The effect of Oncotype DX recurrence score on treatment recommendations for patients with estrogen receptor-positive early stage breast cancer and correlation with estimation of recurrence risk by breast cancer specialists

Purpose.

The Oncotype DX assay predicts likelihood of distant recurrence and improves patient selection for adjuvant chemotherapy in estrogen receptor–positive (ER-positive) early stage breast cancer. This study has two primary endpoints: to evaluate the impact of Oncotype DX recurrence scores (RS) on chemotherapy recommendations and to compare the estimated recurrence risk predicted by breast oncology specialists to RS.

Methods.

One hundred fifty-four patients with ER-positive early stage breast cancer and available RS results were selected. Clinicopathologic data were provided to four surgeons, four medical oncologists, and four pathologists. Participants were asked to estimate recurrence risk category and offer their chemotherapy recommendations initially without and later with knowledge of RS results. The three most important clinicopathologic features guiding their recommendations were requested.

Results.

Ninety-five (61.7%), 45 (29.2%), and 14 (9.1%) tumors were low, intermediate, and high risk by RS, respectively. RS significantly correlated with tumor grade, mitotic activity, lymphovascular invasion, hormone receptor, and HER2/neu status. Estimated recurrence risk by participants agreed with RS in 54.2% ± 2.3% of cases. Without and with knowledge of RS, 82.3% ± 1.3% and 69.0% ± 6.9% of patients may be overtreated, respectively (p = 0.0322). Inclusion of RS data resulted in a 24.9% change in treatment recommendations. There was no significant difference in recommendations between groups of participants.

Conclusions.

Breast oncology specialists tended to overestimate the risk of tumor recurrence compared with RS. RS provides useful information that improves patient selection for chemotherapy and changes treatment recommendations in approximately 25% of cases.     

Change in stated clinical practice associated with participation in the Dental Practice-Based Research Network

Clinical researchers have attempted many methods to translate scientific evidence into routine clinical practice, with varying success. Practice-based research networks (PBRNs) provide an important, practitioner-friendly venue to test these methods. Dentist practitioner-investigators from the Dental Practice-Based Research Network (DPBRN) completed a detailed questionnaire about how they diagnose and treat dental caries. Next, they received a customized report that compared their answers to those from all other practitioner-investigators. Then, 126 of them attended the DPBRN's first network-wide meeting of practitioner-investigators from all five of its regions. During that meeting, certain questions were repeated and new ones were asked about the dentist's intention to change the way that he or she diagnosed or treated dental caries. Less than one-third of practitioner-investigators intended to change how they diagnosed or treated caries as a result of receiving the customized report. However, as a result of the meeting, the majority of these same practitioner-investigators stated an intention to change toward a more conservative, less surgically invasive approach. These findings are consistent with the idea that a highly interactive meeting with fellow practitioner-investigators may be an effective means to translate scientific findings into clinical practice. Practitioner-investigators are open to changing how they treat patients as a result of engaging fellow practitioner-investigators in the scientific process.     

Could alkali production be considered an approach for caries control?

This study investigated the relationship of arginine deiminase (ADS) and urease activities with dental caries through a case-control study. ADS and urease activities were measured in dental smooth-surface supragingival plaque and whole saliva samples from 93 subjects, who were in three different groups: caries-free (n = 31), caries-active (n = 30), and caries-experienced (n = 32). ADS activity was measured by quantification of the ammonia generated from the incubation of plaque and saliva samples in a mixture containing 50 mM arginine-HCl and 50 mM Tris-maleate buffer, pH 6.0. ADS-specific activity was defined as nanomoles of ammonia generated per minute per milligram of protein. Urease activity was determined by quantification of ammonia produced from 50 mM urea. For bacterial identification and enumeration real-time qPCR analysis was used. Groups were compared using Kruskal-Wallis tests. Spearman correlations were used to analyze plaque metabolic activity and bacterial relationships. The results revealed significantly higher ammonia production from arginine in saliva (1.06 vs. 0.18; p < 0.0001) and plaque samples (1.74 vs. 0.58; p < 0.0001) from caries-free subjects compared to caries-active subjects. Urease levels were about 3-fold higher in the plaque of caries-free subjects (p < 0.0001). Although higher urease activity in saliva of caries-experienced and caries-free subjects was evident, no significant difference was found between the groups.     

Change in transferrin sialylation is a potential prognostic marker for severity of acute pancreatitis

ObjectivesEarly prediction of severe acute pancreatitis is one of the problems in clinical practice. Since many diseases are associated with alteration in glycosylation, in this work we studied sialylation of transferrin and serum proteins in acute pancreatitis.Design and methodsSialylation was analyzed during first eight days of hospitalization of 30 patients and compared to 28 healthy controls. Transferrin sialylation was measured using enzyme linked lectin assay, while sialic acid on proteins was measured using resorcinol method.ResultsBoth analyzed parameters changed during studied period. The change in transferrin sialylation between Day1 and Day2 of hospitalization was shown to be an early prognostic marker of acute pancreatitis, with better sensitivity (88.9%) and specificity (90.5%) than other markers tested.ConclusionsSialylation of transferrin and total serum proteins reflects the intensity of inflammatory response during acute pancreatitis and could be used as prognostic parameter for disease severity.     

Clinico-histopathological correlations of venous wall modifications in chronic venous insufficiency

The interest manifested for the conjunctive tissue pathology leaded to the study of the structural disorder that appears in the varicose veins walls. The study is a prospective one initiated in March 2007 made on 11 patients with varicose disease hospitalized at Cluj-Napoca within Surgery Clinic no. II. The purpose of this study is to point out the histopathological modifications in the varicose venous wall (great saphenous vein cross, communicating veins, perforating veins), as well as the correlation of histopathological results with the evolutive stage of chronic vein insufficiency (CEAP classification) and with the clinical score at these patients. The histopathological (HP) results for 2 of the patients revealed hypertrophy of the media, intimal hyperplasia (stage II) corresponding to a CEAP 3. Six patients were integrated in HP stage III due to the partial intimal fibrosis corresponding to a CEAP 6 for one case, CEAP 4 one case, CEAP 3 four cases. One patient had HP stage I with CEAP 3 and two patients had HP stage IV corresponding to CEAP 5, respectively CEAP 6.     

DNA immunization circumvents deficient induction of T helper type 1 and cytotoxic T lymphocyte responses in neonates and during early life

The relative deficiency of T helper type 1 (Th1) and cytotoxic T lymphocyte (CTL) responses in early life is associated with an increased susceptibility to infections by intracellular microorganisms. This is likely to reflect a preferential polarization of immature CD4 T cells toward a Th2 rather than a Th1 pattern upon immunization with conventional vaccines. In this report, it is shown that a single immunization within the first week of life with DNA plasmids encoding viral (measles virus hemagglutinin, Sendai virus nucleoprotein) or bacterial (C fragment of tetanus toxin) vaccine antigens can induce adult-like Th1 or mixed Th1/Th2 responses indicated by production of IgG2a vaccine-specific antibodies and preferential secretion of interferon-γ (IFN-γ) compared with interleukin (IL)-5 by antigen-specific T cells, as well as significant CTL responses. However, in spite of this potent Th1-driving capacity, subsequent DNA immunization was not capable of reverting the Th2-biased responses induced after early priming with a recombinant measles canarypox vector. Thus, DNA vaccination represents a novel strategy capable of inducing Th1 or mixed Th1/Th2 and CTL responses in neonates and early life, providing it is performed prior to exposure to Th2-driving conventional vaccine antigens.