Sternal resection and reconstruction for primary malignant tumors

BACKGROUND: Primary malignant sternal tumors (PMST) are locally aggressive and their optimal surgical management still continues to evolve. METHODS: From 1986 to 2002, 38 patients (25 females/13 males) underwent radical resection of PMST. This series included 33 sarcomas, 17 of which had been radiation-induced, 3 hematologic tumors, and 2 carcinomas. Seventeen were high-grade tumors. Nine patients had received preoperative chemotherapy. Twelve patients required extensive skin excision. Eight total, seven subtotal, and 23 partial sternectomies were performed. Resection was extended to the anterior chest-wall in 4 patients, lung in 4, brachiocephalic vein in 3, superior vena cava in 2, and pericardium in 1. In 36 patients, chest wall stability was obtained by Marlex (n = 21) or Vicryl (n = 2) mesh and polytetrafluoroethylene patch (n = 13), with methylmethacrylate reinforcement in 12 patients. Soft tissue coverage was done by the pectoralis major muscles with skin advancement in 25 patients, a myocutaneous flap in 11, a breast transposition in 1, and a skin flap in 1. Omentoplasty was performed in 3 patients. RESULTS: One patient died from pneumonia. Two patients needed a tracheostomy after total sternectomy. No flap-related complication was observed. Four local septic complications required removal of the composite prosthesis with reoperations. Local recurrence occurred in 9 patients, 7 patients having a repeat resection. Metastases developed in eight. The 5-year overall and disease-free survival was 66% and 53%, respectively. The histologic grade of sarcomas was a survival predictor (high grade versus others p = 0.035). CONCLUSIONS: Wide resection of PMST is necessary to minimize local recurrence. Large sternal defects are safely reconstructed with a musculocutaneous flap. We suggest that the use of methylmethacrylate should be limited to reconstruction after total sternectomy.     

Glycosylation and size of IgA1 are essential for interaction with mesangial transferrin receptor in IgA nephropathy

Transferrin receptor (TfR) has been identified as a candidate IgA1 receptor expressed on human mesangial cells (HMC). TfR binds IgA1 but not IgA2, co-localizes with mesangial IgA1 deposits, and is overexpressed in patients with IgA nephropathy (IgAN). Here, structural requirements of IgA1 for its interaction with mesangial TfR were analyzed. Polymeric but not monomeric IgA1 interacted with TfR on cultured HMC and mediates internalization. IgA1 binding was significantly inhibited (>50%) by soluble forms of both TfR1 and TfR2, confirming that TfR serves as mesangial IgA1 receptor. Hypogalactosylated serum IgA1 from patients with IgAN bound TfR more efficiently than IgA1 from healthy individuals. Serum IgA immune complexes from patients with IgAN containing aberrantly glycosylated IgA1 bound more avidly to TfR than those from normal individuals. This binding was significantly inhibited by soluble TfR, highlighting the role of TfR in mesangial IgA1 deposition. For addressing the potential role of glycosylation sites in IgA1-TfR interaction, a variety of recombinant dimeric IgA1 molecules were used in binding studies on TfR with Daudi cells that express only TfR as IgA receptor. Deletion of either N- or O-linked glycosylation sites abrogated IgA1 binding to TfR, suggesting that sugars are essential for IgA1 binding. However, sialidase and beta-galactosidase treatment of IgA1 significantly enhanced IgA1/TfR interaction. These results indicate that aberrant glycosylation of IgA1 as well as immune complex formation constitute essential factors favoring mesangial TfR-IgA1 interaction as initial steps in IgAN pathogenesis.     

Improving resident research in physical medicine and rehabilitation: impact of a structured training program

OBJECTIVE: This study describes a research training program that implemented several processes and structures with the aim of increasing the quality and quantity of resident research in physical medicine and rehabilitation. Another aim of the program was to address the Accreditation Council for Graduate Medical Education (ACGME) Practice-Based Learning and Improvement competency. DESIGN: Educational program. RESULTS: Data on resident research activity for 11 years before the implementation of the research program were compared with 4 years of data after implementation. There were statistically significant increases in both the total number of publications (P = 0.03) and the number of empirical, data-based publications after implementation of the program (P = 0.03). CONCLUSIONS: The findings from this study suggest that a structured research training program may have a salutary effect on increasing the quality and quantity of resident research.     

