Nerve/Glial Antigen 2: A Novel Target for Anti-Tumor Therapy in Colorectal Cancer.

BACKGROUND/AIMS: To identify cell surface markers selectively expressed by tumor cells and tumor vasculature is the current goal for tumor therapy. One such marker is nerve/glial antigen 2 (NG2), which is a transmembrane glycoprotein. We aimed to investigate the expression of NG2 in colorectal cancer (CRC) and its association with clinicopathological parameters. METHODS: Immunohistochemical staining of NG2, vascular endothelial growth factor, and CD34 in 65 patients diagnosed with CRC over a 5-year period was performed. NG2 expression in both tumor cells and tumor vasculature was scored according to the German Reactive Scoring System. The association between NG2 and patient and tumor characteristics was analyzed. RESULTS: NG2 was expressed by tumor cells in 56.9%, tumor vasculature in 43%, and simultaneously by both in 27.6% of the cases. Tumor cell NG2 was more common in elderly patients (p = 0.023) and vascular NG2 was associated with better tumor differentiation (p = 0.035). Notably, vascular NG2 was expressed in half of the patients with left colon cancer, although it was not expressed in a majority of those with right colon cancer (50.9 vs. 17.7%, p = 0.041). CONCLUSION: Both tumor cell and vascular NG2 expression were shown to be present in a significant number of patients with CRC and this makes NG2 a double target for anti-tumor therapies. Such therapies might be more effective for elderly patients with well-differentiated left colon cancer.

Non-operative therapy for pilonidal sinus in adolescence: crystallised phenol application, 'report of a case'.

Pilonidal sinus (PS) is an acquired disease at the sacrococcygeal region that can be treated by different surgical techniques. Crystallised phenol application seems to be an alternative therapy to surgery with higher success rates, lower costs, faster recovery and earlier return to work. We aimed to state the success of phenol application for PS in adolescence. A 14-year-old boy with recurrent PS, an 18-year-old girl with the history of pilonidal abscess and a 15-year-old girl with PS was hospitalised. All patients underwent phenol application in an outpatient setting. The patients were followed thereafter. The 14-year-old boy and 18-year-old girl did not face any problems and all sinuses healed completely. The 15-year-old girl was followed for 2 weeks because of intergluteal maceration and ongoing drainage. She underwent another phenol application and the course after intervention was uneventful with complete healing of the sinus. Crystallised phenol application seems to be a promising non-operative therapy for PS in adolescents.

Permanent stoma not only affects patients' quality of life but also that of their spouses.

BACKGROUND: Living with a permanent colostomy can significantly diminish a patient's quality of life. However, little is known about the effects on the patient's spouse. Therefore, the aim of the present study was to evaluate the quality of life of spouses whose partners had undergone sphincter-sacrificing surgery for rectal carcinoma. METHODS: We studied 56 couples after one partner underwent sphincter-sacrificing surgery for rectal carcinoma: female spouses (n = 30) and male spouses (n = 26). To identify how surgery affected the life standards of the spousal population, questionnaires were constructed by the Department of Public Health, General Surgery and Psychology at the University of Ankara. RESULTS: Sixteen of 26 male spouses increased time spent at home, whereas 10 of 30 female spouses increased time spent at home (p < 0.05, male spouses versus female spouses). All of the spouses had been sexually active before their partners' operation; however 20 of 26 male spouses and 10 of 30 female spouses were sexually inactive afterward (p < 0.05, male spouses versus female spouses). Ten male patients and 3 female patients wanted their colostomy care to be managed by their spouses (p < 0.01, female spouses versus male spouses). CONCLUSIONS: In a patient with a colostomy, the social and sexual aspects of the life of the patient's spouse are affected. This observation needs to be taken into account when patients are preoperatively counseled. Therefore, preoperative counseling regarding the possible problems after surgery should not only include the patient but also the spouse.

