Gulgun Tahan

Vitamin E has a dual effect of anti-inflammatory and antioxidant activities in acetic acid-induced ulcerative colitis in rats.

BACKGROUND Increased free radical production, decreased antioxidant capacity and excessive inflammation are well-known features in the pathogenesis of inflammatory bowel disease. Vitamin E is a powerful antioxidant and a scavenger of hydroxyl radicals, and it has been shown to have anti-inflammatory activities in tissues. We investigated the effects of vitamin E on inflammatory activities using an acetic acid (AA)-induced ulcerative colitis model in rats. METHODS Wistar rats were divided into 4 groups. Acetic acid was given to 2 groups of animals to induce colitis while the other 2 groups received saline intrarectally. One AA-induced colitis group and 1 control group received vitamin E (30 U/kg/d) intraperitoneally and the pair groups received saline. After 4 days, we evaluated colonic changes biochemically by measuring proinflammatory cytokine levels in tissue homogenates and by histopathologic examination. RESULTS Acetic acid caused colonic mucosal injury, whereas vitamin E administration suppressed these changes in the AA-induced colitis group (p < 0.001). Administration of AA resulted in increased levels of tumour necrosis factor-α, interleukin-1β, interleukin-6, myeloperoxidase and malondialdehyde, and decreased levels of glutathione and superoxide dismutase; vitamin E reversed these effects (all p < 0.001). CONCLUSION Our study proposes that vitamin E is an effective anti-inflammatory and antioxidant and may be a promising therapeutic option for ulcerative colitis.

Melatonin ameliorates methionine- and choline-deficient diet-induced nonalcoholic steatohepatitis in rats.

Abstract:  Nonalcoholic steatohepatitis (NASH) may progress to advanced fibrosis and cirrhosis. Mainly, oxidative stress and excessive hepatocyte apoptosis are implicated in the pathogenesis of progressive NASH. Melatonin is not only a powerful antioxidant but also an anti‐inflammatory and anti‐apoptotic agent. We aimed to evaluate the effects of melatonin on methionine‐ and choline‐deficient diet (MCDD)‐induced NASH in rats. Thirty‐two male Wistar rats were divided into four groups. Two groups were fed with MCDD while the other two groups were fed a control diet, pair‐fed. One of the MCDD groups and one of the control diet groups were administered melatonin 50 mg/kg/day intraperitoneally, and the controls were given a vehicle. After 1 month the liver tissue oxidative stress markers, proinflammatory cytokines and hepatocyte apoptosis were studied by commercially available kits. For grading and staging histological lesions, Brunt et al.’s system was used. Melatonin decreased oxidative stress, proinflammatory cytokines and hepatocyte apoptosis. The drug ameliorated the grade of NASH. The present study suggests that melatonin functions as a potent antioxidant, anti‐inflammatory and antiapoptotic agent in NASH and may be a therapeutic option.

N-acetylcysteine expresses powerful anti-inflammatory and antioxidant activities resulting in complete improvement of acetic acid-induced colitis in rats

Abstract High free radical production, low antioxidant capacity and excessive inflammation are well known features in the pathogenesis of inflammatory bowel disease. N-acetylcysteine (NAC) is a powerful antioxidant and a scavenger of hydroxyl radicals. Recently, NAC has also been shown to have anti-inflammatory activities in tissues. Our study objective was to investigate the effects of NAC on tissue inflammatory activities using an ulcerative colitis model induced by acetic acid (AA) in rats. Wistar rats (n = 32) were divided into four groups. AA-induced colitis was performed in two of the groups while the other two groups were injected with saline intrarectally. One of the AA-induced colitis groups and one of the control groups were administered NAC (500 mg/kg/day) intrarectally, and the other control groups were given saline. After 4 days, colonic changes were evaluated biochemically by measuring proinflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6], myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) levels in tissue homogenates and by histopathological examination. AA caused colonic mucosal injury, whereas NAC administration suppressed these changes in the AA-induced colitis group (p < 0.001). AA-administration resulted in increased TNF-α, IL-1β, IL-6, MPO and MDA levels, and decreased GSH and SOD levels, whereas NAC reversed these effects (all p < 0.001). In conclusion, the present study proposes that intrarectal NAC therapy has a dual action as an effective anti-inflammatory and an antioxidant, and may be a promising therapeutic option for ulcerative colitis.

