Serum epidermal growth factor receptor/HER-2 predicts poor survival in patients with metastatic breast cancer

BACKGROUND: Epidermal growth factor receptor (EGFR, HER-1, and erbB1) is overexpressed in primary breast cancer and had been identified as a poor prognostic factor. METHODS: Pretreatment serum EGFR levels were quantified by using an enzyme-linked immunoadsorbent assay in a Phase III first-line trial of letrozole and tamoxifen and were correlated with patient outcomes. RESULTS: Serum EGFR levels in a control group of 117 healthy, postmenopausal women measured 64.1 +/- 13.3 ng/mL (mean +/- standard deviation). Using a cutoff EGFR level of 44.1 ng/mL from the control group (5% nonparametric method), 53 of 535 patients (10%) had decreased serum levels of EGFR. Patients with decreased serum EGFR had no significant difference in objective response rate (ORR), clinical benefit rate (CBR), time to progression (TTP), or time to treatment failure (TTF); however, they did have significantly reduced survival compared with patients who had normal serum EGFR levels (median survival, 23.3 months vs. 30.9 months; P = .007). A combined analysis of pretreatment serum EGFR and HER-2 yielded no additional predictive information for ORR, CBR, TTP, or TTF compared to serum HER-2 alone. However, in the current analysis, a subgroup of patients who had decreased serum EGFR and normal serum HER-2 was identified (n = 39 of 535 patients; 7.3%) that had significantly reduced survival compared with patients who had normal serum levels of both EGFR and HER-2 (median survival, 23.5 months vs. 37.1 months; P = .005). In multivariate analysis, a decreased serum EGFR level remained a significant independent prognostic factor for decreased survival (hazards ratio, 1.58; P = .007). CONCLUSIONS: In patients who had metastatic breast cancer, decreased serum EGFR/normal serum HER-2 predicted shorter survival compared with patients who had normal levels of serum EGFR/HER-2. This patient subgroup deserves further study to assess their response to and selection for anti-EGFR-directed therapies.     

A priori dietary omega-3 lipid supplementation results in local pancreatic macrophage and pulmonary inflammatory response attenuation in a model of experimental acute edematous pancreatitis (AEP)

BACKGROUND: Acute pancreatitis is often complicated by multiorgan dysfunction, which is postulated to occur in part by macrophage infiltration into the pancreas. Eicosapentaenoic acid (EPA), an omega-3 fatty acid, is the principal biologic component of fish oil and has clinically and experimentally been demonstrated to be anti-inflammatory. We hypothesized that dietary EPA supplementation before the induction of pancreatitis would attenuate both M-mediated local pancreatic and systemic pulmonary inflammatory response in an in vivo model of acute edematous pancreatitis (AEP). METHODS: Male Sprague-Dawley (SD) rats were pretreated 2 times per day with oral gavage with EPA (omega-3 fatty acid; 5 mg/kg/dose) or omega-6 fatty acid control (5 mg/kg/dose) or saline (equal volume) for 2 weeks. AEP was induced in omega-3, omega-6, and saline pretreated rats by 5 hourly subcutaneous (SC) injections of cerulein. Pancreas, lung, and serum were harvested 3 hours after the last cerulein injection. Severity of pancreatitis was confirmed by serum amylase and by histopathologic score. Pancreatic macrophage infiltration was assessed by confocal fluorescent microscopy, and pulmonary leukocyte respiratory burst (LRB) analysis was performed on mononuclear cells obtained from bronchioalveolar lavage (BAL). RESULTS: All animals demonstrated acute pancreatitis through hyperamylasemia and histopathologic examination. Confocal analysis demonstrated significantly lower macrophage infiltration, and BAL analysis by flow cytometry demonstrated significantly lower (p < .05) LRB in the omega-3-treated group compared with the omega-6 and the saline pancreatitis group. CONCLUSIONS: Attenuation of both pancreatic MPhi inflammatory response and pulmonary leukocyte respiratory burst in AEP by EPA supports further investigation into the potential role for EPA dietary supplementation in the progression of pancreatitis-associated sequelae.     

