Important clinical descriptors to include in the examination and assessment of patients with femoroacetabular impingement syndrome: an international and multi-disciplinary Delphi survey.

PURPOSE: Determine which examination findings are key clinical descriptors of femoroacetabular impingement syndrome (FAIS) through use of an international, multi-disciplinary expert panel. METHODS: A three-round Delphi survey utilizing an international, multi-disciplinary expert panel operationally defined from international publications and presentations was utilized. RESULTS: All six domains (subjective examination, patient-reported outcome measures, physical examination, special tests, physical performance measures, and diagnostic imaging) had at least one descriptor with 75% consensus agreement for diagnosis and assessment of FAIS. Diagnostic imaging was the domain with the highest level of agreement. Domains such as patient-reported outcome measures (PRO's) and physical examination were identified as non-diagnostic measures (rather as assessments of disease impact). CONCLUSION: Although it also had the greatest level of variability in description of examination domains, diagnostic imaging continues to be the preeminent diagnostic measure for FAIS. No single domain should be utilized as the sole diagnostic or assessment parameter for FAIS. While not all investigated domains provide diagnostic capability for FAIS, those that do not are able to serve purpose as a measure of disease impact (e.g., impairments and activity limitations). The clinical relevance of this Delphi survey is the understanding that a comprehensive assessment measuring both diagnostic capability and disease impact most accurately reflects the patient with FAIS. LEVEL OF EVIDENCE: V.

Phosphorylation of the mutant K303R estrogen receptor alpha at serine 305 affects aromatase inhibitor sensitivity.

We earlier identified a lysine to arginine transition at residue 303 (K303R) in estrogen receptor alpha (ERalpha) in invasive breast cancers, which confers resistance to the aromatase inhibitor (AI) anastrozole (Ana) when expressed in MCF-7 breast cancer cells. Here, we show that AI resistance arises through an enhanced cross talk of the insulin-like growth factor receptor-1 (IGF-1R)/insulin receptor substrate (IRS)-1/Akt pathway with ERalpha, and the serine (S) residue 305 adjacent to the K303R mutation has a key function in mediating this cross talk. The ERalpha S305 residue is an important site that modifies response to tamoxifen; thus, we questioned whether this site could also influence AI response. We generated stable transfectants-expressing wild-type, K303R ERalpha or a double K303R/S305A mutant receptor, and found that the AI-resistant phenotype associated with expression of the K303R mutation was dependent on activation of S305 within the receptor. Ana significantly reduced growth in K303R/S305A-expressing cells. Preventing S305 phosphorylation with a blocking peptide inhibited IGF-1R/IRS-1/Akt activation and also restored AI sensitivity. Our data suggest that the K303R mutation and the S305 ERalpha residue may be a novel determinant of AI response in breast cancer, and blockade of S305 phosphorylation represents a new therapeutic strategy for treating tumors resistant to hormone therapy.

Surgical experience with carcinoma of the colon and rectum.

From September 1925 through December 1978 at Vanderbilt University Hospital, 1,279 patients with adenocarcinoma of the colon and rectum underwent operations. Reports of this cumulative series have been published previously; the last report in 1970 included 1,022 patients. The current report examines the progress made in our recognition and management of colorectal cancer. During this 54-year period, there has been a relative decrease in the incidence of carcinoma of the rectum and a relative increase in carcinomas elsewhere in large bowel. Resectability rate has steadily increased, culminating in a rate of 98.4% in the recent period (1969-1978). The operative mortality rate fell to 4.3% (1956-1960) but has shown a slight rise to 5.4% in the recent period (1969-1978). This reflects the increased number of patients in the eighth to the tenth decades of life. Five-year survival rates in 99% of 1,218 patients were computed. Absolute five-year survival for the recent period was 43.7%, compared with 17% for the initial period. Five-year survival rates for patients in the recent decade with Dukes A, B, and C lesions were 67%, 58.6%, and 33.3%, respectively. Comparison of survival data in the last two decades shows little improvement. However, in the last 20 years, 78 to 80% of patients had more advanced lesions.