Prediction of Free Bowel Perforation in Patients with Intestinal Behçet’s Disease Using Clinical and Colonoscopic Findings

Background

Gastrointestinal tract involvement in Behçet’s disease (BD) often requires surgical intervention due to serious complications such as intestinal perforation, fistula formation, or massive bleeding.

Aim

The aims of this study were to investigate the clinical and surgical features of free bowel perforation and to determine the risk factors associated with this complication in intestinal BD patients.

Methods

We reviewed the medical records of 129 patients with intestinal BD treated from September 1988 to September 2008. Among them, 33 patients had intestinal perforations and all underwent emergent or elective laparotomy.

Results

The mean age of the patients with bowel perforation was 34.8 ± 15.6 years (range 12–70 years) with a sex ratio of 2.3:1 (male:female). Twenty-seven (81.8%) patients were diagnosed with intestinal BD preoperatively, whereas six (18.2%) patients were diagnosed by pathological examination after operation. Fourteen (42.4%) patients experienced postoperative recurrence of intestinal BD and 11 (33.3%) underwent reoperation. Multivariate Cox hazard regression analysis identified younger age (≤25 years) at diagnosis (HR = 3.25; 95% CI, 1.41–7.48, p = 0.006), history of prior laparotomy (HR = 5.53; 95% CI, 2.25–13.56, p = 0.0001), and volcano-shaped intestinal ulcers (HR = 2.84; 95% CI, 1.14–7.08, p = 0.025) as independent risk factors for free bowel perforation in intestinal BD.

Conclusions

According to the results of our study, patients diagnosed with intestinal BD younger than 25 years, who had a history of prior laparotomy or volcano-shaped intestinal ulcers have an increased risk of free bowel perforation.     

TNF superfamily gene polymorphism as prognostic factor in early breast cancer

Purpose

Since apoptosis may play a role in the prognosis of breast cancer, the present study analyzed the polymorphisms of apoptosis-related genes and their impact on the survival of 240 patients with early invasive ductal breast cancer.

Methods

The genomic DNA was extracted from paraffin-embedded tumor-free tissue or blood, and 12 single nucleotide polymorphisms (SNPs) of 11 apoptosis-related genes in the apoptosis pathway determined using a Sequenom MassARRAY system.

Results

During the median follow-up of 53.4 (range 2.9–205.9) months, 37 relapses and 22 deaths occurred. Among the target polymorphisms, the tumor necrosis factor superfamily member 10 gene polymorphism (TNFSF10 rs1131532) in a recessive model of the T allele and prostaglandin-endoperoxide synthase 2 gene polymorphism (PTGS2 rs5275) in a dominant model of the C allele were associated with survival in a log-rank test. The TT genotype of TNFSF10 (rs1131532) was also significantly correlated with a lower disease-free, distant disease-free, and overall survival in a multivariate analysis (HR = 3.304, 4.757, and 6.459; P = 0.002, 0.001, and 0.009, respectively), while PTGS2 rs5275 was only associated with a higher distant disease-free survival (HR = 0.302; P = 0.041). No clinicopathologic difference was observed according to the genotypes of these two polymorphisms.

Conclusion

The TNFSF10 (rs1131532) polymorphism was identified as a possible prognostic factor of survival in patients with operated invasive breast cancer.     

Capsule endoscopy in small bowel tumors: A multicenter Korean study

Background and Aim: Capsule endoscopy (CE) has proven to be highly effective at detecting small bowel lesions in a variety of clinical conditions, but studies concerning the practical impact of CE on small bowel tumors are still scarce, especially in the Asian population. The aim of this study was to evaluate the diagnostic and therapeutic impact of CE in the field of small bowel tumors. Methods: CE records consecutively pooled from the beginning of use of CE in Korea, October 2001 until April 2008, in 14 centers throughout Korea were reviewed. Clinical information and CE video images of small bowel tumors were analyzed. Results: A total of 1332 cases undergoing CE were reviewed with all clinical indications. Small bowel tumors were diagnosed with CE in 57 (4.3%) of 1332 patients. The tumors were malignant in 33 cases, and included three adenocarcinomas, eight lymphomas, 20 gastrointestinal stromal tumors, and two metastatic cancers. The most frequent indications for CE in malignant tumors were obscure gastrointestinal bleeding, followed by abdominal pain and weight loss. Thirty of 57 tumors were identified exclusively by CE (diagnostic impact = 30/57), and they were smaller in size (mean, range: 14.3 mm, 2–35 mm) compared to the other tumors detected in radiological studies (48.7 mm, 10–110 mm). Seven patients underwent surgical resection (therapeutic impact = 7/57). Conclusion: CE effectively identifies small bowel tumors that are undetectable by conventional radiological studies (diagnostic impact = 52.6%) and can critically change the therapeutic course (therapeutic impact = 12.3%).     

