Can EGFR mutation status be reliably determined in pre‐operative needle biopsies from adenocarcinomas of the lung?

The identification of EGFR mutations in non‐small‐cell lung cancer is important for selecting patients, who may benefit from treatment with EGFR tyrosine kinase inhibitors. The analysis is usually performed on cytological aspirates and/or histological needle biopsies, representing a small fraction of the tumour volume. The aim of the present investigation was to evaluate the diagnostic performance of this molecular test. We retrospectively included 201 patients with primary adenocarcinoma of the lung. EGFR mutation status (exon 19 deletions and exon 21 L858R point mutation) was evaluated on both pre‐operative biopsies (131 histological and 70 cytological) and on the surgical specimens, using PCR. Samples with low tumour cell fraction were assigned to laser micro‐dissection (LMD). We found nine (4.5%) patients with EGFR mutation in the lung tumour resections, but failed to identify mutation in one of the corresponding pre‐operative, cytological specimens. Several (18.4%) analyses of the pre‐operative biopsies were inconclusive, especially in case of biopsies undergoing LMD and regarding exon 21 analysis. Discrepancy of mutation status in one patient may reflect intra‐tumoural heterogeneity or technical issues. Moreover, several inconclusive results in the diagnostic biopsies reveal that attention must be paid on the suitability of pre‐operative biopsies for EGFR mutation analysis.     

A reverse-flow composite flap in the rat.

Reverse-flow flaps are currently particularly used for the reconstruction of defects of the distal part of the extremities. Despite their common usage there have been many reports of postoperative complications, especially resulting in partial or total flap necrosis. There is insufficient knowledge of flap haemodynamics, physiology and wound healing properties in reverse-flow flaps. Development of the proper experimental models is needed to investigate these issues. The purpose of this study was to describe a new reverse-flow flap model in the rat. A total of 20 adult Wistar rats weighing 200-250 g were used in this experiment. In five rats, the vascular anatomy of the auricle of the rat was determined by anatomic dissection and microangiography. In the experimental group (N=5), 1x1 cm reverse-flow composite flaps were harvested as a semi-island shape, based on the distal course of the medial branch of the anterior auricular artery. In the control group, consisting of five rats, the flap was designed and raised based on the proximal course of the medial auricular artery, again in a semi-island shape. In the remaining five animals, a square-shaped composite tissue of the whole layer of the auricle, 1x1 cm in size, was harvested dividing all the bases circumferentially. The composite tissue was replaced in situ. While the former was considered a conventional antegrade-flow flap subgroup, the latter was designated as a graft subgroup. All flaps were replaced in situ. The survival of the flap was evaluated on postoperative day 7 by direct observation and microangiography. The skin island of all the reverse-flow flaps and conventional antegrade-flow flaps survived completely giving a success rate of 100%, whereas all grafts in the control group underwent complete necrosis. Microangiographic studies revealed the vascularity of the reverse-flow and antegrade-flow flaps, identifying the course of the auricular arteries. In conclusion, with its evident advantages of easy to design and harvesting, reliable survival pattern and consistent vascular structure, our new flap model will provide a means for future studies on flap haemodynamics, physiology in reverse-flow flaps.     

A leg ulcer as manifestation of metastatic squamous cell vaginal carcinoma

Cutaneous metastasis of vaginal carcinoma is extremely rare. So far, the total number of reported skin metastasis of vaginal carcinoma is only one. We present another case with an unusual manifestation of vagina carcinoma metastasis: skin metastasis presenting as a leg ulcer on the lower leg.     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.