Publications

YB-1 is a member of the cold shock domain family, with complex roles in DNA structure, gene transcription and translation. YB-1 promotes chromosomal instability, and mammary gland transgenic expression induces tumors with 100% penetrance. YB-1 is linked to poor prognosis in breast carcinoma and is a strong predictor of relapse and disease-specific survival. Survival is directly tied to the extent of local invasion and distal metastasis, processes dependent upon the activity of the membrane type I-matrix metalloproteinase, MT1-MMP. Non-invasive MCF-7 breast adenocarcinoma cells were transfected with YB-1/EGFP. YB-1 protein was detected in the invadopodia of cells with a migratory phenotype. There was increased expression of MT1-MMP protein concentrated at the leading edges of motile cells, which were highly invasive in collagen three-dimensional culture. The rates of MT1-MMP protein endocytosis and recycling to the cell surface were elevated in clones expressing higher levels of YB-1 protein. Control MCF-7 cells formed nonfatal, non-invasive, differentiated adenocarcinomas in vivo. MCF-7 cells expressing a twofold increase in YB-1 formed highly anaplastic tumors with local invasion, pulmonary metastases and high lethality. We conclude that YB-1 contributes to the development of an invasive, metastatic breast carcinoma phenotype by enhanced presentation of MT1-MMP at the sites of cellular invasion.

BACKGROUND AND STUDY AIMS

Water immersion is an alternative colonoscopy technique that may reduce discomfort and facilitate insertion of the instrument. This was a prospective study to compare the success of colonoscopy with minimal sedation using water immersion and conventional air insufflation.

PATIENTS AND METHODS

A total of 229 patients were randomized to either water immersion or the standard air insertion technique. The primary outcome was success of minimal sedation colonoscopy, which was defined as reaching the cecum without additional sedation, exchange of the adult colonoscope or hands-on assistance for trainees. Patient comfort and satisfaction were also assessed.

RESULTS

Successful minimal-sedation colonoscopy was achieved in 51 % of the water immersion group compared with 28 % in the standard air group (OR, 2.66; 95 % CI 1.48 - 4.79; P = 0.0004). Attending physicians had 79 % success with water immersion compared with 47 % with air insufflation (OR, 4.19; 95 % CI 1.5 - 12.17; P = 0.002), whereas trainees had 34 % success with water compared with 16 % using air (OR, 2.75; 95 % CI 1.15 - 6.86; P = 0.01). Using the water method, endoscopists intubated the cecum faster and this was particularly notable for trainees (13.0 +/- 7.5 minutes with water vs. 20.5 +/- 13.9 minutes with air; P = 0.0001). Total procedure time was significantly shorter with water for both experienced and trainee endoscopists ( P < 0.05). Patients reported less intraprocedural pain with water compared with air (4.1 +/- 2.7 vs. 5.3 +/- 2.7; P = 0.001), with a similar level of satisfaction. There was no difference in the neoplasm detection rates between the groups.

CONCLUSION

Colonoscopy insertion using water immersion increases the success rate of minimal sedation colonoscopy. Use of the technique leads to a decrease in discomfort, time to reach the cecum, and the amount of sedative and analgesic used, without compromising patient satisfaction.