Radioguided occult lesion localization (ROLL) for non-palpable breast cancer: A comparison between day-before and same-day protocols

BACKGROUND Although radioguided occult lesion localization (ROLL) has become a widely accepted technique, the optimal time interval between the radioisotope injection and surgery has not yet been determined. AIM To delineate the effects of time from the injection of the radionuclide until surgery on the ROLL success rate in a patient population diagnosed as having non-palpable breast cancer. METHODS Between December 2004 and May 2009, 75 patients underwent ROLL procedure. The day-before protocol and same-day protocols included 50 and 25 breast cancer patients respectively. RESULTS The two study groups were comparable in terms of age, localization technique, radiological findings and the type of surgical procedures (P > 0.05). No statistically significant difference was noticed in the pathological diagnosis, cancer size and the surgical margin clearance between the two groups (P > 0.05). CONCLUSIONS Same-day injection of the radiotracer was not superior to the day-before injection in ROLL. The day-before protocol can be scheduled for the convenience of both patients and hospital staff.

Axillary Web Syndrome after Sentinel Node Biopsy.

Background: Axillary web syndrome (AWS) is a self-limiting cause of morbidity in the early postoperative period after axillary surgery, but it is encountered also after sentinel lymph node biopsy. The syndrome is characterized by cords of subcutaneous tissue extending from the axilla into the medial arm. Case Report: Here, we report a patient presenting with AWS several weeks after sentinel lymph node biopsy. Conclusion: AWS has been reported to be resolved spontaneously in all patients 8–16 weeks after axillary surgery, and shoulder movements improve in this period. There is no definitive treatment modality for AWS. Patients should be reassured and informed that this condition will improve even without treatment.

Association between bactericidal/permeability increasing protein (BPI) gene polymorphism (Lys216Glu) and inflammatory bowel disease

BACKGROUND Increasing evidence suggests that innate immune system may have a key role in the pathogenesis of the inflammatory bowel disease (IBD). Bactericidal/permeability increasing protein (BPI) has an important role in the recognition and neutralization of gram-negative bacteria by host innate immune system. The polymorphism on BPI gene called Lys216Glu is on the suspected list of IBD pathogenesis. METHODS We studied the Lys216Glu polymorphism on BPI gene, in a Turkish IBD patient population. A total of 238 IBD patients; 116 Crohns disease (CD) and 122 ulcerative colitis (UC), besides 197 healthy controls were included in this study. RESULTS The Glu/Glu genotype and allele frequencies were found to be statistically higher compared to healthy control group not only in CD patients [P: 0.03, OR: 1.87 (CI 95% 1.02-3.42) and P: 0.00001 (OR: 2.07 CI 95% 1.47-2.91) respectively] but also in UC patients [P: 0.0002, OR: 2.71 (CI 95% 1.53-4.80) and P: 0.00002 (OR: 2.71 CI 95% 1.53-4.80) respectively]. CONCLUSIONS BPI polymorphism (Lys216Glu) is associated both to CD and UC. Our findings differ from the two Western European studies; one without any association and the other indicating an association only with CD. Our study is the first one reporting a novel association between BPI gene mutation (Lys216Glu) and UC.

Doxycycline-induced ulceration mimicking esophageal cancer

IntroductionDoxycycline-induced esophageal ulcer patients are mostly young persons with no history of esophageal dysfunction. Heartburn, midsternal pain and dysphagia are the most common symptoms. It has generally a benign course. The present case is the first report of doxycycline-induced extensive ulcerations, mimicking esophageal cancer in two esophageal segments alongside, in the literature.Case presentationThis report describes a 16-year-old Caucasian girl who, while taking doxycycline capsules100 mg twice a day for acne vulgaris for 3 months, developed these symptoms. An upper endoscopy revealed multiple circumferential deep ulcerations surrounding fragile, irregular, hyperemic and hypertrophic mucosa at the level of the mid-esophagus and concomitantly in the lower esophageal sphincter. The lesions were biopsied to exclude esophageal carcinoma because of the suspicious appearance in the endoscopic examination. The histopathological examination, haematoxylin and eosin stained sections showed ulceration with a mixed inflammatory infiltrate. Doxycycline was discontinued and she was given sucralfate 1 g qid and omeprazole 20 mg bid orally. All symptoms of the patient were resolved on the third day of the treatment. After 4 weeks of the therapy, an upper endoscopic control examination demonstrated normal findings.ConclusionThe present case has been an uncommon presentation of doxycycline-induced extensive ulcerations, mimicking esophageal cancer in two esophageal segments, concomitantly. Even the lesions were biopsied to exclude esophageal carcinoma. A modification on the behavior of taking drugs can prevent these unpleasant complications.

