A practical approach to manage additional lesions at preoperative breast MRI in patients eligible for breast conserving therapy: results

The aim of this prospective study was to evaluate the efficacy of directives, established to handle additional lesions at preoperative contrast-enhanced magnetic resonance imaging (MRI). Six-hundred-and-ninety consecutive patients with pathology-proven breast cancer planned for BCT based on clinical examination and conventional imaging underwent preoperative breast MRI. The incidence of additional lesions detected at MRI and impact on management were evaluated. Additional findings were pathology-proven or considered benign by follow-up. Findings for which no pathology proof was available prior to surgery, were defined as Unidentified Breast Objects (UBOs). Patients with multicentric or contralateral UBOs underwent BCT as planned with annual follow-up. Multifocal UBOs in the vicinity of the index cancer were excised with wider local margins. Preoperative MRI detected 141 additional lesions in 121 patients (17.5%). Of these lesions, 44.0% were proven malignant. Additional findings classified as UBOs were found in 81 patients (11.7%). None of the UBOs outside the primary tumour region resulted in malignant disease at follow-up after BCT (mean follow-up time: 57.1 months). However, most multifocal UBOs (in the vicinity of the primary) were malignant (77.5%). The strategy to pursue BCT with larger wide-local excisions for multifocal UBOs and to follow-up multicentric and contralateral UBOs with conventional imaging is effective to exclude malignancy at follow-up. After second-look targeted ultrasound has been performed, MRI-guided biopsy of BIRADS-3 multicentric and contralateral additional findings may have limited complementary clinical value.     

46,XX, inv(6)(p21.1p23) in a pedigree with hereditary haemochromatosis.

Hereditary haemochromatosis (HFE) is a recessive genetic disease of iron overload which has been shown by linkage analysis to reside on the short arm of chromosome 6, close to the major histocompatibility complex (MHC). Positional cloning of the putative HFE locus has been hampered, in part, by the lack of a structural alteration on 6p. In this report, we describe a pedigree with HFE which carries a balanced paracentric inversion of chromosome 6, inv(6)(p21.1p23), a rarely reported chromosomal rearrangement in this region. We have determined the inheritance of the chromosome harbouring the inversion, which segregates as an HFE chromosome. Because the HFE locus has been mapped distal to the HLA-F class I locus at 6p21.3, the breakpoints associated with this chromosomal rearrangement may provide a significant genomic landmark for positional cloning of the HFE gene.     

The canine bilateral groove model of osteoarthritis

In studies aimed at local treatment of experimental osteoarthritis (OA) it is optimal to have an internal (untreated) OA control. Such an approach excludes interanimal variation, and allows paired statistical evaluation of treatment efficacy. For this purpose, we developed and characterized a bilateral version of the canine Groove model. We hypothesized that the bilateral version of the canine Groove model would show consistent and clear development of features of OA similar to those found in the unilateral version. In six Beagle dogs, grooves were surgically made in the articular cartilage of the femoral condyles of both knee joints. Six additional dogs underwent bilateral sham surgery. The degree of OA was quantified 20 weeks after surgery and was compared in retrospect to 23 animals that undergone the same procedure in a single knee joint with the contralateral knee serving as a non‐OA control. Bilateral groove surgery resulted in OA. This was based on the observed ineffective repair response in which an increase in proteoglycan synthesis, a diminished retention of these newly formed proteoglycans, and an enhanced loss of resident proteoglycans resulted in a decreased cartilage proteoglycan content. These biochemical effects were corroborated by clear histological features of OA. All these effects were found in femor as well as in the (surgically untouched) tibia. Interestingly, features of OA were slightly more severe in the bilateral model than in the unilateral variant. The bilateral canine Groove model showed consistent and clear development of features of OA, comparable to the unilateral model. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1471–1477, 2008     

HER-family gene amplification and expression in resected pancreatic cancer

Aims

Despite surgical resection, pancreatic cancer carries a poor prognosis. In search for new molecular therapeutic targets, we investigated the expression of the HER-family and gene amplification of HER-2 in pancreatic adenocarcinomas of different stages.

Methods

Tissue of 45 resected patients was analyzed for all HER-family 1-4 expression by immunohistochemistry and HER-2 gene amplification was assessed by multiplex ligation-dependent probe amplification and chromogenic in situ hybridization. The type of surgery, location, stage and grade of the tumor, as well as involvement of the resection margins were correlated with HER-expressions and univariate and multivariate survival analysis performed.

Results

Normal pancreatic tissue lacked HER1-2 expression, but did show HER3-4 expression. In cancers, no membranous overexpression of HER-1 and HER-2 was seen nor gene amplification of HER-2 found. HER-3, HER-4 is physiologically expressed in the normal pancreas and loss of cytoplasmic HER-3 and HER-4 expression was seen in 33/45 (73%) and 8/45 (18%) of pancreatic cancers. Cytoplasmic HER-3 expression decreased from early to late stage (p = 0.05). HER-4 expression was not associated with survival, stage or tumor grade. There were no statistically significant differences in HER1-4 expression between the papilla of Vater (n = 13) and non-papilla cancers (n = 32). Multivariate survival analysis showed only stage to be of independent prognostic value (p = 0.015).

Conclusions

HER-1 and HER-2 are not overexpressed in pancreatic cancers. HER-3 and HER-4 are expressed in the normal pancreas but expression is lost in pancreatic cancer. HER-targeted therapy in pancreatic cancer is not supported by HER-expression of the tumor.