An unusual case of benign hibernoma in the paediatric age group

An unusual case of congenital benign hibernoma, in the submandibular region, in a 2.5 years old girl, is reported, who presented with a progressively increasing neck swelling. A CAT scan of neck revealed a superficial and deep low density mass. Surgical excision revealed a benign hibernoma. A 3-year follow-up shows no recurrence.     

Molecular study of WISP3 in nine families originating from the Middle-East and presenting with progressive pseudorheumatoid dysplasia: identification of two novel mutations, and description of a founder effect

Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive syndrome characterized by the presence of spondyloepiphyseal dysplasia associated with pain, stiffness, and swelling of multiple joints, osteoporosis, and the absence of destructive bone changes. The disorder is caused by mutations of the WISP3 gene located on chromosome 6q22. We hereby report the molecular study of the WISP3 gene in nine unrelated consanguineous families originating from the Middle-East: three from Lebanon, five from Syria, and one from Palestinian Bedouin descent, all affected with PPD. Five different sequence variations were identified in the WISP3 gene, two of them being new mutations: the c.589G --> C transversion at codon 197, responsible for a splicing defect (A197fsX201); and the c.536_537delGT deletion (C179fsX), both in exon 3. In all other families, the affected patients were homozygous for a previously described nonsense mutation, namely c.156C --> A (C52X). Interestingly, in the latter families, the C52X mutation was always found associated with a novel c.248G --> A (G83E) variation, suggesting the existence of a founder effect.     

Purpureocillium lilacinum as a cause of cavitary pulmonary disease: a new clinical presentation and observations on atypical morphologic characteristics of the isolate

The first case of cavitary pulmonary disease caused by Purpureocillium lilacinum is described. The isolate showed atypical microscopic characteristics similar to Acremonium and Fusarium spp., which necessitated molecular identification by sequencing of multiple conserved loci. The patient responded to voriconazole, reinforcing its therapeutic efficacy for P. lilacinum infections.     

Diffuse large B cell lymphoma complicating total knee arthroplasty: case report and literature review of the association of diffuse large B cell lymphoma with joint replacement

Primary lymphoma of bone is extremely rare. There are increasing reports of lymphoma arising in bone adjacent to metallic prostheses. Herein, we describe the case of a 76-year-old man who developed diffuse large B cell lymphoma in the tibia 3 years after total knee arthroplasty for osteoarthritis. A review of the literature has identified 11 other cases of lymphoma arising in the context of orthopaedic metallic implants. To our knowledge this is the first reported case of a primary lymphoma arising in bone adjacent to a knee prosthesis. Possible pathogenetic mechanisms may include chronic antigenic stimulation of lymphocytes, proliferation of EBV-infected B lymphocytes, and direct mutagenic effects of metallic ions. Further research is required to investigate this intriguing link between metallic orthopaedic prostheses and localized lymphoma.     

Acute kidney injury secondary to renal large B-cell lymphoma: role of early renal biopsy

Renal involvement in large B-cell lymphoma represents an exceptional manifestation of non-Hodgkin lymphomas. Acute kidney injury (AKI) by lymphomatous infiltration is extremely rare and so far only 19 cases have been reported in the literature. We report a 67-year-old woman who presented with AKI and was found to have large B-cell lymphoma infiltrating her kidneys. The patient was treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with rituximab, and a dramatic improvement of renal function was noticed after two weeks of treatment. Her renal function completely recovered after four weeks of treatment. In conclusion, lymphomatous infiltration of kidneys can directly lead to AKI. Rapid diagnosis and treatment is essential to preserve the renal function. Renal biopsy is the gold standard for the early diagnosis of non-Hodgkin lymphoma as a cause of AKI.