Patient preferences and predicted relative uptake for targeted therapies in metastatic colorectal cancer: a discrete choice experiment

Abstract

Objective

Ras wild-type metastatic colorectal cancers (mCRC) may be treated with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) agents. We aim to estimate patients’ preferences for mCRC treatment and relative importance of cost, efficacy improvement, avoidance of side effects and therapy convenience, and relative uptake between profiles that resemble Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), two commonly prescribed mCRC targeted therapies.     

A guide to upwardly mobile spermatozoa

Morphological comparison of sperm in raw ejaculates and swim-ups showed that the swim-up process does not simply increase the proportion of 'normal' sperm. Rather, sperm of specific morphologies have characteristic grades of upward motility.     

Management of hip dislocations in children with arthrogryposis

From a review of 131 children with arthrogryposis, we studied 18 patients with hip dislocations. Fourteen patients (10 unilateral, four bilateral) were treated by open reduction. Mean age at surgery was 9.7 months, and follow-up ranged from 9 to 245 months. Range of motion of patients treated by open reduction following the medial approach was greater than in those treated by anterolateral incision and greater than in bilateral cases treated by closed reduction. Acetabular development was satisfactory following the medial approach and there were no re-dislocations, but one hip developed avascular necrosis.     

Investigation and treatment of female urinary incontinence

There are four main types of urinary incontinence in the female namely stress incontinence, urge incontinence, overflow incontinence due to retention of urine and total incontinence. It is important to differentiate them to institute proper treatment. It is the aim of this paper to present a simple clinical evaluation of an incontinent woman. The different methods of surgical correction of stress incontinence are discussed. The latest trend is the paraurethral suspension of the bladder neck. 39 cases of Grade II stress incontinence were treated by paraurethral suspension of the bladder neck at "A" Unit, Kandang Kerbau Hospital and Dept. of Urology, SGH. 33 cases were cured. 4 improved with occasional stress incontinence, frequency and urgency. Of these, 3 were cured with imipramine. One failed because of a fixed, "lead pipe" rigid urethra from previous multiple operations to the bladder neck.     

Detection of diacetyl (caramel odor) in presumptive identification of the "Streptococcus milleri" group.

The caramel odor associated with the "Streptococcus milleri" group was shown to be attributable to the formation of the metabolite diacetyl. Levels of diacetyl in the 22- to 200-mg/liter range were produced by 68 strains of the "S. milleri" group; apart from one strain of Streptococcus mutans, all 92 other strains of streptococci belonging to 12 species produced < 13 mg of diacetyl per liter. Quantitation of diacetyl levels from cultures of streptococci is suggested as a rapid presumptive test for the "S. milleri" group.     

Expression of interleukin-18 by nasopharyngeal carcinoma cells: a factor that possibly initiates the massive leukocyte infiltration

Interleukin-18 (IL-18) is a single-chain cytokine that is produced by various cells. With interleukin-12 (IL-12), it synergistically stimulates activated T cells and natural killer (NK) cells to produce interferon-gamma (IFN-gamma). Nasopharyngeal carcinoma (NPC) is the most common form of nasal and nasopharyngeal malignancy, and in NPC tumor tissues there is an intense leukocyte infiltration comprising predominantly T cells and macrophages. We previously showed an increased expression of IFN-gamma in the infiltrating T cells. To identify the cells that provide IL-12 and IL-18 for stimulating the expression of IFN-gamma in activated T cells, NPC cell lines CNE-2 and HK-1, as well as biopsies obtained from NPC and control individuals, were examined. CNE-2 and HK-1 cells were found to express messenger RNA encoding IL-18, but not IL-12. Secreted IL-18 was detected in the culture supernatant. Addition of a caspase-1 inhibitor decreased the secretion level, indicating that this IL-18 secretion was caspase-1 dependent. Moreover, the in vitro IL-18 production in NPC cell lines correlated with the NPC tumor cells in situ. NPC tumor cells in the biopsies produced IL-18, as detected by immunohistochemistry and immunofluorescent double staining. In contrast, IL-18 expression was not observed in the control biopsies. We suggest that IL-18 secreted by NPC tumor cells plays a role in initiating the leukocyte infiltration process. IL-18 stimulates T cells and NK cells to produce IFN-gamma, which consequently activates macrophages and other immune cells to secrete chemokines to start a leukocyte recruitment cascade.