Enteral glutamine pretreatment does not decrease plasma endotoxin level induced by ischemia-reperfusion injury in rats.

AIM: To investigate whether oral glutamine pretreatment prevents impairment of intestinal mucosal integrity during ischemia-reperfusion (I/R) in rats. METHODS: The study was performed as two series with 40 rats in each. Each series of animals was divided into four groups. The first group was used as a control. Animals in the second group were only pretreated with oral glutamine, 1 g/kg for 4 d. The third group received a normal diet, and underwent intestinal I/R, while the fourth group was pretreated with oral glutamine in the same way, and underwent intestinal I/R. Intestinal mucosal permeability to (51)Cr-labeled EDTA was measured in urine in the first series of animals. In the second series, histopathological changes in intestinal tissue and plasma endotoxin levels were evaluated. RESULTS: Intestinal I/R produced a significant increase in intestinal permeability, plasma endotoxin level and worsened histopathological alterations. After intestinal I/R, permeability was significantly lower in glutamine-treated rats compared to those which received a normal diet. However, no significant change was observed in plasma endotoxin levels or histopathological findings. CONCLUSION: Although glutamine pretreatment seems to be protective of intestinal integrity, upon I/R injury, such an effect was not observable in the histopathological changes or plasma endotoxin level.

Nadroparine blunts lipopolysaccharide-induced hypothermia and behavioral depression in mice.

INTRODUCTION: Despite the use of appropriate antimicrobial therapy and intensive care support, sepsis remains a major cause of morbidity and mortality in surgical clinics. Low-molecular weight heparin treatment may reduce mortality and end-organ failure in sepsis. The purpose of this study was to compare the effects of low-molecular weight heparins such as nadroparine, enoxaparine, and dalteparine on lipopolysaccharide-induced acute phase reaction in mice. METHODS: Lipopolysaccharide was injected intraperitoneally to produce a systemic inflammatory response and septic shock-like effects in adult male BALB/c mice. Mices were treated with low-molecular weight heparins (nadroparine, enoxaparine, dalteparine) and unfractioned heparin in different doses and times. Rectal temperature and spontaneous locomotor activity of the mice were evaluated. RESULTS: Lipopolysaccharide (1 mg/kg, intraperitoneal) produced a hypothermia that occurred 20 minutes after injection. Nadroparine pretreatment (23.75 U/kg, sc) 2 hours before lipopolysaccharide challenge, but not synchronous injection, inhibited the hypothermic response. Pretreatment with equivalent doses of enoxaparine or dalteparine had no effect on the hypothermia. The high dose of lipopolysaccharide (60 mg/kg, intraperitoneal) caused more profound hypothermia and also inhibited spontaneous locomotor activity 24 hours after injection. Synchronous nadroparine administration partially attenuated the hypothermia and significantly abolished the depression of spontaneous locomotor activity. CONCLUSIONS: The results suggest that some low-molecular weight heparins such as nadroparine might be beneficial in high-risk surgical patients because of their potential anti-inflammatory action, in addition to their efficiency in preventing thrombo-embolic complications.

Mucins in the colorectal neoplastic spectrum with reference to conventional and serrated adenomas.

