Anna Fen-Yau Li

The −251T Allele of the Interleukin-8 Promoter Is Associated with Increased Risk of Gastric Carcinoma Featuring Diffuse-Type Histopathology in Chinese Population

Purpose: Persistent interleukin-8 (IL-8) production contributes to chronic inflammation of the stomach. The proinflammatory IL-1β polymorphisms, which enhance the cytokine production, are associated with increased risk of gastric cancer. The −251A/T polymorphism of the IL-8 promoter is involved in several human diseases. Particularly, the −251A is associated with decreased risk of colorectal cancer. We aimed to determine whether the −251 allele resulting in high IL-8 expression was associated with increased risk of gastric carcinoma. Experimental Design: The −251A/T promoters were cloned and analyzed by luciferase assay. Binding of nuclear proteins to the −251A/T promoters was analyzed by electrophoretic mobility shift assay. The −251A/T promoters were differentiated by PCR-RFLP. Comparison of gastric cancer risk between the −251A/T promoters was done by a case-control study. Results: The −251T allele possessed transcriptional activity 2- to 5-fold stronger than the −251A counterpart. Electrophoretic mobility shift assay showed that the −251A promoter had strong ability to bind to an unknown protein or multiprotein complex. The −251T allele was associated with increased risk of noncardia (Ptrend = 0.012) and cardia (Ptrend = 0.029) carcinomas. Gastric carcinoma patients with the low-risk AA genotype had a tendency to sustain intestinal-type carcinomas (χ2 = 6.816; P = 0.033); however, the high-risk −251T allele was associated with >2-fold increased risk of diffuse-type (AA versus AT + TT: odds ratio, 2.52; 95% confidence interval, 1.16-5.49; P = 0.017) and mixed-type (AA versus AT + TT: odds ratio, 2.22; 95% confidence interval, 1.12-4.40; P = 0.019) carcinomas. Conclusions: The IL-8 −251T allele is significantly associated with increased risk of gastric carcinoma, particularly the diffuse and mixed types in Chinese population.

Expression of β-F1-ATPase and mitochondrial transcription factor A and the change in mitochondrial DNA content in colorectal cancer: clinical data analysis and evidence from an in vitro study

PurposeMitochondria play an important role in regulating apoptosis and thus may be involved in tumor progression. This study was conducted to elucidate the role of mitochondrial dysfunction in colorectal cancer (CRC).MethodsMitochondrial DNA (mtDNA) content was analyzed with real-time polymerase chain reaction in 153 CRC patients who had received surgery at the Taipei Veterans General Hospital from January 1999 to December 2000. The expression of mitochondrial transcription factor A (TFAM) and β-F1-ATPase were analyzed using immunohistochemistry. HCT116 cells were cultured in 1% O2 for at least 20 passages. Mitochondrial biogenesis, ATP production, and the apoptotic response to 5-fluorouracil were analyzed in the derived cells.ResultsDisease stage was associated with changes in mtDNA content (p < 0.001), expression of TFAM (p = 0.004), and/or β-F1-ATPase (p < 0.001). CRCs with low expression of TFAM or β-F1-ATPase had a lower mtDNA content. In the multivariate analysis, disease stage was the most significant prognostic factor [95% confidence interval (CI), 2.82–6.23], followed by β-F1-ATPase [95% CI, 1.10–4.10]. In patients receiving 5-FU based chemotherapy, the 5-year disease-free survival rate was only 27% in CRC patients with a low β-F1-ATPase tumor and was significantly lower than that in those with a high β-F1-ATPase tumor (60%; p = 0.042). In the hypoxia-treated cells, mitochondrial mass increased, mtDNA content decreased, sensitivity to 5-fluorouracil decreased, and β-F1-ATPase expression decreased.ConclusionMitochondrial dysfunction may be associated with poor outcomes in CRC patients.

