Malignant orbital schwannoma with massive intracranial recurrence

Background  A 62 year old male presented with progressive diplopia, left orbital pain and impairment of visual acuity. Method and Findings  Neuroradiological investigation disclosed an orbital tumour. The lesion was totally excised. Histopathology examination revealed a malignant peripheral nerve sheath tumour (MPNST). The tumour recurred with intracranial extension. The patient died 13 months after the initial diagnosis. Conclusions  To our knowledge, this is the first reported example of a massive intracranial recurrence of an orbital MPNST. The epidemiological features, clinical course and treatment of these lesions are discussed.     

Chemically induced analgesic nephropathy in the rat monitored by proton-electron double-resonance imaging (PEDRI)

Proton-electron double-resonance imaging (PEDRI) was used to assess renal function by monitoring the flow of the exogenous nitroxide free radical proxyl carboxylic acid (PCA) through normal and injured kidneys in the living rat. Kidney damage was induced by treatment with 2-bromoethylamine (BEA), which provides a well established model for human analgesic nephropathy. PCA clearance rates for liver, abdominal blood vessels, and renal tissues were determined from serial PEDRI images of normal rats (n = 6) and rats treated with BEA (n = 21). Different groups of BEA-treated animals were imaged on day 4 (n = 6), day 6 (n = 6), and day 9 (n = 9) after treatment. In BEA-treated rats, there was an increase in PCA half-life in all tissues studied. This increase was greatest in the kidney tissues and the effect progressed with time after treatment. The effect is probably due to BEA-induced damage to the tubules in the renal cortex and may not be related to the primary lesions in the renal medulla.     

fibrin glue for sealing the needle track in fine-needle percutaneous lung biopsy using a coaxial system: Part II—clinical study

Purpose Following percutaneous lung biopsy (PLB), we used fibrin glue as a sealant in 26 patients for the purpose of decreasing the incidence of pneumothorax.Methods All 26 patients (group A) had chronic obstructive pulmonary disease (COPD). The results for group A were compared with a control group of 32 patients (group B), also with COPD and in whom fibrin glue was not used. All biopsies were conducted under computed tomography (CT) using a coaxial needle system consisting of 19-gauge and 22-gauge needles.Results Pneumothorax developed in five patients (19.2%) in group A and in one instance, drainage was required (3.8%). In group B, pneumothorax developed in 13 patients (40.6%) and in six instances (18.8%) drainage was required. Comparing the use of chest-tube drainage in the two groups, a statistical significance was observed, p < 0.025. No adverse reactions related to the fibrin glue were observed.Conclusion Our results indicate that fibrin glue is a safe sealing material for lung PLB and serves to decrease the incidence and, in particular, the severity of pneumothorax, especially in high-risk patients.     

Multidisciplinary therapy of locally far-advanced or inflammatory breast cancer with fixed perioperative sequence of epirubicin, vinorelbine, and Fluorouracil chemotherapy, surgery, and radiotherapy: long-term results

BACKGROUND: Based on phase II data in advanced breast cancer (BC), the fluorouracil, epirubicin, and vinorelbine (FEN) combination was assessed as perioperative chemotherapy, integrated in a multidisciplinary treatment for locally advanced BC. PATIENTS AND METHODS: Patients with newly diagnosed inoperable (stage IIIB or inflammatory) BC. Multimodality treatment protocol consisted of four preoperative courses of fluorouracil (600 mg/m(2) day 1), epirubicin (75 mg/m(2) day 1), and vinorelbine (25 mg/m(2) day1 and day 8), all i.v. every 21 days, followed by radical or conservative surgery according to clinical response and four postoperative identical chemotherapy courses aimed to eradicate micrometastatic disease. Locoregional radiotherapy was offered to all patients after the completion of chemotherapy followed by hormonotherapy according to hormone receptor status. The primary end points of the study were: (a) clinical and pathological response, (b) downstaging and conversion to operable disease, and (c) recurrence-free survival (RFS) and overall survival (OS). RESULTS: Forty-eight women, one stage IIIA, 27 (56.2%) stage IIIB, two stage IIIC (4.1%), and 12 (25%) with inflammatory BC, aged 34-75 years (median, 52), were accrued. Thirty-eight and 34 patients completed the planned pre- and postoperative chemotherapy, respectively. Totals of 175 and 135 cycles were administered pre- and postoperatively, respectively. Toxicity of both phases, mainly hematologic, was in general acceptable without treatment-related death. Venous reactions were a frequent problem. All but three tumors were converted to operable, 31.3% with breast conservation. The clinical response rate (RR) was 77.7% (22.2% complete) and pathological RR was 73.3% (complete, 20% in both primary and axilla). After a median follow-up of 72 months, 62.5% and 16.7% of patients remain relapse free at 3 and 5 years, respectively, while 83% and 58.3% were alive 3 and 5 years, respectively, after the start of chemotherapy. Median RFS and OS have not yet been reached, and are currently 37+ and 62+ months, respectively. CONCLUSION: This fixed number of FEN perioperative courses schedule followed by radiotherapy is safe and highly active in inducing both local and distant control of locally far-advanced BC. This strategy is at least not inferior to other established regimens or strategies for locally far-advanced BC, while the integration of taxanes or new targeted agents may help show its true value for this challenging clinical entity.     