The metNPQ operon of Bacillus subtilis encodes an ABC permease transporting methionine sulfoxide, D- and L-methionine

The Bacillus subtilis yusCBA operon, which encodes an ABC-type transporter, contains an S-box motif in its promoter region. We showed that the expression of these genes is repressed via the S-box system when methionine is available. The YusCB proteins are involved in the transport of both d- and l-methionine but also methionine sulfoxide. A yusCB mutant is unable to grow in the presence of 5 microM l-methionine or 100 microM methionine sulfoxide, while it grows similarly to the wild type with 100 microM l-methionine and 1 mM methionine sulfoxide. Other uptake systems are therefore present for these two compounds. In contrast, the Yus ABC transporter corresponds to the sole d-methionine uptake system. We propose to rename yusC, yusB and yusA as metN, metP and metQ, respectively.     

Evaluation of a diagnostic questionnaire for nasal polyposis: an observational, cross-sectional study

Nasal polyposis (NP) represents actually a matter of concern for most ear, nose and throat (ENT) specialists. In France, we lack data on NP prevalence due to the unavailability of a validated diagnostic questionnaire easily usable in population-based studies. The present study tested the sensitivity and specificity of an 11-item questionnaire for NP diagnosis from which an algorithm of diagnosis decision was inferred. Outpatients from 3 ENT departments were asked to complete the questionnaire prior to their visit. After the visit, the investigator had to write his final diagnosis (FD) on the envelope containing the questionnaire, without reading the patient's responses. Data from 406 patients showed a good specificity and sensitivity of most items. Awareness of NP, previous cortisone therapy for nasal pathology, and history of nasal surgery were shown to be the most discriminating items. An algorithm was elaborated by aggregation of the different items; its specificity and sensitivity were close to 90%. These diagnostic questionnaire and algorithm, although not substitutable to a clinical diagnosis, should be very useful for population-based studies.     

Lack of relationship between EGFR-1 immunohistochemical expression and prognosis in a multicentre clinical trial of 93 patients with advanced primary ovarian epithelial cancer (GINECO group)

Epidermal growth factor receptor 1 (EGFR-1) overexpression is usually described as linked with a worse prognosis in a variety of tumours of epithelial origin. However, its role in ovarian cancer is still controversial. The aim of the present study was to analyse the prognostic impact of EGFR-1 in a retrospective series of 93 stage III-IV primary ovarian epithelial tumours. All patients, enrolled in a multicentre GINECO prospective clinical trial, were treated with the same platinum-based combination chemotherapy, and were followed up with a median of 69 months. Epidermal growth factor receptor 1 plasma membrane expression, assessed by immunohistochemistry on paraffin-embedded tissues, was correlated with clinical parameters as well as immunohistochemical expression results of HER-2 (c-erbB-2), BAX, BCL-2, p53 and anti-Ki-67, previously studied in the same series of patients. Positive immunostaining for EGFR-1 was seen in 31 of the 93 analysed cases (33%). No correlation was found between EGFR-1 expression and clinical parameters. No correlation was found between EGFR-1 expression and other biological markers, except for HER-2, which was limit for significance. Indeed, among the EGFR-1-negative cases, 10.3% expressed HER-2, whereas the HER-2-expressing tumours accounted for 27.6% of EGFR-1-positive cases (P=0.06). Epidermal growth factor receptor 1 overexpression had no prognostic impact on both overall and progression-free survival through univariate and multivariate analyses. The potential effect of EGFR-1 and HER-2 co-expression on targeted therapy against EGFR-1 and/or HER-2 molecules has to be further analysed.