BackgroundEpiploic appendagitis (EA) is a rare cause of focal abdominal pain in otherwise healthy patients with mild or absent secondary signs of abdominal pathology. It can mimick diverticulitis or appendicitis on clinical exam. The diagnosis of EA is very infrequent, due in part to low or absent awareness among general surgeons. The objective of this work was to review the authors' experience and describe the clinical presentation of EA.MethodsAll patients diagnosed with EA between January 2004 and December 2006 at an urban surgical emergency room were retrospectively reviewed by two authors in order to share the authors' experience with this rare diagnosis. The operations were performed by two surgeons. Pathological examinations of specimens were performed by a single pathologist. A review of clinical presentation is additionally undertaken.ResultsTen patients (3 females and 7 males, average age: 44.6 years, range: 27–76 years) were diagnosed with symptomatic EA. Abdominal pain was the leading symptom, the pain being localized in the left (8 patients, 80 %) and right (2 patients, 20%) lower quadrant. All patients were afebrile, and with the exception of one patient, nausea, vomiting, and diarrhea were not present. CRP was slightly increased (mean: 1.2 mg/DL) in three patients (33%). Computed tomography findings specific for EA were present in five patients. Treatment was laparoscopic excision (n = 8), excision via conventional laparotomy (n = 1) and conservative therapy (n = 1).ConclusionIn patients with localized, sharp, acute abdominal pain not associated with other symptoms such as nausea, vomiting, fever or atypical laboratory values, the diagnosis of EA should be considered. Although infrequent up to date, with the increase of primary abdominal CT scans and ultrasound EA may well be diagnosed more frequently in the future.

The microRNA encoding genes miR-34a and miR-34b/c represent direct p53 target genes and possess tumor suppressive properties as they mediate apoptosis, cell cycle arrest, and senescence. We previously reported that the miR-34a gene is subject to epigenetic inactivation by CpG methylation of its promoter region in primary prostate cancer and melanomas, and in 110 different cancer cell lines of diverse origin. Here we analyzed the methylation status of miR-34a and miR-34b/c in additional primary tumors of divergent sites. We found methylation of miR-34a or miR-34b/c in formalin-fixed, paraffin-embedded (FFPE) tumor samples from 178 patients with the following frequencies: colorectal cancer (74% miR-34a, 99% miR-34b/c; n = 114), pancreatic cancer (64%, 100%; n = 11), mammary cancer (60%, 90%; n = 10), ovarian cancer (62%, 69%; n = 13), urothelial cancer (71%, 57%; n = 7), and renal cell cancer (58%, 100%; n = 12). Furthermore, soft tissue sarcomas showed methylation of miR-34 gene promoters in FFPE samples (64%, 45%; n = 11), in explanted, cultured cells (53%, 40%; n = 40), and in frozen tissue samples (75%, 75%, n = 8). In the colorectal cancer samples a statistically significant correlation of miR-34a methylation and the absence of p53 mutation was detected. With the exception of sarcoma cell lines, the inactivation of miR-34a and miR-34b/c was concomitant in most cases. These results show that miR-34 inactivation is a common event in tumor formation, and suggest that CpG methylation of miR-34a and miR-34-b/c may have diagnostic value. The mutual exclusiveness of miR-34a methylation and p53 mutation indicates that miR-34a inactivation may substitute for loss of p53 function in cancer.

Lipopolysaccharide (LPS) binding protein (LBP) is a keyEndogenous lipopolysaccharides (LPS) have been implicated as a cofactor in promoting liver injury in many models of liver injury, including alcoholic hepatitis. 1,2 In the Tsukomoto and French model of rat alcoholic hepatitis, 3 the degree of liver injury is diminished by treatment with either antibiotics, lactobacillus, or polymixin, all of which decrease endogenous LPS. 4,5 In this model, Kupffer cells, when activated by LPS, play a prominent role in promoting liver injury. 6 Despite its potentially critical importance, the molecular mechanism by which Kupffer cells are activated by LPS remains largely unknown.In peripheral blood monocytes, the pathway of LPS activation has been recently delineated. In serum, LPS binds to LPS-binding protein (LBP), which is a 60-kd acute-phase protein produced by hepatocytes. 7,8 This LPS-LBP complex then binds to membrane CD14 resulting in cell activation, nuclear translocation of NF-␤, and production of cytokines such as TNF-␣. 9,10 The critical importance of LBP during in vivo responses to LPS and gram-negative bacteria is clearly shown by the inability of LBP knock-out mice to fight intraperitoneal infections 11 as well as the ability of anti-LBP monoclonal antibodies to prevent lethality in the LPS/ galactosamine model of endotoxemia. 12 Multiple lines of evidence suggest that the mechanisms by which LPS activates Kupffer cells may differ from those found in blood monocytes. Some authors have suggested that LPS activation in Kupffer cells is not mediated via the LBP/CD14 pathway hypothesized for blood monocytes. 13,14 Support for this idea stems from reports showing relatively low levels of CD14 expression in resting Kupffer cells compared with RAW 264.7 cells (murine macrophage cell line) and peritoneal macrophages. 15 Furthermore, in some studies, LPS activation of Kupffer cells, unlike that in peripheral blood monocytes, is not augmented by the addition of serum, suggesting that the LBP found in serum may act differently in Kupffer cells. 13,14 Because serum contains multiple factors that may alter LPS activation, we sought to focus on LBP' s role in Kupffer cell activation by performing experiments using recombinant rat LBP. In addition, because Kupffer cells express relatively low levels of CD14 in the resting state, we sought to examine the role of another candidate LPS receptor, the Toll-like receptor 4 (Tlr 4), in mediating the effects of LBP on LPS activation of Kupffer cells. MATERIALS AND METHODSReagents. LPS from Escherichia coli (055:B5) was purchased from Sigma (St Louis, MO), and pronase was obtained from Boehringer Mannheim (Indianapolis, IN).Recombinant Rat LBP. Recombinant rat LBP was produced using the baculovirus expression system. Briefly, the full-length rat LBP complementary DNA (cDNA) 16 was cloned in frame into pBluebacHis2c (Invitrogen, Carlsbad, CA) and used in conjunction with the linearized defective baculovirus DNA, Bac-N-Blue (Invitrogen, Carlsbad, CA) to cotransfect Sf9 insect cells. Re...

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