Fibrocalculous pancreatic diabetes in patient residing in the Mediterranean region

A 40-year old male residing in the Mediterranean region and afflicted with chronic pancreatitis and diabetes is presented. This is a case of chronic calcific non-alcoholic pancreatitis with characteristic intraductal calculi on abdominal X-ray. Five years following the initial episode of pancreatitis, the patient developed insulin-requiring diabetes mellitus. This case accords with the criteria for fibrocalculous pancreatic diabetes with the unique feature of the patient having been born in Greece and being a resident of Greece.     

Calciphylaxis: a complication of end-stage renal disease improved by parathyroidectomy

A 43-year old Caucasian male with end-stage renal disease presented with painful skin lesions and high calcium phosphate product that did not respond to medical treatment. Skin biopsy confirmed the diagnosis of calciphylaxis. Urgent parathyroidectomy was performed and resulted in decrease in the calcium phosphate product and improvement of his symptoms and signs.     

Ocular rigidity in patients with age-related macular degeneration

PURPOSE: To compare the ocular rigidity in vivo measurements of patients with age-related macular degeneration (AMD) and control subjects. DESIGN: Prospective comparative clinical study. METHODS: The pressure-volume relation and the ocular rigidity coefficient were compared among 32 patients with AMD (AMD group: 16 with neovascular and 16 with nonneovascular AMD) and 44 age-matched control patients (control group) who underwent operation for cataract. This was achieved by an injection of 200 microl of a balanced salt solution (in steps of 4.5 microl) through the limbus in the anterior chamber, while the intraocular pressure was monitored continually with a transducer, up to the limit of 30 mm Hg. RESULTS: The mean age (AMD group: 69.89 +/- 15.92 years vs control group: 65.28 +/- 12.34 years; P = .195), gender (AMD group: 13 female vs control group: 17 female; P = .513), eye's axial length (AMD group: 23.14 +/- 0.75 mm vs control group: 23.04 +/- 1.16 mm; P = .725) of patients with AMD and the healthy control subjects were comparable. No statistically significant difference in ocular rigidity measurements between patients with AMD and control subjects (AMD group: 0.0142 +/- 0.0077 microl(-1) vs control group: 0.0125 +/- 0.0049 microl(-1); P = .255) was found. When we examined separately the two subgroups of patients with AMD (neovascular and nonneovascular AMD), the average ocular rigidity measurements were higher in patients with neovascular AMD vs both control subjects and patients with nonneovascular AMD (neovascular AMD group: 0.0186 +/- 0.0078 microl(-1) vs control group: 0.0125 +/- 0.0048 microl(-1) [P = .014] vs nonneovascular AMD group: 0.0104 +/- 0.0053 microl(-1) [P = .004]). CONCLUSIONS: Despite the limitations placed by the small sample of the examined cases, patients with neovascular AMD who are treated (with photodynamic therapy) have increased ocular rigidity measurements compared with patients with nonneovascular AMD and control patients.     

PRKAR1A inactivation leads to increased proliferation and decreased apoptosis in human B lymphocytes

The multiple neoplasia syndrome Carney complex (CNC) is caused by heterozygote mutations in the gene, which codes for the RIalpha regulatory subunit (PRKAR1A) of protein kinase A. Inactivation of PRKAR1A and the additional loss of the normal allele lead to tumors in CNC patients and increased cyclic AMP signaling in their cells, but the oncogenetic mechanisms in affected tissues remain unknown. Previous studies suggested that PRKAR1A down-regulation may lead to increased mitogen-activated protein kinase (MAPK) signaling. Here, we show that, in lymphocytes with PRKAR1A-inactivating mutations, there is increased extracellular signal-regulated kinase (ERK) 1/2 and B-raf phosphorylation and MAPK/ERK kinase 1/2 and c-Myc activation, whereas c-Raf-1 is inhibited. These changes are accompanied by increased cell cycle rates and decreased apoptosis that result in an overall net gain in proliferation and survival. In conclusion, inactivation of PRKAR1A leads to widespread changes in molecular pathways that control cell cycle and apoptosis. This is the first study to show that human cells with partially inactivated RIalpha levels have increased proliferation and survival, suggesting that loss of the normal allele in these cells is not necessary for these changes to occur.     

C2028T polymorphism in exon 12 and dinucleotide repeat polymorphism in intron 13 of the HIF-1alpha gene define HIF-1alpha protein expression in non-small cell lung cancer

OBJECTIVES: In this study, we investigated whether polymorphisms of the HIF-1alpha gene may account for the patterns of HIF-1alpha protein expression in non-small cell lung carcinomas (NSCLC) and the expression of HIF-1alpha down-stream proteins. METHODS: Specific HIF-1alpha polymorphisms were assessed in a series of patients with NSCLC: (a) the C to T transition at nucleotide 1744 (position 2028 according to sequence with accession number , which gives rise to Pro/Ser variation at codon 582), (b) the G to A nucleotide substitution at point 1790 (position 2046 according to sequence with accession number , which gives rise to Ala/Thr variation at codon 588), and (c) the dinucleotide GT repeat polymorphism in intron 13. Immunohistochemistry for HIF-1alpha and down-stream proteins (VEGF, LDH-5, GLUT-1) was also performed in tumor material. RESULTS: A strong association of the P582S polymorphism and of GT repeat polymorphism higher than 14/14 with increased HIF-1alpha expression was noted. HIF-1alpha polymorphism did not relate to the expression of the HIF-1alpha downstream proteins analysed, but significant association of HIF-1alpha expression with LDH-5 was confirmed (p=0.008). CONCLUSIONS: HIF-1alpha polymorphisms may have an important impact on HIF-protein stability and, eventually, function.