Purpose: Despite significant progress in understanding the molecular pathology of pancreatic cancer and its precursor lesion: pancreatic intraepithelial neoplasia (PanIN), there remain no molecules with proven clinical utility as prognostic or therapeutic markers. Here, we used oligonucleotide microarrays to interrogate mRNA expression of pancreatic cancer tissue and normal pancreas to identify novel molecular pathways dysregulated in the development and progression of pancreatic cancer. Experimental Design: RNA was hybridized to Affymetrix Genechip HG-U133 oligonucleotide microarrays. A relational database integrating data from publicly available resources was created to identify candidate genes potentially relevant to pancreatic cancer. The protein expression of one candidate, homeobox B2 (HOXB2), in PanIN and pancreatic cancer was assessed using immunohistochemistry. Results: We identified aberrant expression of several components of the retinoic acid (RA) signaling pathway (RARa, MUC4, Id-1, MMP9, uPAR, HB-EGF, HOXB6, and HOXB2), many of which are known to be aberrantly expressed in pancreatic cancer and PanIN. HOXB2, a downstream target of RA, was up-regulated 6.7-fold in pancreatic cancer compared with normal pancreas. Immunohistochemistry revealed ectopic expression of HOXB2 in15% of early PanIN lesions and 48 of 128 (38%) pancreatic cancer specimens. Expression of HOXB2 was associated with nonresectable tumors and was an independent predictor of poor survival in resected tumors. Conclusions: We identified aberrant expression of RA signaling components in pancreatic cancer, including HOXB2, which was expressed in a proportion of PanIN lesions. Ectopic expression of HOXB2 was associated with a poor prognosis for all patients with pancreatic cancer and was an independent predictor of survival in patients who underwent resection.Pancreatic cancer is the fifth leading cause of cancer death in Western societies with a 5-year survival rate of <10% (1). Pancreatic cancer presents at an advanced stage; thus, only 10% to 20% of patients are suitable for surgical treatment at the time of presentation (1). Clinical management of these patients is complicated by inconsistencies in the influence of conventional clinicopathologic variables on outcome suggesting that some of these variables lack accuracy. In addition, preoperative assessment of some variables such as lymph node metastases is difficult. Whereas in other cancers assessment of aberrations in gene expression that cosegregate with therapeutic response and outcome are being adopted routinely to increase predictive power (e.g., ER and HER-2/neu in breast cancer), there remain no molecular markers of clinical utility in pancreatic cancer. This highlights the need for the identification of novel regulatory pathways important in pancreatic cancer that may also have diagnostic, therapeutic and prognostic utility.There is now compelling histopathologic and molecular evidence to support the evolution of pancreatic cancer through a series of noninvasive duct...

The development of pancreatic cancer (PC) several years after curative resection for noninvasive intraductal papillary mucinous neoplasm (IPMN) and the presence of PC distant from IPMN suggest that PC may develop independently of the IPMN. Here, we identified pancreatic intraepithelial neoplasia (PanIN) lesions, the putative precursors of PC, in the ducts of pancreata resected for IPMN and assessed the frequency of molecular aberrations common to PanIN and PC, within these lesions. The protein expression of p53, p21(WAF1/CIP1), cyclin D1, p16(INK4A) and DPC4/Smad4 were examined by immunohistochemistry in 267 PanIN lesions from a cohort of 23 patients with IPMN. Overexpression of p21(WAF1/CIP1) was present in PanIN-1A and -1B lesions and increased in frequency in PanIN-2 and PanIN-3. Overexpression of p53 and cyclin D1, and loss of p16(INK4A) expression were detected in PanIN-2 and PanIN-3 lesions. Loss of DPC4/Smad4 expression occurred only in the PanIN-3 lesions. PanIN lesions that were more dysplastic than the coincident IPMN were identified in 5 of 12 patients, and 2 of these contained a greater number of aberrations in protein expression than the IPMN. PanIN lesions seen in association with IPMN demonstrate molecular and histologic changes identical to PanIN lesions found in association with PC and, in some cases, are more advanced than the associated IPMN. These data suggest that PanIN lesions found in the ducts of a pancreas with IPMN may be relevant to the development of PC either coincident with IPMN or in the remnant pancreas after curative resection of IPMN.

