Higher plasma homocysteine is associated with increased risk of developing colorectal polyps.

Colorectal adenomas are considered to be precursors of colorectal cancer. B-vitamins (i.e., folate, vitamin B(6) and B(12)) are involved in homocysteine metabolism and play an important role as coenzymes in 1-carbon metabolism, which is thought to have a critical role in the progression of colorectal polyps. The purpose of this study was to examine the effects of B-vitamins and homocysteine on the risk of developing colorectal polyps. Forty-eight participants with colorectal polyps [29 adenomatous polyps (AP), 19 hyperplastic polyps (HP)], and 96 age- and sex-matched healthy controls were recruited. Fasting blood was drawn from each participant to measure hematological parameters, plasma pyridoxal 5'-phosphate (PLP), serum folate and vitamin B(12), and plasma homocysteine. Participants with AP and HP had significantly higher plasma homocysteine levels than did healthy controls. There was no significant difference in serum folate and vitamin B(12) and plasma PLP among the 3 groups. B-vitamins had no significant effect on the risk of colorectal polyps. However, participants with higher plasma homocysteine [odds ratio (OR) = 1.87, 95% confidence interval (CI) = 1.13, 3.08) level exhibited significantly increased risk of colorectal polyps after adjusting for potential confounders. Plasma homocysteine was a strong predictor of the risk of colorectal polyps in participants with adequate B-vitamins status.

Safety and efficacy of adefovir therapy for lamivudine-resistant hepatitis B virus infection in renal transplant recipients.

BACKGROUND/PURPOSE: The emergence of lamivudine (LAM)-resistant mutants after prolonged LAM therapy may reduce its therapeutic effects against hepatitis B virus (HBV). Adefovir dipivoxil (ADV) is an effective treatment of LAM-resistant HBV infections. However, only limited data are available regarding the safety and efficacy of ADV for treating HBsAg-positive renal transplant recipients. METHODS: Fourteen HBsAg-positive patients who underwent renal transplantation and developed the YMDD mutation after prolonged LAM therapy were retrospectively analyzed. Five patients were administered ADV monotherapy, while nine patients received ADV plus LAM combination therapy. Data on age, gender, duration of previous LAM treatment, pre-LAM HBV DNA and liver enzyme levels, duration of LAM treatment prior to the emergence of mutations, duration of ADV rescue therapy, and the clinical outcomes of treatment (i.e., normalization of alanine transaminase (ALT) and undetectable HBV DNA levels) were analyzed. RESULTS: The mean age of the patients was 46.8 ± 11.5 years. Males were predominantly studied. The mean follow-up duration of rescue therapy was 38.2 ± 18.3 months. At the beginning of rescue therapy, the mean serum ALT level was 142.2 ± 99.8 IU/mL, while the median serum level of HBV DNA was 7.85 log(10) copies/mL. Patients who received combination therapy tended to demonstrate undetectable serum HBV DNA levels, but no significant differences in terms of clinical outcomes were observed between patients who received ADV monotherapy and patients who received combination therapy. After 12 months of treatment, 13 patients (92.8%) developed normalized ALT levels. Five (35.7%) and six (42.8%) patients achieved undetectable serum HBV DNA levels after 12 months and 24 months of treatment, respectively. No virological breakthroughs were observed. Twenty-nine percent of the patients developed moderate to severe renal insufficiency. CONCLUSION: Although no statistical difference was noted, ADV plus LAM combination therapy tended to demonstrate a higher therapeutic efficacy than ADV monotherapy for treating LAM-resistant HBV infection in renal transplant recipients. Renal function should be closely monitored in order to ameliorate nephrotoxicity.

Human papilloma virus 16 E6 oncoprotein associated with p53 inactivation in colorectal cancer.

