Deletion and Single Nucleotide Polymorphisms in Common Glutathione-S Transferases Contribute to Colorectal Cancer Development.

Glutathione-S transferases (GSTs) are xenobiotic-conjugation enzymes involved in the detoxification process of heterocyclic aromatic amines and polycyclic aromatic hydrocarbons, widely recognized risk factors of colorectal cancer (CRC) development. Polymorphism in GSTs often leads to alteration or complete lack of enzyme activity, which might have an effect on CRC carcinogenesis. Aim of this study was to investigate GST gene variants as risk factors in patients with CRC. A total of 523 CRC patients administered for surgical resection and 400 matched controls were included. Deletion polymorphism of GSTs M1 and T1 was investigated by polymerase chain reaction. Single nucleotide polymorphism of GST A1 and P1 was investigated by restriction fragment length polymorphism method. The association between GST genotype and risk of CRC development was found in carriers of GSTT1-null and GSTP1-variant genotypes individually (p = 0.050 and p = 0.016, respectively). Furthermore, statistically significant association was found when combination of GSTP1-variant genotype with any of other three common GST genotypes was analyzed with respect to CRC susceptibility. Additionally, patients with combined GSTM1-null/GSTT1-null/GSTA1 low-activity/GSTP1-variant genotype showed 2.71-fold increased risk of developing CRC (p = 0.037). This study supports hypothesis that GST polymorphisms might have an important role in the process of the CRC development. Additionally, GSTM1-null/ GSTT1-null/ GSTA1 low-activity/ GSTP1-variant genotype could be combination of GST genotypes whose carriers are more prone to CRC development.

Activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in different stages of colorectal carcinoma.

BACKGROUND: Reactive oxygen species are involved in the pathogenesis of colorectal carcinoma. Clarification of oxidative/antioxidant specificities of different stages of colorectal carcinoma is of special importance. AIM: To determine oxidative/antioxidant status in plasma of patients with different stages of colorectal carcinoma using malondialdehyde concentration, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities and distribution of superoxide dismutase isoforms. METHODS: Lipid peroxidation and antioxidant enzymes activity were estimated using spectrophotometric methods. Reverse zymography was applied for characterization of superoxide dismutase isoforms. RESULTS: Lipid peroxidation is increased in all groups compared to the control, but without differences between different stages of colorectal carcinoma. Total superoxide dismutase activity is lower in all colorectal carcinoma groups than in control, and there is a significant increase in tumor stage IV when compared with tumor stage II. Manganese superoxide dismutase isoform is dominant in all groups and its relative activities are significantly higher than activities of a copper/zinc isoform. Total peroxidase potential reflected in catalase and glutathione peroxidase activity is increased when compared to the control, but without any significant differences between colorectal carcinoma groups. Glutathione reductase activity is lower in all colorectal carcinoma groups than in control, and a significant decrease in glutathione reductase activity was obtained between patients in tumor stage II and III compared to tumor stage IV. CONCLUSIONS: Colorectal carcinoma is characterized by increased oxidative stress and antioxidant disbalance. Progression of disease is followed by an increase in redox disbalance.

Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Bupivacaine extended-release liposome injection is a novel formulation of bupivacaine designed to achieve long-acting postoperative analgesia. OBJECTIVE: The aim of this study was to compare the magnitude and duration of postoperative analgesia from a single dose of bupivacaine extended-release injection with placebo administered intraoperatively in patients undergoing hemorrhoidectomy. DESIGN: This evaluation was a multicenter, randomized, double-blind, parallel-group, placebo-controlled phase 3 study. SETTINGS: Data were obtained from 13 centers in the Republic of Georgia, Poland, and Serbia. PATIENTS: Included in this study were patients aged 18 to 86 years undergoing excisional hemorrhoidectomy. INTERVENTIONS: All patients received either a single dose of bupivacaine extended-release 300 mg or placebo administered intraoperatively via wound infiltration. MAIN OUTCOME MEASURE: The cumulative pain score was assessed by measurement of the area under the curve of pain intensity through 72 hours after study drug administration. RESULTS: One hundred eighty-nine patients were randomly assigned and treated; 186 completed the study. Pain intensity scores were significantly lower in the bupivacaine extended-release group in comparison with the group receiving placebo (141.8 vs 202.5, P < .0001). More patients in the bupivacaine extended-release group remained opioid free from 12 hours (59%) to 72 hours (28%) after surgery compared with patients receiving placebo (14% and 10%; P < .0008 through 72 h). The mean total amount of opioids consumed through 72 hours was 22.3 mg and 29.1 mg in the bupivacaine extended-release and placebo groups (P ≤ .0006). The median time to first opioid use was 14.3 hours in the bupivacaine extended-release group vs 1.2 hours in the placebo group (P < .0001). A greater proportion of patients in the bupivacaine extended-release group were satisfied with their postsurgical analgesia (95% vs 73%, P = .0007) than in the placebo group. CONCLUSIONS: Bupivacaine extended-release demonstrated a statistically significant reduction in pain through 72 hours, decreased opioid requirements, delayed time to first opioid use, and improved patient satisfaction compared with placebo after hemorrhoidectomy.

Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in preoperative serum as independent prognostic markers in patients with colorectal cancer.

