Split-dose sodium picosulfate-magnesium citrate colonoscopy preparation achieves lower residual gastric volume with higher cleansing effectiveness than a previous-day regimen.

BACKGROUND AND AIMS: It is known that sodium picosulfate-magnesium citrate (SPMC) bowel preparations are effective, well tolerated and safe, and that split-dosing is more effective for colon cleansing than previous-day regimens. Anesthetic guidelines consider that residual gastric fluid is independent of clear liquid fasting times. However, reluctance to use split-dosing persists. This may be due to limited data on residual gastric fluid volumes (RGFVs) and split-dosing bowel preparations, and that these may not be perceived as standard clear liquids. Furthermore, no studies are available on RGFV/residual gastric fluid pH (RGFpH) and SPMC. We aimed to evaluate the cleansing effectiveness and the RGFV/RGFpH achieved after an SPMC split-dosing regimen compared with a SPMC previous-day regimen. METHODS: This was a single-center observational study. A total of 328 outpatients scheduled for simultaneous EGD and colonoscopy and following a split-dosing or previous-day regimen of SPMC were included. We prospectively measured colon cleanliness by using the Ottawa Bowel Preparation Scale, RGFV, and RGFpH. RESULTS: Ottawa Bowel Preparation Scale scores for overall, right, mid-colon, and colon fluid were significantly better in the split-dosing group. In the split-dosing group, the 3- to 4-hour fasting time consistently achieved the best cleansing quality. RGFV was significantly lower in the split-dosing group (11.09 vs 18.62, P < .001). No significant differences in RGFpH were detected. CONCLUSIONS: Split-dosing SPMC provides higher colon cleansing quality with lower RGFVs than previous-day SPMC regimens. SPMC in split-dosing acts exactly as a standard clear liquid acts, and thus anesthetic guidelines on this issue may be applied with no concerns.

Epithelial to mesenchymal transition is impaired in colon cancer cells with microsatellite instability.

BACKGROUND & AIMS: Colorectal cancers (CRCs) displaying DNA microsatellite instability (MSI) are associated with a favorable natural history, but the molecular basis for this observation has not been defined. We sought to determine whether the epithelial to mesenchymal transition (EMT) is impaired in MSI-positive CRCs that characteristically have a mutant transforming growth factor-beta receptor type II (TGFBR2) gene. METHODS: The induction of EMT by transforming growth factor-beta1 (TGF-beta1) was analyzed by phase contrast microscopy, immunofluorescence, quantitative reverse transcription polymerase chain reaction, immunoblotting, and cellular migration, and invasion assays. Expression of EMT markers was evaluated by immunohistochemistry and quantitative reverse transcription polymerase chain reaction in a series of human colorectal tumors. RESULTS: TGF-beta1 induced changes in cellular morphology, gene expression, motility, and invasion consistent with EMT in microsatellite stable (MSS) colon cancer cells, whereas cells with MSI and mutant TGFBR2 were unresponsive to TGF-beta1. These effects did not require Smad4, but depended on the recruitment of extracellular signal-regulated kinase. Tumor cells with MSI but wild-type TGFBR2 underwent EMT in response to TGF-beta1, indicating that TGFBR2 genotype is a key determinant of the EMT response in tumors with MSI. In human colorectal tumors, expression of EMT markers was significantly associated with adverse clinicopathologic features and the absence of MSI. CONCLUSIONS: These findings define a unique genotype-phenotype relationship between TGFBR2 and EMT that may contribute to the improved prognosis consistently observed in colon cancers with MSI.

HIF-1alpha and HIF-2alpha have divergent roles in colon cancer.

Hypoxia-inducible factor (HIF)-1 and HIF-2 are heterodimeric transcription factors that mediate the cellular response to hypoxia. Their key regulatory subunits, HIF-1alpha and HIF-2alpha, are induced similarly by hypoxia, but their functional roles in cancer may be distinct and isoform-specific. SW480 colon cancer cells with stable expression of siRNA to HIF-1alpha or HIF-2alpha or both were established. HIF-1alpha-deficient cells displayed lower rates of proliferation and migration, but HIF-2alpha-deficient cells exhibited enhanced anchorage independent growth in a soft agar assay. Xenograft studies revealed that HIF-1alpha deficiency inhibited overall tumor growth, whereas deficiency of HIF-2alpha stimulated tumor growth. In human colon cancer tissues, expression of HIF-1alpha and to a lesser extent, HIF-2alpha, was linked to upregulation of VEGF and tumor angiogenesis. However, loss of expression of HIF-2alpha but not HIF-1alpha was strongly correlated with advanced tumor stage. DNA microarray analysis identified distinct sets of HIF-1alpha and HIF-2alpha target genes that may explain these phenotypic differences. Collectively, these findings suggest that HIF isoforms may have differing cellular functions in colon cancer. In particular, HIF-1alpha promoted the growth of SW480 colon cancer cells but HIF-2alpha appeared to restrain growth. Consequently, therapeutic approaches that target HIF may need to consider these isoform-specific properties.