R72P Polymorphism of TP53 in Ulcerative Colitis Patients is Associated with the Incidence of Colectomy, Use of Steroids and the Presence of a Positive Family History

P53 tumor suppressor protein is one of the pivotal regulators for genome integrity, cell cycle and apoptosis. The most commonly and extensively studied single nucleotide polymorphism (SNP) of p53 is Arg>Pro substitution on codon 72 (R72P). Although we know that the SNP has unique functional effects on the protein, its clinical significance is not clearly identified yet. Aim of the study was to access the relationship between R72P genotype distribution and clinical variables in patients with ulcerative colitis (UC) and colorectal cancer (CRC). Genomic DNA samples were extracted from 95 UC, 50 CRC, and 219 healthy controls. R72P genotype analysis was carried out with polymerase chain reaction following by restriction enzyme digestion. We observed that Pro allele carriage is a strong risk factor for CRC (OR = 3.03; 95%CI = 1.91–2.40; p = 0.003), but only modest association with UC (OR = 1.61; 95%CI = 0.98–2.65; p = 0.059) (Pro/Pro and Pro/Arg genotypes vs. Arg/Arg genotype). We did not find any correlation between genotype distribution of the polymorphism and clinical parameters of CRC, but in UC, Pro/Pro genotype was significantly related to an inflammatory bowel disease family history (OR = 8.0; 95%CI = 1.68–38.08, p = 0.015), and Arg/Pro genotype was significantly associated with the history of disease-related colectomy (OR = 17.77; 95%CI = 0.98–323.34, p = 0.012) and steroid use (OR = 10.14; 95%CI = 2.63–39.12, p = 0.0002). Our data suggest that R72P variant seems to be associated with high risk for development of CRC but carries low risk for development of UC. R72P genotypes might be a useful predictive marker for surgical and medical treatment of UC.

Recurrent granulomatous mastitis mimicking inflammatory breast cancer.

Granulomatous mastitis (GM) is an uncommon benign breast lesion. Diagnosis is a matter of exclusion from other inflammatory, infectious and granulomatous aetiologies. Here, we presented an atypical GM case, which had clinical and radiologic features overlapping with inflammatory breast cancer (IBC). The disease had multiple recurrences. The patient is a 40-year-old Caucasian woman with a sudden onset of left breast swelling accompanied by diffuse skin redness, especially of the subareolar region and malodorous yellow nipple discharge from the left nipple. The disease progressed on antibiotic treatment and recurred after local resection. A similar lesion developed even after bilateral mastectomy. GM may show clinical/radiologic features suggestive of IBC. Multiple recurrences can be occasionally encountered. GM after recurrence could be much more alarming clinically. Pathology confirmation is the key for accurate diagnosis and a multidisciplinary approach is important to rule out IBC.

The Effects of Preoperative Needle-Core Breast Biopsy on Resected Tissue Volume, Margin Status and Cosmetic Outcomes in Breast Conserving Surgery.

Background: The amount of breast volume excised is an important determinant for cosmetic outcomes after breast-conserving surgery. Positive margins after breast conserving surgery negatively influence cosmetic outcomes by necessitating re-excisions. In this study, our aim was to evaluate the hypothesis that preoperative localized needle-core breast biopsy (LNCB) diagnosis can reduce the resected volume, margin positivity and cosmetic discontent after breast conserving surgery. Methods: Two hundred sixty five women (mean age:57; range 16-85 years) operated upon by a single dedicated breast surgeon in the year 2007 form the cohort for this study. All underwent excision of lesion with curative intent. LNCB was performed before breast conserving surgery in 237 (89%) patients. The final pathology result were classified by benign, high risk, DCIS, or invasive cancer and compared with the pre-op pathological diagnosis by LNCB. The cosmetic results were determined as excellent, good, fair, or poor during the post-operative period. Associations between various factors were analyzed using Student-t test, ANOVA test and chi-square test. Results: The resected volume (mean±SD) of the patients with preoperative needle core biopsy was higher than patients without core biopsy (101.11±78.1 cm 3 vs 43.37±30.8 cm 3 ; p=0.001). The core biopsy results were 36 (15%) benign, 45 (19%) high risk, 46 (19.5%) DCIS, and 110 (46.5%) invasive breast cancer. The LNCB and surgical path were concordant in 96% of cases. The resected volumes were higher in invasive cancer and DCIS cases.Re-excision for positive margins were necessary in 9 (19.5%) of DCIS cases and 24 (21.8%) with a diagnosis of invasive cancer. Resection volumes were the same for a LNCB diagnosis of high risk lesion whether the final surgical path was benign or malignant (65.3±52.7 cm 3 v. 69.8±8.7 cm 3 ). The cosmetic outcomes of the surgery were excellent in 98% to 100% of patients who had lower volume resections; however, the outcome was less than excellent in 15% to 26% of patients if the final resection volume was more than 100 cm 3 . Conclusions: Pre-operative LNCB that establishes the benign nature of a lesion allows a more limited resection with improved cosmetic outcomes. Establishing the diagnosis of DCIS or invasive breast cancer by pre-operative biopsy allows for surgical planning of wider resection volumes, but the need for re-excision based on positive margins remains high, suggesting that newer imaging modalities that allow 3-demensional planning of segmental resection or even wider resections employing oncoplastic techniques are necessary. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1032.