The Predictive Role of ERCC1 Status in Oxaliplatin Based Neoadjuvant Therapy for Metastatic Colorectal Cancer (mCRC) to the Liver.

Increased expression of excision repair cross-complementing 1 (ERCC1) in mCRC patients could be related to their response to Oxaliplatin based chemotherapy. We evaluated ERCC1 mRNA expression levels in primary bowel and liver metastases of 51 patients, and correlated with pathologic parameters and clinical outcomes. A significant negative correlation was detected between primary tumor ERCC1 and both the extent of clear surgical margins (P = 0.0011) and the percent of liver metastasis necrosis (P = 0.0167). No relationship was observed between ERCC1 expression and survival. Further study is needed to assess the promising role of ERCC1 expression as a predictive marker benefiting subgroups for Oxaliplatin.

High-throughput mutation profiling in intraductal papillary mucinous neoplasm (IPMN).

BACKGROUND: Specific mutations leading to the development of various histological grades of intraductal papillary mucinous neoplasm (IPMN) have been partially characterized. METHODS: Analysis of 323 oncogenic mutations in 22 tumor-related genes was conducted, using a chip-based matrix-assisted laser desorption time-of-flight mass spectrometer of DNA extracted from microdissected cells of low-grade (n = 14), borderline (n = 6), and invasive IPMN (n = 7). Additional assays were performed on the DNA extracted from dyplastic cells found in the background of the adenocarcinoma. RESULTS: We identified 9 K-ras mutations (low grade, 2/14; borderline, 1/6; invasive, 6/7), 3 p53 mutations (low grade, 1/14; invasive 2/7), and 2 PIK3CA mutations (low grade, 1/14; invasive, 1/7). K-ras, p53, and PIK3CA mutations present in the invasive cancer were absent in the adjacent precursor cells in 50% of the cases. In one patient, K-ras mutation was present in the precursor lesion and absent in the adjacent invasive lesion. CONCLUSIONS: Of the 22 screened tumor-related genes, only K-ras, p53, and PIK3CA mutations were found in IPMN. K-ras mutations are more prevalent in invasive than premalignant IPMN. The variable coexistence of mutations in the invasive cancer and in the adjacent precursor cells may point to the heterogeneous nature of this tumor.

A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Few controlled studies have addressed the issue of effective medical treatment for nonalcoholic fatty liver disease (NAFLD). We herein assessed the effect of orlistat in patients with NAFLD. METHODS: We performed a randomized, double-blind, placebo-controlled study on 52 patients with NAFLD diagnosed by ultrasound (US) and confirmed by liver biopsy (40 patients). The patients were randomized to receive either orlistat (120 mg 3 times daily for 6 months) or placebo. All patients participated in an identical behavioral weight loss program. All patients underwent monthly evaluation by abdominal US; liver enzyme levels, lipid profiles, insulin levels, and anthropometric parameters were monitored, and all patients underwent nutritional follow-up evaluation. Twenty-two patients underwent a second liver biopsy examination at the end of the study. RESULTS: Fifty-two patients were recruited and 44 (mean age, 47.7 y; mean body mass index, 33) completed the study. Serum glucose and insulin levels (P<.03) were significantly higher in the orlistat group, which also presented a higher degree of fibrosis. Body mass index was reduced significantly in each group, with a nonsignificant difference between the groups. Serum alanine transaminase (ALT) levels decreased significantly in both groups, with an almost 2-fold reduction in the orlistat group (48% vs 26.4%). There was a statistically significant reversal of fatty liver by US only in the orlistat group (P<.05). CONCLUSIONS: Orlistat improves serum ALT levels and steatosis on US in NAFLD patients, beyond its effect on weight reduction.

Expression of the intestinal marker Cdx2 in secondary adenocarcinomas of the colorectum.

CONTEXT: Secondary adenocarcinomas of the large bowel can closely mimic primary tumors. The differentiation of secondary from primary adenocarcinomas of the colorectum, however, is important because their clinical management and prognosis are different. Immunostaining with the nuclear transcription factor Cdx2, expressed in normal intestinal epithelia and colorectal adenocarcinomas, could be of potential diagnostic use. OBJECTIVE: To investigate the diagnostic value of Cdx2 immunoexpression in distinguishing primary from common forms of secondary colorectal adenocarcinomas. DESIGN: Cdx2 immunoexpression was analyzed in 20 primary colorectal adenocarcinomas and in 34 secondary colorectal adenocarcinomas and their corresponding primary tumors. All secondary tumors were diagnosed through endoscopic biopsies and included 8 cases of ovarian (4 serous, 2 mucinous, and 2 endometrioid), 6 of mammary (4 lobular and 2 ductal), 4 of gastric (2 intestinal and 2 diffuse), 4 of pulmonary, 4 of pancreatic (ductal), 3 of prostatic, 3 of colorectal, and 2 of endometrial origin. RESULTS: Cdx2 was expressed in normal colorectal epithelium, in primary colorectal adenocarcinomas (20/20 cases), in secondary adenocarcinomas of colorectal (3/3) and gastric (3/4) origin, and in metastatic ovarian mucinous adenocarcinomas (2/2). In contrast, no Cdx2 immunoreactivity was observed in secondary colorectal tumors of ovarian (serous and endometrioid), mammary, pancreatic, pulmonary, prostatic, and endometrial origin. CONCLUSION: Cdx2 immunostaining may be useful in discriminating primary colorectal carcinomas from frequent types of secondary colorectal adenocarcinomas of nongastrointestinal origin. We suggest including Cdx2 in any antibody panel put together to distinguish between primary and secondary epithelial colorectal malignancies.