Early postoperative CEA level is a better prognostic indicator than is preoperative CEA level in predicting prognosis of patients with curable colorectal cancer

PurposeCarcinoembryonic antigen (CEA) measurements performed preoperatively and during the early postoperative period were examined prospectively to assess their prognostic value for colorectal cancer (CRC) patients receiving curative surgery.MethodsBetween 2000 and 2004, 1,361 patients with CRC who underwent curative surgery at the Taipei Veterans General Hospital were enrolled prospectively. CEA was measured prior to surgery and during the third or fourth postoperative week. The endpoint was length of postoperative disease-free survival, and prognostic importance was determined using the log-rank test and Cox regression hazard model.ResultsSix hundred (44.1%) CRC patients had high CEA concentrations preoperatively, and 188 (13.8%) patients retained high values postoperatively. Within the median follow-up period of 61 (6–108) months, CRC recurred in 313 patients. By univariate analysis TNM staging, tumor differentiation, lymphovascular invasion, preoperative CEA concentration, and postoperative CEA concentration affected the outcome. By multivariate analysis, the prognostic importance of postoperative CEA was retained (95% CI, 1.73–3.01; HR = 2.28) but that of preoperative CEA was lost (95% CI, 0.82–1.33; HR = 1.05). CRC recurred earlier in patients with high postoperative CEA concentrations; metastasis to the liver was common (72.3%) among patients in this group.ConclusionsEarly postoperative CEA concentration is an independent prognostic factor for CRC. Patients with high postoperative CEA values should receive aggressive follow-up examinations for early relapse of CRC, with special attention paid to recurrence at the liver.

Regression of high-grade gastric mucosa-associated lymphoid tissue lymphoma with Helicobacter pylori after triple antibiotic therapy ☆ ☆☆

Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach has recently been defined as a distinct histopathologic entity, often associated with Helicobacter pylori infection.1,2 High-grade gastric lymphoma is composed of diffuse large cells with abundant cytoplasm, vesicular nuclei, and prominent nucleoli. It is a distinct disease with aggressive clinical features and a poorer prognosis than that of low-grade MALT lymphomas.3,4 Patients with localized high-grade MALT lymphoma are often treated with either surgical resection or chemotherapy with or without radiotherapy.5,6 Although a high success rate in the regression of low-grade B-cell MALT lymphoma by eradication of H pylori has been reported,7-9 the role of this therapeutic option for highgrade lymphoma is still controversial.10 However, there are several reports of complete remission of H pylori–related high-grade lymphoma after cure of the H pylori infection.11-14

Colonoscopy in abdominal actinomycosis

Abdominal actinomycosis has been called “one of the greatest imitators in clinical practice.”1 In addition, its variety makes it difficult to accumulate experience with the disease. Actinomycosis is a chronic suppurative infection due to a grampositive, non-spore-forming, anaerobic bacteria. The organisms are indigenous in the oral cavity, GI tract, and genital tracts, with opportunistic infection occurring when the mucosal barrier is broken,2 leading to multiple abscess formation, fistula, or a mass lesion. Actinomycosis has three major forms of clinical manifestation: cervicofascial, thoracic,3 and abdominal.4 We present a case of abdominal actinomycosis with an interesting endoscopic and radiologic picture.

Pseudogastroparesis as a presentation of small-bowel malignancy.

&NA; Establishing the diagnosis of small‐bowel malignancy is sometimes an extremely difficult challenge owing to its non‐specific symptoms. The mainstay of treatment is early recognition, diagnosis and surgical resection. The prognosis depends primarily on the degree of spread and stage at presentation. We present two cases with initially obscure presentations of a small‐bowel tumour. One was a jejunal adenocarcinoma, but an initial upper gastrointestinal and small‐bowel series did not disclose the lesion; the other was a primary ileal lymphoma, first thought to be diabetes mellitus gastroparesis. Therefore, a negative small‐bowel series or presentation of a systemic disease‐associated intestinal pseudo‐obstruction or gastroparesis does not exclude the possibility of a small‐bowel malignancy, if the clinical symptoms are not alleviated after prokinetic medications. The clinicians should further pursue the possibility of an obstructing lesion. Eur J Gastroenterol Hepatol 12:351‐355