Experiences from treatment-predictive KRAS testing; high mutation frequency in rectal cancers from females and concurrent mutations in the same tumor

Background  

KRAS mutations represent key alterations in colorectal cancer development and lead to constitutive EGFR signaling. Since EGFR inhibition represents a therapeutic strategy in advanced colorectal cancer, KRAS mutation analysis has quickly been introduced as a treatment-predictive test.     

Strenuous exercise increases late outgrowth endothelial cells in healthy subjects

Endothelial progenitor cells (EPCs) and late outgrowth endothelial cells (OECs) seem to play an important role in vessel formation. While EPCs seem to exert their function mainly through a paracrine effect, the OECs can develop into mature endothelial cells and form tubular structures. Exercise is known to increase angiogenic factors that can mobilize EPCs; however, the effect on OECs is not known. We investigated the response to a single session of strenuous exercise on OECs, vascular endothelial growth factor (VEGF) and inflammatory cell levels in the healthy. Eleven healthy subjects performed 1 h of spinning exercise. Blood samples were collected at 1, 6, 24 and 48 h post-exercise for cell culture and biochemical analysis. OEC colonies doubled one hour after the spinning session (baseline 4.5 ± 4.3 vs. 9.0 ± 3.7, P < 0.05). Serum VEGF increased from 194 ± 107 pg/ml at baseline to 224 ± 111 pg/ml after 1 h, p = ns and neutrophilic granulocytes increased from 3.73 ± 1.38 at baseline to 9.08 ± 10.5 at 1 h (P < 0.01). The increased levels of OECs, VEGF and neutrophilic granulocytes declined gradually at the following time points. VEGF levels and neutrophilic granulocytes were highly correlated to OEC levels, r = 0.903 (VEGF) and r = 0.85 (neutrophilic granulocytes), respectively. Strenuous physical activity increases OEC colonies and is correlated to serum VEGF and neutrophilic granulocytes levels. An acute exercise-induced inflammatory response might be responsible for the VEGF release and subsequent increase of OECs. The clinical importance of these findings remains to be elucidated.     

Persisting Dysphagia After Uvulopalatoplasty Performed With Steel Scalpel

Objectives/Hypothesis: The aim of the present study was to determine the incidence of postoperative persisting dysphagia after uvulopalatoplasty performed with conventional steel scalpel (UPP) and to videoradiographically evaluate the oral and pharyngeal phases of swallowing in patients reporting persisting dysphagia. The hypothesis to be tested was that patients treated with UPP would demonstrate a lower incidence of persisting dysphagia than previously found after uvulopalatoplasty performed with laser technique (LUPP). Study Design: Retrospective. Methods: Sixty-eight of 76 consecutive patients treated with UPP answered a questionnaire concerning outcome and late complications after the operation. The patients who reported postoperative dysphagia were additionally interviewed at a minimum of 1 year postoperatively, and the oral and pharyngeal phases of swallowing were videoradiographically examined in those with persisting dysphagia. Results: The incidence of persisting dysphagia after UPP was 29%. Videoradiographically 71% of the dysphagic patients showed a deviant pharyngeal swallowing pattern. Conclusion: The incidence of persisting dysphagia after UPP did not differ from that reported after laser uvulopalatoplasty. Dysphagia after UPP was mostly associated with videoradiographic signs of deviant pharyngeal swallowing function. Patients should be informed that there is a risk of developing dysphagia after uvulopalatoplasty.     

Parity and risk of thyroid cancer: a nested case-control study of a nationwide Swedish cohort

The association between parity and risk of thyroid cancer was examined in a case-control study nested within a cohort of Swedish women born 1925–60. A total of 1,409 cases of thyroid cancer were compared with 7,019 agematched controls. Odds ratios (OR) and 95 percent confidence intervals (CI) were calculated as estimates of relative risk. A weak association was found between parity and risk of thyroid cancer (OR for ever-parous women cf nulliparous was 1.1, CI=1.0–1.3). For the subset of papillary cancers, there was a significantly increased risk (OR for ever-parous cf nulliparous = 1.3, CI=1.0–1.6), and among women diagnosed at the age of 50 or older, there was a positive linear trend with increasing number of livebirths. Women during the first year after a livebirth had an increased risk of thyroid cancer compared with women who delivered 10 or more years before; this association was most prominent among uniparous women (OR=2.5, CI=1.1–5.9). An increased risk was also apparent for age over 20 years at livebirth (among uniparous women) and age over 25 years at last livebirth (among multiparous women). A negligible effect of parity on thyroid cancer risk was seen, but each livebirth may have a short-term and age-dependent promoting effect.Authors are with the Department of Cancer Epidemiology, University Hospital, Uppsala, Sweden (M.R. Galanti, M. Lambe, A. Ebbora, R. Sparda B. Pettersson): Department of Social Medicine, University Hospital, Uppsala, Sweden (M. Lambe); Department of Epidemiology, Harvard School of Public Health, Boston, USA (A. Ekbom). Address correspondence to Dr M. Rosaria Galanti, Department of Cancer Epidemiology, University Hospital, S-751 85 Uppsala, Sweden. This work was supported in part by grant n. 3136-B92-02XBB from the Swedish Cancer Society.     

Quantification of lymphocytes propagating from rat-kidney allografts--a tool to monitor anti-rejection treatment

BACKGROUND: Morphological evaluation of kidney biopsies applying the Banff Classification is closely correlated to clinical parameters of rejection. However, this classification is insufficient for monitoring the effect of instituted anti-rejection therapy. The objective of the present study was to develop a diagnostic tool enabling rapid assessment of the effects of an attempted anti-rejection treatment. MATERIALS AND METHODS: A kidney allotransplantation model in the rat was applied. All animals were initially maintained on cyclosporine A (CsA). In order to induce an episode of acute cellular rejection, CsA was withdrawn for 5 days. Thereafter, the immunosuppressive treatment was restarted. Core biopsies were taken before, and at various times after, the introduction of anti-rejection therapy. Infiltrating cells were isolated using an in vitro culture system, allowing cells to propagate from the biopsies to culture medium. Propagated cells were counted and analysed for subtype and activation markers using flow cytometry. The results were compared with immunohistochemical and morphological analyses of the grafts. RESULTS: By applying the in vitro culture system it was possible to demonstrate a reduction in outgrowth of mononuclear cells from core biopsies as early as 2 days after the start of anti-rejection therapy. At this time-point, as well as 2 days later, morphological and immunohistochemical analyses of biopsies showed ongoing acute cellular rejection, with no differences between biopsies taken before and after restart of CsA-therapy. The percentage of propagating T lymphocytes expressing the activation markers CD25 or MHC class II did not differ between grafts with ongoing rejection and grafts obtained from CsA-treated rats, neither did the ratio of CD4/CD8-positive cells. CONCLUSION: Our findings indicate that the ex vivo propagation method could function as a complement to routine histology, not only in the diagnosis of cellular rejection but also in order to rapidly reveal a failure of an anti-rejection therapy to halt the rejection process.