experience concerning CEA opposite an occluded ICA, to see whether results differed from those obtained in patients with patent contralateral ICA in terms of relevant neurologic complication rate (RNCR, fatal + disabling stroke), stroke-free rate, and survival rate. From January 1997 to December 2002, 1,381 patients underwent a total of 1,445 CEAs at the Department of Vascular Surgery of Padua University. Patients were divided into two groups: group A included 144 patients with occlusion of the contralateral ICA and group B consisted of 1,237 patients with a patent contralateral ICA. There was no postoperative mortality in patients of group A, while in group B, two patients died as a result of myocardial infarction and cardiac failure and one died as a direct result of perioperative stroke. Postoperative disabling strokes occurred in one (0.7%) patient in group A and 10 (0.8%) patients in group B (p > 0.5). At 72 months, there were no statistical differences between the two groups in terms of RNCR, stroke-free rate, and late death. Our results show that contralateral carotid occlusion does not reduce the safety of CEA. The efficacy in terms of RNCR, stroke-free rate, and late survival is no different in patients with contralateral carotid occlusion.     

Is Early Tracheostomy a Risk Factor for Mediastinitis after Median Sternotomy?

Abstract   Early tracheostomy may increase the risk of mediastinitis after median sternotomy. Patients who had postoperative tracheostomy after cardiac surgery in the period 2000-2005 were retrospectively analyzed (total: 5095 patients) to evaluate the incidence of mediastinitis and sternal wound infections. Fifty-seven cases (1.1% of all operated patients) had postoperative tracheostomy at an average 5.6 ± 0.7 days postoperatively. None of these patients had mediastinitis. Eleven cases of aseptic sternal instability and ten cases of mild-to-moderate infection limited to subcutaneous planes were observed. There was no correlation between the time to performance of tracheostomy and the isolation of bacteria from the thoracic wounds (p = 0.61). The bacterial strains isolated from subcutaneous infection were qualitatively and quantitatively different from those isolated from bronchial secretions. We conclude that in this study there is no demonstrable link between early tracheostomy after sternotomy and mediastinitis. Early tracheostomy should not be denied due to concerns of increasing the risk of mediastinitis.