Knockdown of CSE1L Gene in Colorectal Cancer Reduces Tumorigenesis in Vitro.

Human cellular apoptosis susceptibility (chromosomal segregation 1-like, CSE1L) gene plays a role in nuclear-to-cytoplasm transport and chromosome segregation during mitosis, cellular proliferation, and apoptosis. CSE1L is involved in colon carcinogenesis. CSE1L gene expression was assessed with three data sets using Affymetrix U133 + gene chips on normal human colonic mucosa (NR), adenomas (ADs), and colorectal carcinoma (CRC). CSE1L protein expression in CRC, AD, and NR from the same patients was measured by immunohistochemistry using a tissue microarray. We evaluated CSE1L expression in CRC cells (HCT116, SW480, and HT29) and its biological functions. CSE1L mRNA was significantly increased in all AD and CRC compared with NR (P < 0.001 and P = 0.02, respectivly). We observed a change in CSE1L staining intensity and cellular localization by immunohistochemistry. CSE1L was significantly increased during the transition from AD to CRC when compared with NR in a CRC tissue microarray (P = 0.01 and P < 0.001). HCT116, SW480, and HT29 cells also expressed CSE1L protein. CSE1L knockdown by shRNA inhibited protein, resulting in decreased cell proliferation, reduced colony formation in soft agar, and induction of apoptosis. CSE1L protein is expressed early and across all stages of CRC development. shRNA knockdown of CSE1L was associated with inhibition of tumorigenesis in CRC cells. CSE1L may represent a potential target for treatment of CRC.

Advances in the Endoscopic Diagnosis of Barrett Esophagus.

BACKGROUND: Barrett esophagus (BE) continues to be a major risk factor for developing esophageal adenocarcinoma. METHODS: We review the risk factors, diagnosis, and management of BE, with an emphasis on the most current endoscopic diagnostic modalities for BE. RESULTS: Novel diagnostic modalities have emerged to address the inadequacies of standard, untargeted biopsies, such as dye-based and virtual chromoendoscopy, endoscopic mucosal resection, molecular biomarkers, optical coherence tomography, confocal laser endomicroscopy, volumetric laser endomicroscopy, and endocytoscopy. Treatment of BE depends on the presence of intramucosal cancer or dysplasia, particularly high-grade dysplasia with or without visible mucosal lesions. CONCLUSIONS: Recent advances in endoscopic diagnostic tools demonstrate promising results and help to mitigate the shortcomings of the Seattle protocol. Future research as well as refining these tools may help aid them in replacing standard untargeted biopsies.

Systematic Review and Case Series Report of Acinar Cell Carcinoma of the Pancreas.

BACKGROUND: Acinar cell carcinoma of the pancreas is a rare malignancy representing less than 1% of all pancreatic malignancies. METHODS: We report on a case series of 21 patients with acinar cell carcinoma of the pancreas treated at a high-volume quaternary center. A systematic review of the medical literature was performed that described typical therapeutic management approaches for acinar cell carcinoma of the pancreas and reported on disease control and survival rates. Data for the case series were obtained from a prospective database. RESULTS: In our systematic review of 6 articles, study patients had a median age of 61 years, 66% were male, 52% had stage I/II disease, and 55% of lesions were located in the pancreatic head. The rates of median survival were approximately 47 months after resection with adjuvant therapy, 38 months for nonmetastatic, locally unresectable disease, and 17 months for metastatic disease treated with chemotherapy. Combination fluoropyrimidine-based chemotherapy regimens had better rates of disease control than other therapies. Our case series included 21 study patients, 14 of whom required resection and 7 who had metastatic disease. The rates of median survival were 40.2 ± 31.9 months in those who underwent surgery and were treated with adjuvant therapy and 13.8 ± 11.3 months for patients with metastatic disease. CONCLUSIONS: Multidisciplinary treatment for acinar cell carcinoma of the pancreas should be considered due to the rarity of the disease and its lack of high-level therapeutic data. Progress in the molecular analysis of this tumor may improve outcomes through the use of personalized therapy based on underlying tumor mutations.

EGFR L861Q Mutation in a Metastatic Solid-pseudopapillary Neoplasm of the Pancreas.

Solid-pseudopapillary neoplasm of the pancreas (SPN) is a rare neoplasm that is typically indolent in nature. Surgical resection is the preferred method of treatment and often associated with a good prognosis. Local invasion and metastasis have been reported in a small subset of patients. Currently, there are limited data on the molecular mutation profile of invasive and metastatic SPN. In this report, we present the case of a 38-year-old female with a locally-invasive and unresectable SPN that, despite exhaustive chemoradiotherapy, progressed to liver metastasis. Pyrosequencing of the primary pancreatic tumor antecedent to metastasis showed an uncommon EGFR mutation at L861Q in the kinase domain of exon 21. This finding, if confirmed in additional cases of metastatic SPN, would support preoperative testing for EGFR mutation analysis to detect aggressive SPNs.