Effects of melamine on pregnant dams and embryo‐fetal development in rats

There are worldwide concerns regarding the potential adverse effect of melamine. This study investigated the potential effects of melamine on pregnant dams and embryo‐fetal development in Sprague–Dawley rats following maternal exposure on gestational days (GD) 6–20. Melamine was administered to pregnant rats by gavage at doses of 0, 200, 400 and 800 mg kg^?1 per day (n = 8–10 for each group). All dams were subjected to a Caesarean section on GD 21 and their fetuses were examined for morphological abnormalities. With administration of melamine at 800 mg kg^?1 per day, maternal toxicity manifested as increased incidences of clinical signs and death, lower body weight gain and food intake, and increases in heart, adrenal gland and kidney weights. Histopathological examinations revealed an increase in incidences of congestion, tubular necrosis/degeneration, crystals, casts, inflammatory cells in tubules, tubular dilation and tubular hyaline droplets in the maternal kidneys, while fetal kidneys (one fetus/litter) did not show any histopathological changes. Developmental toxic effects included a decrease in fetal weight, an increase in the incidence of skeletal variations and a delay in fetal ossification. No treatment‐related maternal or developmental effects were observed at doses ≤400 mg kg^?1 per day. These results show that 15‐day repeated oral dosing of melamine is embryo‐/fetotoxic at a maternotoxic dose, but not teratogenic in rats. The no‐observed‐adverse‐effect level of melamine for pregnant dams and embryo‐fetal development is considered to be 400 mg kg^?1 per day. Copyright © 2011 John Wiley & Sons, Ltd.     

Stereocalpin A inhibits the expression of adhesion molecules in activated vascular smooth muscle cells

Up-regulation of cell adhesion molecules on vascular smooth muscle cells (VSMCs) and leukocyte recruitment to the vascular wall contribute to vascular inflammation and atherosclerosis. Stereocalpin A, a chemical compound of the Antarctic lichen Ramalina terebarata, displays tumoricidal activity against several different tumor cell types. However, other biological activities of stereocalpin A and its molecular mechanisms remain unknown. In this study, our work is directed toward studying the in vitro effects of stereocalpin A on the ability to suppress the expression of adhesion molecules induced by TNF-α in vascular smooth muscle cells. Pretreatment of VSMCs for 2h with stereocalpin A at nontoxic concentrations of 0.1-10 μg/ml inhibited TNF-α-induced adhesion of THP-1 monocytic cells and expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Stereocalpin A reduced TNF-α-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38, ERK, JNK and Akt. Stereocalpin A also inhibited NK-κB activation induced by TNF-α. Moreover, stereocalpin A inhibited TNF-α-induced ΙκΒ kinase activation, subsequent degradation of ΙκΒα, and nuclear translocation of NF-κB. Hence, we describe a new anti-inflammatory activity and mechanism of stereocalpin A, owing to the negative regulation of TNF-α-induced adhesion molecule and MCP-1 expression, monocyte adhesion and ROS production in vascular smooth muscle cells. These results suggest that stereocalpin A has the potential to exert a protective effect by modulating inflammation within the atherosclerotic lesion.     

Uridine-based paramagnetic supramolecular nanoaggregate with high relaxivity capable of detecting primitive liver tumor lesions

The water soluble uridine-based paramagnetic self-assembled amphiphilic molecules (LGd2-5) with DTTA binding site were synthesized and have been characterized in regard to their T(1) magnetic resonance imaging (MRI) contrast agent (CA) properties. The water proton relaxivities have been measured in phosphate buffered saline (PBS) at 36 °C at 3 different magnetic fields. Among the self-assembled CAs, LGd3 showed unprecedented, high relaxivities of 30.3 and 23.4 mM(-1) s(-1) in PBS solution at 36 °C at 0.47 and 1.41 T, respectively. The non-covalent interactions between the new CAs and human serum albumin (HSA) have been investigated and the relaxivity was further increased by 135-215% depending on alkyl chain lengths. The chemically inertness of these complexes (LGd1, LGd2, LGd3, LGd4) against biologically most abundant metal ion (i.e. Zn(2+)) have shown within the range of commercial DTPA-based CAs. In vivo pharmacokinetics of the complex LGd3 showed highly specific for hepatocytes resulting in increase of contrast noise ratio by ～240% in T(1)-weighted MR images of mouse liver 2 h after injection of the LGd3. It is capable to detect small hepatocellular carcinoma (HCC) with diameter of 1.5 mm.