Colorectal cancer is one of the leading causes of cancer related death in developed countries. One of the reasons is the absence of tumor specific diagnostic and prognostic markers. The aim of this study was to examine the correlation of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) expressions in serum and clinicopathological features of the colorectal adenocarcinoma. Another aim was to examine expression of MMP-9 in the tissue of the colorectal carcinoma in MMP-9 serum positive patients. In addition, we tried to establish the correlation between preoperative levels of serum markers (CEA and CA 19-9) and presence of MMP-2 or MMP-9. The study was performed on 32 patients with colorectal adenocarcinoma who underwent surgery and 11 patients in a control group who were operated for benign diseases. The samples were analyzed by SDS-PAGE to determine the molecular mass and SDS-PAGE zymography to determine levels of MMP-2 and MMP-9. Expression of MMP-9 was determined immunohistochemically in the tissue of the colorectal carcinoma of MMP-9 serum positive patients. MMP-2 and MMP-9 levels were increased in the serum of the patients with colorectal cancer compared to the control group. There was significant correlation in MMPs levels among the patients with tumor stage I and II and the patients with tumor stage III and IV. Obtained results did not demonstrate correlation between levels of CEA, CA 19-9 and presence of MMP-2 or MMP-9. MMP-9 expression was positive in 85% of MMP-9 serum positive patients with colorectal carcinoma. The overexpression of MMP-2 and MMP-9 strongly suggests its association with colorectal adenocarcinoma. Detection of MMP-2 and MMP-9 in serum might be useful for identification of patients with higher risk for colorectal cancer recurrence.

Primary repair of colon injuries: clinical study of nonselective approach.

BACKGROUND: This study was designed to determine the role of primary repair and to investigate the possibility of expanding indications for primary repair of colon injuries using nonselective approach. METHODS: Two groups of patients were analyzed. Retrospective (RS) group included 30 patients managed by primary repair or two stage surgical procedure according to criteria published by Stone (S/F) and Flint (Fl). In this group 18 patients were managed by primary repair. Prospective (PR) group included 33 patients with primary repair as a first choice procedure. In this group, primary repair was performed in 30 cases. RESULTS: Groups were comparable regarding age, sex, and indexes of trauma severity. Time between injury and surgery was shorter in PR group, (1.3 vs. 3.1 hours). Stab wounds were more frequent in PR group (9:2), and iatrogenic lesions in RS group (6:2). Associated injuries were similar, as well as segmental distribution of colon injuries. S/F criteria and Flint grading were similar.In RS group 15 primary repairs were successful, while in two cases relaparotomy and colostomy was performed due to anastomotic leakage. One patient died. In PR group, 25 primary repairs were successful, with 2 immediate and 3 postoperative (7-10 days) deaths, with no evidence of anastomotic leakage. CONCLUSIONS: Results of this study justify more liberal use of primary repair in early management of colon injuries. TRIAL REGISTRATION: Current Controlled Trials ISRCTN94682396.

Outcome of overlapping anal sphincter repair after 3 months and after a mean of 80 months.

BACKGROUND: The aim of this study was to determine the functional results of anal sphincter repair after a long follow-up (mean 80.1 months). METHODS: In the period 1990-2002, 65 sphincter repairs were performed. Obstetric trauma was the cause of incontinence in 72.3% cases, fistulotomy in 13.8%, nonspecific trauma in 9.2%, and war injury in 4.6%. At the time of surgery, 12 patients had undergone an urgent stoma procedure. In all cases, anal manometry, electromyography, and defecography were performed. The severity of incontinence was evaluated preoperatively using the Wexner score system. Anterior sphincteroplasty was performed in 52 cases, lateral in 9 cases, and posterior in 4 cases. RESULTS: The results were determined according to the Wexner score system and the Browning-Parks scale. The Wexner score was calculated 3 months after operation and during every follow-up visit. Preoperative scores and those at the first and last follow-up visits were analyzed. Three months after operation excellent results were achieved in 55.5%, good in 18.5%, fair in 16.9%, and poor in 9.2% patients. After follow-up (mean 80.1 months), 26.8% had excellent results, 21.4% had good results, 12.5% had fair results, and 39.3% of patients had a poor outcome. Results determined by the Wexner score system improved from 17.8 preoperatively to 3.6 three months after operation, but deteriorated over time to 6.3 after longer follow-up (p<0.001). CONCLUSION: Overlapping sphincter repair provides satisfactory results in more than two-thirds of patients initially, but the results tend to worsen over time and are satisfactory in half of patients after longer follow-up.

Perineal endometriosis in episiotomy scar with anal sphincter involvement: report of two cases and review of the literature.

Perineal endometriosis with anal sphincter involvement is a rare occurrence with only nine cases reported so far. Two such cases are presented, and the literature is reviewed. In presented cases, diagnosis was suspected at clinical exam. Anal manometry was performed in both cases and endoanal ultrasound in one case. Wide surgical excision of endometriotic mass together with part of external anal sphincter was carried out in both cases. The procedure was followed by anal sphincter reconstruction in an "overlapping" fashion in the first and "apposition" technique in the second case. Histopathologic tests confirmed endometriosis. The recovery was uneventful in both cases with excellent functional results. Two years after the operation, patients are asymptomatic and fully continent. According to the literature and our own experience, wide excision of endometrioma with primary sphincteroplasty seems to be the best chance of cure with satisfactory functional results and should be recommended.