AIM: To investigate the association between human papilloma virus (HPV) infection and colorectal cancer. METHODS: Sixty-nine patients with pathologically confirmed primary colorectal cancer including 6 stage I, 24 stage II, 21 stage III, and 18 stage IV patients were enrolled in this study to investigate whether HPV 16 could be involved in colorectal tumorigenesis. Nested-polymerase chain reaction (nested-PCR) was used to detect HPV16 DNA in colorectal tumor tissues and further confirmed by in situ hybridization (ISH). In addition, immunohistochemistry analysis was performed to examine the E6 oncoprotein in colorectal tumors. To verify whether E6 could inactivate the p53 transcriptional function, the levels of p21 and Mdm2 mRNA expression were evaluated by real-time reverse transcription (RT)-PCR. RESULTS: Of the 69 colorectal tumors, HPV16 DNA was detected in 11 (16%) by nested-PCR, and HPV16 DNA was present in 8 of the 11 (73%) tumors which was confirmed by ISH. The presence of HPV16 DNA in colorectal tumors was not associated with patients' clinical parameters including age, gender, smoking status, tumor site; however, HPV16 infection was more common in stage I patients than in late-stages patients (II, III and IV). We next asked whether HPV16 infection could be linked with colorectal cancer development. Immunohistochemical data indicated that 8 of the 11 HPV16 DNA-positive tumors had E6 oncoprotein expression. Moreover, we also observed that the adjacent normal tissues including endothelial cells, lymphocytes, fibroblasts, and gland cells in E6-positive tumors had E6 oncoprotein expression. In addition, 3 of the 4 (75%) E6-positive tumors carrying p53 wild-type had negative immunostaining, but one tumor had less p53 immunostaining. We further examined whether E6-positive and/or p53 mutated tumors reduce p53 transcriptional activity. Real-time RT-PCR analysis indicated that p21 and mdm2 mRNA expression levels in E6/p53-wildtype tumors were significantly lower than in their adjacent normal tissues; as expected, E6-positive/p53-mutated tumors had lower p21 and mdm2 mRNA expression levels compared with their adjacent normal tissues. These results clearly indicate that the E6 oncoprotein expressed in p53 wildtype tumors may reduce p21 and mdm2 expression via p53 inactivation. CONCLUSION: These results suggest that HPV16 infection may be involved in a subset of colorectal cancer, and we suggest that the transmission of HPV to the colon and rectum might occur through peripheral blood lymphocytes.

Extranodal marginal zone B-cell lymphoma of the gastrointestinal tract sparing only the esophagus: a case report.

Lymphomas presented in any organ or tissue other than lymph nodes or the spleen are considered primary extranodal non-Hodgkin's lymphomas, and the most common non-Hodgkin's lymphomas are of the gastrointestinal tract. The most common histological subtypes are marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue and diffuse large B-cell lymphoma, and typically only one to two organs are affected. Patients present with a wide variety of vague complaints, making early diagnosis problematic. Herein, we report the case of a 76-year-old male with extranodal marginal zone B-cell lymphoma involving the entire gastrointestinal tract, sparing only the esophagus, who was Helicobacter pylori-negative. He underwent six courses of chemotherapy with R-CHOP regimen, and achieved complete remission.

Bedside colonoscopy for critically ill patients with acute lower gastrointestinal bleeding.

OBJECTIVE: To determine the clinical impact of bedside colonoscopy for critically ill patients with acute lower gastrointestinal (GI) bleeding. DESIGN AND SETTING: A 3-year retrospective analysis (chart review). Medical intensive care unit (ICU) of a 1,312-bed tertiary-care center in Taiwan. PATIENTS AND PARTICIPANTS: Fifty-five people undergoing bedside colonoscopy for lower GI bleeding that developed while in the ICU. INTERVENTIONS: Bedside colonoscopy. MEASUREMENTS AND RESULTS: Colonoscopy was successful in diagnosing the source of bleeding in 37 patients. Among them, colitis (15 patients, including ischemic, pseudomembranous, or radiation-induced) and acute hemorrhagic rectal ulcer (nine patients) were the most frequent confirmed causes. In seven patients, fresh blood was noticed above the colonoscopically accessible area and considered to originate from the small bowel. No adverse event was associated with colonoscopy. Spontaneous cessation of bleeding was noted in 29 (29/55, 53%) patients, whereas 16 (16/55, 29%) achieved endoscopic hemostasis. Ten (10/55, 18%) patients failed primary hemostasis or localization. Overall in-hospital mortality was 53% (29/55); however, hemorrhage-related death occurred in only two patients. CONCLUSIONS: ICU patients with acute lower GI bleeding have distinctive causes. Bedside colonoscopy is effective for diagnosis in two-thirds of patients, but only a minority of them needs endoscopic hemostasis.