BACKGROUND/AIMS: Alterations in expression of mucins and aberrant expression of various types of mucin genes were observed in colorectal adenomas and carcinomas, though their significance in neoplastic transformation of colorectal epithelium is yet to be determined. The aim of this study was to determine expression of MUC1, MUC2, MUC5AC, and MUC6 through conventional adenoma-carcinoma sequence and polyps involved in the "serrated" pathway of the colorectum using tissue array technique. METHODS: In this study, a total of 172 cases including 100 colorectal polyps [8 hyperplastic polyps, 10 sessile serrated adenomas, 19 tubular, 37 tubulovillous, and 26 villous adenomas], 16 adenomas with intramucosal carcinoma, 28 conventional colorectal cancers, and 28 normal mucosae were examined. Tissue array blocks were prepared and sections were stained immunohistochemically for MUC1, MUC2, MUC5AC, and MUC6. RESULTS: Expression of MUC1 significantly increased in close correlation with the neoplastic process and reached its highest values in intramucosal carcinomas and conventional colorectal cancers (p<0.001). In contrast, MUC2 expression showed a significant decrease in intramucosal carcinoma and conventional colorectal cancer groups (p<0.001). Sessile serrated adenomas exhibited the highest MUC5AC expression while adenomatous polyps showed an increase in MUC5AC expression in parallel with neoplastic progression (p<0.001). Hyperplastic polyps seemed to lie between normal mucosa and sessile serrated adenomas in terms of mucin expression, suggesting that they are morphologically and histogenetically linked. CONCLUSIONS: Upregulation of MUC1 and MUC6 through the adenoma-carcinoma sequence together with downregulation of MUC2 and MUC5AC at the neoplastic end of the spectrum seem to follow the steps of malignant transformation.

Enteral and intraluminal short-chain fatty acids improves ischemic left colonic anastomotic healing in the rat.

BACKGROUND AND AIMS: This study assessed the effect of short-chain fatty acids (SCFAs) on the healing of ischemic colonic anastomosis and compared the enteral and intraluminal (transrectal) forms of SCFAs in the same study. MATERIAL AND METHODS: Left colonic ischemia was induced and a 1-cm left colon resection 2-4 cm above the peritoneal reflection was performed through a midline incision. In all, 160 rats were divided into eight groups: a control group, an ischemia group, a transrectal SCFAs group, an ischemia + transrectal SCFAs group, an enteral guar gum group, an ischemia + enteral guar gum group, an ischemia + enteral sham group, and a control + enteral sham group. The animals in each group were anesthetized again on day 4 or 7 after the operation for in vivo analytic procedures. Wound complications, intestinal obstructions, and anastomotic complications were recorded. Periperitoneal adhesions were graded. The strength of each anastomosis was assessed by measuring its bursting pressure. RESULTS: There were significantly more dense intra-abdominal adhesions in the ischemic group and ischemia + enteral sham group. Five animals in the ischemia group, six in the ischemia + enteral sham group, and one in each of the control and ischemia + transrectal SCFA groups developed anastomotic dehiscence. The median bursting pressures were significantly lower in the ischemic group and in the ischemia + enteral sham group on the 4 day and 7 days. CONCLUSION: Deleterious effects of ischemia on left colonic anastomotic healing were significantly prevented by the administration of either 7 days' pretreatment with enteral guar gum or the intraluminal instillation of SCFAs. There were no significant differences between enteral and intraluminal SCFA groups.

Role of integrins and intracellular adhesion molecule-1 in lung injury after intestinal ischemia-reperfusion.

BACKGROUND: We tested the hypothesis that lung injury after intestinal ischemia-reperfusion (IR) requires the activation of CD11/CD18 glycoprotein complex and its ligand, intracellular adhesion molecule-1 (ICAM-1), on pulmonary endothelial surface. METHODS: Rats were assigned to one of six groups including sham operation, intestinal IR (60/120 min) and IR plus treatment with one of the following monoclonal antibodies against CD11a, CD11b, CD18, and ICAM-1. Pulmonary microvascular permeability, neutrophil accumulation, and expression of adhesion molecules were evaluated. RESULTS: Intestinal IR resulted in lung injury characterized by a marked increase in microvascular permeability, neutrophil accumulation and upregulated expression of leukocyte integrins and ICAM-1. The increase in pulmonary microvascular permability and neutrophil accumulation elicited by intestinal reperfusion was effectively prevented by administration of blocking antibodies against ICAM-1, CD11, and CD18. CONCLUSIONS: These results indicate that adhesion molecules contribute to the lung injury after intestinal IR. Immunoneutralization of certain of these adhesion molecules may prevent intestinal IR-induced lung injury.