A case is reported in which two separate adenocarcinomas were detected in the bypassed distal stomach 13 years after gastric stapling with loop gastro-enterostomy was performed for the treatment of morbid obesity. Retrograde endoscopy via the afferent loop was used to establish the diagnosis. Although gastritis and metaplasia have been described in the bypassed stomach, only one case of carcinoma in this area has previously been reported.

lntussusception in the adult is an uncommon cause of intestinal obstruction. Seventeen cases were seen at two teaching hospitals over a twenty-year period. A local causative lesion was preent in all cases; a malignant tumour was present in two out of seven intussusceptions arising in the small intestine and in seven out of ten arising in the large intestine. More than half the cases had a protracted clinical course prior to diagnosis.

EUS and laparoscopy are useful modalities in the preoperative investigation and staging of patients being considered for PD. PD is a safe procedure with acceptable complication rates when carried out in a specialist unit experienced in this operation.

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Objectives: To determine the frequency of deep vein thrombosis (DVT) associated with minimally invasive cholecystectomy and to determine, using minilaparotomy cholecystectomy as a control operation, the influence of the laparoscopic pneumoperitoneum on DVT formation. Design: Prospective nonrandomized control trial. Setting: Tertiary care university hospital. Patients: One hundred consecutive patients intended to undergo either laparoscopic cholecystectomy (59 patients) or minilaparotomy cholecystectomy (41 patients) with either of 2 surgeons were prospectively enrolled between April 1996 and April 1997. The minilaparotomy cholecystectomy group served as controls to isolate the effect of the pneumoperitoneum. Patient details, operative details, and any thromboembolic or bleeding complications were recorded. The same thromboprophylaxis regimen was prescribed for each group; namely, preoperative and postoperative subcutaneous low-molecular-weight heparin (LMWH), graduated compression stockings, and intraoperative intermittent calf compression. Intervention: Minimally invasive cholecystectomy. Main Outcome Measure: Frequency of DVT. Bilateral lower limb venous color duplex scanning was used to detect DVT. Scans were performed on 3 occasions: (1) preoperatively on admission to hospital, (2) on the first postoperative day, and (3) between 2 and 4 weeks postoperatively. Results: Three patients in the laparoscopic group and 2 patients in the minilaparotomy group underwent con-This article is also available on our Web site: www.ama-assn.org/surgery.

The association of high cyclin E expression with poor outcome in some cancers, in particular breast cancer, suggests that it may play an important role in tumor biology. Because the influence of cyclin E expression on outcome is yet to be examined in pancreatic cancer, we assessed the relationship between the expression of cyclin E, p27 Kip1 , and survival in a large cohort of pancreatic cancer patients with long-term follow-up. Expression of cyclin E and p27Kip1 was assessed by immunohistochemistry using tissue microarrays of tumor samples from 118 patients with pancreatic ductal adenocarcinoma (75 resections and 43 biopsies). High cyclin E expression (>10% positive nuclei) was identified in 39 of 118 (33%) patients. This was associated with poor prognosis on univariate analysis in the whole cohort (P = 0.005), as well as in the subgroup of 75 patients who underwent operative resection (P = 0.04). On multivariate analysis, high cyclin E expression was an independent predictor of poor survival in both the entire cohort (P = 0.005) and the resected subgroup (P = 0.03), and was superior to all tested clinicopathologic factors (tumor size, lymph node metastases, differentiation, margin involvement, and perineural invasion) as a marker of survival. Low p27Kip1 expression (<5% positive nuclei) was present in 41 of 111 (37%) patients, but was not associated with survival, and coexpression of p27Kip1 did not influence the association of high cyclin E expression with poor survival. High cyclin E expression is a strong independent predictor of poor outcome in patients with pancreatic cancer. Thus, if these data are confirmed in independent cohorts, measurement of cyclin E may add significant prognostic information to the currently used clinicopathologic variables and hence have potential clinical utility in the management of this disease. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1941-7)